Hepatitis, autoimmune
D E FI N I T ION
Chronic hepatitis of unknown aetiology, characterized by autoimmune
features, hyperglobulinaemia and the presence of circulating autoantibodies.
AE T IOLOGY
In a genetically predisposed individual, an environmental agent (e.g. viruses
or drugs) may lead to hepatocyte expression of HLA antigens which then become the
focus of a principally T-cell-mediated autoimmune attack. The raised titres of ANA, ASM
and anti-liver/kidney microsomes (anti-LKM) are not thought to directly injure the liver.
The chronic inflammatory changes are similar to those seen in chronic viral hepatitis with
lymphoid infiltration of the portal tracts and hepatocyte necrosis, leading to fibrosis and,
eventually, cirrhosis. Two major forms:
Type I (classic)
: ANA, anti-smooth muscle antibodies (ASMA), anti-actin antibodies (AAA),
anti-soluble liver antigen (anti-SLA).
Type 2
: Antibodies to liver/kidney microsomes (ALKM-1, directed at an epitope of CYP2D6),
antibodies to a liver cytosol antigen (ALC-1).
Patients with variant forms of autoimmune hepatitis have clinical and serologic findings of
autoimmune hepatitis plus features of PBC or PSC.
E P IDEMIOLOGY
Type 1
autoimmune hepatitis occurs in all age groups (although mainly
in young women).
Type 2
is generally a disease of girls and young women.
H ISTORY
May be asymptomatic and discovered incidentally by abnormal LFT.
Insidious onset
: Malaise, fatigue, anorexia, weight loss, nausea, jaundice, amenorrhoea,
epistaxis.
Acute hepatitis (25%)
: Fever, anorexia, jaundice, nausea, vomiting, diarrhoea, RUQ pain.
Some may also present with serum sickness (e.g. arthralgia, polyarthritis, maculopapular
rash).
May be associated with keratoconjuctivitis sicca.
Personal or family history of autoimmune disease, e.g. type 1 diabetes mellitus and vitiligo.
It is important to take a full history to rule out other potential causes of liver disease
(e.g. alcohol, drugs).
EXAMINA T I ON
Stigmata of chronic liver disease, e.g. spider naevi (see Cirrhosis).
Ascites, oedema and encephalopathy are late features.
Cushingoid features (e.g. rounded face, cutaneous striae, acne, hirsuitism) may be present
even before the administration of steroids.
INVE S T I G A T IONS
Blood
: LFT: "" AST and ALT, "" GGT, " AlkPhos, " bilirubin, # albumin in severe disease.
Clotting
: " PT in severe disease. FBC: Mild # Hb, also # platelets and WCC from
hypersplenism if portal hypertension present.
Hypergammaglobulinaemia is typical (polyclonal gammopathy) with the presence of ANA,
ASMA or anti-LKM autoantibodies.
Liver biopsy: Needed to establish the diagnosis. Shows interface hepatitis or cirrhosis.
Other investigations: To rule out other causes of liver disease, e.g. viral serology (hepatitis B
and C) caeruloplasmin and urinary copper (Wilson’s disease), ferritin and transferrin
saturation (haemochromatosis), a1-antitrypsin (a1-antitrypsin deficiency) and antimitochondrial
antibodies (PBC).
Ultrasound, CT or MRI of liver and abdomen: To visualize structural lesions.
ERCP: To rule out PSC.
MANAGEMENT
Indications: Aminotransferases >10 the upper limit of normal, symptomatic, histology:
significant interface hepatitis, bridging necrosis or multiacinar necrosis.
Hepatitis, autoimmune (continued)
Immunosuppression
with steroids (e.g. prednisolone), followed by maintenance treatment
with gradual reduction in dose (treatment is often long term). Azathioprine or
6-mercaptopurine (6-MP) may be used in the maintenance phase as a steroid-sparing
agent with frequent monitoring of LFT and FBC. (Test for TPMT1 activity before starting
azathioprine or 6-MP.)
Monitor
: Ultrasound and a-fetoprotein level every 6–12 months in patients with cirrhosis (to
detect hepatocellular carcinoma). Repeat liver biopsies for evidence of disease progression
(<2 years).
Hepatitis A and B vaccinations.
Liver transplant
: For patients who are refractory to or intolerant of immunosuppressive
therapy and those with end-stage disease.
COMPLICATIONS
Fulminant hepatic failure. Cirrhosis and complications of portal hypertension
(e.g. varices, ascites). Hepatocellular carcinoma. Side-effects of corticosteroid
treatment.
PROGNOSIS
Older patients with type 1 autoimmune hepatitis are more likely to have
cirrhosis at presentation but may be more likely to respond to treatment. Approximately 80%
achieve remission by 3 years. Thirty five to 50% remain in remission when immunosuppression
is withdrawn. Fifty percent require lifelong maintenance. Five-year survival rate is 85% if
treated and 50% if untreated. Five-year survival after liver transplantation is >80%.
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