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دکتر علی قویدل فوق تخصص گوارش

دکتر علی قویدل فوق تخصص گوارش. ژورنال کلاب گوارش پنجشنبه 19/12/95. IN THE NAME OF GOD. PRACTICE GUIDELINE. AASLD Guidelines for Treatment of Chronic Hepatitis B. HEPATOLOGY, January 2016. Supervised by dr gavidel Presentated : m- r.rohani , MD gasteroenterology & hepatology fellow.

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دکتر علی قویدل فوق تخصص گوارش

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  1. دکتر علی قویدل فوق تخصص گوارش • ژورنال کلاب گوارش • پنجشنبه 19/12/95 Tabriz Medical University Gasteroentrology&Hepatology Department

  2. IN THE NAME OF GOD Tabriz Medical University Gasteroentrology&Hepatology Department

  3. PRACTICE GUIDELINE AASLD Guidelines for Treatment of Chronic Hepatitis B HEPATOLOGY, January 2016 Supervised by drgavidel Presentated: m-r.rohani, MD gasteroenterology &hepatology fellow Tabriz Medical University Gasteroentrology & Hepatology Department

  4. Target Audience • This guideline is intended primarily for health care professionals caring for patients with CHB • this guideline may assist policy makers in optimizing the care of individuals living with CHB Tabriz Medical University Gasteroentrology&Hepatology Department

  5. Background • 240 million persons have CHB with a varying prevalence geographically highest in Africa and Asia. • In USA,704,000adults with CHB, but the upper estimate of CHB in the United States may be as high as 2.2 million. • deaths from cirrhosis and HCC were estimated at 310,000 and 340,000 per year, respectively. Tabriz Medical University Gasteroentrology&Hepatology Department

  6. serial monitoring of HBV DNA and ALT • “gray zones,” meaning that their HBV DNA and ALT levels do not fall into the same phase. • Longitudinal follow-up of ALT and HBV DNA levels and/or assessment of liver histology can serve to clarify the phase of infection. Tabriz Medical University Gasteroentrology&Hepatology Department

  7. Tabriz Medical University Gasteroentrology&Hepatology Department

  8. Immune-tolerant phase: Tabriz Medical University Gasteroentrology&Hepatology Department • HBV DNA levels elevated, • ALT normal(<19 U/L for f and <30 U/L for m) • significant inflammation or fibrosis • The durationvariable, longestwho are infected perinatally • With increasing age, increased of transitioningto the HBeAg+immuneactivephase.

  9. ii. HBeAg-positive immune-active phase: • Elevated ALT&HBV DNA + liver injury • Median age 30 y • seroconversionfrom HBeAg to anti-HBeAb: • less than 2% /year in children <3 y • puberty & adults to 8% &12%/Y, respectively Tabriz Medical University Gasteroentrology&Hepatology Department

  10. iii. Inactive CHB phase: • HBV DNA ;low or undetect, • ALT ; NL& • HBeAb+ • minimalnecro inflammation &fibrosis • 67%-80%remain inactive • 4%-20% reversions back to HBeAgpositive Tabriz Medical University Gasteroentrology&Hepatology Department

  11. 10%-30% continue to have .. • 10%- 20% :reactivation • Most in the precore or core promoter • histology :necro inflammation &fibrosis • have lower HBV DNA levels & fluctuating course iv. HBeAg-negative immune reactivation phase: Tabriz Medical University Gasteroentrology&Hepatology Department

  12. Resolved CHB infection is defined by clearance of HBsAg +/HBSAbpos • clearance of HBsAg: • 0.5% /Y • Low levels of HBV DNA are transiently in the minority • reduces risk of hepatic decompensation and improves survival Tabriz Medical University Gasteroentrology&Hepatology Department

  13. Among untreated CHB cumulative 5-year incidence of: • cirrhosis is 8%-20% • among those with cirrhosis, 5-year cumulative risk of: • hepatic decompensation is 20% • and risk of HCC is 2%-5% Tabriz Medical University Gasteroentrology&Hepatology Department

  14. risk of progression to cirrhosis & HCC HBV DNA levels, ALT levels, and HBeAgstatus the most important determinants A biological gradient of risk has been shown in adults with HBV DNA levels above 2,000 IU/mL Tabriz Medical University Gasteroentrology&Hepatology Department

  15. Tabriz Medical University Gasteroentrology&Hepatology Department

  16. Diagnosis, Staging and Monitoring of Persons With CHB • The initial evaluation :Hx & PE ,RF for co infection, alcohol use, and FHof HBV infection and liver cancer • Lab: liver disease activity and function, markers of HBV replication, and tests HCV,HDV,HIV( Table 3) Tabriz Medical University Gasteroentrology&Hepatology Department

  17. Tabriz Medical University Gasteroentrology&Hepatology Department

  18. Tabriz Medical University Gasteroentrology&Hepatology Department

  19. the accuracy of one high HBV DNA level in predicting prognosis is poor • ULNs for ALT values based on healthy subjects are lower than laboratory values • Liver biopsy: • severity of necro inflammation and fibrosis, • R/Oother causes of liver disease, • persons who lack clear-cut indications for treatment Tabriz Medical University Gasteroentrology&Hepatology Department

  20. noninvasive methods to assess fibrosis severity • Acute-on-chronicof hepatitis B lead to overestimation of fibrosis stage • APRI (AST to-platelet ratio index ), FIB-4, FibroTest, and elastography • have only moderate accuracy in fibrosis (stage>= 2 ) Tabriz Medical University Gasteroentrology&Hepatology Department

  21. Antiviral Therapy • The goals of antiviral treatment are to decrease the morbidity and mortality related to CHB • sustained suppression of HBV associated with: • normalization of serum ALT, • loss of HBeAg +/- HBeAb • &histologyimprovement Tabriz Medical University Gasteroentrology&Hepatology Department

  22. the term “cure” was avoided in Tx of CHB • even in resolved infection, poses a lifelong risk for reactivation • immunological cure : • HBsAgloss • sustained HBV DNA suppression • virological cure :eradication of virus Tabriz Medical University Gasteroentrology&Hepatology Department

  23. Side effects more with IFN than nucleos(t)ide analogs (NAs) • all NAs :safety in decompensated cirrhosis &transplant recipients • HDVcoinfection: only effective ; Peg-IFN • HIV coinfection: tenofovir, entecavir, lamivudine, and telbivudine Tabriz Medical University Gasteroentrology&Hepatology Department

  24. Tabriz Medical University Gasteroentrology&Hepatology Department

  25. Treatment assessment • Biochemical • serological • virological • Histological • performed on continuous therapy (NAs)and after discontinuation (Peg- IFN) • The best predictor of sustained remission off-treatment is HBsAgloss Tabriz Medical University Gasteroentrology&Hepatology Department

  26. Tabriz Medical University Gasteroentrology&Hepatology Department

  27. Tabriz Medical University Gasteroentrology&Hepatology Department

  28. Treatment of Persons With Immune-Active CHB • Recommendations • 1A. The AASLD recommends antiviral therapyfor adults with immune-active CHB (HBeAg negative or HBeAgpositive) to decrease the risk of liver-related Complications Quality/Certainty of Evidence: Moderate Strength of Recommendation: Strong Tabriz Medical University Gasteroentrology&Hepatology Department

  29. 1B. The AASLD recommends Peg-IFN, entecavir, or tenofovir as preferred initial therapy for adults with immune-active CHB • Quality/Certainly of Evidence: Low • Strength of Recommendation: Strong Tabriz Medical University Gasteroentrology&Hepatology Department

  30. Immune-active CHB is defined by: an elevation of ALT >2 ULN or evidence of significant histological disease plus elevated HBV DNA above 2,000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive) Tabriz Medical University Gasteroentrology&Hepatology Department

  31. indication for Tx • recommendation to consider treatment of adults with ALT > 2 times * ULN • (M>60 U/L and F>38 U/l ) Tabriz Medical University Gasteroentrology&Hepatology Department

  32. Therapy is recommendedfor immune-active CHB &cirrhosis if HBV DNA >2,000 IU/mL, regardless of ALT level The ULN for ALT in healthy adults is 30 U/L M and 19 U/L F Tabriz Medical University Gasteroentrology&Hepatology Department

  33. ALT<2 ULN & HBV DNA below thresholds Age >40 y FH of HCC extrahepatic manifestations & no Previous treatment Tabriz Medical University Gasteroentrology&Hepatology Department

  34. NO superiority of one therapy over another • Peg-IFN, tenofovir, entecaviras preferred • the lack of resistanceis the most important factor Tabriz Medical University Gasteroentrology&Hepatology Department

  35. choosing between Peg- IFN, entecavir, and tenofovir include: Desire for finite therapy Anticipated tolerability Hx of lamivudine resistance :entecaviris not preferred Family planning HBV genotype Medication costs Comorbidities Tabriz Medical University Gasteroentrology&Hepatology Department

  36. contraindicatedication of Peg-IFN autoimmune disease, uncontrolled psychiatric disease, cytopenia, severe cardiac disease, uncontrolled seizures , decompensated cirrhosis. • A and B genotypes are more likely to achieve HBeAg and HBsAg loss with Peg-IFN than non-A/B genotypes Tabriz Medical University Gasteroentrology&Hepatology Department

  37. Duration of NA Tx influenced by • HBeAg status • duration of HBV DNA suppression • cirrhosis/decompensation • All NAs require dose adjustment in persons with crcl<50 mL/min Tabriz Medical University Gasteroentrology&Hepatology Department

  38. Evaluation for stage of disease using noninvasive or liver Bx • Noninvasive tests are less accurate in predictingfibrosis • After Txwith antivirals ,surveillance for HCC should continue in persons at risk Tabriz Medical University Gasteroentrology&Hepatology Department

  39. predictive of risk of liver complications : • Elevated serum ALT &HBV DNA levels are strongly predictive • Others : older age, Malesex, FH of HCC, alcohol use, HIV infection, diabetes, HBV genotype C, and HBV precore and core promoter variants Tabriz Medical University Gasteroentrology&Hepatology Department

  40. Antiviral therapy was associated with significant risk reductions in cirrhosis &HCC • only NAs were associated with reduced rates of decompensation & death Tabriz Medical University Gasteroentrology&Hepatology Department

  41. liver-related complicationsincreaseswith HBV DNA >2,000 IU/mL • High necroinflammatory activity and high ALT levels are associated with increasedstiffness Tabriz Medical University Gasteroentrology&Hepatology Department

  42. Treatment of Adults With Immune-Tolerant CHB • 2A. The AASLD recommends against antiviral therapy for adults with immune-tolerant CHB • Quality/Certainly of Evidence: Moderate • Strength of Recommendation: Strong Tabriz Medical University Gasteroentrology&Hepatology Department

  43. 2B. The AASLD suggests that ALT levels be tested at least every 6 months for adults with immunetolerant CHB to monitor for potential transition to immune-active or -inactive CHB • Quality/Certainly of Evidence: Very low • Strength of Recommendation: Conditional Tabriz Medical University Gasteroentrology&Hepatology Department

  44. 2C. The AASLD suggests antiviral therapy in the select group of adults >40 years of age with normal ALT and elevated HBV DNA (1,000,000 IU/mL) and liver biopsy showing significant necroinflammation or fibrosis • Quality/Certainly of Evidence: Very low • Strength of Recommendation: Conditional Tabriz Medical University Gasteroentrology&Hepatology Department

  45. Moderate-to-severe necroinflammation or fibrosis on liver biopsy is a reason to consider initiation of antiviral therapy, if other causes of liver disease are excluded. Tabriz Medical University Gasteroentrology&Hepatology Department

  46. strong association betweenserum HBV DNA levels and HCC & cirrhosis, independent of ALT level, HBV genotype & HBeAg • significant histological disease is found in 20% of HBeAg+ & HBV DNA >10*6 IU/mL Tabriz Medical University Gasteroentrology&Hepatology Department

  47. Age >40 y is associated with highersignificant histological disease in HBeAg+ / nlALT Tabriz Medical University Gasteroentrology&Hepatology Department

  48. There are no studies demonstrating that antiviral therapy is beneficial in reducing rates of HCC, cirrhosis, and liver-related death Tabriz Medical University Gasteroentrology&Hepatology Department

  49. there are no data to inform a recommendation for earlier treatment initiation of immune tolerant persons with FH of HCC Tabriz Medical University Gasteroentrology&Hepatology Department

  50. Txof HBe Ag + Immune-Active CHB Who Seroconvert to Anti-Hbeon NA Therapy Recommendations 3A. The AASLD suggests that HBeAg+ adults w/o cirrhosis w CHB who seroconvert to HBeAbon therapy ,discontinue NAs after a period of Tx consolidation Quality/Certainty of Evidence: Very Low Strength of Recommendation: Conditional Tabriz Medical University Gasteroentrology&Hepatology Department

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