Pathological Evaluation of Hepatitis 2024 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pathological Evaluation of Hepatitis Class Year 2 Course Pathology Lecturer Dr Clive Kilgallen Date October 11th 2024 LEARNING OUTCOMES Define acute and chronic hepatitis Name the causes of acute h...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pathological Evaluation of Hepatitis Class Year 2 Course Pathology Lecturer Dr Clive Kilgallen Date October 11th 2024 LEARNING OUTCOMES Define acute and chronic hepatitis Name the causes of acute hepatitis and chronic hepatitis Describe the consequences and assessment of chronic hepatitis Distinguish hepatitis A, B & C: transmission & chronicity Discuss the pathogenesis of HBV infection Describe the worldwide burden of chronic HBV and chronic HCV infection Describe HBV serology: the significance of HBe and HBs antigens, anti-HBs antibody Describe HCV diagnosis and disease progression HEPATITIS Acute hepatitis: abnormality resolved 6/12 Some diseases cause only acute hepatitis (HAV) Others by definition cause only chronic hepatitis ▪ Autoimmune hepatitis (AIH), Wilson’s disease Some causes of acute hepatitis may become chronic ▪ Proportion of HBV depending on age, most HCV, very rare HEV Severe acute hepatitis may rarely cause acute liver failure Inflammatory cell in prototypical cases of hepatitis is the lymphocyte, regardless of duration  HEPATITIS (CONTINUED) Flares/exacerbations of chronic hepatitis of any cause (e.g. AIH, Wilson’s, chronic HBV or chronic HBV with HDV superinfection) may mimic acute hepatitis Other causes of chronic liver disease/damage (+/- acute flares, e.g. alcohol) have distinctive features They are therefore not considered under the heading of conventional, stereotypical “chronic hepatitis”: ▪ Alcohol-related liver disease ▪ Non-alcoholic fatty liver disease (a/w metabolic syndrome) ▪ Chronic inflammatory biliary tract diseases (PBC, PSC) ▪ Hereditary haemochromatosis CAUSES OF ACUTE HEPATITIS Acute diffuse liver damage with inflammation ▪ Short of acute liver failure ▪ Viruses (esp. hepatotropic viruses HAV, HBV, HCV, HEV but also EBV, CMV, rubella) ▪ Drugs (may be identical to virus) ▪ adults) May be vague symptoms: nausea, anorexia, malaise Very rare: acute liver failure Signs Enlarged, tender liver Clinical jaundice may occur (but often anicteric, esp. in children) No signs of chronic disease (clinical, blood test, histology) Blood High AST/ALT (may be very high, but normal by 6/12) Bilirubin elevated, albumin normal Lengthened PT (usually mild, except if risk of ALF)  CHRONIC HEPATITIS Persisting abnormality >6/12 Ongoing effects resembling acute hepatitis – i.e. hepatocellular damage as demonstrated by: Biochemical, histological or clinical evidence Syndrome with many causes, similar histology Presentation Routine testing/screening (blood donation, health check) - general population, pregnant women or high risk groups Chronic disease picked up on investigation of symptoms ▪ Vague symptoms like anorexia/malaise ▪ Flares (+/- jaundice) mimicking acute hepatitis Follow-up of acute hepatitis (e.g. HBV, does it resolve?) Cirrhosis +/- decompensation CAUSES OF CHRONIC HEPATITIS Chronic viral hepatitis (B, C, B+D or unknown) Chronic drug hepatitis (rare) Auto-immune hepatitis (always chronic) Wilson’s disease (very rare, always chronic) Alpha-1-antitrypsin deficiency (very rare) Other causes of chronic liver disease/damage have distinctive features Not categorised under the label “chronic hepatitis” (e.g. PBC/ PSC, alcohol-related liver disease, NAFLD, haemochromatosis) But: they share risk of fibrosis, progression to cirrhosis, risk of HCC  ASSESSMENT OF CHRONIC HEPATITIS Blood tests (ALT/AST) Viral load (e.g. HBV, HCV) or genotype (HCV) Biopsy ▪ ‘Grade’ of necroinflammatory activity ▪ ‘Stage’ of fibrosis (from normal to cirrhosis) ▪ Scoring systems guide prognosis, treatment Non-invasive assessments of fibrosis ▪ FibroScan Effectiveness and tolerability of treatment (changing) Aim: eliminate, reduce or delay progression to cirrhosis, reduce risk of HCC  PIECEMEAL NECROSIS/INTERFACE INFLAMMATION Portal tract (centre & bottom right) inflamed, inflammation blurring sharp boundary with liver parenchyma and a/w damage to involved liver cells (upper left) = interface inflammation with piecemeal necrosis. Prototypical pattern of chronic hepatitis (esp. HBV, autoimmune)  VIRAL HEPATITIS Hepatotropic viruses ▪ Hepatitis A & Hepatitis E (“infective hepatitis”) - Faecal-oral/enteral transmission - No chronic state for HAV, very rare HEV ▪ Hepatitis B & Hepatitis C (“serum hepatitis”) - Parenteral transmission - Risk of chronic state ▪ Yellow fever virus - Monkey-mosquito-man transmission Other viral causes acute hepatitis: EBV, CMV, rubella Coinfection/superinfection possible ▪ HCV and/or HBV and/or HIV, HBV+HDV ACUTE VIRAL HEPATITIS Acute Viral Hepatitis Pathological features: Spotty focal necrosis individual hepatocytes Confluent bridging necrosis, confluent necrosis linking vascular structures, typically zone 1 & 2. Where zones 1, 2 & 3 show necrosis that is panacinar necrosis  HEPATITIS A Faecal/oral spread with enteral transmission ▪ Personal/sexual contact, epidemic (institutions) ▪ Contaminated water/shellfish ▪ Most typically a/w travel to endemic areas Usually subclinical or mild illness ▪ More often symptomatic (jaundice & fever) in adults ▪ Silent infection in childhood = reservoir of infection ▪ Very rare cause of ALF, jaundice can be prolonged ▪ No chronic disease/carrier state HEPATITIS A - HISTOLOGY Appearances are of acute hepatitis in general Periportal inflammation with plasma cells Cholestasis Acidophil bodies, apoptosis, “councilman body” HEPATITIS A (CONTINUED) Anti-HAV antibody gives lifelong immunity ▪ IgM anti-HAV indicates acute (recent) infection Active immunisation, esp. if ‘at risk’ ▪ Vaccine induces protective anti-HAV antibody HAV worldwide prevalence CLINICAL COURSE OF HAV INFECTION HEPATITIS E Similar illness/epidemiology to hepatitis A Mainly developing countries, water-borne outbreaks ▪ Commonest cause of ALF South Asia (genotype 1) ▪ Sporadic cases in non-endemic countries (zoonotic, genotype 3) Serological & molecular tests now available Mostly subclinical/mild, rarely acute liver failure Higher risk in pregnant woman of more serious disease In general, no chronic disease/carrier state ▪ Chronic disease described a/w immunosuppression Histology resembles Hepatitis A HEV WORLDWIDE PREVALENCE HEPATITIS B 300m worldwide chronic HBV disease Leading cause chronic hepatitis, cirrhosis, liver cancer worldwide (15-30% of chronic HBV patients) Up to 1m deaths annually Prevalence 0.1->10%, depending on geography/risk ▪ High prevalence >8% SE Asia, China, Africa ▪ Intermediate prevalence 2-8% S Asia, Middle East ▪ Low prevalence 90% chronic HBV (immune tolerance) Childhood ▪ 20-30% infected get chronic HBV Adult ▪ 2% prevalence ▪ Pregnant women (infants get vaccinated, HBIG) ▪ Patients for immunosuppression ▪ High risk (IDUs, frequent sex partners/MSM, contacts, children of parents from >8% areas) HEPATITIS D = Delta agent “Passenger” RNA virus: requires presence of HBV for replication Either co-infection with HBV or superinfection on background of existing chronic HBV Increases risk of chronic disease a/w HBV Typically in IDUs Rare in Ireland HEPATITIS C Prior to HCV identification (1987) blood or blood-product associated hepatitis = “non-A, non-B hepatitis” HCV major cause Major burden chronic infection worldwide (?180m) Prevalence varies widely 6 genotypes (determine behaviour, treatment response) Transmission: blood, IDUs, sporadic (how?) Pathogenesis uncertain Acute infection typically silent, seldom recognised Most cases (>80%) progress to chronic infection Chronic infection often identified incidentally Chronic HCV vague symptoms (fatigue, arthralgia) Small % develop extra-hepatic manifestations HEPATITIS C WORLDWIDE PREVALENCE DIAGNOSIS OF HEPATITIS C Serology: ▪ Anti-HCV antibody just indicates exposure, but: ▪ Most with anti-HCV will have active chronic infection ▪ Anti-HCV not protective HCV RNA in blood = confirms ongoing infection ▪ Amount? HEPATITIS C HISTOLOGY Mild chronic hepatitis Portal tract lymphoid aggregates and follicles Bile duct infiltration by lymphocytes Fatty change Sometimes portal and lobular granulomas Giant cell formation HEPATITIS C EXTRA HEPATIC MANIFESTATIONS Arteritis Cryoglobulinaemia plus glomerulonephritis Porphyria cutanea tarda (PCT) Higher incidence of diabetes Association with lichen planus, Sicca syndrome and non Hodgkin lymphoma DIAGNOSIS OF HEPATITIS C (CONTINUED) Genotype? ▪ Type 1a commonest in US, least responsive to interferon ▪ Type 1b commonest in Europe ▪ Types 2, 3 elsewhere ▪ Polymorphism in IFNL3/IL28B gene predicts response in type 1 Tx response – nil/minimal RNA after 12 or 24/52 = SVR Sustained virological response (SVR) reduces progression, risk cirrhosis, HCC HEPATITIS C CLINICAL COURSE Chronic HCV ▪ Risk of progression varies (men, age>50, +HIV or HBV, alcohol, obese worse) ▪ May take 20-30 years ▪ 20% cirrhosis over 20 years is typical estimate Histology indication of damage, requires biopsy ▪ Predicts risk of progression ▪ Up to recently: guidance to treatment (esp. genotype 1) for interferon-based regimens ▪ Now: non-invasive assessments of fibrosis (FibroScan) Biochemistry may be normal, clinically may be silent CLINICAL COURSE OF CHRONIC HCV CLINICAL COURSE OF UNTREATED HCV INFECTION  END OF LECTURE