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CHRONIC HEPATITIS

CHRONIC HEPATITIS. The contours of the liver and spleen as well as the gall bladder in the right and left hypochondrium. THE ANATOMY OF THE PORTAL VENOUS SYSTEM. CHRONIC HEPATITIS. Chronic hepatitis is generally defined as disease that has lasted for 6 months or longer. Inflammation.

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CHRONIC HEPATITIS

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  1. CHRONIC HEPATITIS

  2. The contours of the liver and spleen as wellas the gall bladder in the right and left hypochondrium

  3. THE ANATOMY OF THE PORTAL VENOUS SYSTEM

  4. CHRONIC HEPATITIS Chronic hepatitis is generally defined as disease that has lasted for 6 months or longer

  5. Inflammation Walls of scar tissue begin to form Healthy liver cells become trapped by a wall of scar tissue

  6. CYTOLYTIC SYNDROME • alanine aminotransferase increased, • aspartate aminotransferase increased • Increased LDH • Increased ferritin • Hyperbilirubiemia

  7. abdominalmass (e.g. cancer) biliaryatresiaandotherpediatricliverdiseases biliarytrauma congenitalanomaliesofthebiliarytract gallstones intrahepaticcholestasisofpregnancy (obstetriccholestasis) primarybiliarycirrhosis, anautoimmunedisorder primarysclerosingcholangitis, associatedwithinflammatoryboweldisease somedrugs, (e.g. flucloxacillinanderythromycin) ABCC2 genepolymorphism Alkalinephosphatase elevations of serum bile acid levels elevatedlevelsofGammaGlutamylTransferase [GGT] itchiness (pruritus). Pruritus is the primary symptom of cholestasis jaundice. pale stool. This symptom implies obstructive cholestasis. darkurine Cholestasis

  8. Mesenchymal inflammation Hepatocellularinsufficiency • Hyper-γ globulinemia • CRP • ESR • Albumin • Transferrine • Cholesterol • protro,mbine • Cholinesterasa • Α-lipoproteins • Hyperbilirubinemia

  9. Signs of CLD

  10. CHRONIC HEPATITIS CLASSIFICATION • Chronic Viral Hepatitis B • Chronic Viral Hepatitis C • Chronic Viral Hepatitis D • Chronic Viral Hepatitis nonidentificated • Autoimmune Hepatitis (type 1, 2 ,3) • Toxic Hepatitis, Drug-Induced Hepatitis • Cryptogenic Hepatitis • Alcoholic Hepatitis • Metabolic Hepatitis • Cholestatic Hepatitis • Nonspecific Reactive Hepatitis

  11. Grades of Inflammationand Stages of Fibrosis on Liver Biopsies

  12. CHRONIC HEPATITIS CLASSIFICATIONACCORDING TO SEVERITY (level of Aminotransferases)

  13. CHRONIC HEPATITISCOMPLICATIONS • HEPATIC ENCEPHALOPATHY • VARICEAL BLEEDING • ASCITES • GLOMERULONEPHRITIS • OTHERS

  14. General Concepts • Hepatitis = 'inflammation of the liver'. • six medically important viruses are commonly described as “hepatitis viruses”: HAV,HBV,HCV,HDV,HEV,HGV.

  15. Viral Hepatitis - Historical Perspectives Enterically transmitted “Infectious” A E Viral hepatitis NANB Parenterally transmitted B D C “Serum” F, G, TTV ? other

  16. CHRONIC VIRALHEPATITIS • 5 to 10% of cases of hepatitis В (with or without hepatitis D virus co-infection) • and about 75% of cases of hepatitis C become chronic. • Infection with hepatitis A virus or hepatitis E virus is not a cause of ChronicHepatitis.

  17. HBV: Structure

  18. HBV Structure & Antigens Dane particle HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr) HBcAg = inner core protein (a single serotype) HBeAg= secreted protein; function unknown

  19. Possible Outcomes of HBV Infection Acute hepatitis B infection 3-5% of adult-acquiredinfections 95% of infant-acquired infections Chronic HBV infection Chronic hepatitis 12-25% in 5 years Cirrhosis 20-23% in 5 years 6-15% in 5 years Hepatocellularcarcinoma Liver failure Liver transplant Death Death

  20. Laboratory Diagnosis

  21. CHRONIC VIRALHEPATITIS • Hepatitis B virusandhepatitis C virusarethemajorcausesofchronichepatitisintheworld. • Approximately 80% ofindividualsinfectedwith HCV willbecomechroniccarriers, ofwhom a majoritywilldevelop a degreeofliverdamagerangingfromfattylivertocirrhosis. • Chronic HBV and HCV infectionpredisposepatientstodevelopinghepatocellularcarcinoma.

  22. Only 20% will show symptoms Initially ! Natural History of Hep C 20% Clear the Virus Chronic Infection Acute Infection Healthy Liver 80% Virus Continues to Damage Liver Adapted from Lauer and Walker, NEJM 2001

  23. Natural History Con’t Liver Cancer 1-4%/year Cirrhosis 20-30% Chronic Hepatitis Most symptoms begin to show only when liver is more severely damaged

  24. AUTOIMMUNE HEPATITIS • Patientswithseverediseasewhoare treatedwithcorticosteroidshave a 10-year survivalrateof 60% to 70%, whereasuntreatedpatientshave a survivalrateoflessthan 30%.

  25. Autoimmune HepatitisHistology • Lymphoplasmacytic infiltrate • Interface hepatitis Portal inflammation and invasion of limiting plate

  26. Autoimmune HepatitisHistology • Prominent lobular infiltrate composed of mononuclear and plasma cells Lobular infiltrate

  27. Autoimmune HepatitisHistology • Prominent plasma cells appreciated in this specimen Plasma cells

  28. DRUG-INDUCED CHRONIC HEPATITIS Hepatotoxic drugs: - Paracetamol - Isoniazid - Oestrogens - Antibiotics -Methotrexate -others

  29. DIVERSITY > 1000 Hepatotoxic drugs Diverse mechanisms Variety of liver diseases

  30. METABOLIC ACTIVATION Drug CYP Reactive metabolite (High Amounts) • (Low Amounts) Extensive covalent binding  GSH Protein Immune reactions Direct toxicity

  31. MITOCHONDRIAL DYSFUNCTION Drugs  Beta- oxidation  Respi- ration Cell dysfunction Cell death Lactic acidosis Steatosis

  32. FATTY LIVER Fatty Liver • Fat droplets appear in the cytoplasm ofhepatocytes; • they may appear a few daysafter an alcohol binge, but are almostalways present in heavy drinkers (> 80 gof alcohol per day for > 5 years). • Fattyliver may occur, however, with obesity,diabetes mellitus, starvation and chronichepatitis C virus infection

  33. ALCOHOLIC HEPATITIS • Alcohol abuse is a massive international problem which has huge resource implicationsboth for the community as a whole and also for health care. • Alcohol is enjoyed by many and used safely by the majority of people who drink it. • Alcohol abuse may be denied or not recognized by individuals or their families andfriends. • Alcohol damages not only the liver, but many other organs also.

  34. Effects of alcohol abuse

  35. Altered membrane proteins Neoantigens formation Impaired cytoskeletal transport Stimulation of HSC Immunological injury Damage to cell membranes Alcoholic Hepatitis Mechanisms of liver injury Free radicals Oxidative injury Heat Gut Permeability Endotoxaemia Kupfer cell activation Gultathione depletion ROS & Free radicals TNFα Alcohol dehydrogenase (ADH) Peroxisomal Catalase Genetics Polymorphisms Male vs Female Race Damage Acetaldehyde Ethanol Miscrosomal ethanol-oxidising system (CYP 2E1) Acetaldehyde dehydrogenase Downregulated in chronic alcohol use TNFα IL-1, IL-8 Acetate

  36. ALCOHOLIC HEPATITIS • Alcoholicliverdiseasemaydevelopinwomenafterlessalcoholconsumptionthanisnecessarytocausehepatitis or cirrhosisinmen. • Dailyalcoholconsumptionofapproximately 50 g for 10 to 15 yearsisassociatedwithalcoholicliverdisease inwomen, whereas 80 gisassociated withalcoholiccirrhosis inmen.

  37. Pathology of Alcoholic Hepatitis Mallorys Hyaline Centrilobular necrosis Fatty change Hepatocyte ballooning PMN infiltrate Pericellular fibrosis

  38. ALCOHOLIC HEPATITIS • AlcoholichepatitisreferstothepathologicMallorystainfindingsofalcoholichyalinsurroundedbypolymorphonuclearcellinflammation

  39. CHRONIC HEPATITISDIAGNOSIS LABORATORY SYNDROMES: • Cytolitic syndrome (↑AST, ↑ALT, ↑GGT, ↑Bilirubin ) • Cholestatic syndrome (↑conjugated Bilirubin, ↑Alkalinephosphatase, ↑GGT, ↑cholesterol) • Liver cellular insufficiency syndrome (↓Albumine, ↓prothrombin, ↓cholesterol, ↓fibrinogen) • Mesenchyme-inflammatory syndrome (↑ESR, ↑ﻻ-globulins, ↑timol test ↑Le, ↑C-react. protein) • Hypersplenism(anemia, thrombocytopenia, leukocytopenia)

  40. CHRONIC VIRAL HEPATITISTREATMENT • ANTIVIRAL THERAPY (Interferon therapy, Lamivudine therapy) • Corticosteroids are contraindicated, because viral replication is enhanced

  41. Autoimmune Hepatitis

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