Autoimmune Hepatitis ✅

Related Subjects: |Hepatitis A |Hepatitis B |Hepatitis D |Hepatitis E |Chronic liver disease |Cirrhosis |Alkaline phosphatase (ALP) |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Autoimmune Hepatitis |Primary Biliary Cirrhosis |Primary Sclerosing Cholangitis |Wilson disease |Hereditary Haemochromatosis |Alpha-1 Antitrypsin (AAT) deficiency |Non alcoholic steatohepatitis (NASH) |Spontaneous Bacterial Peritonitis |Alcoholism and Alcoholic Liver Disease |Liver Transplantation

⚠️ Autoimmune Hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease caused by loss of immune tolerance to hepatocytes. It typically causes a hepatocellular pattern of liver injury with raised ALT/AST, raised IgG and positive autoantibodies. Untreated AIH can progress to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma, but most patients respond well to immunosuppression.

ℹ️ About

• 🛡 AIH is an autoimmune liver disease, not a viral hepatitis.
• 👩 It is more common in females and can present at any age, including childhood and older adulthood.
• 🧪 Suspect AIH when hepatitis is present with negative viral tests, no clear drug/toxin cause, raised IgG and positive autoantibodies.
• 🔬 Liver biopsy typically shows interface hepatitis with lymphoplasmacytic inflammation.
• 🔁 Presentation may be insidious, acute hepatitis-like, or rarely acute liver failure.
• 🧬 AIH is associated with other autoimmune diseases such as autoimmune thyroid disease, type 1 diabetes, coeliac disease, Sjögren’s syndrome and vitiligo.

🧠 Pathophysiology

• AIH results from immune dysregulation in a genetically susceptible person.
• Autoreactive T cells target hepatocytes, causing hepatocellular inflammation and necrosis.
• Plasma cell-rich portal inflammation causes interface hepatitis, where inflammation crosses the limiting plate into periportal hepatocytes.
• Persistent inflammation drives fibrosis, bridging fibrosis and eventually cirrhosis.
• The high IgG reflects polyclonal B-cell activation and is useful for diagnosis and monitoring response.

🩺 Clinical Features

• 😴 Fatigue, malaise and anorexia.
• 🤢 Nausea, abdominal discomfort or right upper quadrant pain.
• 🟡 Jaundice, dark urine, pale stools or pruritus.
• 🦴 Arthralgia, rash, amenorrhoea or non-specific systemic symptoms.
• 🧪 May be asymptomatic and found on abnormal liver blood tests.
• 🕰 Chronic disease may present with hepatomegaly, splenomegaly, ascites, varices or other signs of cirrhosis.
• ⚡ Acute severe AIH may present with jaundice, coagulopathy and encephalopathy.

📊 Types of Autoimmune Hepatitis

🧬 Associated Autoimmune Conditions

• 🦋 Autoimmune thyroid disease, including Hashimoto’s thyroiditis and Graves’ disease.
• 🍬 Type 1 diabetes mellitus.
• 🌾 Coeliac disease.
• 👁 Sjögren’s syndrome.
• 🦴 Rheumatoid arthritis or inflammatory arthropathy.
• 🎨 Vitiligo.
• 🩸 Autoimmune haemolytic anaemia, immune thrombocytopenia or other autoimmune cytopenias.
• 🧫 Primary biliary cholangitis or primary sclerosing cholangitis overlap syndromes.

🔎 Diagnosis - Key Principle

🧪 AIH is a diagnosis made from a pattern, not one single test. The usual pattern is raised ALT/AST, raised IgG, positive autoantibodies, compatible liver biopsy and exclusion of viral hepatitis, alcohol-related liver disease, metabolic disease and drug-induced liver injury.

🧪 Investigations

• Liver blood tests: ALT/AST usually raised more than ALP/GGT, giving a hepatocellular pattern.
• Synthetic function: bilirubin, albumin, PT/INR; urgent concern if INR is prolonged or encephalopathy develops.
• Immunoglobulins: raised polyclonal IgG supports AIH and helps monitor response.
• Autoantibodies: ANA, SMA, anti-LKM1, anti-LC1 and anti-SLA/LP depending on local panels.
• Exclude viral hepatitis: HAV, HBV, HCV, HEV; consider EBV/CMV/HSV depending on context.
• Exclude metabolic/genetic causes: ferritin/transferrin saturation, caeruloplasmin/copper studies in young patients, alpha-1 antitrypsin where appropriate.
• Exclude drug-induced liver injury: prescription drugs, over-the-counter medicines, herbal products and supplements.
• Ultrasound liver: exclude biliary obstruction, vascular disease, focal lesions and assess for chronic liver disease.
• Liver biopsy: confirms compatible histology, grades inflammation and stages fibrosis unless contraindicated.

🔬 Liver Biopsy Features

• Interface hepatitis: inflammation at the portal–parenchymal interface.
• Lymphoplasmacytic infiltrate: plasma cells are typical but not always present.
• Hepatocyte rosettes and emperipolesis may be seen.
• Bridging necrosis may occur in severe disease.
• Fibrosis or cirrhosis may be present at diagnosis if disease has been longstanding.

⚠️ Complications

• Progressive fibrosis and cirrhosis.
• Portal hypertension, ascites and variceal bleeding.
• Hepatic encephalopathy in decompensated disease.
• Acute severe hepatitis or acute liver failure.
• Hepatocellular carcinoma, mainly in patients with cirrhosis.
• Relapse after treatment reduction or withdrawal.
• Complications of long-term steroids and immunosuppression, including osteoporosis and infection risk.

💊 Management - UK/NICE-Compatible Approach

• 👨‍⚕️ Specialist referral: suspected AIH should be referred to hepatology/gastroenterology.
• 🎯 Treatment aim: induce and maintain remission with normal ALT/AST and IgG, prevent fibrosis progression and minimise steroid toxicity.
• 💊 Induction therapy: corticosteroids such as prednisolone are used to control active inflammation.
• 💊 Steroid-sparing therapy: azathioprine is commonly added once appropriate, especially for maintenance.
• 🧬 Before azathioprine: check TPMT activity or genotype according to local policy, and monitor FBC/LFTs for myelosuppression or hepatotoxicity.
• 🔁 Maintenance: many patients need long-term immunosuppression; withdrawal is specialist-led and only considered after sustained biochemical remission.
• 💊 Alternatives: mycophenolate mofetil, tacrolimus, ciclosporin or 6-mercaptopurine may be used by specialists if intolerance or poor response occurs.
• 🦴 Bone protection: assess fracture risk, vitamin D, calcium intake and consider DEXA because corticosteroids increase osteoporosis risk.
• 💉 Vaccination: offer hepatitis A and B vaccination if non-immune; ensure routine vaccines are up to date before significant immunosuppression where possible.
• 🚫 Lifestyle: avoid alcohol excess and unnecessary hepatotoxic drugs; review herbal supplements.
• 🫀 Liver transplant: considered for acute liver failure, decompensated cirrhosis or treatment-refractory end-stage liver disease.

📈 Monitoring

• Biochemical response: monitor ALT/AST and IgG.
• Synthetic function: monitor bilirubin, albumin and INR if severe disease or cirrhosis.
• Azathioprine safety: monitor FBC and LFTs regularly, especially during initiation and dose changes.
• Steroid toxicity: monitor weight, BP, glucose, mood, infection risk, cataracts and bone health.
• Fibrosis/cirrhosis: assess fibrosis stage and monitor for portal hypertension where relevant.
• HCC surveillance: ultrasound surveillance is for patients with cirrhosis or high-risk advanced liver disease, guided by hepatology.
• Do not rely on antibody titres alone: treatment response is mainly judged by symptoms, ALT/AST, IgG and clinical status.

🚩 Urgent Referral / Admission

• 🧠 Confusion, drowsiness or encephalopathy.
• 🩸 Prolonged INR or bleeding tendency.
• 🟡 Marked jaundice with systemic illness.
• 📈 Rapidly rising ALT/AST or bilirubin.
• 🤮 Persistent vomiting or dehydration.
• 🫀 Ascites, variceal bleeding or suspected decompensated cirrhosis.
• ⚡ Suspected acute severe AIH or acute liver failure.

📝 Exam Pearls

• 👩 AIH classically affects young or middle-aged women, but it can occur at any age.
• 🧪 Typical pattern: raised ALT/AST, raised IgG, positive ANA/SMA and negative viral serology.
• 🔬 Interface hepatitis with plasma cells is the classic biopsy finding.
• 🧬 Type 1: ANA/SMA; Type 2: anti-LKM1, often younger patients.
• 💊 Treatment is immunosuppression: corticosteroids for induction, azathioprine for maintenance.
• 🧪 Check TPMT before azathioprine and monitor FBC/LFTs.
• 🚨 Encephalopathy plus INR elevation suggests acute liver failure and needs urgent specialist care.

🧠 Teaching Note

AIH is a good example of why “hepatitis” does not always mean viral infection. The immune system targets hepatocytes, creating interface inflammation and a hepatocellular blood-test pattern. Raised IgG reflects polyclonal immune activation and is useful because it often falls with effective treatment. Steroids suppress the active immune attack quickly, while azathioprine allows longer-term maintenance with less steroid exposure.

📚 References & UK Resources

• British Society of Gastroenterology – Diagnosis and management of autoimmune hepatitis
• Gut / BSG guideline – Autoimmune hepatitis
• British Liver Trust – Autoimmune hepatitis
• British Liver Trust – Treatment for autoimmune hepatitis
• BNF/NICE – Medicines and monitoring