Acute and chronic hepatitis Year 4 Internal Medicine Notes

Acute and chronic hepatitis Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.1 / ALEX / Gastroenterology -- Slide 1 DR ALEX W.MOGERE consultant physician ACUTE AND CHRONIC HEPATITIS A Slide 2 Acute hepatitis Causes Viral hepatitis, hepatotropic viruses{A,B,C,D,E} Other viruses; EBV, CMV, herpes, yellow fever in immunocompromised Non viral; leptospira, klebsiella, toxoplasma Drugs- direct toxic e.g. acetaminophen, amoxicillin, /idiosyncratic e.g. chlorpromazine Toxins- mushroom, carbon tetrachloride, alfa toxins Alcohol Hypo perfusion/shock pts, severe hypotension, severe LV failure Hereditary- Wilson’s dx Pregnancy associated dx. Slide 3 Rare causes Factor interfering with venous return to heart- hepatic occlusion/ veno occlusive dx, constrictive pericarditis malignancies Slide 4 Acute viral hepatitis Incubation period Prodromal symptoms Jaundice phase Recovery phase Slide 5 TYPES OF VIRAL HEPATITIS HAV- picornaviridae,1973 HBV-hepadnaviridae,1970 HCV,flaviviridae,1988 HDV HEV HFV-not a separate virus, a mutant of HBV HGV,flaviviridae Slide 7 Hepatitis A Related to enteroviruses Difficult to grow in cell culture 7 genotypes exist Human- I-III, and VII\nSimian- IV- VI Slide 8 Transmission of hepatitis A Contaminated water/food close personal contact Slide 9 Symptoms/SIGNS(Hepatitis A) Preicteric/prodromal phase:fatigue, jnt and abdominal pain,anorexia, vomiting, Hepatomegaly Icteric phase: icterus/jaundice, high bilirubin Slide 10 Pathogenesis hepatitis A Feco oral transmission Intestinal epithelium multiplication Hematogenous spread to liver Reach liver in 1 week Shed into intestine with bile Then appearance in faeces Incubation period 2-6/52 Slide 11 Cont.pathogenesis hep A After replication and discharge hepatic injury begins Activated T-cell release Y-INF that promote the representation of HLA on liver cells CTL may kill the target cell infected with HAV Slide 12 LAB DX hep A Nucleic acid testing (NAT) is the gold standard for the diagnosis of viremic stages of hepatitis infection. (HAV RNA, HBV DNA, HCV RNA, HDV RNA, and HEV RNA) Demonstration of virus in faeces Detection of ab by ELISA LFTs: ALT, AST(ALT AST)( usu return to reference ranges over 5-20 weeks)bilirubin, protein(modest fall), ALP marginally elevated(esp cholestatic phase) Imaging: abd u/s, CT scan Slide 14 HEPATITIS B Member of the hepadnaviridae Circular, partially double stranded DNA virus Replication involves a RT Impossible to propagate in cell culture Slide 17 HBV replication Reverse transcriptase RNA intermediate Integration Slide 19 HBV transmission Parenteral Vertical(HBeAg+ve) sexual Slide 20 epidemiology 350m carriers globally 120m carriers in China 50% of children born to mothers with chronic HBV in US are Asian American Prevalence high in sub-Saharan Africa and accounts for 80% of the adult pts with sporadic hepatitis. Slide 21 Ct. epidemiology (Kenya) Prevalence rate of HBsAg of 8.8% Prevalence rate in urban areas 8- 30% In pts with HCC 70% are +ve for HBsAg Slide 22 People at high risk of hepatitis B infection IVD abusers Babies of mothers with chronic HBV People with multiple sexual partners Healthcare personnel HIV positive pts Pts requiring blood and blood products Slide 24 Pathogenesis &immunity Virus enters hepatocytes hematogenously Immune response to viral Ags expressed on hepatocyte cell surface is responsible for clinical presentation 5% become chronic carriers Hep B surface ab may confer lifelong immunity Low transmissibility if there is hep Be ab Slide 25 Clinical manifestation hep B Incubation period: av. 60-90/7,range 45-180/7 Insidious onset 1/3 of adults asymptomatic Jaundice 30- 50% Premature death from chronic liver failure-15- 25% Anorexia fatiguability Slide 28 Categorisation of pt The different grps reflect different phases in the natural progression of the disease The main parameters in this categorization include: Serological markers HBV DNA-viral load Presence and level of necro-inflammation on histology Slide 29 Factors that influence progress Gender Age of infection Host immune status Viral mutations Hepatitis Be Ag status Alcohol use Co- infection with HCV /HIV Slide 30 Phases of progression Immune tolerant phase- high viral replication, presence of HBeAg,normal or minimally elevated ALT Immune clearance phase- HBeAg pos CHB, intermittent/persistent ALT elevation, high HBV DNA levels Inactive HBV carrier state(Latent phase)- chronic HBV, very low/undetectable HBV DNA levels,normal ALT Reactivation phase Slide 31 Goals of Tx Reduce risk of progressive to CLD Prevent transmission to others Prevent long-term complications Slide 32 Relevance of HB Ag status HBeAg Positive:\n-HBeAb Negative- Tx at HBV DNA \n 20,000IU/ml HBeAg Neg: -HBeAb positive –Tx at HBV DNA 2000 IU/ml Slide 33 Eligibility for tx requires: ALT HBeAg status HBV DNA levels +/- liver biopsy when indicated +/- HBsAg serum levels-quantification Slide 34 Who to Tx: for HBeAg +ve HBV DNA 20000IU/ML ALT 2ULN-commence t