Chronic active hepatitis

Definition and modern terminology. Chronic hepatitis is hepatic necroinflammation persisting for more than 6 months. The old histological labels "chronic active hepatitis" (interface hepatitis/piecemeal necrosis extending beyond the limiting plate, progressing to cirrhosis) and "chronic persistent hepatitis" have been replaced by classification according to aetiology + grade of activity + stage of fibrosis.

Causes. Chronic hepatitis B ± D, chronic hepatitis C, autoimmune hepatitis, drugs (nitrofurantoin, minocycline, methyldopa, isoniazid), Wilson disease, alpha-1 antitrypsin deficiency and MASH.

Autoimmune hepatitis in the elderly. Often presents acutely or as already established cirrhosis, or is found incidentally; features are fatigue, arthralgia, jaundice and amenorrhoea (not applicable in old age), with associated autoimmune disease such as thyroiditis and rheumatoid arthritis. Type 1 — ANA and anti-smooth muscle antibody with raised IgG; Type 2 — anti-LKM1 (a disease of the young).

Diagnosis. Raised transaminases with hypergammaglobulinaemia (raised IgG), autoantibodies, and liver biopsy showing interface hepatitis with a lymphoplasmacytic infiltrate, hepatocyte rosettes and emperipolesis. The IAIHG simplified criteria (autoantibody titre, IgG, histology, exclusion of viral hepatitis) are used for diagnosis; grade by METAVIR or Ishak and stage with transient elastography.

Treatment. Prednisolone 0.5–1 mg/kg induction with azathioprine 1–2 mg/kg as steroid-sparing maintenance; budesonide may be used in non-cirrhotic patients but must be avoided in cirrhosis because portosystemic shunting bypasses first-pass metabolism. Check TPMT activity before azathioprine. Older patients respond well biochemically but tolerate steroids poorly — give osteoporosis prophylaxis, monitor glucose and blood pressure, and consider PCP prophylaxis. Treat hepatitis B with tenofovir or entecavir, and hepatitis C with direct-acting antivirals (SVR >95%, well tolerated in the elderly).

CAMARO trial (J Hepatol 2024;80:576) — in treatment-naive autoimmune hepatitis, mycophenolate mofetil with prednisolone achieved biochemical remission more often and with fewer adverse events than azathioprine with prednisolone, challenging azathioprine's position as standard first-line maintenance. In parallel, the accepted treatment endpoint is now complete biochemical response — normalisation of both ALT and IgG — ideally within 6 months, rather than transaminase normalisation alone.