Hepatitis B. ECHO November 29, Joseph Ahn, MD, MS Associate Professor of Medicine Director of Hepatology Oregon Health & Science University

Transcription

1 Hepatitis B ECHO November 29, 2017 Joseph Ahn, MD, MS Associate Professor of Medicine Director of Hepatology Oregon Health & Science University

2 Disclosures Advisory board Gilead

3 Comments The speaker Joseph Ahn, Associate Professor, SM.GST Administration Have no relevant financial relationships to disclose

4 HBV- an Unmet Medical Need Under-diagnosed Under-treated million chronic infections 2 5% are diagnosed 3 Less than 1% are treated 3 14 million chronic infections 1 12% are diagnosed 1 12% are treated million chronic infections 4 19% are diagnosed 4 Asia-pacific Europe USA 1. BMS Market Research. Information available upon request from Bristol-Myers Squibb; 2. Mohamed R, et al. J Gastroenterol Hepatol 2004;19:958-69; 3. Decision Resources. Hepatitis B virus in China Emerging markets study #5; 4. BMS Market Research. 4

5 HBV Modes of Transmission Host Recipient Mother Sexual Parenteral- needles, transfusion, blood products, health care work Horizontal- Blood, wound, household contact Infant Perinatal/Vertical No clear risk factors in ~ 20% of patients N Engl J Med. 1997;337(24): J Viral Hepat. 2004;11(2):

6 Risk of Chronic HBV Infection is Inversely Related to Age at Infection 100 % Risk Chronic HBV J Infect Dis 1985;151: Gastroenterology 1987;92: J Gastroenterol Hepatol 2000;15 Suppl:E Neonates Infants Children Adults Age at Infection

7 Hepatitis B Disease Progression Liver Cancer (HCC) 30% of chronic HBV-infected individuals 2 Acute Infection Chronic Infection Cirrhosis Liver Transplantation Death >90% of infected children progress to chronic disease <5% of infected adults progress to chronic disease 1 Torresi J. Gastro. 2000;118:S ; Moyer LA Am J Prev Med. 1994;10: ; Fattovich G. Hepatology. 1995;1: ; Perrillo RP. Hepatology. 2001;33: Liver Failure (Decompensation) 23% of patients decompensate within 5 years of developing cirrhosis 3 Chronic HBV is the 6th leading cause of liver transplantation in the United States 4

8 HBV: Phase I Tests HBsAg = infection Anti-HBs = immunity if anti-hbc is negative Anti-HBc = exposure Anti-HBcIgM= Acute exposure to HBV

9 HBV: Phase II Tests HBV DNA = risk of progression to HCC / cirrhosis Anti-HBe (+) = Inactive disease or PC/CP mutants (DNA~~) HBeAg(+) = wild type or mixed infection ~ active disease

10 Interpretation of HBV Serologies HBs Ag Serologic Marker Results Total Anti-HBc IgM Anti-HBc Anti- HBs Interpretation Never infected and no evidence of immunization Acute infection Chronic infection Exposure, false positive Exposure and clearance of HBV infection Immune (immunization) Modified from Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20.

11 4 Phases of Chronic HBV Infection 1) Immune tolerant/trained phase HBeAg positive High HBV DNA (> 20,000 IU/ml) Normal ALT 2) HBeAg-positive chronic hepatitis (immune clearance) wild-type High HBV DNA (> 20,000 IU/ml) High or fluctuating ALT Active inflammation on liver biopsy N Y Pungpapong S, et al. Mayo Clin Proc. 2007;82:

12 4 Phases of Chronic HBV Infection (cont.) 3) Inactive HBsAg carrier (non-replication) HBeAg negative Low HBV DNA (< 2,000 IU/ml) Normal ALT 4) HBeAg-negative chronic hepatitis pre-core Intermediate to high HBV DNA (> 2,000 IU/ml) High or fluctuating ALT Active inflammation on liver biopsy N Y Pungpapong S, et al. Mayo Clin Proc. 2007;82:

13 Goals of Treatment eag Chronic Hepatitis eag- DNA ALT Abnl Inactive Carrier eag- DNA ALT<ULN eag + Chronic Hepatitis eag+ DNA ALT Abnl

14 Tenofovir (TDF, TAF) Advantages Potent Effective in suppressing HBV with no resistance ( wild type ) and with LAM, telbivudine and entecavir resistance Pregnancy category B Antiviral activity against both HBV and HIV Disadvantages Nephrotoxicity (Fanconi s syndrome)

15 Entecavir (ETV) Advantages: Potent Effective against wild type and adefovir-resistant Low rate of drug resistance Disadvantages: Can lead to HIV resistance Increased risk of resistance in those with LAMresistance

16 HBV Reactivation Well-Characterized Syndrome Abrupt reappearance or rise of HBV DNA in previously inactive or resolved HBV infection Often, but not always, accompanied by reappearance of disease activity May occur spontaneously or as a result of immunosuppression Potential Consequences May lead to clinically apparent acute hepatitis - Can be severe - Can result in acute liver failure and death Many cases are subclinical and resolve spontaneously, or result in persistent infection May go undetected until - Advanced liver disease is present - Disease has been transmitted to sexual or family contacts Bessone F, et al. World J Hepatol. 2016;8:

17 Immune Profiles in Chronic Hepatitis: HBV/HCV Coinfection HBV and HCV active Occult HBV in chronic active HCV HCV active in HBsAg carrier HBV active in inactive or prior HCV HBsAg HBV DNA Anti- HCV HCV RNA Comment Highest risk of progression to cirrhosis and liver decompensation Highest risk of progression to cirrhosis and liver decompensation Behaves similar to HCV monoinfection Less common, may indicate HBV suppression of HCV Mauss S, et al. Hepatology: A Clinical Textbook. 7 th Edition. Medizin Fokus Verlag:Hamburg Available at:

18 AASLD-IDSA: Recommended Assessments Prior to and Monitoring During Antiviral Therapy for HCV Test for HBV in all patients beginning DAA regimens (HBsAg, anti-hbs, and anti-hbc) Test HBV DNA levels prior to DAA therapy in HBsAg positive patients Start HBV treatment for active HBV infection (before or same time as DAA therapy) Monitor low or undetectable HBV DNA levels at regular intervals (usually not more frequently than every 4 weeks) for HBV reactivation during treatments Initiate HBV treatment if HBV DNA levels meet criteria outlined in AASLD HBV treatment guidelines AASLD-IDSA. Version April 27, 2017.

19 Joseph Ahn, MD, MS Associate Professor of Medicine Director of Hepatology Oregon Health & Science University