Liver disease

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16 Liver disease

The liver weighs up to 1500 g in adults and as such is one of the largest organs in the body. The main functions of the liver include protein synthesis, storage and metabolism of fats and carbohydrates, detoxification of drugs and other toxins, excretion of bilirubin and metabolism of hormones, as summarised in Fig. 16.1. The liver has considerable reserve capacity reflected in its ability to function normally despite surgical removal of 70–80% of the organ or the presence of significant disease. It is noted for its capacity to regenerate rapidly. However, once it has been critically damaged multiple complications develop involving many body systems. The distinction between acute and chronic liver disease is conventionally based on whether the history is less or greater than 6 months, respectively.

The hepatocyte is the functioning unit of the liver. Heptocytes are arranged in lobules and within a lobule hepatocytes perform different functions depending on how close they are to the portal tract. The portal tract is the ‘service network’ of the liver and contains an artery and a portal vein delivering blood to the liver and bile duct which forms part of the biliary drainage system (Fig. 16.2). The blood supply to the liver is 30% arterial and the remainder is from the portal system which drains most of the abdominal viscera. Blood passes from the portal tract through sinusoids that facilitate exposure to the hepatocytes before the blood is drained away by the hepatic venules and veins. There are a number of other cell populations in the liver, but two of the most important are Kuppfer cells, fixed monocytes that phagocytose bacteria and particulate matter, and stellate cells responsible for the fibrotic reaction that ultimately leads to cirrhosis.

Chronic liver disease

Chronic liver disease occurs when permanent structural changes within the liver develop secondary to long-standing cell damage, with the consequent loss of normal liver architecture. In many cases, this progresses to cirrhosis, where fibrous scars divide the liver cells into areas of regenerative tissue called nodules (Fig. 16.3). Conventional wisdom is that this process is irreversible, but therapeutic intervention in hepatitis B and haemochromatosis has now repeatedly documented cases of reversal of cirrhosis. Once chronic liver disease progresses, patients are at risk of developing liver failure, portal hypertension or hepatocellular carcinoma. Cirrhosis is a sequel of chronic liver disease of any aetiology and it develops over very variable time periods from 5 to 20 or more years.

Causes of liver disease

Viral infections

Viruses commonly affect the liver, resulting in a transient and innocuous hepatitis. Viruses which target the liver are primarily described as hepatotropic viruses, and each of these can lead to clinically significant hepatitis and in some cases to the development of chronic viral hepatitis with viral persistence. Five human viruses have been well described to date, including hepatitis A (HAV), B (HBV), C (HCV), D (HDV) and E (HEV). Each type of viral hepatitis causes a similar pathology with acute inflammation of the liver. Types A and E are classically associated with an acute and sometimes severe hepatitis which is invariably self-limited, but occasionally fatal. Hepatitis B causes acute hepatitis in adults and 5% of patients become chronic carriers, while 95% of patients infected in the neonatal period are chronically infected. Hepatitis C rarely causes an acute hepatitis but up to 85% of patients become chronic carriers. Both viruses cause chronic liver inflammation or hepatitis, cirrhosis and hepatocellular carcinoma.

Hepatitis B

Up to 500 million people worldwide are chronically infected with the hepatitis B virus (HBV). Chronic HBV is defined as the presence of hepatitis B surface antigens (HBsAg) for a period of more than 6 months. In endemic areas of Africa and the Far East, up to 15–20% of the population are chronic carriers of HBV and exposure to HBV at birth (vertical transmission) is the single most important risk factor for the development of chronic HBV infection. Acquisition of HBV in adulthood is often via sexual transmission and is usually associated with a discrete episode of hepatitis. HBV can also be transmitted parenterally, by the transfusion of blood or blood products from contaminated stocks and by intravenous drug use or needle sharing.

There are many factors that determine the outcome of HBV infection, ranging from age and genetic factors of the host to virus characteristics. Acute HBV infection has a peculiarly long incubation period of 3–6 months, which is generally self-limiting and does not require antiviral therapy. Most patients recover within 1–2 months of the onset of jaundice. The protracted incubation period and the ability of the virus to escape the host immune response contribute to the development of chronic HBV. Chronic HBV is associated with varying levels of viraemia and hepatic inflammation. The level of viraemia, and thus infectivity, was conventionally determined by the presence of the hepatitis Be antigen (HBeAg); and HBeAg loss resulted in a reduction in HBV viraemia and a more favourable outcome. However, HBeAg negative chronic hepatitis with significantly elevated levels of HBV DNA is now recognised as a growing health care problem and is associated with a poorer prognosis. HBeAg negative chronic HBV results as a consequence of the emergence of escape mutants from the core promoter or pre-core regions of the virus. It is estimated that 15–40% of HBV carriers will develop serious sequelae during their lifetime, namely liver cirrhosis and/or hepatocellular carcinoma, which can develop in chronic HBV in the absence of cirrhosis. Childhood infection is associated with a different disease outcome with a higher percentage of patients developing chronic HBV infection, and owing to the protracted exposure to the virus a higher proportion develop cirrhosis and hepatocellular carcinoma.

Alcohol

Alcohol is the single most significant cause of liver disease throughout the Western world accounting for between 40% and 60% of cases of cirrhosis in different countries. In general, deaths from alcoholic liver disease in each country correlate with the consumption of alcohol per head of population, although additional factors can influence this trend. Liver disease related to recent alcohol consumption presents a broad spectrum, ranging from the relatively benign fatty liver disease to the development of alcoholic hepatitis, a condition with an immediate mortality of between 30% and 60%. An estimated 20% of alcohol abusers develop progressive liver fibrosis, which can eventually lead to alcoholic cirrhosis, typically after a period of 10–20 years of heavy indulgence.

The central event in the development of hepatic fibrosis is the transformation of hepatic stellate cells into matrix secreting cells producing pericellular fibrosis. This network of collagen fibres develops around the liver cells and gradually leads to hepatocyte cell death. The extent of fibrosis progresses and micronodular fibrotic bands develop characterising alcoholic cirrhosis. The anatomical changes within the liver increase resistance to blood flow from the portal system, causing an increase in pressure within this system resulting in portal hypertension. As the number of normally functioning liver cells reduces further, because of continued liver cell failure and death, the clinical condition deteriorates progressively with the development of liver failure. The rate of disease progression, and indeed regression, is very strongly linked to whether or not patients continue to consume alcohol.

Immune disorders

Autoimmune disease can affect the hepatocyte or bile duct and is characterised by the presence of auto-antibodies and raised immunoglobulin levels.

Metabolic and genetic disorders

There are various inherited metabolic disorders that can affect the functioning of the liver.

Clinical manifestations

Signs of liver disease

Cutaneous signs

Hyperpigmentation is common in chronic liver disease and results from increased deposition of melanin. It is particularly associated with PBC and haemachromatosis. Scratch marks on the skin suggest pruritus which is a common feature of cholestatic liver disease. Vascular ‘spiders’ referred to as spider naevi are small vascular malformations in the skin and are found in the drainage area of the superior vena cava, commonly seen on the face, neck, hands and arms. Examination of the limbs can reveal several signs, none of which are specific to liver disease. Palmar erythema, a mottled reddening of the palms of the hands, can be associated with both acute and chronic liver disease. Dupuytren’s contracture, thickening and shortening of the palmar fascia of the hands causing flexion deformities of the fingers, was traditionally associated with alcoholic cirrhosis. It is now considered to be multifactorial in origin and not to reflect primary liver disease. Nail changes, highly polished nails or white nails (leukonychia) can be seen in up to 80% of patients with chronic liver disease. Leukonychia is a consequence of low serum albumin. Finger clubbing is most commonly seen in hypoxaemia related to hepato-pulmonary syndrome, but is also a feature of chronic liver disease (Table 16.1)

Table 16.1 Physical signs of chronic liver disease

Common findings End-stage findings
Jaundice Ascites
Gynaecomastia & loss of body hair Dilated abdominal blood vessels
Hand changes: Fetor hepaticus
Palmar erythema Hepatic flap
Clubbing Neurological changes:
Dupuytren’s contracture Hepatic encephalopathy
Leuconychia Disorientation
Liver mass reduced or increased Changes in consciousness
Parotid enlargement Peripheral oedema
Scratch marks on skin Pigmented skin
Purpura Muscle wasting
Spider naevi  
Splenomegaly  
Testicular atrophy  
Xanthelasma  
Hair loss  

Sexual characteristics

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