Chronic Hepatitis

Chronic hepatitis is defined as inflammatory disease of the liver lasting for more than six months. The histological differentiation between chronic persistent hepatitis (no cell necrosis) and chronic active hepatitis (cell necrosis) does not correlate with prognosis and is therefore now much less used.

• Chronic Hepatitis B, Hepatitis C or Hepatitis D infection
• Autoimmune hepatitis
• Alcoholic liver disease
• Sarcoidosis
• Drug induced hepatitis, e.g. isoniazid, methyldopa, nitrofurantoin
• Metabolic, e.g. Wilson's disease, alpha-1 antitrypsin deficiency, haemochromatosis

• Unknown cause, but autoantibodies (e.g. antinuclear antibody, anti-smooth muscle antibody, antimitochondrial antibody, antiphospholipid antibodies) are frequently present and are often associated with other autoimmune diseases.
• Autoimmune hepatitis is associated with HLA types A1, B8, DR3 and Dw3.
• Autoimmune hepatitis is a heterogeneous disorder and is sometimes divided into three types depending on which autoantibodies are present:¹
  • Type 1: Anti Smooth Muscle, ANA and/or Antiactin
  • Type 2: Anti-LKM, P-450 IID6 or Synthetic core motif peptides 254-271
  • Type 3: Soluble liver-kidney antigen, Cytokeratins 8 and 18

Epidemiology

• Most common in those aged between 20 and 50 years but can occur at any age. Incidence of type 1 autoimmune hepatitis in Northern European populations is between 0.1 and 1.9 per 100,000 population.²
• Type 2 is more frequent in Southern Europeans.
• Autoimmune hepatitis is more common in women.
• 60% have other autoimmune diseases as well. Associated diseases include autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura, coeliac disease, Graves' disease, autoimmune thyroiditis, rheumatoid arthritis, systemic sclerosis, uveitis.

• Acute hepatitis: fever, liver tenderness, jaundice; may develop acute liver failure, ascites and hepatic encephalopathy.
• Chronic hepatitis: features include fatigue, upper abdominal discomfort, hepatomegaly, jaundice, splenomegaly and hypersplenism, ascites, pruritus, anorexia, muscle pains, arthralgia, spider naevi, non-specific skin rashes, hirsutism, weight loss.
• Cirrhosis

• Full blood count (associated anaemia, thrombocytopenia, raised MCV with alcohol abuse), clotting studies (clotting impairment with hepatic dysfunction)
• Renal function and electrolytes (associated renal dysfunction)
• Liver function tests
• Hepatitis B and C serology
• Autoantibodies: antinuclear antibodies, smooth muscle antibodies, anti-mitochondrial antibodies.
• Alpha-1 antitrypsin
• Caeruloplasmin, copper
• Iron studies
• Ultrasound, CT scan or MRI: local liver or biliary tract abnormality, especially hepatocellular carcinoma which may occur as a complication of cirrhosis
• Liver biopsy

Supportive management will depend on general and hepatic clinical status.

Autoimmune Hepatitis

• First line treatment is combination prednisolone and azathioprine.³
• Approximately 60% respond but 80% of those responding to treatment will relapse when treatment is stopped.
• Other drugs, including Cyclosporin A, are used for those who don't respond to prednisolone and azathioprine.⁴

Chronic Hepatitis B

• Lamivudine is an option for the initial treatment of chronic hepatitis B. It can also be used in patients with decompensated liver disease but Hepatitis B viruses with reduced susceptibility to lamivudine have emerged following extended therapy.
• Peginterferon alfa-2a is recommended as a possible first treatment for adults with chronic hepatitis B.⁵ Peginterferon alfa-2a may be preferable to interferon alfa. Peginterferon alfa-2a and interferon alfa are effective in less than half of patients treated and relapse is frequent. Treatment should therefore be discontinued if no improvement occurs after 3-4 months.
• Adefovir dipivoxil is effective in lamivudine-resistant chronic hepatitis B. Treatment is continued long-term in patients with decompensated liver disease or cirrhosis. Adefovir dipivoxil is recommended as a possible treatment for a person with chronic hepatitis B if:⁵
  • Treatment with peginterferon alfa-2a or interferon alfa has not worked for that person, or
  • Treatment with an interferon worked at first, but the person has had a relapse, or
  • The person can't take peginterferon alfa-2a or interferon alfa, or has had serious side effects from taking these medicines.
• Adefovir dipivoxil should not normally be given before the person has had lamivudine treatment. It may be given on its own or with lamivudine when the person's hepatitis B virus has become resistant to lamivudine, or the virus is likely to become resistant to lamivudine quickly.⁵
• Entecavir is effective in patients resistant to lamivudine.
• Tenofovir in combination with either emtricitabine or lamivudine may be used with other antiretrovirals in patients who require treatment for both HIV and chronic hepatitis B.

Chronic Hepatitis C

• Patients with Hepatitis C should be screened for their suitability to receive combination therapy with peginterferon alfa and ribavirin in line with current NICE guidelines⁶ (also see separate article on Hepatitis C). Peginterferon alfa and ribavirin should be used for treating moderate to severe chronic hepatitis C in patients aged over 18 years:
  • Not previously treated with interferon alfa or peginterferon alfa;
  • Treated previously with interferon alfa alone or in combination with ribavirin;
  • Whose condition did not respond to peginterferon alfa alone or responded but subsequently relapsed.
• Peginterferon alfa alone should be used if ribavirin is contra-indicated or not tolerated. Interferon alfa for either monotherapy or combined therapy should be used only if neutropenia and thrombocytopenia are a particular risk.
• Combination of peginterferon alfa and ribavirin can be used for treating mild chronic hepatitis C in patients over 18 years. Delaying treatment until the disease has reached a moderate stage is also an option. Peginterferon alfa alone can be used if ribavirin is contra-indicated or not tolerated.⁷
• Liver transplantation: long-term outlook after liver transplantation is excellent, with 5-year survival rates reported at 90% or more. Recurrence of autoimmune hepatitis after liver transplantation is uncommon.

Chronic hepatitis may lead to cirrhosis and hepatocellular carcinoma, hepatic failure, portal hypertension and osteoporosis.

• The ten year survival for patients with chronic active hepatitis is now approximately 85%.
• Cirrhosis on initial liver biopsy indicates a poor prognosis.⁸

• Hepatitis B prevention, Hepatitis C prevention.