Hepatitis B and C: Update

Transcription

1 Hepatitis B and C: Update Thomas D. Amankonah, M.D. Associate Clinical Professor GI/Hepatology & Liver Transplantation University of California Davis

2 Chronic Hepatitis C Goals: - Recognize disease burden - Recognize risk factors for chronic hepatitis C - Interprete diagnostic tests - Evaluate patients for antiviral therapy - Recognize treatment options - Monitor patients with cirrhosis for hepatocellular carcinoma

3 Hepatitis C (HCV) in U.S. 2.7 mln chronically infected 10,000 deaths per year 50% of liver transplantations $4 billion health care costs per year Responsible for in Liver Cancer

4 HCV Screening Blood product for clotting problems produced < 1987 (i.e.hemophilia) Injected drugs use(ivdu) Long-term kidney dialysis Blood transfusion or solid organ transplant < July, 1992 Born from HCV+ mother Tattoos, intranasal drug use, body piercing

5 Diagnostic Tests Hepatitis C Anti-HCV Ab RIBA II HCV RNA

6 HCV: Diagnosis 1 Screening: (ALT) and HCV Ab 2 Confirmation: HCV-RNA

7 Approach to Patient with Chronic Hepatitis C class Hepatitis C Assess stage of liver disease(biochemical, liver biopsy) Discuss Treatment Options Immunize for Hepatitis A and B - Lifestyle modification(obesity, Alcohol or Tobacco use) Hepatocellular carcinoma screening(cirrhosis)

8 HCV: Severity of Liver Disease Symptoms and Liver Function Tests: usually in late stages ALT levels: often normal Ultrasound Examination: not sensitive for fibrosis/staging Liver Biopsy: gold standard, until better serological markers

9 Assessing the Severity of Liver Disease Noninvasive - Fibrotest: alpha-2-macroglobulin, haptoglobulin, gammaglutamyltranspeptidase; bilirubin and apolipoprotein A1 - Fibroscan(transient elastography): measures liver stiffness. Invasive - Liver biopsy

10 Assessing the Severity of Liver Disease Liver biopsy: Gold standard Disease severity = Fibrosis(stage 0-4) - Indicator of prognosis - Helpful in guiding treatment options

11 Hepatitis C Who Should Be Treated? - Patients with moderate or severe disease - Patients with progressive disease - Whoever is affected in some way by chronic disease - Fully understands the risks and benefits of therapy

12 Chronic Hepatitis Pretreatment evaluation - exclude other liver diseases - genotype(treatment duration) - liver biopsy - viral load - HIV status - BMS evaluation

13 Goals of Antiviral Therapy Reduce hepatic inflammation Viral clearance Prevent fibrosis or progression of fibrosis Delay decompensation Prevent HCC Prevent HCV recurrence after liver transplantation

14 Evolution of Treatment of HCV Sustained Response (%) = CURE IFN IFN 12m IFN+RIBA PEG+RIBA

15 Treatment Response by Genotype and Duration of Therapy Geno 1 : 12 mos Geno 2, 3 : 6 mos IFN IFN+RBV PEG+RBV

16 Monitoring During Treatment Labs HCV RNA(Baseline, 4, 12 weeks) Manage side effects Phone calls to patient

17 Ribavirin: : Side Effects Hemolytic Anemia Pregnancy Risks

18 Side effects of Interferons FLU-like symptoms Behavioral changes: Depression, Irritability Myelosuppression: Neutropenia Thrombocytopenia Skin, GI, Thyroid, Hair loss, Wt. loss

19 Side effects of Treatment: management of anemia and myelosuppression (in selected cases) Erythropoietin: 40K/week GCSF: 5μg/kg tiw or daily Dose reduction or discontinuation (~10%)

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21 Chronic Hepatitis B Goals: - Recognize disease burden - Recognize risk factors for chronic hepatitis B - Interprete diagnostic tests - Evaluate patients for antiviral therapy - Recognize treatment options - Monitor patients with cirrhosis for hepatocellular carcinoma

22 Chronic Hepatitis B: Prevalence 400 million people worldwide have chronic hepatitis B million Americans have chronic hepatitis B 2 80,000 Americans infected each year 2 New infections increasing in men over the age of 20 and women over the age of Lai CL, Ratziu V, Yuen M-F, Poynard T. Viral hepatitis B. The Lancet. 2003;362: Centers for Disease Control and Prevention. Disease burden from viral hepatitis A, B, and C in the United States. 3 Centers for Disease Control and Prevention. Incidence of acute hepatitis B -- United States, MMWR. 2004;52:

23 Areas with high rates of chronic HBV infection 8% - High 2-7% - Intermediate <2% - Low World Health Organization. Hepatitis B. Available at: distribution.html. Accessed June 1, 2004.

24 Candidates for Screening for Hepatitis B Persons born in high endemic areas Men who have sex with men Injection drug users Dialysis patients HIV-infected patients Pregnant women (USA) Family, household and sexual contacts of known HBV carriers Residents/staff of institutions for the developmentally disabled Prisoners (male) Healthcare workers (frequent blood contact) Heterosexuals with multiple partners CDC. Epidemiology & Prevention of Vaccine-Preventable Diseases. The Pink Book. 9th ed, Lok ASF. Hepatology. 2001;34:

25 Hepatitis B Screening & Evaluation Serological Markers HBV DNA Liver Status Liver Function Tests Liver Biopsy Lok A, Heathcote E, Hoofnagle J, Gastroenterology 2001.

26 Viral Serologies Hepatitis B HBsAg, HBeAg HBcAb, HBeAb

27 Concentration of HBV in Various Body Fluids High blood serum wound exudates Moderate semen vaginal fluid saliva Low/Not Detectable urine feces sweat tears breast milk

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29 Disease Progression Occurs in 15% to 40% of Chronic HBV Patients 5% - 10% Liver Cancer (HCC) 10% - 15% in 5 yr Chronic Infection 30% Cirrhosis Liver Transplantation* Death 23% in 5 yr Acute flare Liver Failure * HBV is 6 th leading cause of liver transplantation in the US. Fattovich G. Gastroenterology. 2004;127:S Seef LB. Hepatology. 2001;33: Torresi J. Gastroenterology. 2000;118:S Fattovich G. Hepatology. 1995;21:77-82.

30 Chronic Hepatitis B HBeAg Positive vs. HBeAg Negative HBeAg + (wild Type) High HBV DNA HBeAg produced Less difficult to treat Slower rate of progression to liver disease Natural resolution over time (8-10%) HBeAg (Precore or Core Promoter) Lower HBV DNA No HBeAg produced Diff to treat Fast rate of disease progression to liver disease No natural resolution over time

31 Approach to patient with Chronic Hepatitis B - Assess stage of liver disease - Evaluate for antiviral therapy - Lifestyle modification(alcohol and tobacco use) - Immunize for hepatitis A - Household Immunization - Monitor for HCC

32 Goals of Antiviral Therapy Reduce hepatic inflammation Viral clearance Prevent fibrosis or progression of fibrosis Delay decompensation Prevent HCC

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39 HCC Screening High Risk Patients 1. Patients with Chronic Hepatitis B - Male, Age > 40 years - HBeAg(+); High HBV DNA 2. Family history of Hepatocellular carcinoma 3. Cirrhosis

40 HCC Screening Cirrhosis - Alcohol(6-fold) - Tobacco(5-fold) - Obesity(4-fold) - Diabetes mellitus J Hep 2005;42: Surveillance: AFP q 6 months; Imaging study of the Liver annually

41 Summary(1) Screen patients with risk factors Confirm diagnosis of HCV Hepatitis B/C class and Hepatitis B/C Support Groups Pretreatment evaluation(exclude other etiologies of liver disease; Assess stage of disease; obtain HCV RNA(quantitative) and genotype

42 Summary(2) Evaluate patients for antiviral therapy Vaccination(HAV and HBV) Lifestyle modification(obesity, Diabetes Mellitus, Alcohol, Smoking) Monitor for HCC with AFP biannually and imaging studies of the liver annually Refer to GI/Hepatology