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Introduction
AIH is the commonest autoimmune disease of the liver. Driven by a plasma-cell rich inflammatory infiltrate, uncontrolled hepatocyte injury can ultimately lead to cirrhosis. With recognition and timely instigation of immunosuppression, permanent liver damage can be avoided and normal hepatic function preserved.
Epidemiology
The incidence of AIH ranges between 0.67 to 2 per 100,000 person years depending on the region (accurate Australian data is lacking). The prevalence is estimated at 8 in 100,000. It affects women more than men at a ratio of 8:1 and age of onset is bimodal with peaks at 10-30 as well as 40-60 years.
Pathogenesis
As with many autoimmune conditions, AIH arises in genetically susceptible individuals (both HLA and non-HLA genetic associations have been identified) who experience a loss of self-tolerance to hepatic antigens due to an unidentified environmental trigger. An inflammatory cascade is triggered leading to hepatic necrosis.
Presentation
AIH typically presents non-specific systemic symptoms such as fatigue or weakness. It also often presents as asymptomatic elevation of LFTs. Seldom does it present with severe hepatitis and acute liver failure (“fulminant liver failure”) with jaundice, encephalopathy and ascites.
Diagnosis
Biochemistry – LFTs, IgG
A hepatocellular pattern of damage is common featuring elevations of alanine and aspartate transaminase (ALT, AST) more so than alkaline phosphatase (ALP) and gamma glutaryl transferase (GGT). When ALP and GGT are raised concurrently, an overlap syndrome with primary biliary cholangitis or primary sclerosing cholangitis should be suspected. Bilirubin elevation is a sign of severe disease, as is hypoalbuminaemia. Before confirmation of the condition histologically, telltale signs of AIH include raise total protein and globulins which reflect raised IgG levels.
Serology
Anti-nuclear antibody (ANA) is typically elevated and the higher the titre the higher the specificity for AIH. Immunofluorescence pattern is usually homogenous. One caveat is that low titre ANA levels can be seen in other hepatic conditions though such as non-alcoholic fatty liver disease, primary sclerosing cholangitis, hepatitis C and alcohol-related liver disease. Smooth muscle antibodies are the second most common autoantibody and the VG as well as VGT immunofluorescence patterns are most specific for AIH.
Liver-kidney-microsomal antibody is elevated in ‘type II AIH’, a designation assigned to a subtype of this disease that most commonly presents at younger ages and tends to be less responsive to immunosuppression.
The absence of chronic viral hepatitis is a key diagnostic criteria and so hepatitis B and C serologies should be ordered.
Histopathology
AIH cannot be diagnosed without a liver biopsy. Though not specific to AIH, typical features are of an ‘interface hepatitis’, meaning inflammation between the portal tracts (zone 1) and hepatic parenchyma (zone 2). The inflammation is plasma-cell rich. More advanced cases will feature varying degrees of fibrosis through to ‘bridging fibrosis’, i.e. cirrhosis.
AIH scoring system
Given the serological markers can occur in other disease and histological findings are not specific to AIH, scoring systems have been devised to determine the ‘likelihood’ that AIH is present as is used as an aid to clinical judgement. The most common of these is the simplified AIH score below:
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Treatment
High dose steroids (eg starting dose of prednisolone 40mg) with a steroid-sparing agent (such as azathioprine 50-75mg) introduced concurrently or soon after steroid induction is standard therapy for confirmed AIH. Oral formulations of budesonide are an alternative to prednisolone with a less systemic side effects due to high first pass metabolism (they should not however be used in those with established portal hypertension given the formation of portal-systemic shunts, nor in severe presentations where systemic steroids are preferable). Over a period of six to twelve months, steroids are weaned to their lowest possible dose but not entirely withdrawn as remission rates are higher with dual therapy. Complete withdrawal of immunosuppression may be considered after 24 months of biochemical remission though recurrence rates can be as high as 50%. Liver biopsy is preferable to exclude histological activity prior to withdrawal of treatment. In those with severe index presentations or advanced fibrosis, treatment withdrawal should be discouraged.
Severe cases unresponsive to immunosuppression or progressed to cirrhosis with end-stage complications are candidates for liver transplantation.
Monitoring
Once remission is achieved, regular monitoring of liver biochemistry, IgG and lymphocyte count is still necessary. Extra-hepatic considerations include bone densitometry at baseline and regular intervals thereafter due to steroid exposure, as well as skin cancer prevention and screening because of azathioprine usage. Seasonal influenza and pneumococcal vaccinations are also recommended given long-term immunosuppression. In those with established cirrhosis, regular liver ultrasound for hepatocellular carcinoma screening along with endoscopic screening for oesophageal varices is needed. |
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Article by Dr Duy Pham
Duy’s clinical interests include all aspects of liver disease including viral hepatitis B and C, fatty liver disease, alcohol-related liver disease, autoimmune and metabolic conditions, liver lesions and cirrhosis.
Click here to read more about Dr Duy Pham
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