Samar

• Autoimmune hepatitis


  Immune-mediated liver injury
• Autoimmune hepatitis


  • Associated with other autoimmune disease
  • High level of serum immune globulin IgG
  • Auto antibodies in serum
  • Mostly in women, 2nd & 3rd decade
• Diagnosis


  1. Liver diseases

  2. Differential diagnosis of liver disease

  3. Infection (HAV, HBC)

  4. Male (ALD)

  5. Female (autoimmune)

  6. Fatty liver

  
• Types of autoimmune hepatitis

  • Type I: ANA+, anti-smooth muscle AB, IgG, young adult female
  • Type II: anti-LKM, pediatric population, anti-LKM, adult onset (HCV)
  • Type III: Adult patients, AB against soluble liver Ag

  
• Liver kidney microsomal antibodies

  Occur in adult if associated with HCV
• Clinical features of autoimmune hepatitis

  • Insidious onset
  • Fatigue, anorexia
  • 1/4 of cases, acute hepatitis but resolution not occur
  • Fever, arthralgia, vitiligo, epistaxis, amenorrhea
  • Jaundice mild, moderate or absent
  • Signs of chronic liver disease
  • Cushingoid face, acne, hirsutism, pink cutaneous striae, thigh, abdomen
  • Features of other autoimmune disease

  
• Autoimmune hepatitis starts gradually with fatiguability, tiredness and anorexia

  
• Autoimmune hepatitis can sometimes mimic acute viral hepatitis and patient present with jaundice, fatigue, dark colour urine but unlike hepatitis it doesn't resolve in 2 weeks
• Diagnosis and investigations


  1. Liver blood test

  2. Antibodies

  3. Elevated serum immunoglobulin (invariable)

  4. Liver biopsy: interface hepatitis with or without cirrhosis

  
• If not improved after 6 months, consider other diagnoses like Gilbert's disease
• Management


  1. Corticosteroid, 2 years after LFT improve (not prevent cirrhosis)

  2. Azathioprine, to reduce dose of steroid & its side effect

  3. Mycophenolate mofetil (MMF)
• Immune suppressants are used, with a minimum dose of 5mg steroid, may continue up to if others don't work
• Immunosuppressants are used to make enzymes and decrease the liver progress, until no need for steroid
• Prognosis of autoimmune hepatitis

  • Exacerbation & remissions
  • Most patients eventually develop cirrhosis
  • Hepatocellular carcinoma, uncommon
  • 50% of symptomatic die of liver failure, if no treatment
  • 10% with treatment

  
• Non-alcoholic fatty liver disease (NAFLD)

  • Fatty infiltration (steatosis)
  • Fat & inflammation (NASH) & cirrhosis
  • 10X Increase risk of liver related death & cardiovascular risk

  
• Risk factors for NAFLD

  • Obesity, type 2 DM, metabolic syndrome, dyslipidaemia
  • Drug: amiodarone

  
• NAFLD is associated with increased prevalence of obesity, insulin resistance and sedentary lifestyle
• NAFLD can also occur in normal BMI patients
• Non-alcoholic steatohepatitis (NASH)


  • Liver fibrosis
  • Cirrhosis
  • Liver cancer
  • Cardiovascular risk
  • 10x liver related death

  
• Two-hit theory of NAFLD/NASH etiology

  First hit: steatosis (fatty liver), inflammation

  Second hit: oxidative stress, lipotoxicity, endotoxin, TNF

  Fibrosis (Stellate activation)

  
• Most NAFLD is associated with insulin resistance
• Clinical features of NAFLD/NASH

  • Asymptomatic abnormal LFTs
  • Fatigue, mild abdominal discomfort
  • Complications of cirrhosis & PHT, HCC
  • Jaundice only when cirrhosis established
  • Average age of NASH (40-50)
  • NASH-CIRRHOSIS (50-60)

  
• Exclude alcohol history in NAFLD/NASH
• Risk factors for NAFLD/NASH

  • Age more than 45
  • Diabetes, degree of insulin resistance
  • Obesity
  • Hypertension
  • PCOS
  • Obstructive sleep apnea
  • Small bowel bacterial overgrowth
• Investigations for NAFLD/NASH


  Elevated ALT & AST

  To differentiate simple fatty liver from NASH:

  1. Transaminase < 2

  2. AST>ALT toward cirrhosis

  3. GGT, low ANA, S ferritin

  4. Metabolic syndrome, BMI>25 with truncal obesity

  Imaging: US, MRI, CT, Fibroscan

  Liver biopsy: fat, macrovesicular, cirrhosis (exclude alcohol history)

  
• GGT is elevated in both NASH and autoimmune hepatitis, so not pathognomonic

  
• Management of NAFLD/NASH


  Reduce BMI 7-10% through diet and physical activity

  Glitazone (Insulin sensitising agent)

  Vitamin E?

  Treat dyslipidemia
• Antioxidants like vitamin E may help in NAFLD/NASH, but cannot be given to patients with diabetes
• Micro nodular cirrhosis


  < 1mm in alcoholic cirrhosis

  
• Macro nodular cirrhosis


  > 1mm with variable size

  
• Cirrhosis


  • Diffuse hepatic fibrosis & nodule formation
  • Chronic viral hepatitis
  • Alcoholic hepatitis
  • Autoimmune
  • MAFLD
• Other causes of cirrhosis


  • Prolong biliary obstruction
  • Post biliary stricture
  • Persistent blockage of venous return
• Cirrhosis leads to replacement of parenchyma by fibrotic tissue
• Metabolic syndrome is the most common cause of cirrhosis
• Clinical features of cirrhosis

  • Asymptomatic: u.s or surgery
  • Jaundice, ascites
  • Spider telangiectasia, palmar erythema, cyanosis
  • Isolated hepatomegaly (alcoholic, hemochromatosis)
  • Shrunken liver
  • Splenomegaly
  • Signs of PHT: splenomegaly, collateral vessel, varecial bleeding
  • Nonspecific symptoms: weakness, fatigue, muscle cramp weight loss anorexia, nausea, vomiting upper abdominal discomfort
  • Signs of CLD

  
• Parotid enlargement in alcoholic cirrhosis
• Pigmentation in hemochromatosis cirrhosis
• Pulmonary A.V shunt causes hypoxia and cyanosis in cirrhosis
• Endocrine changes can occur in cirrhosis
• Hemorrhagic tendency can occur in cirrhosis