This document provides an overview of common liver problems, including identifying causes of abnormal liver function tests, approaches to acute hepatic injury and chronic hepatitis, viral marker interpretation, and treatment of ascites and hepatic encephalopathy. It discusses evaluation and treatment of acute viral hepatitis and asymptomatic abnormal liver function tests. It also covers chronic hepatitis B and C, including serological markers, natural history, and diagnosis. Treatment of spontaneous bacterial peritonitis with antibiotics is emphasized.

1. Common Liver Problems for Extern Siwaporn Chainuvati, MD GI Division

4. Liver function test Hepatocellular damage.not specific for liver Lactate dehydrogenase Synthetic function Albumin Cholestasis.biliary obstruction  -glutamyltransferase Synthetic function Prothrombin time Cholestasis, infiltrative disease, biliary obstruction Alkaline phosphatase Cholestasis, impaired conjugation, biliary obstruction Bilirubin Hepatocellular damage Aspartate aminotransferase Hepatocellular damage Alanine aminotransferase Clinical implication of abnormality Liver chemistry test

5. Acute Hepatic Injury & Acute Viral Hepatitis

11. Patients of Laboratory Tests in Types of Acute Hepatic Injury X- times, URL - upper reference limit

17. Ischemic Hepatitis Days U/L Giltin N,et al ,Am J Gastroenterol,1992 The patients had a rapid striking elevation of AST and LDH, with rapid resolution

26. HBsAg positive Anti-HBc IgM + Anti-HCV negative Anti-HAV IgM negative Acute hepatitis B infection

28. Typical Serologic Course of Acute Hepatitis A Virus Infection Fecal HAV ALT IgM anti-HAV Months after exposure Symptoms 0 1 2 3 4 5 6 12 24 Total anti-HAV

29. Acute Infection 0 2 4 6 HBsAg Anti-HBs Anti-HBc Anti-HBc IgM Months Years HBeAg HBV DNA Anti-HBe Incubation Prodrome ,

30. Acute Hepatitis C Time After Exposure 0 400 600 800 1000 ALT (IU/L) 0 2 4 6 8 10 12 24 1 2 3 4 5 6 Anti-HCV Symptoms Weeks Months HCV RNA positive 200 7 Normal ALT

34. Asymptomatic Abnomal Liver Function Tests, What should we do ?

45.  ALT in an asymptomatic person History of drugs, alcohol , co morbid conditions, family history and PE HBsAg Anti-HCV consider - - NASH (DM, obese: ALT>AST) Wilson( neuro, family: ceruloplasmin Autoimmune(female:ANA, SAM) Hemochromatosis(Fe, ferritin, TIBC) elevated > 6 months without cause Biopsy HCV-RNA HBeAg, DNA

46. Chronic Hepatitis B & C

47. Serological Markers of Chronic HBV Infection HBV DNA HBeAg Months Years Anti-HBc IgM Anti-HBc IgG Anti-HBe HBsAg

48. HBV: Risk of chronic infection Age at Infection 0 20 40 60 80 100 Neonates Infants Children Adults % Risk

49. Natural history of chronic HBV Immune tolerance Immune clearance Asymptomatic with normal ALT HBe +, HBV DNA + Spontaneous HBe to Anti-HBe: rare Symptoms + Increase ALT with active histology HBV DNA + but usually low HBe to Anti-HBe : 2.7-25% /year No symptom with normal ALT HBeAg -, HBsAg + (cytoplasm), HBV DNA (host DNA) 15-35 yr. rapid silence prolonged fluctuating Adult acquired Nonreplicative

50. Natural History of Chronic HBV Infection Acute Infection 5-10% Chronic Carrier 90-95% Resolution 30–50 Years Chronic Hepatitis Stabilisation Progression Cirrhosis Compensated Cirrhosis Liver Cancer Death Adapted from Feitelson, Lab Invest 1994 Decompensated Cirrhosis (Death) 15-25%

52. Chronic Hepatitis C in Thailand Routes of Transmission Tanwandee T, 1999

54. HCV Genotypes and Subtypes (P. Simmonds, Philos Trans R Soc Lond B Biol Sci 2001;356:1013-26) 1 6 3 4 5 2

55. Diagnosis Risk Factors Increased ALT Anti-HCV Positive HCV RNA Genotype Liver Biopsy Confirm virus presence Measure viral level Predicts treatment response Determines treatment duration Best predictor of prognosis

56. HCV All abnormal ALT 1/3 jaundice 2-20 wks > 80% chronic Resolved normal ALT 1/3 2/3 Abnormal ALT All abnormal pathology cirrhosis HCC 20-30% in 10-20 yr. 3%/yr.

57. Ascites & SBP

59. Signs and Symptoms of SBP Hoefs JC, et al. Dis Mon 1985 %

61. Ascitic Fluid Inoculation

62. Ascitic fluid culture : Inoculation of 10 ml of ascitic fluid in hemoculture bottle : 25% reduction of positivity if inoculation was delayed for 4 hours Runyon BA. etal. J Clin Microbiol. 1990. : Conventional method 50% 80% 60%

66. Spontaneous Ascitic Fluid Infection

67. Proposed Pathogenesis of SBP Gut Flora Abdominal lymphatics Bacteremia Bacterascites CNNA Intermediate opsonic activity MNB SBP Resolution Serum complement activity RE function Invasive procedure Good opsonic activity Translocation Poor opsonic activity

68. Classification of ascitic fluid infection PMN = polymorphonuclear

71. Treatment of spontaneous bacterial peritonitis Runyun BA,et al.Gastroenterology 1991 486 + 117 259 + 34 Drug and administration costs/patient 20 14 Hospital mortality 6 5 Recurrence of infection 50 + 68 31 + 38 Days of hospitalization 47 43 Patients, n 10-day course 5-day course

76. Hepatic Encephalopathy

82. West Haven Criteria

84. Ammonia as the key factor of HE NH 3 from Gut NH 3 from Kidney Glutamine--> Glutamic NH 3 from muscle, exogenous Hepatic function Porto-systemic Shunt Muscle wasting NH 3 in circulation Brain

87. Precipitating cause of hepatic encephalopathy 0 10 20 30 Unknown Hepatic injury Constipation Infection Protein Hypokalemia GI Bleeding Sedative Azotemia

88. Precipitating Factors for HE Antidote (flumazenil) Activation of inhibitory neurotransmission Psychoactive drugs Bowel cleaning Ammonia generation by enteric flora Constipation Specific measure and treatment Liver injury, activation cytokines Acute hepatitis Withhold diuretic Hypokalemia, azotemia Diuretics Rehydration Hepatic hypoperfusion Dehydration Withhold diuretic and nephrotoxic drug Ammonia generation Azotemia Potasium replacement Ammonia generation Hypokalemia Specific treatment according to site of bleeding Hepatic hypoperfusion Nitrogen load GI bleeding Antibiotic Protein catabolism Activation of cytokines Sepsis Management Mechanism of action Precipitating factor