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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 Definition.
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The contours of the liver and spleen as wellas the gall bladder in the right and left hypochondrium
CHRONIC HEPATITISDefinition • Chronic hepatitis is a broad clinical and pathologic syndrome that encompasses an etiologically diverse group of diseases characterized by long-term elevation of liver chemistries and the finding of hepatic inflammation on liver biopsy. • Chronic hepatitis is generally defined as disease that has lasted for 6 months or longer
Anxiety Arthritis Ascites (swelling in the stomach area) Blurred Vision Chills Dark Urine Decline in sex drive Depression Dizziness Dry Skin Edema (swelling of the hands, feet & legs) Excessive Bleeding Excessive gas Eye or eyesight problems (blurred vision or dry eyes) Fatigue Fever Flu-like symptoms Gallstones Gray, yellow, white or light colored stools Headaches Hepatalgia (pain or discomfort in liver area) Hot flashes Indigestion Inflammation in the joints Insomnia Irritability Itching Jaundice (yellowing of eyes and/or skin) Joint pain Mood changes or swings Memory loss, mental confusion Menstrual problems Muscle aches Nausea Rashes/Red spots Red palms Sensitivity to heat or cold Sleep disturbances Slow healing and recovery Susceptibility to illness/flu Sweating Vertigo Vomiting Water retention Weakness Weight gain Weight loss
CYTOLYTIC SYNDROME • alanine aminotransferase increased, • aspartate aminotransferase increased • Increased LDH • Increased ferritin • Hyperbilirubiemia
abdominal mass (e.g. cancer) biliary atresia and other pediatric liver diseases biliary trauma congenital anomalies of the biliary tract gallstones intrahepatic cholestasis of pregnancy (obstetric cholestasis) primary biliary cirrhosis, an autoimmune disorder primary sclerosing cholangitis, associated with inflammatory bowel disease some drugs, (e.g. flucloxacillin and erythromycin) ABCC2 gene polymorphism Alkaline phosphatase elevations of serum bile acid levels elevated levels of Gamma Glutamyl Transferase [GGT] itchiness (pruritus). Pruritus is the primary symptom of cholestasis jaundice. pale stool. This symptom implies obstructive cholestasis. dark urine Bile is secreted by the liver to aid in the digestion of fats. Drugs such as gold salts, nitrofurantoin, anabolic steroids, chlorpromazine, prochlorperazine, sulindac, cimetidine, erythromycin, estrogen can cause cholestasis and may result in damage to the liver. Cholestasis
hepatocellular insufficiency • Albumin • Transferrine • Chplesterol • protro,mbine • Cholinesterasa • Α-lipoproteins • Hyperbilirubinemia
Mesenchymal inflammation • Hyper-γ globulinemia • CRP • ESR
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
Grades of Inflammationand Stages of Fibrosis on Liver Biopsies
CHRONIC HEPATITIS CLASSIFICATIONACCORDING TO SEVERITY (level of Aminotransferases)
CHRONIC HEPATITISCOMPLICATIONS • HEPATIC ENCEPHALOPATHY • VARICEAL BLEEDING • ASCITES • GLOMERULONEPHRITIS • OTHERS
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
General Concepts • Hepatitis = 'inflammation of the liver'. • six medically important viruses are commonly described as “hepatitis viruses”: HAV,HBV,HCV,HDV,HEV,HGV.
Viral Hepatitis - Historical Perspectives Enterically transmitted “Infectious” A E Viral hepatitis NANB Parenterally transmitted B D C “Serum” F, G, TTV ? other
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 Chronic Hepatitis.
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
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
CHRONIC VIRALHEPATITIS • Hepatitis B virus and hepatitis C virus are the major causes of chronic hepatitisin the world. • Approximately 80% of individuals infected with HCV will become chronic carriers, ofwhom a majority will develop a degree of liver damage ranging from fatty liver tocirrhosis. • Chronic HBV and HCV infection predispose patients to developing hepatocellularcarcinoma.
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
AUTOIMMUNE HEPATITIS • Autoimmune hepatitis is four times more common in women than in men, • and is most aggressive when it presents in the third and fourth decades. • AIH can be associated with other autoimmune diseases. • Important differential diagnoses include viral hepatitis, Wilson's disease and drugreactions. • There is a rise in IgG, a positive anti-smooth-muscle antibody present in 60%, and antinuclear antibody and liver-kidney microsomalantibody (LKM-1) may be present. • Long-term immunosuppression is required with corticosteroids and often azathioprine. Response rate to therapy (corticosteroids) is 80-90%.
AUTOIMMUNE HEPATITIS • Patients with severe disease who are treated with corticosteroidshave a 10-year survival rate of 60% to 70%, whereasuntreated patients have a survival rate of less than 30%.
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
DRUG-INDUCED CHRONIC HEPATITIS Hepatotoxic drugs: - Paracetamol - Isoniazid - Oestrogens - Antibiotics -Methotrexate -others
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
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.
ALCOHOLIC HEPATITIS • Alcoholic liver disease may develop in women after less alcohol consumptionthan is necessary to cause hepatitis or cirrhosis in men. • Daily alcoholconsumption of approximately 50 g for 10 to 15 years is associated with alcoholic liver diseasein women, whereas 80 gis associatedwith alcoholic cirrhosis in men.
ALCOHOLIC HEPATITIS • AlcoholichepatitisreferstothepathologicMallorystainfindingsofalcoholichyalinsurroundedbypolymorphonuclearcellinflammation
METABOLIC HEPATITIS • HEMOCHROMATOSIS: Characterized by excessive deposition of iron in liver • WILSON DISEASE: Characterized by excessive deposition of copper in liver (mostly in young patients) • α1-ANTITRYPSIN DEFICIENCY:results in cirrhosis and emphysema
CHRONIC HEPATITISDIAGNOSIS LABORATORY SYNDROMES: • Cytolitic syndrome (↑AST, ↑ALT, ↑GGT, ↑Bilirubin ) • Cholestatic syndrome (↑conjugated Bilirubin, ↑Alkaline phosphatase, ↑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)
CHRONIC HEPATITISPLAN of INVESTIGATIONS • Total blood count • Biochemical analysis (Glucose, Bilirubin, ALT, AST, GGT, Alkaline phosphatase, Albumin, ﻻ-globulins, Cholesterol, Liver tests, Sodium, Potassium, Urea, Creatinine) • Urinanalysis, Diastase of urine • Coagulogram • Markers of Viral Hepatitis (chain polimerase reaction, immunoenzyme analysis) • Immunogram • Coprogram • ECG • Endoscopy • USD, CT • Needle liver biopsy