Common liver problems for extern

2,299 views

Published on

Published in: Health & Medicine
1 Comment
17 Likes
Statistics
Notes
  • why it could'nt br downloaded?
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Views
Total views
2,299
On SlideShare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
0
Comments
1
Likes
17
Embeds 0
No embeds

No notes for slide
  • Slide 46 Serological Course of Acute Hepatitis A HAV replicates in the liver, is excreted in bile, and is shed in the stool. Most patients with hepatitis A become symptomatic after an average incubation period of 28 days (range 15-50 days). Peak infectivity occurs during the two-week period before the onset of elevated aminotransferases and jaundice. Fecal shedding of the virus usually disappears by the time patients become symptomatic. Specific antibodies develop rapidly in patients with HAV infection. IgM antibodies against HAV are usually detectable 5-10 days before the onset of symptoms and can persist for up to 6 months after infection. IgG antibodies, which appear early in the infection, persist indefinitely and confer lifetime protection against reinfection. The diagnosis of acute hepatitis A is made by detecting IgM anti-HAV in the serum. Skinhøj P, Mathiesen LR, Kryger P, Møller AM. Faecal excretion of hepatitis A virus in patients with symptomatic hepatitis A infection. Scand J Gastroenterol 1981; 16:1057-1059. Liaw YF, Yang CY, Chu CM, Huang MJ. Appearance and persistence of hepatitis A IgM antibody in acute clinical hepatitis A observed in an outbreak. Infection 1986; 14:156-158. Stapelton JT. Host immune response to hepatitis A virus. J Infect Dis 1995; 171(suppl 1):S9-S14.
  • Slide 80 Serological Markers of Acute HBV Infection Incubation period of HBV infection ranges from 60 to 180 days. HBsAg is the first serological marker of acute HBV infection. Early in the course of acute HBV infection, markers of active viral replication (HBeAg and HBV DNA), are also detectable. As the patients recover, serum HBV DNA level markedly decrease but may remain detectable by PCR assay for up to several decades, HBeAg to anti-HBe seroconversion occurs and finally HBsAg becomes undetectable. Persistence of HBsAg for more than 6 months indicates progression to chronic HBV infection. Anti-HBc IgM is the first antibody to be detected and usually persists for several months. It may be the only marker of acute HBV infection during the ‘window’ period after HBsAg is cleared and before anti-HBs is detected. Recovery from acute HBV infection is indicated by the presence of anti-HBc IgG and anti-HBs.
  • Slide 81 Serological Markers of Chronic HBV Infection Chronic HBV infection is indicated by the presence of HBsAg persisting for more than 6 months and detection of anti-HBc IgG. During the early phase of chronic HBV infection, markers of HBV replication: HBeAg and high serum HBV DNA levels are also present. Over time, patients seroconvert from HBeAg to anti-HBe, accompanied by decrease in serum HBV DNA levels.
  • Slide 67 Risk of chronic infection The risk of progression to chronic HBV infection is inversely proportional to the age at infection. Up to 50 to 90% of neonates and infants born to HBeAg positive mothers become HBV carriers, as compared to 20 to 30% among children infected between the age of 1-5 years, and less than 5% among immunocompetent adults. McMahon BJ, Alward WL, Hall DB, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 1985;151:599-603. Tassopoulos NC, Papaevangelou GJ, Sjogren MH, et al. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology 1987;92:1844-50. Chang MH, et al. Natural history of hepatitis B virus infection in children. J Gastroenterol Hepatol 2000;15 Suppl:E16-9.
  • Dr. Teerha has shown us this consequence So we all agree that we need some kinds of treatment to modify the disease progression
  • FIGURE 1
  • Slide 287 TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP) Appropriate empiric antibiotic therapy is based on the administration of a safe antibiotic that will cover the most likely causative pathogens and should be initiated as soon as the diagnosis of SBP is established (ascites PMN count >250/mm3). Based on controlled and uncontrolled trials, the recommended antibiotics are third-generation cephalosporins (cefotaxime and ceftriaxone have been the most utilized) or amoxicillin-clavulanic acid, administered intravenously. In patients with uncomplicated SBP, oral ofloxacin has been shown to be as useful as intravenous cefotaxime, however the use of quinolones depends on the local prevalence of quinolone-resistant organisms. Aminoglycosides, however, should be avoided as they are associated with high incidence of renal toxicity in cirrhotic patients. The minimal duration of therapy should be at least 5 days although, in clinical trials, the median duration of therapy needed for a reduction in ascites PMN below 250/mm 3 is 7 days. A repeat diagnostic paracentesis should be performed 2 days after starting antibiotics and at this time ascites PMNs should have decreased by >25% from baseline. Lack of response should prompt further investigations to rule out secondary peritonitis. Rimola A, et al., J Hepatol 2000; 32: 142
  • Slide 240 MANAGEMENT OF UNCOMPLICATED ASCITES Sodium (salt) restriction is effective in only 10-20% of patients with cirrhotic ascites. Those with mild to moderate ascites and those with adequate natriuresis are more likely to respond to sodium restriction alone. Diuretic therapy is the mainstay of management of uncomplicated ascites. Spironolactone is more effective than loop diuretics such as furosemide and therefore therapy of ascites should be spironolactone-based. A progressive diuretic schedule (spironolactone followed by furosemide) requires adjustment less frequently than a combination schedule (spironolactone + furosemide from the outset) and may be preferable, particularly in the outpatient setting.
  • Slide 241 MANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION Dietary sodium intake should be restricted to 2 g (or 5.2 g of dietary salt) a day. A more restrictive diet is not recommended as diet unpalatability may compromise nutritional status. Fluid restriction is not required unless hyponatremia (serum sodium <125 mEq/L) is present.
  • Slide 242 MANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPY Spironolactone should be started at 100 mg/day (once a day in the morning). The dose should be adjusted every 3-4 days to a maximal effective dose of 400 mg/d. If weight loss is inadequate or if hyperkalemia develops, furosemide can be added at an escalated dose from 40 to 160 mg/day. The weight loss goal is 1 kg in the first week and 2 kg/week subsequently. However, diuretics should be reduced if rate of weight loss is more than 0.5 kg/day (or 1 kg/day in patients with peripheral edema). The common side effects of diuretic therapy include electrolyte abnormalities, renal dysfunction, encephalopathy, and painful gynecomastia (with spironolactone).
  • Common liver problems for extern

    1. 1. Common Liver Problems for Extern Siwaporn Chainuvati, MD GI Division
    2. 2. Objectives <ul><li>Identify causes of abnormal liver functions tests </li></ul><ul><li>Approach to acute hepatic injury and chronic hepatitis </li></ul><ul><li>Interpretation of viral markers </li></ul><ul><li>Treatment of ascites, SBP </li></ul><ul><li>Treatment of hepatic encephalopathy </li></ul>
    3. 3. Liver Function Tests <ul><li>Liver function tests usually do not tell true function of the liver </li></ul><ul><li>Normal values do not mean “normal” </li></ul><ul><ul><li>eg. normal ALT is Mean + 2 SD and was set as early as 1950s </li></ul></ul><ul><li>Level of abnormality does not reflect severity but may help in differential diagnosis </li></ul><ul><li>Decrease of the value does not mean improvement </li></ul>
    4. 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. 5. Acute Hepatic Injury & Acute Viral Hepatitis
    6. 6. Causes of Hepatic injury <ul><li>Ischemia </li></ul>Immune reaction (AIH,PBC,PSC) Infection (virus, bacteria) Medications Toxin / Alcohol Endogenous Exogenous Hepatocyte Aminotransferase Copper/Iron overload (Wilson’s disease/ Hemochromatosis)
    7. 7. AST/ALT <ul><li>Best discriminant of AST/ALT in acute hepatic injury is 200/300 IU/L </li></ul><ul><li>(Rozen P Isr J Med Sci 1970) </li></ul><ul><li>Uncomplicated alcoholic hepatitis rarely has level AST/ALT >8-10 times ULN (look for paracetamol?) </li></ul>
    8. 8. ALT and AST activity <ul><li>Useful in narrowing the DDX for cause of the liver injury </li></ul><ul><li>Level of aminotransferase elevation </li></ul><ul><li>Predominant AST elevation </li></ul><ul><li>Rate of aminotransferase declination </li></ul>
    9. 9. ALT and AST activity <ul><li>Level of aminotransferase elevation </li></ul><ul><li>Acute hepatic injury </li></ul><ul><ul><li>Hepatocyte damage occurs abruptly and over a short period of time </li></ul></ul><ul><ul><li>Aminotransferase elevation : >10-15 times UNL </li></ul></ul>
    10. 10. ALT and AST activity <ul><li>Level of aminotransferase elevation </li></ul><ul><li>Chronic hepatic injury </li></ul><ul><ul><li>Hepatocyte damage occurs more than 6 months </li></ul></ul><ul><ul><li>Aminotransferase elevation : < 5 times UNL </li></ul></ul>
    11. 11. Patients of Laboratory Tests in Types of Acute Hepatic Injury X- times, URL - upper reference limit
    12. 12. Etiology of ALT and AST elevations: Lesser Than 5 Times Normal <ul><li>Chronic Hepatitis B and C </li></ul><ul><li>Alcohol </li></ul><ul><li>Medication,Toxin </li></ul><ul><li>Nonalcoholic Fatty liver Disease </li></ul><ul><li>Autoimmune Hepatitis </li></ul><ul><li>Wilson disease </li></ul><ul><li>Hemochromatosis </li></ul>
    13. 13. Marked Elevation of ALT (>15-20 times ULN) <ul><li>Acute viral hepatitis (rarely >2000-3000 IU/L) </li></ul><ul><li>Ischemic liver </li></ul><ul><li>Heat stroke </li></ul><ul><li>Toxic and drugs: </li></ul><ul><ul><li>Paracetamol, Halothane </li></ul></ul><ul><li>Acute Budd-Chiari Syndrome </li></ul><ul><li>Hepatic infarct or artery ligation </li></ul>
    14. 14. AST and ALT activity <ul><li>Most types of liver disease </li></ul><ul><li>: ALT>AST activity </li></ul><ul><li>AST come from non hepatic tissue </li></ul><ul><li>: heart ,skeletal tissue and red blood cell </li></ul><ul><li>ALT is low concentrations in tissue other than liver </li></ul>1 Scola RH, et al. Arg Neurosiquiatr 2000 2 Lin YC, et al. Taiwan Erch Ko I Hsueh Hut Tsa Chili 1999
    15. 15. ALT and AST activity <ul><li>Predominant AST elevation </li></ul><ul><ul><li>Alcoholic liver disease </li></ul></ul><ul><ul><li>Extrahepatic source of AST: </li></ul></ul><ul><ul><ul><li>Haemolysis </li></ul></ul></ul><ul><ul><ul><li>Skeletal muscle disease: rhabdomyolysis,dermatomyositis </li></ul></ul></ul><ul><ul><ul><li>Cardiac muscle: </li></ul></ul></ul><ul><ul><ul><li>myocardial infarction </li></ul></ul></ul>
    16. 16. ALT and AST activity <ul><li>Rate of aminotransferase declination </li></ul><ul><ul><li>Rapid declination of aminotransferase </li></ul></ul><ul><ul><ul><li>Ischemic hepatic injury </li></ul></ul></ul><ul><ul><ul><li>Drug induced hepatitis : short half life drug </li></ul></ul></ul><ul><ul><ul><li>Acute biliary tract obstruction </li></ul></ul></ul><ul><ul><ul><li>Fulminant hepatitis </li></ul></ul></ul><ul><ul><li>Slow declination of aminotransferase </li></ul></ul><ul><ul><ul><li>Acute viral hepatitis </li></ul></ul></ul><ul><ul><ul><li>Drug induced hepatitis : long half life drug </li></ul></ul></ul><ul><ul><ul><li>Autoimmune disease,Metabolic disease </li></ul></ul></ul>
    17. 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
    18. 18. Marker of Severity in Acute Liver Disease <ul><li>Level of AST/ALT do not reflect severity </li></ul><ul><li>Severity in viral hepatitis </li></ul><ul><ul><li>Total bilirubin > 257µmol/L (15 mg/dL) </li></ul></ul><ul><ul><li>PT > 4 sec above (IIB, AASLD) </li></ul></ul><ul><ul><li>Clinically worse (hypoglycemia, HE) </li></ul></ul><ul><li>Paracetamol </li></ul><ul><ul><li>Persistent elevation or rising of PT more than 4 days (IIB, AASLD) </li></ul></ul>
    19. 19. Monitoring LFTs <ul><li>AST/ALT </li></ul><ul><ul><li>After reaching peak, the AST/ALT levels decrease at rate 11.7-10.5%/day </li></ul></ul><ul><ul><li>Once consistently decrease, no need for frequent follow-up </li></ul></ul><ul><li>Bilirubin </li></ul><ul><ul><li>Pattern of bilirubin is not reliable for differential hepatocellular and obstructive </li></ul></ul><ul><ul><li>As total bilirubin decline, the proportion of δ -bilirubin increase </li></ul></ul><ul><ul><li>No need for follow-up unless worse </li></ul></ul>
    20. 21. Case AJ <ul><li>25 yr man previously healthy </li></ul><ul><li>1 week- fatigue, right upper quadrant pain, nausea, headache, appetite </li></ul><ul><li>2 days PTA- dark urine and yellowish skin </li></ul><ul><li>No travel history, no illicit drugs </li></ul><ul><li>ETOH: social drink </li></ul>
    21. 22. Physical Examination <ul><li>Icteric sclera, no asterixis </li></ul><ul><li>Abdomen: soft, no shifting dullness, </li></ul><ul><li>No tenderness, liver 1 FB </li></ul><ul><li>spleen not palpable </li></ul>
    22. 23. Laboratory <ul><li>CBC 11,000 mm 3 Hct 38% </li></ul><ul><li>PLT 150,000 /mm 3 </li></ul><ul><li>BUN 15 Cr 1.0 </li></ul><ul><li>AST 780 U/L ALT 1170 U/L ALP 180 U/L </li></ul><ul><li>TB 4.0 mg/dl DB 3.0 mg/dl </li></ul><ul><li>albumin/globulin 4.2/3.8 g/dl </li></ul>
    23. 24. What is the most likely diagnosis? <ul><li>A. Autoimmune hepatitis </li></ul><ul><li>B. Acute cholecystitis </li></ul><ul><li>C. Acute viral hepatitis </li></ul><ul><li>D. Drug induced hepatitis </li></ul>C. Acute viral hepatitis
    24. 25. What laboratory tests should be done initially, except? <ul><li>A. HBsAg </li></ul><ul><li>B. Anti-HBc IgM </li></ul><ul><li>C. Anti-HAV IgM </li></ul><ul><li>D. Anti-HBs </li></ul><ul><li>E. Anti-HCV </li></ul>D. Anti-HBs
    25. 26. HBsAg positive Anti-HBc IgM + Anti-HCV negative Anti-HAV IgM negative Acute hepatitis B infection
    26. 27. Acute Viral Hepatitis:Serology <ul><li>B: HBsAg </li></ul><ul><li>Anti HBc-IgM </li></ul><ul><li>(Anti HBs, Anti HBc, HBeAg : no benefit) </li></ul><ul><li>A: Anti HAV-IgM </li></ul><ul><li>Anti HAV- total </li></ul><ul><li>C: Anti HCV: not helpful in acute </li></ul>
    27. 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
    28. 29. Acute Infection 0 2 4 6 HBsAg Anti-HBs Anti-HBc Anti-HBc IgM Months Years HBeAg HBV DNA Anti-HBe Incubation Prodrome ,
    29. 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
    30. 31. Acute Viral Hepatitis Treatment : Diet <ul><li>N/V usu. least in the morning. </li></ul><ul><li>Well balance diet is appropriated </li></ul><ul><li>Fatty foods need not be restricted unless they produce nausea-vomiting </li></ul><ul><li>Avoid excess CHO: </li></ul><ul><ul><li>Impair free water clearance in AVH </li></ul></ul><ul><ul><li>Induce fatty liver </li></ul></ul>
    31. 32. Acute Viral Hepatitis: Treatment <ul><li>Symptomatic and supportive </li></ul><ul><li>Hospitalization for isolation purposes is not warranted </li></ul><ul><li>Enzymes value may be done weekly at the beginning then biweekly during subsiding phase </li></ul><ul><li>Routine biopsy is unnecessary </li></ul>
    32. 33. Acute Viral Hepatitis: When admission is needed? <ul><li>Severely symptomatic: </li></ul><ul><ul><ul><li>marked nausea-vomiting </li></ul></ul></ul><ul><ul><ul><li>encephalopathy </li></ul></ul></ul><ul><li>Lab </li></ul><ul><ul><li>Rising bilirubin > 15-20 mg/dL </li></ul></ul><ul><ul><li>Persistence of bilirubin at plateau for 2-3 wks. </li></ul></ul><ul><ul><li>Prolonged PT </li></ul></ul><ul><ul><li>Rapidly fall in AST/ALT </li></ul></ul><ul><ul><li>Hypoglycemia </li></ul></ul><ul><ul><li>Hepatocellular failure (drops in albumin, ascites) </li></ul></ul>
    33. 34. Asymptomatic Abnomal Liver Function Tests, What should we do ?
    34. 35. Case SB <ul><li>36 y/o female, height 155 cm. BW 80 Kg., seen for persistent abnormal LFT </li></ul><ul><li>Reported occasional RUQ pain, no </li></ul><ul><li>Jaundice </li></ul><ul><li>PHx: DM (diet-controlled), hyperlipidemia </li></ul><ul><li>Meds: simvastatin 20 mg/day </li></ul>
    35. 36. Case SB <ul><li>Exam: slight obese, BP 150/80 mmHg </li></ul><ul><li>Abd: soft, no shifting dullness, no signs of chronic liver disease, liver just palpable, spleen not palpable </li></ul><ul><li>Ext: no edema </li></ul>
    36. 37. Case SB <ul><li>WBC 7,500 mm 3 Hct 37 % </li></ul><ul><li>PLT 150,000 mm 3 </li></ul><ul><li>AST 50 U/L ALT 85 U/L ALP 90 U/L </li></ul><ul><li>TB 1.1 mg/dl DB 0.5 mg/dl </li></ul><ul><li>albumin/globulin 4.3/3.7 g/dl </li></ul>
    37. 38. What is your provisional diagnosis? <ul><li>Hepatitis C cirrhosis </li></ul><ul><li>Nonalcoholic fatty liver disease </li></ul><ul><li>Statin induced hepatitis </li></ul><ul><li>Primary biliary cirrhosis </li></ul>
    38. 39. What is your provisional diagnosis? <ul><li>Hepatitis C cirrhosis </li></ul><ul><li>Nonalcoholic fatty liver disease </li></ul><ul><li>Statin induced hepatitis </li></ul><ul><li>Primary biliary cirrhosis </li></ul>
    39. 40. What is chronic hepatitis? <ul><li>In the absence of liver biopsy showing chronic hepatitis; </li></ul><ul><li>Persistence abnormal ALT > 6 months </li></ul><ul><li>or </li></ul><ul><li>Abnormal ALT > one occasion in 6 months without another explanation (may be less with high risk) </li></ul>
    40. 41. <ul><li>Chronic Hepatitis B </li></ul><ul><li>Chronic Hepatitis C </li></ul><ul><li>Alcohol </li></ul><ul><li>Medication </li></ul><ul><li>NAFLD </li></ul><ul><li>Autoimmune Hepatitis </li></ul><ul><li>Wilson disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>Very rare: PBC, PSC, Alpha-1-antitrypsin </li></ul><ul><li>Unknown </li></ul>Common Causes of abnormal ALT
    41. 42. Risk factors for chronic viral hepatitis <ul><li>Injection drug use </li></ul><ul><li>Birth to mother with HBV </li></ul><ul><li>Blood transfusion or blood factor con c </li></ul><ul><li>prior to 1992 (HCV) </li></ul><ul><li>Needle stick from a donor subsequently </li></ul><ul><li>testing positive for HCV or HBV </li></ul><ul><li>Chronic hemodialysis </li></ul><ul><li>Unvaccinated health care workers </li></ul><ul><li>Homosexual </li></ul><ul><li>Body piercing or tattooing * </li></ul>*Possible risk factors
    42. 43. Common medication which cause elevated transminases <ul><li>Lipid lowering agents : Statin </li></ul><ul><li>NSAIDs </li></ul><ul><li>Antibiotic </li></ul><ul><li>Anti-tuberculosis </li></ul><ul><li>Anti-epileptic </li></ul><ul><li>Herbal medicine </li></ul>
    43. 44. Screening for chronic hepatitis in asymptomatic high risk <ul><li>ALT is most cost-effective </li></ul><ul><li>Specific viral serologies (HBsAg, Anti-HCV) + ALT in high risk for chronic viral hepatitis </li></ul>
    44. 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
    45. 46. Chronic Hepatitis B & C
    46. 47. Serological Markers of Chronic HBV Infection HBV DNA HBeAg Months Years Anti-HBc IgM Anti-HBc IgG Anti-HBe HBsAg
    47. 48. HBV: Risk of chronic infection Age at Infection 0 20 40 60 80 100 Neonates Infants Children Adults % Risk
    48. 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
    49. 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%
    50. 51. Hepatitis C Routes of Transmission <ul><li>Blood transfusion </li></ul><ul><li>Blood products </li></ul><ul><li>Perinatal </li></ul><ul><li>Intrafamilial </li></ul><ul><li>Hemodialysis </li></ul><ul><li>Shared needles </li></ul><ul><li>Tattooing </li></ul><ul><li>Needle-stick and sharps injuries </li></ul><ul><li>Sexual </li></ul><ul><li>Saliva? </li></ul>
    51. 52. Chronic Hepatitis C in Thailand Routes of Transmission Tanwandee T, 1999
    52. 53. Diagnosis of HCV <ul><li>Antibody Tests (EIA, RIBA) </li></ul><ul><li>Tests for HCV-RNA </li></ul><ul><ul><li>HCV Qualitative (PCR) </li></ul></ul><ul><ul><li>HCV Quantitative (bDNA, PCR) </li></ul></ul><ul><ul><li>HCV Genotype </li></ul></ul>
    53. 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
    54. 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
    55. 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.
    56. 57. Ascites & SBP
    57. 58. <ul><li>New onset ascites </li></ul><ul><li>At the time of admission </li></ul><ul><li>Rapid decompensation of ascites </li></ul><ul><li>Clinical deterioration: fever, abdomial pain, tenderness, mental change, ileus, hypotension </li></ul><ul><li>Suspicious for infection: leukocytosis , acidosis, azotemia </li></ul>Ascites
    58. 59. Signs and Symptoms of SBP Hoefs JC, et al. Dis Mon 1985 %
    59. 60. <ul><li>Routine : </li></ul><ul><ul><li>Cell count and differentiate, albumin, gram stain and culture </li></ul></ul><ul><li>Option : </li></ul><ul><ul><li>Glucose, LDH, total protein, amylase </li></ul></ul><ul><li>Unusual : </li></ul><ul><ul><li>Smear and culture for AFB, cytology </li></ul></ul>Ascites
    60. 61. Ascitic Fluid Inoculation
    61. 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%
    62. 63. <ul><li>High gradient > 1.1 gm/dl Low gradient < 1.1 gm/dl </li></ul><ul><ul><ul><li>- Cirrhosis - Peritoneal carcinomatosis </li></ul></ul></ul><ul><ul><ul><li>- Alcoholic hepatitis - TB peritonitis </li></ul></ul></ul><ul><ul><ul><li>- Cardiac ascites - Pancreatic ascites </li></ul></ul></ul><ul><ul><ul><li>- Mixed ascites - Bowel obstruction /infarction </li></ul></ul></ul><ul><ul><ul><li>- Massive liver metastasis - Biliary ascites </li></ul></ul></ul><ul><ul><ul><li>- Fulminant hepatic failure - Nephrotic syndrome </li></ul></ul></ul><ul><ul><ul><li>- Budd-Chiari syndrome - Postop lymphatic leak </li></ul></ul></ul><ul><ul><ul><li>- Veno-occlusive disease - Serositis in connective tissue disease </li></ul></ul></ul><ul><ul><ul><li>- Myxedema </li></ul></ul></ul><ul><ul><ul><li>- Fatty liver of pregnancy </li></ul></ul></ul>Serum albumin- ascitic albumin(SAAG) Runyon BA, et al. Ann Intern Med 1992
    63. 64. Investigation <ul><li>Ascitic fluid analysis: </li></ul><ul><ul><li>Cell count 2,450/mm 3 , </li></ul></ul><ul><ul><li>PMN 80%, L20% </li></ul></ul><ul><ul><li>Ascitic albumin 0.9 g/dl </li></ul></ul><ul><ul><li>(serum albumin 2.4 g/dl) </li></ul></ul><ul><ul><li>Gram stain: no organism </li></ul></ul><ul><ul><li>Ascitic fluid culture: pending </li></ul></ul>
    64. 65. <ul><li>What is the treatment of choice for SBP? </li></ul><ul><li>A. Ampicillin plus Gentamicin iv </li></ul><ul><li>B. Cefotaxime 1 gm iv every 8 hrs </li></ul><ul><li>C. Olfloxacin 400 mg oral BID </li></ul><ul><li>D. Cefazolin plus Metronidazole iv </li></ul>Question
    65. 66. Spontaneous Ascitic Fluid Infection
    66. 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
    67. 68. Classification of ascitic fluid infection PMN = polymorphonuclear
    68. 69. <ul><li>Microorganisms </li></ul><ul><li>Escherichia coli 34(56.7) </li></ul><ul><li>Klebsiella spp. 3(5) </li></ul><ul><li>Enterobacter cloacae 1(1.7) </li></ul><ul><li>Citrobacter freundii 1(1.7) </li></ul><ul><li>Aeromonas sobria 1(1.7) </li></ul><ul><li>Streptococcus pneumoniae 1(1.7) </li></ul><ul><li>Enterococcus faecalis 3(5) </li></ul><ul><li>Streptococus spp 1(1.7) </li></ul><ul><li>Bacteroides distasonis 1(1.7) </li></ul><ul><li>Polymocrobial infection 1(1.7) </li></ul>Causative Organisms in SBP Gomez-Jimenez. et al. Antimicrob. Agents Chemother. 1993. Klawprom P and Kachintorn U: 1998
    69. 70. TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP) Treatment of Spontaneous Bacterial Peritonitis <ul><li>Recommended antibiotics for initial empiric therapy </li></ul><ul><ul><ul><li>i.v . cefotaxime, amoxicillin-clavulanic acid </li></ul></ul></ul><ul><ul><ul><li>oral ofloxacin (uncomplicated SBP) </li></ul></ul></ul><ul><ul><ul><li>avoid aminoglycosides </li></ul></ul></ul><ul><li>Minimum duration: 5 days </li></ul><ul><li>Re-evaluation if ascitic fluid PMN count has not decreased by at least 25% after 2 days of treatment </li></ul>Rimola et al., J Hepatol 2000; 32:142
    70. 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
    71. 72. Features Suggestive of Secondary Bacterial Peritonitis in Patients with Cirrhotic Ascites <ul><li>Ascitic fluid PMN count > 10,000/ml </li></ul><ul><li>No response to antibiotics </li></ul><ul><li>> 2 organisms (anaerobes, fungi) </li></ul><ul><li>2 of the following in ascitic fluid </li></ul><ul><ul><li>Glucose < 50 mg/dL </li></ul></ul><ul><ul><li>Protien > 1 g/dL </li></ul></ul><ul><ul><li>LDH > normal serum level </li></ul></ul><ul><ul><li>Sensitivity 100%, Specificity 45% </li></ul></ul>
    72. 73. MANAGEMENT OF UNCOMPLICATED ASCITES Conclusions: Management of Uncomplicated Ascites Definition: Ascites responsive to diuretics in the absence of infection and renal dysfunction <ul><li>Sodium restriction </li></ul><ul><ul><li>Effective in 10-20% of cases </li></ul></ul><ul><ul><li>Predictors of response: mild or moderate ascites, Urine Na excretion > 50 mEq/day </li></ul></ul><ul><li>Diuretics </li></ul><ul><ul><li>Should be spironolactone-based </li></ul></ul><ul><ul><li>A progressive schedule (spironolactone  furosemide) requires fewer dose adjustments than a combined therapy (spironolactone + furosemide) </li></ul></ul>
    73. 74. MANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION <ul><li>Sodium Restriction </li></ul><ul><li>2 g (or 5.2 g of dietary salt) a day </li></ul><ul><li>Fluid restriction is not necessary unless there is hyponatremia (<125 mmol/L) </li></ul><ul><li>Goal: negative sodium balance </li></ul><ul><li>Side effect: unpalatability may compromise nutritional status </li></ul>Conclusions: Management of Uncomplicated Ascites
    74. 75. MANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPY <ul><li>Diuretic Therapy </li></ul><ul><li>Dosage </li></ul><ul><ul><li>Spironolactone 100-400 mg/day </li></ul></ul><ul><ul><li>Furosemide (40-160 mg/d) for inadequate weight loss or if hyperkalemia develops </li></ul></ul><ul><li>Increase diuretics if weight loss <1 kg in the first week and < 2 kg/week thereafter </li></ul><ul><li>Decrease diuretics if weight loss >0.5 kg/day in patients without edema and >1 kg/day in those with edema </li></ul><ul><li>Side effects </li></ul><ul><ul><li>Renal dysfunction, hyponatremia, hyperkalemia, encephalopathy, gynecomastia </li></ul></ul>Conclusions: Management of Uncomplicated Ascites
    75. 76. Hepatic Encephalopathy
    76. 77. <ul><li>ผู้ป่วยชายอายุ 48 ปี อาชีพรับราชการ กรุงเทพฯ </li></ul><ul><li>อส : ซึม 2 วันก่อนมารพ . </li></ul><ul><li>ปป : 3 เดือน ผู้ป่วยมีอาการตัวตาเหลืองมากขึ้นเรื่อยๆ ท้องโตมากขึ้น แน่นอึดอัด ขาบวม 2 ข้าง ไม่มีไข้ ปัสสาวะสีเหลืองเข้ม ไม่แสบขัด อุจจาระปกติ </li></ul><ul><li>2 วันก่อนมารพ . ญาติสังเกตุว่าผู้ป่วยซึมลง กินอาหารได้น้อย ไม่มีไข้ ไม่ไอหรือปวดท้อง ปัสสาวะปกติ ไม่ถ่ายอุจจาระมา 2 วัน </li></ul><ul><ul><li>ผู้ป่วยดื่มสุรา 1 ขวดกลม / วันนาน 20 ปี </li></ul></ul><ul><ul><li>5 ปีก่อนบริจาคเลือดแล้วตรวจพบ HBs Ag-positive </li></ul></ul><ul><ul><li>ปฏิเสธการใช้ยาใดๆเองทุกชนิด </li></ul></ul>Case SI
    77. 78. <ul><li>VS: T 36.8 0 C, R 22/min, P 88/min, BP 110/70 mmHg </li></ul><ul><li>GA: Drowsiness, cachexia, not pale, moderately </li></ul><ul><li>jaundice, spider nevi +, palmar erythemar +, </li></ul><ul><li>flapping tremor,leg edema both 2+ </li></ul><ul><li>HEENT : Parotid gland enlargement </li></ul><ul><li>RS: Normal breath sound,no adventitious sound </li></ul><ul><li>CVS: JVP 2 cms, regular rhythm, normal S 1 S 2 </li></ul><ul><li>Abd: Tense ascites, superficial dilated vein, </li></ul><ul><li>not tender, decrease bowel sound, </li></ul><ul><li>liver can’t palpate, splenomegaly ~ 1 FB </li></ul><ul><li>below LCM </li></ul><ul><li>NS: No stiffneck and Kernig’s sign, </li></ul><ul><li>no localized sign, flexer plantar response </li></ul>Physical Examination
    78. 79. Question <ul><li>What is the cause of drowsiness? </li></ul><ul><li>A. Hypoglycemia </li></ul><ul><li>B. Hepatic encephalopathy </li></ul><ul><li>C. Subdural haematoma </li></ul><ul><li>D. Post ictal phase </li></ul>
    79. 80. <ul><li>Hepatic encephalopathy </li></ul><ul><li>Alcoholic withdrawal , seizure </li></ul><ul><li>Nutrition: Werni c ke’ s encephalopathy </li></ul><ul><li>Drugs: Sedative-hypnotic </li></ul><ul><li>Metabolic: </li></ul><ul><ul><li>Hypo/hypernatremia </li></ul></ul><ul><ul><li>Hypo/hyperglycemia </li></ul></ul><ul><ul><li>Uremia </li></ul></ul><ul><li>Intracranial : stroke, trauma, infection </li></ul>Change of Consciousness
    80. 81. Diagnosis of HE <ul><li>Base on clinical evidence </li></ul><ul><li>Recognition of underlying liver disease </li></ul><ul><ul><li>Risk factor etc. HBV, HCV, Alcohol </li></ul></ul><ul><ul><li>Signs of chronic liver desease </li></ul></ul><ul><ul><li>Laboratory: low albumin/high globulin, pancytopenia </li></ul></ul><ul><li>Cardinal features of HE </li></ul><ul><li>Exclude other causes of encephalopathy </li></ul>
    81. 82. West Haven Criteria
    82. 83. <ul><li>What is the appropriated investigation </li></ul><ul><li>in cirrhotic patient with hepatic </li></ul><ul><li>encephalopathy? </li></ul><ul><li>A. Electroencephalogram(EEG) </li></ul><ul><li>B. Lumbar puncture </li></ul><ul><li>C. Brain computed tomography(CT) </li></ul><ul><li>D. Clinical diagnosis </li></ul>Question
    83. 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
    84. 85. Question <ul><li>What is treatment for hepatic encephalopathy? </li></ul><ul><li>A. Neomycin </li></ul><ul><li>B. Lactulose </li></ul><ul><li>C. Branched amino acids formula </li></ul><ul><li>D. Flumazenil </li></ul>
    85. 86. <ul><li>General supportive care </li></ul><ul><ul><li>Nutrition: calories, vitamin, hypoglycemia </li></ul></ul><ul><ul><li>Avoid iatrogenic complication: drugs, infections, pressure ulcer </li></ul></ul><ul><li>Identification and removal of precipitating factors </li></ul><ul><li>Reduction of nitrogenous load from the Gut </li></ul><ul><li>Assessment of the need for long term therapy </li></ul><ul><ul><li>Control likelihood of recurrent encephalopathy </li></ul></ul><ul><ul><li>Assessment of the need for liver transplantation </li></ul></ul>Therapy of Hepatic encephalopathy
    86. 87. Precipitating cause of hepatic encephalopathy 0 10 20 30 Unknown Hepatic injury Constipation Infection Protein Hypokalemia GI Bleeding Sedative Azotemia
    87. 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
    88. 89. <ul><li>Promote reduction of nitrogenous products </li></ul><ul><li>Protein restriction (adequate calories) </li></ul><ul><li>Prevent constipation (2-3 BM/day) </li></ul><ul><li>Nonabsorbable disaccharide (lactulose, lactitol) </li></ul><ul><li>Antibiotics to suppress ammoniagenic bacteria (neomycin, metronidazole) </li></ul><ul><li>plus laxative </li></ul><ul><li>Combined treatment in some cases </li></ul>Therapy of Hepatic encephalopathy
    89. 90. Nonabsorbable Disaccharide <ul><li>Lactulose is  -galactosidofructose </li></ul><ul><li>Mechanism: </li></ul><ul><ul><li>Metabolized by enteric bacteria in colon to lactate and acetate </li></ul></ul><ul><ul><li>The decrease in pH is necessary for lactulose to be active form </li></ul></ul><ul><ul><li>Reduction of ammonia-producing bacteria metabolism and trapping of NH 3 as NH 4 + </li></ul></ul><ul><ul><li>Reduce colonic transit time: decrease production and absorption of gut toxin </li></ul></ul><ul><li>Result: decrease in the generation of nitrogenous compounds in the intestine </li></ul>
    90. 91. Lactulose <ul><li>Standard therapy for acute HE </li></ul><ul><li>Dosage of lactulose </li></ul><ul><ul><li>Initially: use a large dose of lactulose 30-50 mL every 1-2 hours until defecation </li></ul></ul><ul><ul><li>After catharsis: adjusted 15-30 mL x 1-4 for defecation 2-3/day </li></ul></ul><ul><ul><li>Patient with ileus or comatose: </li></ul></ul><ul><ul><li>Enema 300 mL lactulose in 1-3 L of water in Trendelenburg left lateral decubitous position </li></ul></ul>
    91. 92. Neomycin <ul><li>Alternative to nonabsorbable disaaccharide </li></ul><ul><ul><li>Not tolerate or difficult to monitor effect of lactulose esp. patient with diarrhea </li></ul></ul><ul><li>Mechanism </li></ul><ul><ul><li>Decrease intestinal flora that generate ammonia </li></ul></ul><ul><li>Dosage </li></ul><ul><ul><li>Neomycin 3-6 g/d for 2 or 3 days followed by 1-2 g/d thereafter </li></ul></ul><ul><li>Avoid prolonged use </li></ul><ul><ul><li>Due to auditory and renal toxicity </li></ul></ul>
    92. 93. Branched-chain amino acids <ul><li>BCAA correct the imbalance of plasma amino acid </li></ul><ul><li>Clinical trials of BCAA </li></ul><ul><ul><li>No major beneficial effects on acute HE </li></ul></ul><ul><ul><li>Mild effects on chronic HE: improvement of nutritional status of cirrhoyic patient </li></ul></ul><ul><ul><li>Addition of BCAA to the diet of protein intolerant patients without worsening of cerebral function </li></ul></ul>Horst D. et al. Hepatology. 1984 Plauth M, et al. Clin Nutr 1997
    93. 94. Flumazenil <ul><li>Detection of BZs not universal (laporatory-dependent) </li></ul><ul><li>Source of BZs uncertain </li></ul><ul><li>Flumazenil is BZ antagonist </li></ul><ul><li>Only 20-30% of patients with severe PSE respond tempolary to flumazenil </li></ul><ul><li>Widespresd occult use of prescription benzodiazepine </li></ul>
    94. 95. <ul><li>Prevent further liver damage </li></ul><ul><li>Withdraw alcohol </li></ul><ul><li>Viral Hepatitis B or C </li></ul><ul><li>Wilson’s disease, Autoimmune hepatitis </li></ul><ul><li>Avoid preventable precipitating factors </li></ul><ul><li>Variceal bleeding </li></ul><ul><li>Complication of ascites: SBP </li></ul><ul><li>Diuretic complication </li></ul><ul><li>Drugs etc. sedative drug </li></ul><ul><li>Early detection and treatment </li></ul>Prevention of recurrent HE

    ×