1.CHRONIC HEPATITIS BG.PRUTHVI PG IN GENERAL MEDICINE

2. OVERVIEW Introduction and epidemiology Virology Pathogenesis Natural History, Clinical features Diagnosis Liver Biopsy and Noninvasive Assessmentof Fibrosis Treatment 3. Introduction & Epidemiology Definition - Chronic necroinflammatory disease of the livercaused by persistent infection with hepatitis B virus. Approximately one third of the worlds population has serological evidence of past or present infection with HBV and 350400 million people are chronic HBV surface antigen (HBsAg) carriers. Up to 2 million die each year from HBV infection, making it the 9th leading cause of death worldwide. 4. Worldwide Prevalence of Chronic Hepatitis BHBsAg Prevalence (%) 8: High 2-7: Intermediate C or D Not advanced disease. Specific patient demographics Generally young people Young women wanting pregnancy in near future Absence of comorbidities Patient preference Concomitant HCV infection1. Lok AS, et al. Hepatology. 2009;50:661-662. 2. Lok AS. Hepatology. 2010;52:743-747. 3. Janssen HL, et al, Lancet. 2005;365;123-129. 4. Lau GK, et al. N Engl J Med. 2005;352:2682-2695. 5. Flink HJ, et al. Am J Gastroenterol. 2006;101:297-303. 32. Nucleos(t)ide Analogs Lamivudine (100mg) Adefovir (10mg) Entecavir (0.5mg),(1mg) Telbivudine (600mg) Tenofovir (300mg)/(245mg) 33. Nucleos(t)ide Analogs 34. Nucleos(t)ide Analogs 35. Nucleos(t)ide Analogs 36. Nucleos(t)ide Analogs 37. Response HBe Ag +ve 38. Response HBe Ag +ve 39. Response HBe Ag +ve 40. Response HBe Ag - ve 41. Potential Barriers to HBV TreatmentsPatient resistance or cultural beliefs about treatment Potential adverse effects (particularly interferon) Challenges with long-term therapy Understanding endpoints and monitoring strategies Lack of symptoms Lack of ability to cure disease with current regimens in most patients Adherence 42. PREDICTORS OF RESPONSE 43. For IFN/PEG-IFN based treatment In HBeAg-positive CHB, predictors of anti-HBeseroconversion are low viral load (HBVDNAbelow 2000 IU/ml), high serum ALT levels (above 25 times ULN), HBV genotype and high activity scores on liver biopsy (at least A2). HBV genotypes A and B have been shown to be associated with higher rates of anti-HBe seroconversion and HBsAg loss than genotypes D and C, respectively, after treatment with PEGIFN. 44. For NAs treatment In HBeAg-positive CHB, factors predictive of anti-HBe seroconversion are low viral load (HBV DNA below 2 IU/ml), high serum ALT levels, high activity scores on liver biopsy . HBVgenotype does not influence the virological response to any NA. 45. TREATMENT IN HIV CO-INFECTED PtS HIV-positive patients with CHB were at increased riskof cirrhosis and HCC . The indications for therapy are the same as in HIV-negative patients, based on HBV DNA levels, serum ALT levels and histological lesions. In agreement with recent HIV guidelines, it isrecommended that most co-infected patients should be simultaneously treated for both HIV and HBV de novo . Tenofovir combined with emtricitabine or lamivudineplus a third agent active against HIV are indicated. 46. In a small number of patients with CD4 count>500/ml, HBV can be treated before the institution of anti-HIV therapy; PEGIFN, adefovir and telbivudine, which are not proven to be active against HIV, should be preferred. However, if any of these two NAs with a low barrier to resistance does not reach the goal of undetectable HBV DNA after 12 months of therapy, treatment of HIV infection should be envisaged. 47. TREATMENT IN HDV COINFECTED PtS Chronic infection after acute HBV-HDV hepatitis is less common, while chronic delta hepatitis develops in 7090% of patients with HDV superinfection. Active co-infection with HDV is confirmed by detectable HDV RNA, immuno-histochemical staining for HDV antigen, or IgM anti-HDV. (PEG-)IFN is the only drug effective against HDV. The efficacy of (PEG-)IFN therapy can be assessed during treatment (after 36 months) by measuring HDV RNA levels. More than 1 year of therapy may be necessary, as there may be some benefit from treatment prolongation. 48. TREATMENT IN HCV COINFECTED PtS In HBV-infected patients, HCV co-infectionaccelerates liver disease progression and increases the risk of HCC. HBV and HCV replicate in the same hepatocyte without interference. However, HBV DNA level is often low or undetectable and HCV is responsible for the activity of chronic hepatitis in most patients. Thus, patients should usually receive treatment for HCV. 49. Treatment in Pregnant Women 50. Pre-emptive therapy before immunosuppressive therapy or chemotherapy HBsAg-positive candidates for chemotherapy andimmunosuppressive therapy should be tested for HBV DNA levels and should receive pre-emptive NA administration during therapy (regardless of HBV DNA levels) and for 12 months after cessation of therapy. When HBV DNA levels are