Cirrhosis is a diffuse process and the damage is usually irreversible. The scarring disrupts and impairs blood flow through the liver, elevating the portal venous pressure (portal hypertension). As a consequence, blood flow increasingly bypasses the liver and flows through lower resistance vessels that communicate between the portal and systemic circulations. These anastomoses arise at four main sites:

There are two serious consequences of this vascular shunting:

Portal hypertension also causes splenomegaly and contributes to the development of ascites. Portal hypertension can be caused by other lesions that obstruct hepatic blood flow in the absence of cirrhosis, such as portal vein thrombosis and Budd–Chiari syndrome (see Section 18.3).

Cirrhosis is associated with development of hepatocellular carcinoma, although the degree of risk varies with the underlying disease.

Liver failure can be acute or chronic, and results when hepatic functional impairment is extreme. Mortality exceeds 70%. It is often precipitated by an event such as gastrointestinal haemorrhage or infection in a patient with chronic liver disease. Acute liver failure is uncommon, but may follow viral infection, drug exposure (e.g. paracetamol overdose, halothane), toxin damage (carbon tetrachloride), acute fatty liver of pregnancy and Reye’s syndrome (Section 18.3). In acute liver failure without pre-existing hepatic disease, there is extensive liver necrosis with shrinkage of the organ, and clinical features of hepatic failure – clotting deficiencies, jaundice, hepatic encephalopathy – developing over 2–3weeks. Massive liver destruction may prove fatal without transplantation, or cause irregular scarring in survivors.

Viral infection of the liver has various clinical manifestations, according to the specific agent involved:

Hepatitis B infection occurs worldwide, but is extremely common in southeast Asia, where the disease is frequently transmitted from mother to fetus. Exposure early in life creates a permanent carrier state in over 90% of patients. Infection in the UK is usually acquired in adult life, through sexual contact, infected needles (drug misusers and healthcare workers) or an unknown source. Needlestick injury from a hepatitis B carrier confers a 30% risk of infection. The virus is present in blood and body fluids during incubation (which can be up to 6months from inoculation) and during periods of acute liver inflammation. The viral antigens and host antibodies detected in the serum reflect the stage of disease and infectivity of the patient. Core antigen (HbcAg) and the related HBe antigen are infective. The presence of IgM anti-HBc indicates recent infection. As the time period from infection increases, the antibody class switches to IgG. Surface antigen (HbsAg) positivity indicates acute infection or carrier state. HbsAb appears late and indicates immunity.

Hepatitis C prevalence is uncertain, but estimated at between 0.1% and 1% of the UK population. There is an estimated 3% risk of transmission from an infected needlestick injury. Acute infection is asymptomatic in the majority. HCV antibodies are found in many patients with previously unexplained cirrhosis and hepatocellular carcinoma. Liver function tests characteristically fluctuate throughout the course of the disease, and HCV RNA is detectable despite anti-HCV antibodies (the latter do not appear to confer immunity). Liver damage in part appears immunologically mediated. Patients may benefit from immune modulation therapy with interferon. Selection for such treatment is based on histological assessment of the degree of active inflammatory damage and the extent of fibrosis in a liver biopsy specimen.

Other causes of infectious hepatitis include:

Hydatid disease is a systemic infection due to the canine tapeworm Echinococcus. Although uncommon in the UK, hydatid disease occurs worldwide and incidence is increased in sheep- and cattle-farming areas. The liver is frequently involved with formation of single or multiple infected cysts, causing mass effects. There is a risk of disease dissemination or fatal anaphylactic shock if the cyst contents are liberated and care must be taken during surgical removal.

Liver abscess is uncommon in the UK and is usually due to bacterial infection. Organisms reach the liver via the bloodstream, biliary system or direct spread. Abscesses can be single or multiple. Surgical drainage is usually necessary. Parasitic and protozoal abscesses are more common in the developing world.

Autoimmune liver disease typically occurs in young and middle-aged adult females. Patients have a chronic hepatitis, which clinically and histologically resembles viral hepatitis, but serological tests show raised serum IgG and specific autoantibodies. The latter include antinuclear antibodies (ANA), antimitochondrial antibodies (AMA), antismooth-muscle and antimicrosomal antibodies. There is often associated extrahepatic autoimmune disease such as thyroiditis or rheumatoid arthritis.

Fatty change is the accumulation of fat droplets within the cytoplasm of hepatocytes, usually as a single large vacuole (macrovesicular steatosis). The change occurs throughout the liver, and may develop in chronic alcohol misuse or following ‘binge’ drinking in non-habituated individuals. Fatty change is reversible over several days of abstinence, but with repeated attacks, fibrosis can develop.

In alcoholic hepatitis (steatohepatitis) fatty change is accompanied by acute inflammation, with neutrophil polymorph infiltration around degenerate and necrotic hepatocytes. Abnormal liver cells may contain condensed intracytoplasmic proteins, known as Mallory bodies. Alcoholic hepatitis is associated with developing liver fibrosis, which characteristically starts around centrilobular veins. Whereas simple fatty change usually produces no clinical symptoms, patients with alcoholic hepatitis present with right upper quadrant pain and jaundice. Either condition may cause hepatomegaly.

With or without recurrent attacks of alcoholic hepatitis, individuals who maintain a high regular alcohol intake over several years are at risk of progressive fibrosis, cirrhosis and liver failure. Women appear to be at greater risk with a relatively lower alcohol intake. Coexistent liver disease, particularly haemochromatosis and hepatitis C infection, can be important contributory factors in progression to cirrhosis. Current recommendations are for women to drink no more than 14 units of alcohol per week, and men fewer than 21 units. Moderate regular intake seems less harmful than erratic, heavy, binge drinking. Indeed, regular, low ethanol intake seems to have a protective influence in coronary heart disease.

Acute alcohol intoxication causes injury and death through accidents, hypoglycaemia, epilepsy and direct cerebral toxicity. Chronic alcohol misuse can result in pancreatitis, cardiomyopathy, physical dependence, malnutrition and neurological disease (Wernicke–Korsakoff syndrome – confusion, ataxia and ocular disturbances due to thiamine deficiency; if untreated, severe, irreversible amnesia often results).

Hepatic fat accumulation is most frequently seen in association with ethanol but other causes include:

Drugs can cause many morphological changes in the liver; more common examples are shown in Table 31. As the histological features often mimic endogenous liver disease a thorough clinical history is essential. Mechanisms of drug damage are:

Drug damage may be predictable