Outline Updates in the Clinical Management of Hepatitis B and C Jennifer C. Lai, MD, MBA Transplant Hepatologist Associate Professor of Medicine In Residence University of California, San Francisco Initial evaluation Identifying candidates for therapy Therapeutic options Additional monitoring Who should be screened for HBV? Chronic Hepatitis B Individuals born in high (8%) or intermediate (2-7%) prevalence areas Asia, Africa, Middle East (except Israel), Spain, Eastern Europe, Central/South America Pregnant women Infants of HBsAg+ mothers, household contacts Behavioral contacts: HIV+, MSM, IVDU, inmates Renal dialysis patients Patients receiving immunosuppressive therapy Abnormal ALT of unknown cause Terrault, AASLD HBV Practice Guidance 2018. 1
Who should be screened for HBV? Worldwide prevalence of chronic HBV Individuals born in high (8%) or intermediate (2-7%) prevalence areas Asia, Africa, Middle East (except Israel), Spain, Eastern Europe, Central/South America Pregnant women Infants of HBsAg+ mothers, household contacts Behavioral contacts: HIV+, MSM, IVDU, inmates 2010 Census: % Asian Bay Area: 23% SF: 33% Renal dialysis patients Patients receiving immunosuppressive therapy Abnormal ALT of unknown cause Terrault, AASLD HBV Practice Guidelines 2015. www.who.int Initial tests to determine HBV status Interpretation of tests Next steps Immunity HBsAb HBcAb HBsAg Interpretation Next Step HBV surface antigen (sag) HBV surface antibody (sab) HBV core antibody (cab) Not immune Vaccinate + Immune Nothing + + Immune Nothing + Prior exposure/ False(+) core Ab + Chronic infection Educate re: risk of reactivation Determine state of infection 2
Interpretation of tests Next steps Exposure HBsAb HBcAb HBsAg Interpretation Next Step Not immune Vaccinate + Immune Nothing + + Immune Nothing + Prior exposure/ False(+) core Ab + Chronic infection Educate re: risk of reactivation Determine state of infection Interpretation of tests Next steps Chronic HBsAb HBcAb HBsAg Interpretation Next Step Not immune Vaccinate + Immune Nothing + + Immune Nothing + Prior exposure/ False(+) core Ab + Chronic infection Educate re: risk of reactivation Determine state of infection Interpretation of tests Next steps Initial approach to the HBsAg+ patient HBsAb HBcAb HBsAg Interpretation Next Step Not immune Vaccinate + Immune Nothing STEP 2 STEP 3 + + Immune Nothing + Prior exposure/ False(+) core Ab + Chronic infection Educate re: risk of reactivation Determine state of infection STEP 1 3
Initial approach to the HBsAg+ patient Initial approach to the HBsAg+ patient STEP 3 STEP 3 STEP 2 STEP 2 STEP 1 Fibrosis Stage Platelet count INR Albumin Abd U/S: liver contour, spleen size, portal vein STEP 1 Fibrosis Stage Platelet count INR Albumin Abd U/S: liver contour, spleen size, portal vein Risk Factors for Accelerated Disease HIV/HCV/HDV coinfection Heavy alcohol consumption Hepatitis A immunity vaccinate if not immune Initial approach to the HBsAg+ patient STEP 3 State of Infection for chronic (>6mo) HBV Chronic active If HBeAg(+): ALT 1-2x ULN If HBeAg(-): HBV DNA>2,000 IU/mL + ALT 1-2x ULN STEP 1 Fibrosis Stage Platelet count INR Albumin Abd U/S: liver contour, spleen size, portal vein STEP 2 Risk Factors for Accelerated Disease HIV/HCV/HDV coinfection Heavy alcohol consumption Hepatitis A immunity vaccinate if not immune State of Infection ALT HBV DNA HBV e antigen / antibody (See next slide) Chronic inactive ( carrier ) HBeAg(-), HBeAb(+) HBV DNA <2,000 IU/mL Persistently normal ALT (<20 for women, <30 for men) Resolved infection HBcAb(+), HBsAg(-) ndetectable HBV DNA ormal ALT (<20 for women, <30 for men) 4
State of Infection for chronic (>6mo) HBV Chronic active Refer to If HBeAg(+): ALT 1-2x ULN hepatology If HBeAg(-): HBV DNA>2,000 IU/mL + ALT 1-2x ULN Chronic inactive ( carrier ) HBeAg(-), HBeAb(+) HBV DNA <2,000 IU/mL Persistently normal ALT (<20 for women, <30 for men) Resolved infection HBcAb(+), HBsAg(-) Undetectable HBV DNA Normal ALT (<20 for women, <30 for men) State of Infection for chronic (>6mo) HBV Chronic active Refer to If HBeAg(+): ALT 1-2x ULN hepatology If HBeAg(-): HBV DNA>2,000 IU/mL + ALT 1-2x ULN Chronic inactive ( carrier ) HBeAg(-), HBeAb(+) yhbv DNA <2,000 IU/mL Persistently normal ALT (<20 for women, <30 for men) Resolved infection HBcAb(+), HBsAg(-) Undetectable HBV DNA Normal ALT (<20 for women, <30 for men) State of Infection for chronic (>6mo) HBV Chronic active Refer to If HBeAg(+): ALT 1-2x ULN hepatology If HBeAg(-): HBV DNA>2,000 IU/mL + ALT 1-2x ULN Chronic inactive ( carrier ) HBeAg(-), HBeAb(+) HBV DNA <2,000 IU/mL Persistently normal ALT (<20 for women, <30 for men) Resolved infection HBcAb(+), HBsAg(-) Undetectable HBV DNA Normal ALT (<20 for women, <30 for men) Monitor ALT/HBV DNA Q3mo x 1 yr, then Q6-12 mo State of Infection for chronic (>6mo) HBV Chronic active Refer to If HBeAg(+): ALT 1-2x ULN hepatology If HBeAg(-): HBV DNA>2,000 IU/mL + ALT 1-2x ULN Chronic inactive ( carrier ) HBeAg(-), HBeAb(+) HBV DNA <2,000 IU/mL Persistently normal ALT (<20 for women, <30 for men) Resolved infection HBcAb(+), HBsAg(-) Undetectable HBV DNA Normal ALT (<20 for women, <30 for men) Monitor ALT/HBV DNA Q3mo x 1 yr, then Q6-12 mo Consider HBV treatment if immunosuppressed. 5
Indications for anti-hbv treatment Indications for anti-hbv treatment Immune Active Infection HBeAg positive: ALT 2x ULN, HBV>20K IU HBeAg negative: HBV>2000u + ALT 2X ULN Immune Active Infection HBeAg positive: ALT 2x ULN, HBV>20K IU HBeAg negative: HBV>2000u + ALT 2X ULN Stage 2 fibrosis Liver biopsy Fibroscan Available at UCSF Hepatology! Covered by most insur. except Medi-Cal ($200) Indications for anti-hbv treatment Indications for anti-hbv treatment Immune Active Infection HBeAg positive: ALT 2x ULN, HBV>20K IU HBeAg negative: HBV>2000u + ALT 2X ULN Stage 2 fibrosis Liver biopsy Fibroscan Available at UCSF Hepatology! Covered by most insur. except Medi-Cal ($200) Immune Active Infection HBeAg positive: ALT 2x ULN, HBV>20K IU HBeAg negative: HBV>2000u + ALT 2X ULN Stage 2 fibrosis Liver biopsy Fibroscan Available at UCSF Hepatology! Covered by most insur. except Medi-Cal ($200) HBV core Ab + Undergoing immunosuppressive therapy Chemotherapy High dose corticosteroids Anti-TNF alpha History of other liver disease HIV/HCV/HDV Hepatocellular carcinoma Family history of cirrhosis or HCC HBV core Ab + Undergoing immunosuppressive therapy Chemotherapy High dose corticosteroids Anti-TNF alpha 6
1 st -line HBV Treatment Options 1 st -line HBV Treatment Options NucleoSide analog Mechanism NucleoTide analog 0.5 mg per day Dose 300 mg per day Reduce for egfr<50 Renal dosing Reduce for egfr<50 NucleoSide analog Mechanism NucleoTide analog 0.5 mg per day Dose 300 mg per day Reduce for egfr<50 Renal dosing Reduce for egfr<50 Headache, fatigue, dizziness, nausea (but generally very well tolerated) Side effects Nausea, headache, dizziness (but generally very well tolerated) Headache, fatigue, dizziness, nausea (but generally very well tolerated) Side effects Nausea, headache, dizziness (but generally very well tolerated) Lactic acidosis (rare) Adverse effects Fanconi s syndrome C Pregnancy Category B Lactic acidosis (rare) Adverse effects Fanconi s syndrome C Pregnancy Category B 1 st -line HBV Treatment Options 1 st -line HBV Treatment Options NucleoSide analog Mechanism NucleoTide analog 0.5 mg per day Dose 300 mg per day AASLD 2018 guidance suggests no Reduce for egfr<50 Renal dosing Reduce for egfr<50 preference b/n entecavir and Headache, fatigue, Nausea, headache, dizziness, tenofovir nausea (but regarding potential dizziness longterm (but generally Side effects generally very well risks of renal complications. very well tolerated) tolerated) Lactic acidosis (rare) Adverse effects Fanconi s syndrome C Pregnancy Category B NucleoSide analog Mechanism NucleoTide analog 0.5 mg per day Dose 300 mg per day Reduce for egfr<50 Renal dosing Reduce for egfr<50 Headache, fatigue, dizziness, nausea (but generally very well tolerated) Side effects Nausea, headache, dizziness (but generally very well tolerated) Lactic acidosis (rare) Adverse effects Fanconi s syndrome C Pregnancy Category B 7
Other HBV medications HCC screening criteria Lamivudine Adefovir Truvada (tenofovir/emtricitabine) HBVcAb positive prophylaxis Previously prescribed Low barrier to resistance Previously prescribed No longer available Not as effective as other medications HIV coinfection Lamivudine resistance HCC screening (abdominal U/S + AFP Q6mo) for: Population group Male >40 years Female >50 years Family history of HCC at any age African Cirrhosis Incidence of HCC 0.4-0.6% per year 0.3-0.6% per year Higher than without a family history HCC risk is high at any age 3-8% per year Bruix, AASLD HCC practice guidelines 2010. Monitoring HBV HBV: Key Points If on treatment: ALT and HBV DNA every 6 months If on tenofovir: Creatinine and phosphorus every 6 months (Fanconi s syndrome) Dose reductions needed with renal insufficiency for both entecavir and tenofovir If not on treatment: ALT/HBV DNA every 3 mo for the first year Then every 6 months if no indication for treatment HBeAg and HBeAb every year Optional: platelet count, albumin, and INR All patients from intermediate/high prevalence HBV countries or with behavioral risk factors should be screened Screening labs: HBsAb, HBcAb, HBsAg Initial work-up for HBsAg+ patient: State of infection: ALT, HBV DNA, HBeAg, HBeAb Stage of disease: Platelet, Albumin, INR, Abdominal ultrasound Risk factors for disease progression: HCV, HIV, HDV coinfection 1 st line treatment options are: entecavir, tenofovir HCC screening with abdominal ultrasound +/- AFP in: Males >40 years, females >50 years, all Africans, HCC fhx, cirrhotics 8
HCV: The Cure is Here!!!! Chronic Hepatitis C Who should be screened? Who should be screened? Individuals at high risk: IVDU current and past Recipients of clotting factors before 1987 or blood transfusions/organ transplant before July 1992 Patients on chronic hemodialysis Persons with HIV infection Current sexual partners of HCV-infected individuals CDC and USPSTF recommendations (2013): All individuals born between 1945-1965 (50-70 yo) should be screened 45% are expected to have cirrhosis by 2020! Individuals at high risk: IVDU current and past Recipients of clotting factors before 1987 or blood transfusions/organ transplant before July 1992 Patients on chronic hemodialysis Persons with HIV infection Current sexual partners of HCV-infected individuals CDC and USPSTF recommendations (2013): All individuals born between 1945-1965 (50-70 yo) should be screened 45% are expected to have cirrhosis by 2020! CDC MMWR 2012; Chou, Ann Intern Med 2012. Armstrong, Ann Intern Med 2006. CDC MMWR 2012; Chou, Ann Intern Med 2012. Armstrong, Ann Intern Med 2006. 9
Which patients should be evaluated for treatment? Commonly-used HCV regimens Everyone! (who is interested) Harvoni (ledipasvir / sofosbuvir) Epclusa (sofosbuvir / velpatasvir) Mavyret (glecaprevir / pibrentasvir) Vosevi (sofosbuvir / velpatasvir / voxilaprevir) Zepatier (elbasvir / grazoprevir) Highly successful! 94%+ rates of sustained virologic response Choice of treatment depends on Please send this information with referral HCV RNA HCV genotype Markers of liver disease severity Platelet Total bilirubin Albumin PT/INR Creatinine HCV Fibrosure / Fibrotest Abdominal ultrasound HIV Ag/Ab, HBV (sag, sab, cab) 10
HCV: Key Points Screen all individuals with at high risk for HCV transmission and/or born between 1945-1965 (CDC) Screening test: HCV antibody. If positive: HCV RNA, HCV genotype, liver panel, creatinine Non-invasive staging: Plt, INR, Alb, complete abdominal U/S, HCV Fibrosure Many all-oral treatment regimens available, effective, and tolerable UCSF Hepatology has a dedicated HCV treatment team Thank you Jennifer C. Lai, MD, MBA Associate Professor Medicine In Residence Division of Gastroenterology & Hepatology UCSF Jennifer.lai@ucsf.edu 11