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Abnormal liver function tests Australian tor


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                                                                                                                                  What are LFTs?

                                                                                                                                  patterns of
                                                                                                                                  LFT changes

                                                                                                                                  LFTs and
                                                                                                                                  investigation of
                                                                                                                                  liver disease

                                                                                                                                  Five common
                                                                                                                                  LFT challenges

                                                                                                                                  The authors

                                                                                                                                  PROFESSOR GEOFF FARRELL,
                                                                                                                                  professor of hepatic medicine,
                                                                                                                                  Australian National University
                                                                                                                                  Medical School, and
                                                                                                                                  gastroenterology and
                                                                                                                                  hepatology unit, The Canberra
                                                                                                                                  Hospital, Garran, ACT.

    Abnormal liver                                                                                                                ASSOCIATE PROFESSOR

    function tests
                                                                                                                                  NARCI TEOH,
                                                                                                                                  associate professor of
                                                                                                                                  medicine, Australian National
                                                                                                                                  University Medical School,
                                                                                                                                  and gastroenterology and
                                                                                                                                  hepatology unit, The Canberra
                                                                                                                                  Hospital, Garran, ACT.

CONTEMPORARY practitioners                         encounters with non-specific and       next, interspersed with some general
are well versed in how to manage                   non-spectacular changes in LFTs,       comments on the significance of
symptomatic patients with diagnos-                 often performed for health screen-     abnormal LFTs for people taking
tic patterns of liver biochemical                  ing or miscellaneous reasons and in    medications, the overweight, those
tests, such as those that suggest hep-             people who are overtly well.           living with hepatitis B or C virus
atitis, biliary obstruction or medical               This article discusses some typi-    infections, and those who may have
cholestasis, or hepatic malignancy.                cal scenarios for reflection on what   cirrhosis.
More challenging are the everyday                  doctors need to think about and do                          cont’d next page
 HOW TO TREAT Abnormal liver function tests

     Five common LFT challenges
 BEFORE reading on, GPs                                                                                 all normal). He has gained          Case 4                                recent change in medication.
 are invited to consider the                                                                            10kg in weight since his            VW, a 32-year-old IT con-                As his new GP, now that
 following cases in light of                                                                            second marriage 18 months           sultant who emigrated from            he has moved to a rural
 their current knowledge.                                                                               ago. What further investi-          Burma in 1998, has known              area, you find he is mildly
                                                                                                        gations might be useful,            since student days that, like         anaemic (Hb 11.5g/L) with
 Case 1                                                                                                 and how would you treat             several other family mem-             iron deficiency, and a platelet
 AF is a 24-year-old son of a                                                                           him?                                bers, he is hepatitis B posi-         count of 120 × 10 /L
 family friend who recently                                                                                                                 tive. He has always assumed           (normal range 150-400 ×
 returned from Mexico. He                                                                               Case 3                              he is healthy because only            10 /L). ALT was 30 U/L,
 complains of profound                                                                                  NO, a 55-year-old executive         “two of three” tests are pos-         AST 50 U/L, bilirubin
 malaise for 10 days, with                                                                              assistant to a government           itive (HBsAg positive, anti-          normal, albumin 32g/L,
 intermittent vomiting and                                                                              minister, was diagnosed with        HBc positive, HBeAg nega-             normal alkaline phos-
 dark urine. He completed a                                                                             chronic hepatis C virus (HCV)       tive). You confirm this               phatase; alfa-fetoprotein 3
 four-week course of doxycy-                                                                            infection in 1992. When             serological picture, and anti-        kU/mL (normal range <12).
 cline two weeks ago, taken                                                                             reviewed from time to time,         HCV is not detectable. LFTs           Abdominal CT is normal
 for recurrence of acne.                                                                                LFTs have been normal and           appear satisfactory, with             apart from possible early
    He had combined hepati-                                                                             she became lost to follow-up.       ALT 38 U/L. Is this normal?           portal hypertension.
 tis A and B vaccination                                                                                   On presenting for a much-        How would you test                       You send him to a city
 before travel, and has anti-                                                                           delayed Pap smear, NO’s GP          whether he is indeed a                gastroenterologist, who per-
 bodies to both hepatitis A                                                                             persuades her to have repeat        ‘healthy carrier’?                    forms gastroscopy and
 (total, not IgM) and hepatitis                                    Case 2                               LFT testing, and also orders                                              colonoscopy. Finding no
 B (anti-HBs alone). His                                           BL, a 45-year-old success-           an AST test. The results show       Case 5                                abnormality other than gas-
 bilirubin level is 25mmol/L                                       ful car dealer, presents with        bilirubin 25mmol/L, ALT 60          DT, a 56-year-old retired             tric erosions, which he
 (normal range <20), AST                                           a letter from an insurance           U/L, AST 80 U/L, GGT 250            submariner, has had three             attributes to aspirin use, the
 5800 U/L (normal range                                            company indicating he has            U/L, albumin 34g/L (normal          drinks a day for the past five        gastroenterologist sends DT
 <40), ALT 4600 U/L (normal                                        been refused an income-              range 35-53). What could be         years but drank more heav-            back to you, indicating he
 <40), with albumin, total                                         protection policy because of         going on here? How would            ily during his time in the            would be happy to see him
 protein and alkaline phos-                                        abnormal LFTs (ALT 70                you approach the situation          Navy. He has type 2 diabetes          again “if hepatic synthetic
 phatase normal. What are the                                      U/L; GGT 90 U/L [normal              with NO, who is far from            (HbA1C 6.8%), easy-to-con-            function deteriorates”. How
 possible diagnoses, and does                                      range <50]; bilirubin, albu-         enchanted with the ‘medical         trol hypercholesterolaemia            should you manage this
 he need urgent referral?                                          min, alkaline phosphatase            model’?                             and hypertension, without a           patient?

     What are LFTs?
 ‘LIVER function tests’ is a time-
                                                       Table 1: Causes of elevated liver enzymes                                     Table 2: Different reasons for elevated serum bilirubin
 honoured term for tests performed
                                          Pattern                          Possible causes                                                                concentration
 in clinical chemistry laboratories
 when one is considering or wants to      Hepatocellular pattern                                                              A. Not liver disease (other LFTs normal)
 exclude liver or biliary disease.        • ALT more than five times the   • Acute viral hepatitis
                                                                                                                                Haemolytic anaemia (eg, spherocytosis)
 However, LFTs is a misnomer, as            upper limit of normal (ULN)      (A,B,C,E in travellers)
                                          • GGT raised                     • Drug-induced liver injury                          Gilbert’s syndrome
 few of the individual tests are spe-
                                          • Alkaline phosphatase less      • Chronic hepatitis B or C                           Cardiac failure
 cific for the liver, and most do
 not truly reflect liver function          than twice the ULN              • Alcoholic hepatitis (remember to order             Severe bacterial infection and critically ill patients (pneumonia, Gram-
 (though several do indicate disease)                                         an AST test — see text)                           negative septicaemia, ‘ICU jaundice’)
 (table 1).                                                                • Non-alcoholic fatty liver disease (NAFLD)        B. Hepatobiliary disease
    For example, serum bilirubin                                              and non-alcoholic steatohepatitis (NASH)          Hepatitis — acute or chronic, any cause (ALT typically elevated > fivefold,
 level may be elevated for diverse                                         • Autoimmune hepatitis                               except with alcoholic liver disease)
 reasons (table 2). Importantly, even                                      Rarer causes
                                                                                                                                Cholestasis — biliary obstruction or medical causes (alkaline phosphatase
 minor increases in serum bilirubin                                        CMV or EBV hepatitis; Wilson’s disease
                                                                                                                                and GGT substantially elevated, ALT less so)
 accurately reflect impaired liver                                         (children, young adults); alfa-1-antitrypsin
                                                                           deficiency                                           Cirrhosis — the only condition in which level of bilirubin reflects liver
 function in the presence of cirrhosis,                                                                                         function (minor changes may be important)
 and bilirubin is a key prognostic                                         NB: Haemochromatosis alone rarely
 factor in chronic cholestasis with                                        causes abnormal LFTs — consider alcohol
 cirrhosis, such as primary biliary                                        and NAFLD (diabetes) in C282Y                                   Table 3: Common causes of low serum albumin
 cirrhosis. Likewise, serum albumin                                        homozygotes with abnormal biochemistry
                                                                                                                              • Impaired synthesis due to poor nutrition (lack of amino acid building blocks)
 concentration may be low for a
                                          Cholestatic pattern                                                                 • Enhanced breakdown (cachexia of malignancy, HIV, etc)
 variety of reasons (table 3).
                                          • Alkaline phosphatase more      Biliary obstruction:                               • Haemodilution (second trimester of pregnancy, venous blood taken from
                                           than twice the ULN              • Choledocholithiasis                                drip arm)
 Utility of AST (as well as ALT)
 Most auto-analysers perform ALT          • GGT raised more than five      • Pancreatic cancer                                • Protein loss (nephrotic syndrome, protein-losing enteropathy)
 assays when ‘LFTs’ are ordered,           times the ULN                   • Cholangiocarcinoma                               • Cirrhosis — even ‘borderline low’ values may be significant
 and this is the most sensitive and       • ALT less than five times       Medical:
 specific test for hepatocyte injury.      the ULN                         • Drug-induced liver injury                         In both cases, the usual ALT:AST            hepatic drug reactions also feature
 However, it can be very useful to                                         • Primary biliary cirrhosis                       ratio of >2 is lost; instead, it falls to     disproportionate increases in AST
 order AST as well when one sus-                                           • Primary sclerosing cholangitis                  0.8. An ALT:AST ratio of ≤0.8 has             as well as ALT levels, as does
 pects alcoholic liver disease or cir-                                     • Neoplastic infiltration of liver                relatively poor sensitivity but high          Wilson’s disease in children and
 rhosis (any cause).                                                       • Sarcoidosis                                     specificity for cirrhosis. Some               young adults.

     Diagnostic patterns of LFT changes
 Hepatitis                                                            However, up to 10% of             hospital inpatients (figure 1A).    mune conditions, autoanti-            line phosphatase is elevated
 MAJOR elevations of ALT                                           cases may be due to drugs.             Major elevations of ALT,          bodies, high serum IgG).              more than twofold in associ-
 (more than fivefold) indicate                                     These include those prescribed       often with jaundice and                When suspected, phone con-         ation with major elevation of
 hepatitis, which in the com-                                      by doctors (or alternative           reduced serum albumin level,        sultation with a specialist is rec-   GGT.
 munity is usually viral:                                          medicine practitioners) within       are also found with autoim-         ommended, as treatment with              Practitioners       should
 • Hepatitis A, B or C.                                            the previous 6-12 weeks in the       mune hepatitis. Note that the       prednisone and azathioprine           remember that cholestasis is
 • Hepatitis E after travel to                                     case of adverse drug reactions,      older term ‘chronic active hep-     needs to be instituted promptly       not only due to biliary
   endemic regions (Mexico,                                        but occasionally inadvertent         atitis’ is no longer used by        in severe cases while awaiting        obstruction        (so-called
   south-east and south Asia,                                      or deliberate paracetamol poi-       hepatologists because 25% of        formal review by the hepatolo-        ‘obstructive jaundice’), but is
   western China).                                                 soning, or the use of recre-         cases present acutely. The          gist as soon as possible.             often attributable to non-sur-
 • In young people, occasion-                                      ational agents, such as ecstasy.     diagnosis and treatment of this                                           gical conditions, especially
   ally Epstein–Barr virus, with                                      Hepatotoxicity due to drug        condition rest on recognising       Cholestasis                           drug reactions (figure 1B). It
   other features of infectious                                    overdose and adverse drug            the autoimmune pathogenesis         The other classic pattern of          may also:
   mononucleosis, or cytomega-                                     reactions are more frequent          (association with family or         LFT abnormalities is                  • Occur in pregnancy
   lovirus.                                                        causes of abnormal LFTs in           personal history of autoim-         cholestasis, when serum alka-                          cont’d page 32

30   | Australian Doctor | 9 April 2010                                        
 HOW TO TREAT Abnormal liver function tests

 from page 30
                                          Figure 1: Drug reactions are a relatively common and important cause of abnormal LFTs in general            Table 4: What does a raised serum GGT level mean?
   (cholestasis of pregnancy).
                                          practice, or in hospital settings. Patterns of LFT changes may resemble viral hepatitis.                   More than any other liver biochemical test, GGT needs to be
 • Complicate viral hepatitis.
                                          A: A case of enalapril hepatitis — liver cell injury with lobular and portal-tract inflammation are
 • Reflect other autoimmune                                                                                                                          considered in context of the clinical problem and the results of
                                          evident, the latter including neutrophils and eosinophils; ALT peaked at 800 U/L;) or cholestasis
   liver diseases, such as pri-           B: Terbinafine hepatitis — there is no portal tract oedema or inflammation to suggest biliary              other LFTs
   mary biliary cirrhosis, scle-          obstruction. Instead bile plugs are evident (orange pigment collectors) and there is feathery              • GGT level increases with any pattern of hepatobiliary disease
   rosing cholangitis and atyp-           degeneration of liver cells containing bile pigment. The patient presented with elevation of serum           (hepatitis, cholestasis, infiltration, cirrhosis)
   ical cases of autoimmune               alkaline phosphatase, thought to be due to biliary obstruction.
   hepatitis.                                                                                                                                        • For increases in serum alkaline phosphatase level,
    Jaundice and bilirubinuria                                                                                                                         concomitant elevation of GGT level indicates alkaline
                                                                                                                                                       phosphatase is of liver origin, not bone origin as in disorders
 (reflecting conjugated hyper-              A                                                                                                          such as Paget’s disease or metastases
 bilirubinaemia) is often pres-
 ent with cholestasis, but not                                                                                                                       • Changes in GGT level are one of the few biochemical markers
 always, depending on the                                                                                                                              of excessive alcohol intake: useful when monitoring patients
 severity of impaired bile flow                                                                                                                        attempting alcohol abstinence
 or extent of biliary obstruc-
                                                                                                                                                     • Isolated elevated GGT level may occur in NAFLD, but usually
                                                                                                                                                       with ALT abnormalities, fluctuating with weight changes, and
    One feature of the cholesta-
                                                                                                                                                       other results (lipids, blood glucose)
 tic pattern of LFTs that often
 confuses doctors is the con-                                                                                                                        • Isolated elevated GGT level may be explained by drug therapy,
 comitant elevation of ALT;                                                                                                                            particularly anticonvulsants
 this often occurs with                                                                                                                              • In a well person with normal hepatic/abdominal imaging,
 cholestasis because bile-acid                                                                                                                         isolated elevation of GGT level is sometimes never explained
 accumulation in the liver is                                                                                                                          (and should then be ignored)
 hepatotoxic. The resultant
 ‘mixed picture’ is not particu-
 larly helpful diagnostically,                                                                                                                        acids may cleave GGT from            phatase, increases are a rela-
 except that it is rather                                                                                                                             the plasma membrane by               tively sensitive marker for
 common with hepatic drug                                                                                                                             their detergent effects).            hepatic malignancy, or dis-
 reactions.                                                                                                                                            Thus, serum GGT levels              orders such as sarcoidosis.
    In a patient with biliary                                                                                                                       increase no matter what the            But in the 21st century, a rise
 pain or acute pancreatitis,                                                                                                                        pathophysiological type of             in GGT level typically, but
 ALT elevation is more indica-                                                                                                                      hepatobiliary         disease,         not always in association
 tive of gallstone disease than             B                                                                                                       whether it be hepatitis or             with minor ALT elevation,
 concomitant liver disease.                                                                                                                         cholestasis (most causes,              is most often indicative of
 However, the latter is possible                                                                                                                    although not in pregnancy).            fatty liver disease, as dis-
 when there is cholestasis with                                                                                                                     In addition, unsafe levels of          cussed later.
 coincident non-alcoholic fatty                                                                                                                     alcohol intake and a wide                 In summary, more than any
 liver disease (NAFLD) —                                                                                                                            range of drugs increase GGT            other liver biochemical test,
 especially with type 2 diabetes                                                                                                                    levels by acting as enzyme-            GGT needs to be considered
 or alcoholic liver disease.                                                                                                                        inducing agents that stimulate         in the context of the clinical
    The more severe and acute                                                                                                                       its synthesis and release from         problem and the results of
 the biliary obstruction, the                                                                                                                       the liver.                             other LFTs (table 4).
 higher the ALT level. Values                                                                                                                          Changes in GGT are one of              We have been known to
 exceeding 500 IU/L are occa-                                                                                                                       the few biochemical markers            recommend to occasional
 sionally seen the day after                                                                                                                        of alcohol dependence.                 ‘worried well’ individuals to
 complete biliary obstruction,                                                                                                                      Improvement during absti-              discontinue measuring their
 and such patients must be                                                                                                                          nence, or exacerbation with            repeatedly abnormal GGT
 referred urgently for ultra-                                                                                                                       recidivism, is useful when             when it is an isolated abnor-
 sonography and gastroentero-                                                                                                                       monitoring patients in general         mality. However, such
 logical intervention to relieve                                                                                                                    practice. In dealing with this         people must:
 the obstruction.                                                                                                                                   common problem, blood test             • Be asymptomatic.
                                                                                                                                                    results such as GGT can                • Not be alcohol dependent.
 The distractions of GGT                                                                                                                            sometimes serves as a focus            • Have a healthy lifestyle
 elevation                                                                                                                                          for discussion about progress            (exercise, food portions,
 Among currently used LFTs,                                                  ple, the value of raised GGT      of hepatocytes, and so is read-      and unfinished business.                 diet).
 the one that causes doctors the                                             in supporting a diagnosis of      ily shed into blood when:               Another attribute in                • Have normal waist cir-
 most confusion is the GGT. In                                               cholestasis was mentioned         • Hepatocellular        injury       favour of GGT testing is its             cumference.
 some ways it is the least useful                                            above.                              occurs.                            sensitivity as an indicator of         • Have repeatedly normal
 single test, but it is invaluable                                             GGT is located on the sur-      • Synthesis is stimulated.           hepatic infiltration. Along              appearances on hepatic
 in niche contexts. For exam-                                                face (outer plasma membrane)      • Bile-acid levels rise (bile        with serum alkaline phos-                ultrasound (or CT).

     Other assessments
 Physical signs                                 • In ill patients, serum creatinine and                                             chronic hepatitis C or NAFLD, even            tion early enough to consider transfer
 Cardinal physical signs of cirrhosis             serum sodium.                                                                     borderline thrombocytopenia is a              to a liver transplantation unit (which
 include:                                                                                                                           fairly accurate indicator of stage 3          should be consulted when such a
 • Hard liver edge.                             Platelet count                                                                      (bridging) fibrosis or cirrhosis (stage 4     patient is under observation).
 • Spider naevi.                                As a matter of course, patients sus-                                                fibrosis).
 • Splenomegaly and other signs of              pected or known to have chronic liver                                                  The traditional explanation for this       Serum creatinine and sodium
   portal hypertension.                         disease will be ordered an FBC as                                                   and the sometimes accompanying                These indices are very valuable in
 • Ascites.                                     well as LFTs. Anaemia is an impor-                                                  leucopenia is ‘hypersplenism second-          considering the prognosis for patients
 • Muscle wasting.                              tant complication of portal hyperten-                                               ary to portal hypertension’. Decreased        with decompensated cirrhosis. For
 • Subclinical hepatic encephalopathy           sion, most often from iron deficiency                                               platelet survival is likely to play a role,   example, creatinine is now part of
   (neuro-psychiatric and neuro-phys-           caused by chronic blood loss due to                                                 but more important is reduced blood           the Method for assessment of End-
   iological deficits but with a normal         portal hypertensive gastropathy, but                                                levels of thrombopoietin, a protein           stage Liver Disease (MELD) score
   mental and neurological status on            occasionally from more substantial                                                  that regulates platelet synthesis and         used to determine the priority for
   global clinical examination).                bleeding from the same lesions, a                                                   release and whose synthesis is                organ allocation in Australia/New
                                                peptic ulcer or oesophago-gastric                                                   decreased in the cirrhotic liver. The         Zealand, and all international liver
 Other ‘liver tests’                            varices. Leucocytosis may indicate                                                  readily available platelet count has          transplantation programs. This spe-
 After clinical examination, hepatol-           bacterial infection, alcoholic hepatitis                                            become the hepatologist’s ‘surrogate          cialised aspect will not be discussed
 ogists wondering whether a patient             or hepatocellular carcinoma.                                                        liver function test’.                         further here.
 may have cirrhosis pay as much                    However, gastroenterologists and
 attention to tests that are not part           hepatologists are most concerned                                                    PT and INR                                    Serum bile acids
 of routine LFTs (plus AST) as they             with checking for thrombocytopenia.                                                 Impaired synthesis of clotting facIn          Specialists sometimes use two other
 do to serum bilirubin and albumin              Circulating levels of platelets fall as                                             acute hepatitis, paracetamol hepato-          tests as supportive evidence when
 concentrations. Key additional                 fibrotic liver disease progresses,                                                  toxicity and other instances of clini-        assessing particular patterns of liver
 ‘liver’ tests include:                         almost linearly in relation to fibrotic                                             cally significant liver injury, daily         test abnormalities.
 • Platelet count.                              severity. In a patient with what might                                              monitoring of PT or INR is essential             The first is measurement of serum
 • Prothrombin time (PT) or INR.                otherwise seem like ‘run of the mill’                                               to detect hepatic functional deteriora-       bile acid levels. This test is rarely

32   | Australian Doctor | 9 April 2010                                               
Figure 2: Hepatocellular carcinoma complicates cirrhosis. It is usually incurable
when >5cm in diameter and when presenting with symptoms. Screening by
                                                                                                                       Use of LFTs for monitoring drug safety
six-month ultrasound and alpha fetoprotein is an important aspect of
preventive medicine for the patient with cirrhosis, along with varices and bone                                   A large number of drugs has been associ-
                                                                                                                                                                     Table 5: Medications for which
health.                                                                                                           ated with drug-induced liver injury.
                                                                                                                                                                       regular LFT monitoring is
                                                                                                                  However, there are only a few instances
                                                                                                                  in which monitoring with LFTs is rec-
                                                                                                                  ommended (other than in package inserts         Isoniazid
                                                                                                                  for these agents).                              Methotrexate
                                                                                                                     For most agents, evidence supporting
                                                                                                                  efficacy of LFT screening to prevent the        Synthetic retinoids
                                                                                                                  onset of severe hepatotoxicity is com-          Ketoconazole
                                                                                                                  pletely lacking. Symptoms are more
                                                                                                                                                                  Terbinafine (see figure 1B)
                                                                                                                  important than LFT changes for early
                                                                                                                  detection of adverse drug reactions.            Certain anticancer drugs
                                                                                                                  Thus, patients should be advised to             Prolonged therapy with minocycline
                                                                                                                  report even non-specific symptoms such
                                                                                                                  as malaise, nausea, dyspepsia, facial dis-
                                                                                                                  comfort and fever.                                     Table 6: The undeserved
                                                                                                                     For truly problematic agents — isoni-               reputation of statins as
                                                                                                                  azid remains at the top of the list, with a                  hepatotoxins
                                                                                                                  risk of serious liver injury of about 1%,
                                                                                                                  depending on age — LFTs should be               On the evidence of hundreds of
                                                                                                                  measured to ensure practitioners discuss        thousands of cases:
                                                                                                                  openly with patients the risk of liver          • Fewer than 5% of people taking statins
                                                                                                                  injury and the need to report onset of            develop LFT changes
performed these days, and needs to        10-50 kU/mL (normal range <12).                                         new symptoms. Only in this way will the
be sent to reference laboratories.        Higher values are more suggestive                                       continuing instances of acute liver failure     • These are nearly always minor and
Its value is to confirm cholestasis       of primary liver cancer. Hepatic                                        referred for liver transplantation be             resolve spontaneously, even during
in contexts where other evidence is       imaging (CT) should therefore                                           avoided.                                          drug continuation
ambiguous. With the advent of             always be performed before con-                                            Agents in which LFT monitoring is            • Severe drug-induced liver injury from
more sophisticated ways to image          cluding that a raised AFP is due to                                     recommended are listed in table 5. It is          statins is exceedingly rare
the liver, biliary tract and pancreas,    uncomplicated cirrhosis.                                                sometimes neglected with methotrexate
this is rarely required, but fasting                                                                              use, and although the importance of             • Patients with abnormal LFTs are no
serum bile acid levels may be useful      Imaging                                                                 methotrexate as a cause of cirrhosis is           more likely to develop significant liver
for monitoring early onset of             When LFTs are abnormal, other                                           much reduced with use of contemporary             injury while on statins, and so …
cholestasis of pregnancy in a             tests are used to diagnose the cause                                    safe doses (up to 25mg/week as a single         • LFT monitoring is not warranted
woman at high risk (because of a          and severity of liver disease. GPs                                      dose), LFT measurement on a quarterly
previous episode).                        can perform hepatitis serology, and                                     basis is advisable to monitor patients at       • Most patients taking statins have
                                          judicious hepatic imaging (ultra-                                       higher risk.                                      metabolic syndrome, and are therefore
Serum alphafetoprotein                    sonography if they suspect biliary                                         Note that the list in table 5 does not         at high risk of NAFLD, itself a very
The second test is serum alpha-feto-      obstruction or fatty change, CT                                         include the statins. These incredibly             common cause of ALT abnormality
protein (AFP), an oncofetal protein       scan if they suspect malignancy).                                       important agents (to prevent cardiac
whose serum levels rise during preg-        Patients with cholestasis or severe                                   events, and possibly reduce risk of
nancy, with hepatocellular carci-         hepatitis should usually be referred                                    dementia) have garnered a reputation as
noma (HCC) (figure 2) and rare            for urgent specific diagnosis and                                       hepatotoxins that is totally undeserved.
sarcomas. However, in a patient           treatment. The timing and pre-                                          The evidence against statins being an
suspected of having chronic liver         referral workup depend on individ-                                      important cause of liver disease is sum-
disease, a minor rise in AFP is often     ual clinical and social contexts (see                                   marised in table 6. They must be pre-
found with cirrhosis, minor being         case study discussions below).                                          scribed when they are indicated.

 Five common LFT challenges revisited
Hepatitis — usually but            Figure 3: Just as for every patient with metabolic and               evident — sore throat,             liver failure; likewise, any          exclude alcohol as a cause
not always                         cardiovascular problems, those with abnormal LFTs should             headache, monocytosis.             abnormality of PT/INR.                with a reliable history, sup-
straightforward                    have proper anthropometric assessment by their doctor,                  Tetracyclines are a rela-          Failure of other symptoms          ported by absence of ‘bio-
Case 1 revisited                   including measurement of waist circumference as well as BMI.         tively common cause of             and ALT to settle over 1-2            markers’ such as a dispro-
AF has some form of acute          As in the older Australian male below, central obesity (>94cm in     drug-induced liver injury in       weeks should prompt the GP            portionately high GGT level
hepatitis. Possible diagnoses      men, >80cm in women) is nearly always present in those with          today’s society. The absolute      to refer for specialist investi-      or macrocytosis on the
include viral hepatitis, drug-     non-alcoholic fatty liver disease, even without obesity.             risk is low (<1 per 100,000        gation and treatment.                 blood film.
induced liver injury, autoim-                                                                           exposed), but these agents                                                  He may also have
mune hepatitis and Wilson’s                                                                             are often prescribed in            Fatty liver disease — so              acquired HCV or HBV from
disease (because he is only                                                                             repeated or prolonged              common and so treatable               earlier behaviours (IV drug
24 years old).                                                                                          courses. This seemed the           Case 2 revisited                      use, sexual exposure), about
   Hepatitis A and B are                                                                                most likely diagnosis in AF’s      With his recent change in life        which the GP should judi-
unlikely if recommended                                                                                 case, as he recovered rapidly      circumstances, increasingly           ciously enquire before order-
immunisation schedules                                                                                  and was anti-HEV negative.         sedentary occupation and              ing hepatitis B and C serol-
were completed, but hepati-                                                                                However, it was also            age, BL is now over-nour-             ogy. Assuming this history is
tis C still needs to be                                                                                 important to exclude               ished. Careful doctors will           negative, it is important to
excluded. If risk factors for                                                                           autoimmune hepatitis, which        perform BMI and waist cir-            go straight to the ‘nitty
HCV are present (injecting                                                                              can present acutely. Antinu-       cumference measurements               gritty’ and look for evidence
drug use or recent sexual                                                                               clear (ANA), smooth muscle,        on a large proportion of              of the metabolic abnormali-
exposure [with someone                                                                                  and liver/kidney microsomal        their patients (many of               ties so strongly associated
who could have had acute                                                                                antibodies were all negative       whom are overweight but               with NAFLD/NASH, and
hepatitis C]), perform PCR                                                                              in this case. ANA may be           not huge) (figure 3).                 look for steatosis by hepatic
for HCV RNA even with a                                                                                 positive with tetracycline           BL is now motivated by              imaging. Ultrasound is
negative anti-HCV.                                                                                      hepatitis.                         his rejection by the insurance        appropriate for this, as it is
   The travel history is                                                                                   Should AF be referred           company and his personal              reasonably sensitive for more
important here, and negative                                                                            urgently? It is often helpful      need to provide security for          severe forms of NAFLD
tests for hepatitis A, B and C                                                                          to discuss such a case by          his new family. So this is a          (figure 4).
should prompt ordering of a                                                                             phone with a specialist col-       great time to intervene for              The metabolic abnormali-
hepatitis E test. Mexico is a                                                                           league. If the PT is normal        someone with over-nutrition.          ties associated with fatty
high-risk country for this                                                                              and the patient is reasonably        Most likely his minor LFT           liver include:
waterborne virus, which                                                                                 comfortable, hospital admis-       abnormalities are due to              • Serum lipids (low HDL,
causes severe acute hepatitis.                                                                          sion is not required.              NAFLD. The more severe                  high LDL, hypertriglyceri-
Hepatitis E antibody tests                                                                              Repeated vomiting or any           form of this condition is               daemia).
need to be sent to a refer-                                           hepatitis in young adults;        suggestion of clouding of          pathologically similar to             • Fasting hyperglycaemia.
ence laboratory.                                                      other clinical and laboratory     consciousness are reasons for      alcoholic hepatitis and is            • Abnormal glucose toler-
   Cytomegalovirus and                                                features of infectious            urgent referral, as they may       termed NASH.                            ance test (this should be
Epstein–Barr virus can cause                                          mononucleosis are usually         indicate impending acute             However, first we need to                           cont’d next page

                                                                                                                                         9 April 2010 | Australian Doctor |   33
 HOW TO TREAT Abnormal liver function tests

 from previous page
   performed if fasting blood
                                          Figure 4: Use of hepatic ultrasonography to detect fatty liver disease. This illustration shows not only increased echogenicity anteriorly
                                          (towards top of figure) as appreciated by the ‘snow storm’ appearance, but also deep attenuation of the ultrasound signal posteriorly         Summary
   glucose level is ≥5.6mmol/L).          (because so much signal is reflected, none remains to penetrate that far) and blurring of hepatic vessels.
    Hypertension may also be                                                                                                                                                           IN summary, non-specific
 present.                                                                                                                                                                              abnormalities of LFTs are
    The metabolic syndrome                                                                                                                                                             common in asymptomatic
 per se requires lifestyle inter-                                                                                                                                                      patients. They most often
 vention, with or without a                                                                                                                                                            indicate NAFLD in over-
 fatty liver. In BL’s case, a                         Liver/kidney contrast                                             Blurring of vessels                                            weight patients. NAFLD
 family history of diabetes                                                                                                                                                            increases standardised mor-
 and its complications in his                                                                                                                                                          tality by 80%. Treatment of
 maternal grandmother and                                                                                                                                                              such patients should there-
 two aunts might be com-                                                                                                                                                               fore include full work-up
 pelling reasons to reduce                                                                                                                                                             and management for dia-
 food portions, adopt a ‘heart                                                                                                                                                         betes, dyslipidaemia and
 healthy’ or diabetic diet, and                                                                                                                                                        metabolic syndrome.
 engage in 20-30 minutes of                                                                                                                                                               Patients with HCV or
 aerobic exercise on a daily                                                                                                                                                           HBV infections and those
 basis (using a pedometer                                                                                                                                                              with a history of heavy alco-
 might help with motivation                                                                                                                                                            hol intake and abnormal
 and objective measurement).                                                                                                                                                           liver tests need careful inves-
    If serum cholesterol is ele-                                                                                                                                                       tigation and specialist refer-
 vated and there is a strong                                                                                                                                                           ral to establish whether cir-
 family history of CVD there
                                                                                                                   Deep attenuation                                                    rhosis is likely. The GP
 is a strong indication to pre-                                                                                                                                                        should continue to play a
 scribe a statin. Presence of                                                                                                                                                          role with such patients, not
 minor LFT abnormalities is                                                                                                                                                            only with supportive and
 far from a contraindication              • Hepatic imaging (ultra-          will be >10,000 IU/mL and          better informed and moti-           includes reminders to per-         general medical care but in
 (table 6) — it is almost an                sound or CT).                    referral is strongly recom-        vated specialist colleagues         form the tests regularly every     assisting in preventing nutri-
 indication! Nonetheless,                    Irrespective of whether a       mended.                            would take a broader per-           six months (our tip is to          tional, bone and gastroin-
 LFTs are useful ‘biomarkers’             reliable alcohol history is           If HBV DNA is <100              spective of preventive issues       ‘anchor’ the program to the        testinal and liver complica-
 to monitor BL’s progress with            obtained, referral to a spe-       IU/mL, the borderline ALT is       in GI and liver disease.            patient’s birthday month).         tions.
 his metabolic challenges.                cialist or liver clinic is         not due to hepatitis B. People        However, GPs do have an             Being male, coupled with
    Modest weight reduction               strongly advisable here            with chronic HBV infection         important role to play in           previous and possibly ongo-
 with normalisation of waist              because NO is no longer on         are not immune from                caring for patients with cir-       ing excessive alcohol intake
 circumference (<95 cm)                   a smooth course; whatever          NAFLD, so measure the              rhosis such as DT, who are          (>20g/day) and diabetes (the        Online resource
 should greatly improve his               has changed, she is now very       waistline and proceed to           at risk of serious complica-        latter two risk factors aggra-      • Gastroenterological
 LFTs, while resuming an                  likely to have, or be develop-     investigate as for case 3. ‘In-    tions. Some of these are            vate ongoing liver injury and         Society of Australia:
 exercise program may also                ing, cirrhosis. Further, the       between’ cases of HBV DNA          highly preventable and their        inflammation) increase DT’s 
 contribute to blood pressure             challenges of discontinuing        (100-10,000 IU/mL) might           impending onset can readily         risk for HCC. His glycaemic
 and glycaemic control.                   alcohol and considering hep-       appropriately be referred to a     be detected by simple screen-       control and weight likewise
                                          atitis C antiviral therapy         hepatologist.                      ing tests (see below).              need to be fastidiously man-
 Hepatitis C — what has                   before it is too late need to         People with chronic hepa-          In addition, DT should be        aged.
 changed?                                 be tackled.                        titis B should also be advised     strongly encouraged and regu-          Early detection of suspi-
 Case 3 revisited                                                            to alert their healthcare pro-     larly reminded to reduce his        cious lesions or AFP changes
 We need to know how long                 The ‘healthy hepatitis B           fessionals to their infection,     alcohol intake to a maximum         should lead to referral to a
 NO has had chronic HCV                   carrier’ no longer exists          especially if they are about       of two standard drinks a day,       multidisciplinary liver cancer
 infection, most likely since             — B aware!                         to undergo immunosuppres-          with several alcohol-free days      team for management. Most
 she was a teenager experi-               Case 4 revisited                   sive therapies (eg, chemother-     during the week, or to abstain      Australian cities have devel-
 menting with drugs (ie, >35              Despite normal physical            apy for solid or haematolog-       from alcohol altogether if these    oped such units now, and
 years). The presence of                  examination and normal             ical malignancies, anti-TNF        levels of restraint cannot be       patients with small (asymp-
 normal LFTs during the last              ALT levels, people with            agents or high-dose pred-          achieved consistently.              tomatic) HCCs may be
 decade would generally indi-             chronic HBV infection (often       nisone). Under such circum-           In all patients with cirrho-     offered curative treatment by
 cate less active hepatitis and           called ‘carriers’) should not      stances, the risk of HBV           sis, pay attention to optimal       resection or, ideally, by liver
 lower risk of developing                 be presumed to be, or told,        reactivation is very high and      nutrition and avoid excessive       transplantation.
 fibrotic liver disease leading           that they are ‘healthy’. Like      can lead to death from ful-        salt (which may precipitate            Finally, remember the bone
 to cirrhosis and its complica-           other HBsAg-positive indi-         minant hepatic failure.            ascites) and aspirin and            health of your patients with
 tions of liver failure and               viduals, VW should still see          All patients who are            NSAIDs because of their gas-        chronic liver disease. Patients
 hepatocellular carcinoma.                his doctor or specialist annu-     HBsAg positive should there-       trointestinal bleeding and          such as DT (male and
    So the most immediate                 ally for review.                   fore be referred to a hepatol-     renal side effects — both           female) are at risk of osteo-
 concerns would be the                       He still has a risk of devel-   ogist or specialist experienced    important issues in cirrhosis.      porosis and fractures, espe-
 modest (but highly informa-              oping fibrosis, cirrhosis          in the management of                  Screening for oesophageal        cially if they:
 tive) rise in bilirubin level            and/or liver cancer. This is       chronic hepatitis B before         and gastric varices should          • Smoke.
 and the borderline low serum             even more likely if the HBV        starting profound immuno-          still be undertaken, despite        • Are aged over 60.
 albumin level (normal range              was acquired vertically and        suppressive therapy, so that       the recent normal gas-              • Are obese or underweight
 35-53g/L); her value of 36g/L            if he has persistently high        antiviral prophylaxis can be       troscopy. The findings of             (BMI <25).
 would be unusual in a                    levels of HBV replication,         instituted (lamivudine or          mild splenomegaly on DT’s           • Are using corticosteroids.
 healthy person.                          determined by serum HBV            entecavir). During and after       CT scan result is suggestive        • Have had a previous frac-
    The real clue, though, is             DNA level (one test is reim-       chemotherapy, close monitor-       of early portal hypertension.         ture.
 the reverse ratio of AST:ALT             bursable, but discuss the reli-    ing of liver tests (at least       His next surveillance gas-             Annual bone densitometry
 (see earlier), and possibly the          ability      of     pathology      monthly) and HBV DNA (at           troscopy should be scheduled        (DEXA, MBS #12315:
 rather high value of GGT.                providers with the specialists     least three monthly) should        for two years hence. The fre-       chronic liver disease) and 25-
 These changes can occur                  in your area, as there can be      be undertaken under the            quency of screening gas-            hydroxy-vitamin D level are
 with hepatitis C alone, in               major differences in tests         guidance of a specialist.          troscopy and institution of         useful investigations. If vita-
 which case cirrhosis is likely,          used).                                                                prophylactic banding of             min D levels are <60nmol/L,
 but they are also features of               Referral to a hepatologist      Yellow submarine —                 varices depends on the size         treat with a vitamin D sup-
 alcoholic liver disease. Given           for ongoing follow-up/man-         preventing your cirrhotic          and number of varices, and          plement, 3000-5000 IU/day.
 her attitude to healthcare,              agement is highly recom-           patient from sinking               signs of recent haemorrhage         Advise optimal calcium
 this aspect will need to be              mended in this situation, as       further with                       detected on each occasion of        intake, regular weight-bear-
 addressed with considerable              antiviral therapy may be           complications                      surveillance.                       ing exercise and consider bis-
 skill and sensitivity, particu-          indicated; agents such as          Case 5 revisited                      Regular screening for HCC        phosphonate therapy (eg,
 larly on this first visit.               tenofovir and entecavir are        This patient’s thrombocy-          is strongly advised for             risedronate 35mg once a
    Investigations to be per-             highly effective, with mini-       topenia and low albumin            patients with cirrhosis (figure     week) if:
 formed during this ‘holding              mal adverse effects or             level are fairly accurate indi-    2). The schedule is six-            • The DEXA T score is
 operation’ should include:               drug–drug interactions.            cators of advanced fibrosis        monthly ultrasound and AFP,           <–3.0.
 • FBC, with particular atten-               In VW’s case, LFTs show         or cirrhosis. Not surprisingly,    and screening is ineffective        • The T score is < –1.5 and
   tion to platelets and macro-           ALT 38 U/L (NR <40),               you (and we) are concerned         unless a supervised program           the patient has been using
   cytosis.                               which hepatologists do not         that DT’s gastroenterologist       is undertaken, that is, one in        corticosteroids for longer
 • PT/INR.                                regard as normal for a lean        has taken a narrow view of         which the patient and their           than three months.
 • AFP.                                   individual. If it is due to        the patient’s normal endo-         doctor are committed to take        • The patient has had a previ-
 • HCV RNA (PCR).                         chronic hepatitis B with or        scopic procedures and poten-       appropriate action based on           ous minimal trauma frac-
 • HCV genotyping.                        without cirrhosis, HBV DNA         tial health issues; hopefully      test results, and ideally which       ture.                                            cont’d page 36

34   | Australian Doctor | 9 April 2010                                                
 HOW TO TREAT Abnormal liver function tests

     GP’s contribution
                                          and she was placed on Busco-                                                                                      tion of new stones within the            circumference) has been
                                          pan and a low-fat diet. Initial                                                                                   biliary system sometimes                 reversed. Follow-up imaging is
                                          investigations were organised.                                                                                    occurs. Sclerosing cholangitis           indicated here to make sure
                                             Ultrasound showed absent                                                                                       should also be considered.               that biliary dilation has
                                          gallbladder, mild fatty infiltra-                                                                                                                          resolved, and there is no
                                          tion of the liver and mild                                                                                        Are there any other tests we             hepatic infiltration other than
                                          prominence of the intrahepatic                                                                                    should have done at the time?            with steatosis.
                                          ducts. Blood tests revealed all                                                                                     It was reasonable to use                  Her gut symptoms also
     DR SANDRA VAN DER                    LFTS elevated: ALP 115, GGT                                                                                       clinical judgement and                   appear unresolved, and it may
           WATER                          303, AST 270, LD 428 and                                                                                          observe, but if the clinical pic-        be advisable to order an
           Gordon, NSW                    ALT 169. Serology showed                                                                                          ture had not settled rapidly,            abdominal CT — which
                                          immunity to hepatitis A and                                                                                       the next test would be mag-              would help find diverticular
 Case study                               B and was negative for hepati-                                                                                    netic resonance cholang-                 disease, etc., while providing
 ESTELLE, 34, and mother of               tis C.                              abdominopelvic CT scan               biliary colic. The test results          iopancreatography. Lipase                reassurance about hepatobil-
 four children, usually comes                On review three days later       detected no abnormality. Her         (AST higher than ALT) are                should also be tested. One               iary/pancreatic disease — and
 to the practice for routine Pap          she was asymptomatic, with          abdominal pains settled with         also atypical for viral or drug          would also consider referral to          consider       referral     for
 smears and repeat prescrip-              the abdomen not tender.             mebeverine and a low-caffeine        hepatitis, but would be consis-          a gastroenterologist for possi-          colonoscopy.
 tions of her oral contraceptive          Progress LFTs one week later        diet.                                tent with choledocholithiasis,           ble endoscopic retrograde
 pill (Yaz).                              were normal apart from an                                                as would the intrahepatic duct           cholangiopancreatography.                What role, if any, does her
    In October 2009 she pre-              isolated raised GGT (176).          Questions for the author             dilatation. Rapid resolution of                                                   contraceptive pill (Yaz), play
 sented with severe right-sided           Three months later she re-pre-      At the initial presentation,         ALT elevation, as in this case,          Are the persistent elevations of         in this scenario?
 upper-quadrant abdominal                 sented with spasmodic right-        Estelle had some form of acute       also occurs with passage of              GGT and ALT three months                    This combination contains
 pain radiating subcostally.              sided pains and tender right        hepatitis, which settled very        gallstones. Naturally, one               later indicative of fatty liver          oestradiol, which may increase
 Although it reminded her of              colon. She had lost 12kg on         quickly in three days. What          would want to be very confi-             disease? She has lost 12kg in            her risk of gallstone forma-
 previous biliary colic, she had          the low-fat diet and was using      are the possible causes (given       dent about the alcohol history.          weight, bringing her BMI near            tion, but she appears to have
 had a cholecystectomy in                 Nexium prn for epigastric dis-      she claims to be a social               Biliary colic more than five          to the normal range. Does                been taking this agent for
 2004.                                    comfort.                            drinker only)?                       years after cholecystectomy is           weight loss result in reversal           some years and, unless there is
    She is a social drinker and              LFTS were repeated and              Presentation with severe          highly unlikely to be due to             of fatty liver and return of             a hepatic space-occupying
 moderately overweight, with              showed GGT 128, ALT 47              right-sided upper quadrant           retained stones, but in such a           LFTs to normal?                          lesion (which was not seen on
 a BMI of 30. She was very                and normal serum amylase            pain radiating subcostally is        gallstone-prone person (note                Yes. She is still overweight,         ultrasonography), there is no
 tender in the right upper quad-          level. She was Helicobacter         not suggestive of either hepati-     her cholecystectomy age 28               and the critical consideration is        likely implication of Yaz in
 rant, urinalysis was negative            pylori negative and an              tis or fatty liver disease, but of   and obesity [BMI 30]), forma-            whether central obesity (waist           this clinical picture.

                                 How to Treat Quiz                                                                 Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points. We no longer accept quizzes
                                                                                                                   by post or fax.
                                                                                                                   The mark required to obtain points is 80%. Please note that some questions have more than one correct answer.
                                 Abnormal liver function tests
                                                                                                                    ONLINE ONLY
                                 — 9 April 2010                                                            for immediate feedback
 1. Which TWO statements are correct?                       d) In severe cases of autoimmune hepatitis,               indicative of fatty liver disease                            retinoids, ketoconazole, terbinafine, and
 a) All ‘liver function’ tests performed in a                   urgent treatment with prednisone and               c) The platelet count and prothrombin time (PT)                 long-term use of tetracyclines
    routine biochemical screen accurately and                   azathioprine is needed                                or INR are valuable additional tests in
    specifically reflect liver function                                                                               assessing liver disease                                   9. Which THREE statements are correct?
 b) Elevated serum bilirubin level is specific for          4. Which TWO statements are correct?                   d) The anaemia that can occur with liver                     a) Antinuclear, smooth muscle, and liver/kidney
    hepatitis or cholestasis                                a) In cholestasis, serum alkaline phosphatase             disease is due to vitamin B12 deficiency                     microsomal antibodies are associated with
 c) Serum bilirubin level accurately reflects                  level is elevated more than twofold, with high                                                                      autoimmune hepatitis
    impaired liver function in the presence of                 levels of GGT                                       7. Which TWO statements are correct?                         b) Minor and isolated LFT abnormalities such as
    cirrhosis                                               b) In cholestasis the biliary obstruction is always    a) Platelet levels increase in parallel with the                ALT 70 U/L and GGT 90 U/L are consistent
 d) Non-hepatic causes of low albumin include                  due to a surgical cause                                severity of fibrotic liver disease                           with non-alcoholic fatty liver disease (NAFLD)
    poor nutrition, enhanced catabolism, loss by            c) Medical causes of cholestasis include drugs,        b) Thromobocytopenia is in part due to reduced               c) NAFLD is associated with elevated serum
    proteinuria or protein-losing enteropathy                  hepatitis, automimmune liver diseases and              blood levels of thrombopoietin, a hepatic                    lipid levels, hyperglycaemia, and
                                                               liver malignancy                                       protein whose synthesis is decreased in                      hypertension
 2. Which THREE statements are correct?                     d) Jaundice and bilirubinuria is invariably               cirrhosis                                                 d) Statins are contraindicated in people with
 a) Serum AST is the most sensitive and                        present with cholestasis                            c) Impaired synthesis of clotting factors 2, 7, 9               NAFLD and hypercholesterolaemia because
    specific test for hepatocyte injury                                                                               and 10, leading to PT prolongation, always                   of their hepatic side effects
 b) The usual ALT:AST ratio of >2 may fall to               5. Which THREE statements are correct?                    responds to vitamin K administration
    ≤0.8 in alcoholic liver disease or cirrhosis            a) ALT level may be elevated in cholestasis            d) Serum alpha-fetoprotein (AFP) is an oncofetal             10. Which THREE statements are correct?
 c) Some hepatic drug reactions also feature                   because bile-acid accumulation in the liver is         protein whose serum levels rise during                    a) People with chronic hepatitis B virus (HBV)
    disproportionate increases in AST as well as               hepatotoxic                                            pregnancy and with cirrhosis or                              infection may have progressive liver disease
    ALT                                                     b) Increased serum levels of GGT occur when               hepatocellular carcinoma                                     despite a normal physical examination and
 d) ALT levels >5 times normal indicate hepatitis              there is hepatocellular injury, when synthesis                                                                      normal ALT level
                                                               is stimulated, or when bile acid levels rise        8. Which TWO statements are correct?                         b) In those with chronic hepatitis B, persistently
 3. Which THREE statements are correct?                     c) An increase in serum GGT levels is specific         a) Liver CT is the most appropriate imaging                      high levels of HBV replication (serum HBV
 a) In the community, the most common causes                   for the cholestasis of pregnancy                       investigation when biliary obstruction or fatty               DNA level >10,000 IU/mL) warrant referral to
    of acute hepatitis are hepatitis viruses (A, B,         d) Alcohol excess and a wide range of drugs               change is suspected                                           a hepatologist for antiviral therapy
    C), and drugs                                              increase GGT levels by acting as enzyme-            b) LFT changes are more important than                       c) Immunosuppressive therapies (eg,
 b) Drug-induced hepatitis can be caused by                    inducing agents that stimulate its synthesis           symptoms for early detection of adverse drug                 chemotherapy, anti-TNF agents or high-dose
    antibiotics, NSAIDs, antidiabetic agents,                  and release from the liver                             reactions                                                    prednisone) in those with chronic hepatitis B
    antihypertensives, paracetamol poisoning,                                                                      c) Non-specific symptoms such as malaise,                       may reactivate the hepatitis and lead to death
    herbal and over-the-counter medicines, and              6. Which THREE statements are correct?                    nausea, dyspepsia, facial discomfort and                     from fulminant hepatic failure
    recreational drugs                                      a) GGT is a sensitive marker of hepatic                   fever are important early indicators of drug-             d) Regular screening for hepatocellular
 c) Autoimmune hepatitis does not present with                 infiltration such as that of hepatic malignancy        related hepatic reactions                                    carcinoma is not recommended for people
    the typical elevation in ALT characteristic of          b) A rise in GGT level, typically but not always in    d) Drugs for which LFT monitoring is                            with cirrhosis, as there is no curative
    other types of hepatitis                                   association with minor ALT-level elevation, is         recommended include isoniazid, synthetic                     treatment available

 The RACGP now requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2008-10 triennium. You
 can complete this online along with the quiz at Because this is a requirement, we are no longer able to accept the quiz by post                  HOW TO TREAT Editor: Dr Giovanna Zingarelli
 or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.                                        Co-ordinator: Julian McAllan
                                                                                                                                                                               Quiz: Dr Giovanna Zingarelli

 NEXT WEEK The prevalence of atopy in our population is about 20%, and atopic dermatitis (also known as atopic eczema) appears to be on the increase, not just in Australia but worldwide. The next How
 to Treat focuses on management of this condition. The author is Dr Gayle Fischer, paediatric dermatologist, The Royal North Shore Hospital, St Leonards, and senior lecturer in dermatology, University of
 Sydney, NSW.

36   | Australian Doctor | 9 April 2010                                                   

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