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Alcohol is the most important cause of liver disease in western societies. It is almost
entirely metabolised in the liver where it is a significant inducer of oxidases, thus
increasing the liver’s ability to metabolise not only alcohol itself but also a range of other


Alcohol produces three distinctive pathological changes in the liver.
These are fatty liver, alcoholic hepatitis and cirrhosis.

The severity of the liver damage is dose related.

It is estimated that hepatic changes occur after five years of daily consumption of alcohol
at the levels of 3 standard drinks for men and two for women, this is the equivalent of 30g
of alcohol and 20g respectively. Other da ta, however, suggests that an intake of 100g per
day of alcohol is necessary before a toxic reaction results. Even at this level of
consumption for 3-5 years only 35% of alcoholics develop alcoholic hepatitis and only
one-third of them progress to cirrhosis. This suggests that individual factors, which have
not yet been determined, bear an important role in the development of liver damage.
The precise mechanisms underlying the liver damage are not well understood. The first
change is fatty liver when the hepatocytes become swollen with fatty acids. This occurs as
a result of destruction of the rough endoplasmic reticulum and the consequent reduction of
protein synthesis and lipoprotein secretion causing an increased level of triglycerides in
the liver cells. This is reversible if alcohol is no longer ingested.
If severe, however, and affecting a large number of hepatocytes the result can be
cholestasis and liver failure.
Alcoholic hepatitis is usually superimposed on fatty liver. Hepatocytes necrose and are
surrounded by inflammatory cells. Fibrosis occurs early and distorts the normal liver
architecture. If severe, liver failure can ensue. Otherwise the process leads to cirrhosis as
the fibrotic tissue replaces normal hepatocytes.
Cirrhosis due to alcohol progresses more slowly than other causes and maybe associated
with a range of extrahepatic manifestations.

Clinical features

Fatty liver has few associated signs or symptoms apart from hepatomegaly. Liver function
is normal.
Alcoholic hepatitis may present with fever, jaundice, tender hepatomegaly, ascites and if
severe encephalopathy, which we shall discuss in more detail when we consider the
presenting features of cirrhosis. This usually occurs after a heavy drinking bout.
Cirrhosis may be the presenting problem.


Cease alcohol, improve nutrition, treat the complications such as the ascites,
encephalopathy and variceal bleeding.



Is a condition which involves the entire liver. The parenchyma forms nodules separated
from each other by fibrous tissue. It is the result of long-standing liver damage and reflects
the fact that the regenerating hepatocytes do not conform to the normal liver structure and
fibrous tissue further distorts the liver architecture. It is irreversible and the abnormal
structure creates obstruction to blood flow further compromising hepatocyte function. The
condition usually causes death by portal hypertension, hepatocellular failure or a
combination of both.


Alcohol, as discussed above, causes 60 – 70%.
Autoimmune hepatitis is associated with the elevated levels of autoantibodies, especially
the anti-mitochondrial antibody which is an indicator of primary biliary cirrhosis and may
occur with other autoimmune disorders such as pernicious anaemia.
Metabolic disorders such as Hemochromatosis and Wilson's disease.
Cholestasis, ie obstruction anywhere in the biliary tree if long term can cause cirrhosis.
Primary biliary cirrhosis produces obstruction in the interlobular bile ducts. Also bilia ry
strictures, or, sclerosing cholangitis acting outside the liver can also cause chronic
obstruction and back pressure which eventually leads to cirrhosis.
Congenital causes include Hemochromatosis, Wilson’s disease and thalassemia.


The two basic processes are the death of hepatocytes and their replacement cells forming
nodules in combination with chronic inflammation and progressive fibrosis which are
characteristic of chronic hepatitis. As the architecture is so disordered the blood flow is
significantly reduced and hepatocytes die as a result of ischaemia regardless of whether
the original cause is continuing or not.
It is important to know that the development of cirrhosis is not as predictable as might be
expected. The role of host factors make a significant impact and these are not well

Complications of cirrhosis

Portal hypertension can be caused by obstruction to the portal vein outside the liver for
example by congenital hepatic fibrosis, but 90% of intrahepatic cases are due to cirrhosis.
Normally all the portal blood flows through the liver but as resistance to this develops the
portal flow is redirected to the collateral circulation that develops particularly in the
gastrointestinal tract around the oesophagus, stomach and rectum and the anterior
abdominal wall, although there are other collaterals to the kidneys, testes and ovaries.
The anastomoses that develop between the portal veins and the systemic veins results in
varices at the latter sites.
Another consequence of the increased liver resistance to portal flow is that most of the
portal blood is shunted away from the liver.

Splenomegaly occurs due predominantly to passive congestion. This in turn may give rise
to thrombocytopenia and although anaemia and granulocytopenia are theoretically
possible they rarely occur.
Massive, life-threatening, haemorrhage can develop if an oesophageal varix
spontaneously ruptures. Rectal varices are often misdiagnosed as haemorrhoids.
Caput medusae is the name given to the dilatation of the superficial veins of the anterior
abdominal wall. Portal hypertension is a significant factor in the development of ascites
and contributes to renal failure and hepatic encephalopathy.

Hepatocellular failure Although the liver has a large reserve capacity , liver failure occurs
due to either cirrhosis or severe acute liver disease. Acute problems such as a massive
haemorrhage, bacterial infection or narcotic drugs can result in the development of liver
failure in the patient with previously manageable cirrhosis. Because the liver has so many
functions the consequences of the organs failure are complex and include hepatic
encephalopathy, jaundice, blood coagulation defects and renal failure as well as ascites,
endocrine disorders and circulatory changes.

Other important clinical features of cirrhosis/liver failure are,

Jaundice but this depends on the nature of the hepatocytic damage and may not be
Coagulation defects as the liver cannot manufacture the required coagulation factors.
Hypersplenism may result in thrombocytopenia, anaemia and leukopenia. Thus easy
bruising, purpura and epistaxis can occur.
Endocrine changes are caused by the failure of the liver to deactivate oestrogens and
result in gynecomastia, and via suppression of pituitary gonadotrophin there is often
testicular atrophy and impotence. Women may suffer menstrual irregularities and breast
atrophy. Liver palms, described as exaggerated mottling of the palms and spider naevi are
vascular manifestations of the alteration in hormone metabolism.
Ascites is caused by portal hypertension and sodium retention by the kidneys (there is not
an adequate explanation for the renal retention of sodium and water yet). Some textbooks
also claim a role for hypoalbuminemia while others ignore this as a factor.
Cirrhosis is only one of several causes of ascites, others are hepatic and peritoneal
neoplasms and cardiac failure.
The clinical features are abdominal distension, shifting dullness to percussion and a fluid
thrill, but these do not develop until there is at least one litre of fluid accumulated.
Peripheral oedema can develop as a result of a low plasma oncotic pressure due to the
lower levels of albumin.
Hepatomegaly may be present however in advanced stages of cirrhosis the liver may be
reduced in size.
Circulatory disturbances due to circulating levels of vasoactive agents, or impaired
sympathetic responsiveness, there is a peripheral vasodilation and increased cardiac
output and blood volume. Pulmonary arterio-venous shunting may occur and produce
arterial hypoxia and cyanosis, clubbing develops in a small number of patients.
Renal failure may develop in association with liver failure. The mechanism is not clear but
as the kidney disorder is entirely reversible it is thought to derive from reduced blood flow
to the organ. If the liver function is restored the renal function returns to normal. The renal
failure results in proteinuria and uraemia which can worsen the central nervous system

Other features include fever, anorexia, nausea, vomiting, upper abdominal discomfort,
weakness, fatigue, weight loss, foetor hepaticus which is a sweet smell on the breath and
is possibly the outcome of failure of the liver to detoxify certain non-specified chemicals.


There is no treatment to reverse the cirrhosis or to halt the progression of the disorder,
however avoiding aggravating factors such as alcohol, ensuring good nutrition and
carefully monitoring any drug ingestion can aid in the comfort and general health of the


Is poor overall as most people present in the later stages of the disease. Thus the 5-year
survival is 25%. If the liver function is good 50% of patients survive for 5 years and 25%
for 10 years. These figures apply especially if the underlying disorder can be treated such
as Wilson’s disease or hemochromatosis.



It is believed that the liver’s failure to breakdown nitrogenous substances produced by the
bacteria of the gut results in these agents, which are neurotoxins, entering the cerebral
circulation and causing reversible brain irritation. This explanation is supported by the
temporal connection between gastrointestinal haemorrhage and large protein intakes,
both of which increase the nitrogen load, and the rapid precipitation of encephalopathy.


Reversible enlargement of nuclei of astrocytes, (one of the supporting cells of the CNS.).

Clinical features

Gradual onset of changes in intellect, emotions, mood which can be dramatically
exacerbated if an additional stress such as a large haemorrhage, renal failure, excess
dietary protein occurs. As the disorder progresses the symptoms become more severe
and apathy, confusion, disorientation, drowsiness, slurred speech and eventually coma
Signs include asterixis (flapping tremor), inability to perform simple mathematical tasks
hyper-reflexia and bilateral plantar responses can be found.

Note, there are other psychiatric disorders associated with excess alcohol consumption
such as delirium tremens in which profound confusion, delusions and vivid hallucinations
occur but the patient is alert.
Wernicke’s encephalopathy presents with disorientation, marked reduction in recent
memory, confabulation, ophthalmoplegia and limb ataxia. These should not be confused
with hepatic encephalopathy as the pathological bases are different although the
presenting features may be somewhat similar.


1. Draw a diagram which will enable you to distinguish the different causes and clinical

   signs of jaundice. How could you differentiate between them using only clinical


2. Discuss the marked differences between Hepatitis A, B and C.

3. Describe the possible clinical features of Infectious Hepatitis. How could someone with

   this disease present to an Osteopath?

4. Briefly describe the pathophysiology of Alcoholic Liver disease.

5. Discuss the pathological changes of Cirrhosis.

6. Describe the process which leads to the development of Portal Hypertension.

7. List and discuss briefly the possible clinical features of Cirrhosis. What are the

   differences between liver failure and cirrhosis?