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.

What causes chronic hepatitis? (Aetiology)

• Viral hepatitis: hepatitis B, hepatitis C, cytomegalovirus, Epstein-Barr virus.

• Metabolic: non-alcoholic fatty liver disease (NAFLD), haemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency.

• Toxic and drugs: alcoholic liver disease, amiodarone, isoniazid, methyldopa, methotrexate, nitrofurantoin.

• Autoimmune: autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis.

• Sarcoidosis.

Presentation of chronic hepatitis

See also the separate Abdominal Examination article.

Symptoms

• Nonspecific symptoms - eg, fatigue, anorexia, muscle pains, arthralgia, weight loss.

• Right hypochondrial pain (liver distension).

• Abdominal distension (ascites).

• Ankle swelling (fluid retention).

• Haematemesis and melaena (gastrointestinal haemorrhage).

• Pruritus (cholestasis).

• Breast swelling (gynaecomastia), testicular atrophy, loss of libido and amenorrhoea due to endocrine dysfunction.

• Confusion and drowsiness (encephalopathy).

Signs

• Spider naevi (chest and upper body), slate-grey appearance in haemochromatosis.

• Palmar erythema.

• Jaundice.

• Clubbing.

• Dupuytren's contracture (alcoholic cirrhosis).

• Xanthomas: palmar creases or above the eyes in primary biliary cirrhosis.

• Initial hepatomegaly may be followed by a small liver in well-established cirrhosis.

• Splenomegaly (portal hypertension).

• Hirsutism.

Hepatitis B assessment and referral in primary care

Arrange the following tests in primary care for adults who are hepatitis B surface antigen (HBsAg) positive:

• Hepatitis B e antigen (HBeAg)/antibody (anti-HBe) status.

• HBV DNA level.

• IgM antibody to hepatitis B core antigen (anti-HBc lgM).

• Hepatitis C virus antibody (anti-HCV).

• Hepatitis delta virus antibody (anti-HDV).

• HIV antibody (anti-HIV).

• lgG antibody to hepatitis A virus (anti-HAV).

• Additional laboratory tests including alanine aminotransferase (ALT) or aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), serum albumin, total bilirubin, total globulins, full blood count and prothrombin time.

• Tests for hepatocellular carcinoma (HCC), including hepatic ultrasound and alpha-fetoprotein testing.

Refer all adults who are HBsAg positive to a hepatologist or to a gastroenterologist or infectious disease specialist with an interest in hepatology. Refer all children and young people who are HBsAg positive to a paediatric hepatologist or to a gastroenterologist or infectious disease specialist with an interest in hepatology. Include the results of the initial tests with the referral.

Pregnant women who test HBsAg positive at antenatal screening

Refer pregnant women who are HBsAg positive to a hepatologist, or to a gastroenterologist or infectious disease specialist with an interest in hepatology, for assessment within 6 weeks of receiving the screening test result and to allow treatment in the third trimester.

Adults with decompensated liver disease

Refer adults who develop decompensated liver disease immediately to a hepatologist or to a gastroenterologist with an interest in hepatology. Symptoms of decompensated liver disease include (but are not limited to) ascites, encephalopathy and gastrointestinal haemorrhage.

Other investigations for chronic hepatitis

• Urinalysis: bilirubin and urobilinogen.

• Blood tests:
  

  • FBC (associated anaemia, thrombocytopenia, raised MCV with alcohol abuse), clotting studies (clotting impairment with hepatic dysfunction).

  • Renal function and electrolytes (associated renal dysfunction).

  • LFTs, serum albumin, prothrombin time.

  • Immunoglobulins (IgG raised in autoimmune hepatitis; IgM raised in primary biliary cirrhosis).

  • Autoantibodies: antinuclear antibodies, smooth muscle antibodies, anti-mitochondrial antibodies.

  • Alpha-1-antitrypsin (deficiency of which can affect the liver as well as the lungs).

  • Iron studies.

  • Alpha-fetoprotein (hepatocellular carcinoma).

• Ultrasound, CT or MRI scan: local liver or biliary tract abnormality, especially hepatocellular carcinoma which may occur as a complication of cirrhosis.

• Point shear wave elastography and transient elastography have been shown to be simple and effective methods of assessing liver fibrosis.¹

• Genetic testing - eg, haemochromatosis, viral hepatitis genotyping.

• Upper gastrointestinal endoscopy (diagnosis and management of oesophageal varices).

• Liver biopsy: improved non-invasive diagnostic techniques mean that in chronic viral hepatitis liver biopsy can be reserved for assessment of the severity of necro-inflammation (grade) and fibrosis (stage).² The increasing availability of biomarkers and sophisticated imaging techniques means that the need for liver biopsy in children with chronic viral hepatitis should be reduced in the future³ . Likewise, the development of serological techniques can be used to identify the subset of patients with potential liver injury who would most likely benefit from liver biopsy.⁴

Differential diagnosis

Other causes of chronic liver failure or the development of cirrhosis.

Chronic hepatitis treatment and management⁵

See the separate articles on specific causes - eg:

• Viral hepatitis: Hepatitis B, Hepatitis C, Cytomegalovirus, Epstein-Barr virus.

• Metabolic: NAFLD - Steatohepatitis and Steatosis (Fatty Liver), Haemochromatosis, Wilson's disease, Alpha-1-Antitrypsin Deficiency.

• Autoimmune: Autoimmune Hepatitis, Primary Biliary Cholangitis, Primary Sclerosing Cholangitis.

• Sarcoidosis.

• Where indicated, address alcohol consumption: Alcoholism and Alcohol Misuse - Management. Stop/replace any implicated medication.

Chronic hepatitis B

• Entecavir, peginterferon alfa, tenofovir alafenamide, and tenofovir disoproxil are options for the treatment of chronic hepatitis B infection.

• Entecavir and tenofovir disoproxil can be used in patients with decompensated liver disease.

• Other drugs licensed for the treatment of chronic hepatitis B infection include adefovir dipivoxil and lamivudine.

• If drug-resistance emerges during treatment, consider switching to, or adding another antiviral drug to which the virus is sensitive; ensure the antiviral drug does not share cross-resistance. Hepatitis B viruses with reduced susceptibility to lamivudine have emerged following extended therapy.

• Duration of treatment is dependent on several factors including response (eg, viral suppression, antigen loss, seroconversion), patient characteristics (eg, liver disease), and treatment tolerability. Treatment is usually continued long-term in patients with decompensated liver disease.

Chronic hepatitis C

Before starting treatment, the genotype of the infecting hepatitis C virus should be determined and the viral load measured as this may affect the choice and duration of treatment. All patients with chronic hepatitis C infection should be assessed for treatment with direct-acting antiviral agents.

• Sofosbuvir in combination with ribavirin (with or without peginterferon alfa), sofosbuvir with velpatasvir (with or without ribavirin), sofosbuvir with velpatasvir and voxilaprevir, and glecaprevir with pibrentasvir are licensed for the treatment of chronic hepatitis C infection of all genotypes.

• Ledipasvir with sofosbuvir (with or without ribavirin) is licensed for the treatment of chronic hepatitis C infection of genotypes 1, 3, 4, 5, or 6.

• Elbasvir with grazoprevir (with or without ribavirin) is licensed for the treatment of chronic hepatitis C infection of genotypes 1 or 4.

• Other drugs licensed for the treatment of chronic hepatitis C infection include ribavirin in combination with peginterferon alfa, or peginterferon alfa as monotherapy if ribavirin is contra-indicated or not tolerated.

Complications

• Liver failure.

• Portal hypertension: ascites, hypersplenism, lower oesophageal and rectal varices.

• Hypoalbuminaemia.

• Coagulopathy.

• Osteoporosis.

• Hepatopulmonary syndrome (defect in arterial oxygenation induced by pulmonary vascular dilatation in patients with liver disease).

• Hepatorenal syndrome.

• Encephalopathy.

• Cirrhosis.

• Hepatocellular carcinoma: most cases of hepatocellular carcinoma are associated with cirrhosis related to chronic hepatitis B virus or hepatitis C virus infection.⁶

Prevention of chronic hepatitis

Immunisation against hepatitis B.

Prevention of hepatitis C focuses mostly on counselling for high-risk behaviours such as sex with multiple partners and the use of intravenous drugs and/or intranasal cocaine because of sharing of potentially contaminated equipment. Although commercial body piercing and tattooing are not definitely associated with the risk acquiring HCV, self-tattooing and self-piercing with shared needles should be discouraged.⁷

Appropriate medicines management, particularly with those medications at particular risk of causing chronic hepatitis.

Prevention is covered in the separate articles Hepatitis B Vaccination and Prevention and Hepatitis C.