Hepatitis Lecture Notes PDF

H E PAT I T I S P R O F. DINA ELHAMMADY TOPICS 1. Hepatitis (acute / chronic) 2. Active viral hepatitis (causes, clinical picture, sequelae, complications, investigations, management) 3. Chronic viral hepatitis (clinical picture, investigations, treatment)  Hepat...

H E PAT I T I S P R O F. DINA ELHAMMADY TOPICS 1. Hepatitis (acute / chronic) 2. Active viral hepatitis (causes, clinical picture, sequelae, complications, investigations, management) 3. Chronic viral hepatitis (clinical picture, investigations, treatment)  Hepatitis 1. Acute hepatitis a. Infections i. Viral hepatitis: A, B, C, D, E. ii. Other viruses causing hepatitis: EBV, CMV, HSV, Yellow fever. iii. Bacterial hepatitis: Neisseria meningitidis and gonorrhea, salmonella, brucella, campylobacter. b. Drugs and toxins: Alcohol, halothane, isoniazid, paracetamol. c. Metabolic: Wilson's disease. 2. Chronic hepatitis: Inflammation of the liver lasting for at least six months. a. Viral Hepatitis: B, C, D. b. Autoimmune hepatitis. c. Drugs and toxins: Alcohol, isoniazid (INH), methyldopa. d. Metabolic: Wilson's disease, 𝛼-1 antitrypsin deficiency. ACUTE VIRAL H E PAT I T I S  Acute Viral Hepatitis HAV HBV HCV HDV HEV Genome RNA DNA RNA RNA RNA Transmission Oral Blood Blood Blood Oral IP 2-6w 1-6 m 1-6 m 1-6 m 2-6 w Sporadic or Sporadic Sporadic Sporadic Sporadic or Incidence epidemic epidemic Age Young Any Any Any Young Mild Severe Mild Severe Mild (except Acute attack in pregnant) No No chronicity + no Chronicity + Chronicity + chronicity + After hepatitis Chronicity relation to HCC HCC HCC no relation to HCC Prophylaxis Prevented by Vaccine Vaccine ---------- ---------- (active) HBV vaccine Prophylaxis Immuno- Immunoglobulins ---------- ---------- (Passive) globulin Hepatitis A Virus (HAV) → RNA virus.  Fecal-oral transmission → children and young adults affected → sporadic or epidemic incidence.  IP 2-6 weeks → acute attack is usually mild → NO chronicity / HCC.  Prophylaxis with vaccination or immunoglobulin. Hepatitis E Virus (HEV) → RNA virus.  Fecal-oral transmission → children and young adults affected → sporadic or epidemic incidence.  IP 2-6 weeks → acute attack is usually mild except in pregnant females → NOT associated with chronicity or HCC.  No prophylaxis Hepatitis B Virus (HBV) → DNA virus.  Blood, sexual, or vertical (from mother to child) transmission → affects any age → sporadic incidence.  IP 1-6 months → acute attack is usually severe → associated with both chronicity and HCC.  Prophylaxis with vaccination or immunoglobulins. Hepatitis C Virus (HCV) → RNA virus.  Transmitted by blood and community acquired (unknown etiology) → affects any age (more common in adults) → sporadic incidence.  IP 1-6 months → acute attack is usually mild or may go unnoticed → associated with both chronicity and HCC.  No prophylaxis. Hepatitis D Virus (HDV) Weak incomplete RNA virus "Delta agent" dependent on HBsAg → affects only those infected with HBV, either as: 1. Co-infection: HBV and HDV infection occurs simultaneously → C/P of acute hepatitis which may be fulminant. 2. Super-infection: HDV infection occurs in a chronic HBV carrier → activation of hepatitis in a previously stable patient. Blood, sexual, and vertical transmission → affects any age → sporadic incidence. IP 1-6 months → acute attack is usually severe → associated with chronicity. Prophylaxis is vaccination against HBV. Clinical Picture 1. Anicteric hepatitis (usually missed in diagnosis)  Mild cases with influenza-like symptoms and no jaundice. 2. Icteric hepatitis a. Pre - icteric stage (3 days-2 weeks) Symptoms 1. Acute onset fever / marked anorexia / nausea / vomiting 2. Dull aching pain in the right hypochondrium / epigastrium Signs 1. Fever with non-specific skin rash 2. Enlarged, tender, soft liver b. Icteric stage (1 - 4 weeks) Symptoms 1. Fever subsides / anorexia, nausea, vomiting improve. 2. Dark urine at first (bilirubinuria) → then pale stools (no bilirubin entering the gut) → then jaundice Signs 1. Liver is enlarged, tender, soft. 2. Spleen and LN are slightly enlarged. c. Convalescence stage  Symptoms and signs gradually improve, then disappear.  Complete recovery of the liver (clinical / biochemical / histological) may take up to 6 months. Sequelae 1. Complete recovery a. Most cases: HAV and HEV b. Many cases: HBV and HDV c. Few cases: HCV 2. Complications a. Hepatic complications i. Relapse: Original attack recurs and jaundice reappears → serum bilirubin + enzymes  once again ii. Cholestatic hepatitis (especially with HAV): Prolonged cholestasis →  ALP, pruritus, jaundice (may persist for 8-28 weeks) → complete recovery. iii. Fulminant hepatitis: Massive hepatic necrosis → features of acute liver failure (rare). iv. Post-hepatitis syndrome: Transaminitis (all investigations are normal EXCEPT mild  of transaminases). Presents with fatigue, anorexia, pain in right hypochondrium. v. Chronic sequelae (only in HBV, HCV, HDV) Chronic hepatitis Cirrhosis Hepatocellular Carcinoma. Carrier state b. Extrahepatic complications (antigen-antibody complexes) i. Arthritis. ii. Aplastic anemia. iii. Guillain-Barré syndrome (nerve weakness → paralysis). iv. Extrahepatic complications occurring only with HBV / HCV: Glomerulonephritis. Polyarteritis nodosa (inflammation of BV → nodules). Cryoglobulinemia (cryoglobulins = abnormal proteins → precipitated by cold in body tissues → arthralgia, myalgia, fatigue, kidney affection). Investigations 1. Liver function tests a.  Serum bilirubin, transaminases, ALP, gamma globulins. b. Normal albumin. 2. Abdominal ultrasound: Hepatomegaly / splenomegaly (20%). 3. Urine analysis a. Dark, frothy urine due to the presence of bilirubin and bile salts. b. Slight proteinuria and hematuria (due to glomerulonephritis). 4. Stool analysis: Pale stool with steatorrhea. 5. Blood picture: Leucopenia with relative lymphocytosis. 6. Hepatitis markers in blood a. Hepatitis A: Anti-HAV antibodies i. IgM ± IgG = recent / acute infection. ii. IgG (without IgM) = immunity to HAV. b. Hepatitis B (HBV has 3 antigens: surface, core, e): i. HBsAg (Hepatitis B surface antigen): Appears 6 weeks after infection → disappears after 3 months (persistence >6m = carrier state OR chronic state) ii. Anti-HBs antibodies: Appear after 3m and persist = recovery OR immunity from infection and in vaccinated individuals. iii. Anti-HBc antibodies Appear with symptoms of acute hepatitis and persist for life. The only markers of hepatitis B detectable in the "window period" (between clearance of HBsAg and appearance of anti- HBs). IgM positive = recent infection