Hepatology Updates on Chronic Liver Disease

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					                           co-infection. Progression to cirrhosis is accelerated in co-infected patients and they also                                            Imaging in liver disease
                           experience a higher incidence of ARV drug-related hepatotoxicity and side effects, such as
                           anaemia, hyperlactataemia, pancreatitis and severe weight loss. The SVR to pegIFN and                                                  Dr H Fenlon
                           RBV is also reduced; however, a good SVR is associated with regression of liver fibrosis                                               According to Dr Fenlon, the top three challenges when imaging in liver disease are screening
                           in HIV-HCV co-infected patients. Good clinical outcomes can be achieved using high
                                                                                                                                                                  for HCC in chronic liver disease, evaluation and management of incidental, often benign, liver
                           doses of pegIFN and RBV.
                                                                                                                                                                  lesions, and dealing with outsourced imaging while maintaining multidisciplinary input.
                             Key points                                                                                                                           Early detection of HCC is important because treatment is most effective when the tumours are
                                                                                                                                                                  small, and treatment options depend on the size and extent of the tumour. HCC detection may
                             G   In patients with HIV infection ARV drugs have successfully reduced mortality, morbidity and
                                 maternal-infant transmission, but with this has come an increase in chronic liver disease.
                                                                                                                                                                  affect prioritisation for transplantation, particularly as tumours can double in size in as little as
                                                                                                                                                                  100 days. Early HCC detection can be difficult because the liver parenchyma is altered by fibrosis,
                                                                                                                                                                                                                                                                                                            Hepatology 2007: Updates on
                             G   HIV-HCV co-infected patients can respond well to high doses of pegIFN and RBV.                                                   scarring and nodular regeneration, and patterns of enhancement are also altered in portal
                                                                                                                                                                  hypertension. Furthermore, benign lesions are common in cirrhotic livers and can mimic HCC.
                                                                                                                                                                                                                                                                                                            Chronic Liver Disease
                                                                                                                                                                  However, neovascularity within HCCs can be used to help distinguish HCC from regenerative and                                             Royal College of Physicians of Ireland, Friday 23 February 2007
                                                                                                                                                                  dysplastic nodules using arterial phase multi-slice CT (MSCT) and breath-hold MR imaging (MRI).
                           Imaging in liver disease
                                                                                                                                                                  Difficult benign liver lesions include small or complex cysts, haemangiomas, focal nodular
                                                                                                                                                                  hyperplasias, which may be confused with adenomas or fibrolamellar HCC, and unusual fatty                                                 Portal hypertension
                           Liver biopsy: essential information or unnecessary and risky

                                                                                                                                   IMAGING IN LIVER DISEASE
                                                                                                                                                                  infiltration or fat sparing.
                           intervention?                                                                                                                                                                                                                                                                    Acute variceal haemorrhage: prophylaxis and management
                                                                                                                                                                  Given the difficulties inherent in evaluating liver images, outsourcing of imaging tests can be
                           Dr K Sheahan                                                                                                                           problematical because scans at different sites are not necessarily equivalent and patient care is                                         Professor A McCormick
                           In outlining the indications for liver biopsy and its use as the gold standard for diagnosing and                                      often fragmented because healthcare professionals at external sites do not know the patient’s                                             In patients with acute variceal haemorrhage, mortality has declined from about 50% in 1960 to
                           evaluating many types of liver disease, Dr Sheahan explained that complications can occur; the                                         history. Thus, the patient’s work-up may be interrupted and multi-disciplinary review impeded,                                            <30% at present, according to Professor McCormick. This improved prognosis is due to a
                           estimated mortality rate is 1/10,000–12,000 for percutaneous biopsies and 1/200–1000 for                                               particularly if incomplete analyses are performed elsewhere.                                                                              number of factors. Improved treatment of infection is particularly important. In patients with
                           transjugular biopsies. The average biopsy sample ranges from 1–3 cm in length and 1–2 mm in                                                                                                                                                                                      cirrhosis, bacterial endotoxins appear to be associated with a biochemical cascade which
                                                                                                                                                                     Key points                                                                                                                             eventually raises intrahepatic portal resistance and increases variceal pressure. Prophylactic
                           diameter, representing about 1/50,000 of liver mass. Following an adequate biopsy, the
                                                                                                                                                                                                                                                                                                            antibiotics have been shown to prevent infection and improve survival. Recommended
                           pathology report should include information on the main disease pattern, the liver architecture,
                                                                                                                                                                     G   Early detection of HCC is challenging, but best addressed using arterial phase MSCT and MRI.                                       treatments include oral norfloxacillin (400 mg twice daily) or ciprofloxacin (400 mg twice daily)
                           and presence/ severity of fibrosis. Comment on the aetiology of the disease should also be                                                                                                                                                                                       or ciprofloxacin (500 mg twice daily) for 7 days.
                                                                                                                                                                     G   MRI is useful for characterising incidental, usually benign, lesions of the liver.
                           included. Biopsy can be used to interpret the grade and stage of liver disease, if present, and
                           also the natural history of the disease as it develops or responds to treatment.                                                          G   Outsourcing of patients for liver imaging leads to fragmentation of patient care and impedes                                       Treatment of variceal bleeding should include resuscitation, antibiotics, and early use of
                                                                                                                                                                         multi-disciplinary review.                                                                                                         vasoconstrictors, such as terlipressin, to control the bleeding and clear the field of view for
                           Following liver transplantation, biopsy can be used to diagnose acute or chronic rejection,                                                                                                                                                                                      endoscopy. Endoscopy is used to confirm the diagnosis and for subsequent banding or
                           infection, drug toxicity or recurrent disease such as HCV. Four different scoring systems exist for                                                                                                                                                                              sclerotherapy. The evidence is strongest for the use of terlipressin (glypressin). Bleeding from
                           chronic hepatitis: the Knodell, Ishak, Ludwig and Metavir scoring systems. Important features to                                                                                                                                                                                 gastric varices is often more severe and results in higher mortality than from oesophageal
                           consider when grading the disease are confluent necrosis in HCV, acute flare, co-infection,                                                                                                                                                                                      varices. Treatment of gastric varices is more difficult than for oesophageal varices and options

                           concomitant autoimmune hepatitis, and drug toxicity. There are five clinical, non-invasive                                                                                                                                                                                       include glue injection or a transjugular intrahepatic portosystemic shunt (TIPS).

                                                                                                                                                                                                                                                                                      PORTAL HYPERTENSION
                           predictors of fibrosis in patients with chronic HCV: age, AST levels, total cholesterol level,                                                                                                                                                                                   In salvage therapy, repeated sclerotherapy results in a 10% survival rate; this compares with a
                           insulin resistance and previous alcohol intake. They have been shown to accurately predict                                                                                                                                                                                       survival rate of 25–30% after transection, and 40–60% after TIPS. One recent study suggests that
                           significant fibrosis in 87% of people with chronic HCV and could be used in cases where biopsy                                                                                                                                                                                   a portal pressure gradient >20 mm Hg selects high risk patients who may benefit from early TIPs.
                           is contraindicated. Other non-invasive alternatives to biopsy include hepatic ultrasonic transient                                                                          Your comments and suggestions please
                                                                                                                                                                                                                                                                                                            Patients with portal venous thrombosis should have a thrombophilia screen and be checked for
                           ultrasonography and serum biomarkers, but to date these are not widely used.                                                                                                Please send your comments on this issue of         Published by                                      the JAK2 mutation, which makes them prone to fibrosis, haemorrhage and thrombosis.
                                                                                                                                                                                                       Falkforum to:                                      Prime Medica Ltd
                                                                                                                                                                                                                                                          Tel: +44 (0) 1565 752 100
                                                                                                                                                                                                                                                                                                            Anticoagulation is indicated in non-cirrhotic patients. The evidence is less clear for cirrhosis,
                             Key points                                                                                                                             Falkforum is supported by an       Professor Bill Winlow
                                                                                                                                                              unrestricted educational grant from:                                                        Fax: +44 (0) 1565 752 121                         but it is important to maintain portal vein patency, particularly if liver transplantation is considered.
                                                                                                                                                                                                       Managing Editor, Falkforum               
                             A liver biopsy is:                                                                                                                             Dr Falk Pharma UK          Prime Medica Ltd
                                                                                                                                                                      Bourne End Business Park         Mere House, Brook Street,
                                                                                                                                                                                                                                                                                                              Key points
                             G   The most specific test for the nature and severity of liver disease (gold standard).                                                       Bourne End, Bucks          Knutsford, Cheshire
                             G   The most useful monitor of the natural history of liver disease and the best way to monitor the                                                   SL8 5AS, UK         WA16 8GP, UK                                                                                           G   Patients with acute variceal haemorrhage should receive early treatment with antibiotics and
                                 efficacy of various treatments.                                                                                                                                                                                                                                                  vasoconstrictors and should be assessed quickly for possible salvage therapy.
                                                                                                                                                                                     DrF 06/082      client to supply new code no.                                                                            G   Portal vein patency should be maintained, particularly in patients being considered for liver
                        Ascites                                                                                                                           Treatment endpoints for HBeAg+ patients are: a reduction in levels of HBV-DNA, ALT and                                            Finally, Dr Dooley briefly described the currently understood role of hepcidin in iron metabolism
                                                                                                                                                          aspartate transaminase (AST), loss of HBeAg with generation of anti-HBe antibodies and                                            and postulated that when serum assays are developed, these may help direct management of
                        Professor K Moore                                                                                                                 ultimately loss of HBV surface antigen (HBsAg). However, continuous surveillance of these                                         HH in the future.
                        Ascites may be caused by cirrhosis and portal hypertension in 75% of cases, malignancy (10%),                                     patients is necessary and the only definite endpoint is the loss of HBsAg.
                                                                                                                                                                                                                                                                                              Key points
                        cardiac failure or constrictive pericarditis (3%), tuberculosis (2%), pancreatitis (1%) and various                               In patients who are HBeAg negative (HBeAg-), rapid and profound viral suppression reduces
                        other conditions (9%). Professor Moore illustrated the successful treatment of ascites in a                                       the risk of viral resistance. With lamivudine (a nucleoside) the median time to the                                                     Patients with HH are probably not overdiagnosed, but may be overmanaged because current
                        53-year-old male with a poor dietary intake and substantial daily alcohol intake who presented                                    development of viral resistance is shorter than with adefovir (a nucleotide). Switching between                                         guidelines are not evidence based.
                        with general weight loss and respiratory difficulties. Following paracentesis, the patient lost 21 kg                             monotherapies is inappropriate and adefovir should be used as an add-on therapy to                                                  G   Future research into optimal therapy for patients with HH should identify which C282Y
                        in weight in 1 week. He was also given a high protein diet with no added salt and prescribed the                                  lamivudine. Treatment endpoints for HBeAg- patients are declining HBV-DNA, ALT and AST                                                  homozygotes are at risk of developing HH, study the delayed introduction of venesection, and
                        diuretic spironolactone, which inhibits the effects of aldosterone in the distal tubule of the kidney                             levels and ultimately loss of HBsAg.                                                                                                    investigate the hepcidin assay as a management tool.
                        and increases water and sodium excretion and decreases potassium excretion. In some patients,
                        refractory ascites are either diuretic resistant or diuretic intractable, e.g. in renal failure. During                             Key points
                        paracentesis, fluid should be removed as rapidly as possible, e.g. 10 l in 3–6 hours; this should
                                                                                                                                                            G   For many patients with HBV infection, pegIFN should be the first-line treatment, but it is not
                        be followed by volume expansion with albumin (8 g/l), which reduces the incidence of
                                                                                                                                                                appropriate for all patients; for many patients, nucleosides/nucleotides will be the first choice
                                                                                                                                                                                                                                                                                            Chronic hepatitis C: value of shorter treatment programmes
                        hypovolaemia to 18% and prevents circulatory dysfunction.
                                                                                                                                                                of drug.                                                                                                                    Professor S Zeuzem
                        Complications associated with ascites include spontaneous bacterial peritonitis (SBP), pleural                                          For those patients who are HBeAg+, the main treatment aim is HBeAg/anti-HBe seroconversion,
                        effusion, para-umbilical hernia, hepatorenal syndrome, electrolyte disturbances and respiratory                                         while patients who are HBeAg- should receive maintenance anti-viral therapy. Both groups of                                 Chronic hepatitis C virus (HCV) infection is common and is the most frequent cause of chronic

                        difficulties. SBP is found on admission in 10–15% of patients with ascites and 60% of these                                             patients require continued surveillance.                                                                                    liver disease, cirrhosis and HCC. HCV has several different genotypes HCV-1–6, which respond
                        patients have abdominal pain, but many are asymptomatic. According to Professor Moore, the                                                                                                                                                                          differently to treatment, according to Professor Zeuzem. In general terms, patients with HCV
                        prognosis of patients with SBP is poor, with an immediate mortality rate of 30% and a 1-year                                                                                                                                                                        respond well to combination therapy with pegIFN and ribavirin (RBV), but treatment should be
                        mortality rate of 75%. After successful treatment, recurrence of SBP is likely within 6 months in                                                                                                                                                                   individualised according to HCV genotype, baseline viral load and initial response to therapy.
                        50% of cases and prophylactic norfloxacin or ciprofloxacin should be administered.                                                Hereditary haemochromatosis: a cause of chronic morbidity or an                                                                   Patients infected with HCV-1, who have a low baseline viral load (<600,000 IU/ml) and who
                                                                                                                                                          overdiagnosed and overmanaged condition?                                                                                          respond early (at week 4), may only require 24 weeks of combination therapy; however, slow
                          Key points                                                                                                                                                                                                                                                        viral responders infected with HCV-1 benefit from more than 48 weeks of combination therapy.
                                                                                                                                                          Dr J Dooley                                                                                                                       Sustained virological response (SVR) rates are usually better in HCV-2- than HCV-3-infected
                          G   Cirrhosis is the most common cause of ascites; on admission, clinicians should first identify
                                                                                                                                                          Dr Dooley described hereditary haemochromatosis (HH) as an autosomal recessive                                                    patients, and some HCV-2-and HCV-3-infected patients may be treated successfully with only
                              the cause of ascites and detect any complications.
                                                                                                                                                          condition in which iron continues to be absorbed despite replete body stores. Unrecognised                                        12–16 weeks of combination therapy. However, patients infected with HCV-3, and who have a
                          G   Management of ascites should include modest salt restriction, nutritional support as required,
                                                                                                                                                          accumulation of iron leads to tissue damage to the liver (cirrhosis), pancreas (diabetes                                          high viral load, may require longer than 24 weeks of combination therapy.
                              paracentesis and administration of the diuretic spironolactone.
                                                                                                                                                          mellitus) and other organs. HCC may complicate cirrhosis. Early symptoms of excess body
                                                                                                                                                          iron are non-specific, leading to delay in diagnosis, and include lethargy, joint pain and loss of                                  Key points
                                                                                                                                                          potency. Treatment (venesection) may improve symptoms in some patients, depending on the
                                                                                                                                                                                                                                                                                              G   HCV may be expressed as several different genotypes.
                                                                                                                                                          stage of disease at which treatment was started. Thus HH is a cause of chronic morbidity, but
                        Chronic liver disease                                                                                                             the threshold of iron overload at which clinical symptoms appear has not been defined.                                              G   The dose and duration of combination therapy (pegIFN and RBV) required is dependent on the
                                                                                                                                                                                                                                                                                                  genotype, baseline viral load and initial virological response of the HCV-infected patient.
                                                                                                                                                          The HFE gene was cloned in 1996: 90–95% of HH individuals are homozygous for the C282Y
                        Chronic hepatitis B: an emerging problem for Ireland and the UK
                                                                                                                                  CHRONIC LIVER DISEASE

                                                                                                                                                                                                                                                                    CHRONIC LIVER DISEASE
                                                                                                                                                          mutation. The prevalence of this genotype is around 1/200 in the UK and USA, and 1/83 in
                        Professor S Zeuzem                                                                                                                Ireland. However, the disease penetrance (e.g. cirrhosis, diabetes) is low (< 5%). Liver damage
                                                                                                                                                          may be present in homozygotes when clinically not apparent.                                                                       Liver disease associated with HCV and HIV co-infection
                        The hepatitis B virus (HBV) is spread by vertical transmission and sexual activity. Universal
                                                                                                                                                          HH should not be overdiagnosed. Thus if measurements of iron overload are above normal
                        vaccination is not available in Ireland or the UK. Professor Zeuzem explained that there are several                                                                                                                                                                Dr S Norris
                                                                                                                                                          (ferritin, transferrin saturation) and the genotype is C282Y/C282Y, the diagnosis of HH is
                        stages to chronic HBV infection: immune tolerance, immune clearance, a low replicative phase
                                                                                                                                                          made. Hyperferritaemia in patients with other genotypes, however, needs careful evaluation.                                       The incidence of human immunodeficiency virus (HIV) infection increased dramatically
                        and a reactivation phase of HBV-DNA. In patients with chronic, uncleared HBV infection, chronic
                                                                                                                                                          Individuals with normal iron measurements who are homozygous C282Y/C282Y should not                                               in Ireland between 1990 and 2005, mainly in the heterosexual population. This was
                        hepatitis may occur, leading to cirrhosis after several years. HBV-DNA levels predict the risk of
                                                                                                                                                          be labelled as having HH, but carry a potential susceptibility to iron overload. Treatment                                        largely due to increased intravenous drug use and substantial immigration from sub-
                        hepatocellular carcinoma (HCC) and correlate closely with histological changes in the liver.
                                                                                                                                                          guidelines from the UK, USA and Europe recommend broadly similar protocols for                                                    Saharan Africa. Current treatment of HIV with antiretroviral (ARV) drugs is successful
                        Patients with chronic HBV infection and who are hepatitis B ‘e’ antigen positive (HBeAg+)                                         therapeutic and maintenance therapy by venesection. However, although these protocols are                                         and has resulted in reduced mortality, morbidity and maternal-infant transmission.
                        respond well to treatment with pegylated interferon (pegIFN). These patients are usually                                          not evidence based, they remain important as targets, which are thought to be best practice,                                      As a result of this, the life expectancy of patients with HIV infection has increased, but
                        young, infected with HBV genotype A and possibly B, have low HBV-DNA levels, high alanine                                         but as yet it is not clear whether the threshold and the targets for initial therapeutic strategies                               with this has come an increase in the incidence of chronic illness, including end-stage
                        transaminase (ALT) levels (>200 IU/ml), no comorbidities and no decompensated cirrhosis.                                          represent overtreatment.                                                                                                          liver disease. Thus, there are overlapping HIV and HCV epidemics, leading to HIV-HCV