Hepatitis B Virus. Taylor Page PharmD Candidate 2019 February 1, 2019

Transcription

1 Hepatitis B Virus Taylor Page PharmD Candidate 2019 February 1, 2019

2 Epidemiology 3218 cases of acute HBV reported in ,000 non-institutionalized persons living with chronic HBV in Viral Hepatitis. Centers for Disease Control and Prevention.

3 Hepatitis B Virus Family: Hepadnaviridae Partially double-stranded DNA enveloped virus 10 genotypes (named A-J); not required in order to treat

4 HBV Transmission Transmission via blood, semen, infectious bodily fluids Perinatal, percutaneous, or sexual exposure Tattoos & Body Piercings Mother to Newborn Sexual Activity Healthcare Workers

5 High Risk Populations Unvaccinated persons Children of parents from endemic areas/hbv positive mothers Travelers to/from HBV endemic areas IV drug users Men who have sex with men Multiple sex partners Chronically elevated liver enzymes Pregnancy HIV or HCV coinfection Immunosuppressed Dialysis patients

6 Pathophysiology HBV doesn t cause direct injury to hepatocytes Cell injury results from immune response to HBV Acute infection: cytotoxic T-cell response triggered Chronic infection: may result from decreased immune response Destruction of hepatocytes leads to elevated transaminases

7 HBV Clinical Timeline Transmission Acute Infection Hepatitis Chronic Infection Fulminant

8 HBV Clinical Timeline Transmission Acute Infection Recovery (Antibodies prevent later re-infection) Hepatitis Chronic Infection

9 HBV Clinical Timeline Transmission Inactive Carrier Cirrhosis Hepatitis Chronic Infection Chronic Hepatitis Hepatocellular Carcinoma (HCC)

10 HBV Clinical Timeline Transmission Hepatitis Fulminant Death

11 Risk Factors for Chronic Infection Male Persistent HBV DNA in serum HBV genotype C infection Coinfection with HCV, hepatitis D, or HIV Older age at time of diagnosis Degree of liver damage at diagnosis Frequency of severe flares S/Sx of abnormal liver function Alcohol or tobacco use

12 Clinical Presentation: Acute Infection Onset: days (average is 90) after exposure Duration: several weeks to 6 months Flu-like symptoms, N/V, abdominal pain, jaundice, pale stools, dark urine Labs + HBsAg + HBeAg + Anti-HBc IgM + HBV DNA

13 Clinical Presentation: Chronic Infection Chronic Active Infection Acute HBV symptoms PLUS ascites, hepatic encephalopathy, and/or asterixis Labs: + HbsAg > 6 months + or - HBeAg in active carriers HBV DNA levels >10 5 copies/ml AST/ALT intermittent elevations Chronic Inactive Carriers Disease course generally benign with long-term remission common Chance of reactivation poses risk of long-term liver damage Labs: + HbsAg > 6 months + or HBeAg HBV DNA levels <10 5 copies/ml AST/ALT consistently normal

14 Complications of Chronic Infection Cirrhosis Jaundice Hepatic Encephalopathy Ascites/ Edema Coagulopathy HCC

15 Clinical Course Rate of spontaneous seroconversion to anti-hbeag is 8-12% per year in adults 10-30% of seroconverted patients continue to have high ALT and high HBV DNA levels Roughly 10-20% of inactive carriers may have reactivation and hepatitis exacerbations Risk of reactivation increases with age AASLD 2018 Hepatitis B Guidance, 2018.

16 Treatment HBV cannot be cured Goals of treatment: Suppress viral replication Increase chances for seroconversion (or sustained suppression in inactive carriers) Lose replication markers (HBeAg, HBsAg) Normalize AST/ALT Prevent disease progression to cirrhosis and HCC Minimize disease complications in existing liver damage

17 Indications for Treatment of Chronic Infection In patients with immune markers of active disease: ALT > 2x ULN OR Significant histological disease PLUS HBV DNA > 2,000 (if HBeAg negative) HBV DNA >20,000 (if HBeAg positive) May consider other factors if above are not met Age >40 Family history of HCC Extrahepatic symptoms

18 Therapeutic Response to Treatment Biochemical Normalized AST/ALT levels Histological Liver biopsy shows 2-point decrease in activity from baseline Biopsy = gold standard for fibrosis staging Fibrosis stage biggest predictor of prognosis Noninvasive means: METAVIR score, Fibrosure, APRI score Virologic Undetectable HBV DNA Undetectable HBeAg in previously positive persons and presence of anti-hbe antibodies

19 Duration of Treatment Pegylated interferon α Treat for 48 weeks Nucleoside analogs Optimal treatment duration unknown 1 year or 6 months after seroconversion (whichever is longer) Continue treatment if no seroconversion but HBV DNA is suppressed

20 First Line Treatment Options Immune Modulator Nucleoside Analogs Pegylated interferon α Entecavir (Baraclude ) Tenofovir disoproxil fumarate (Viread ) AASLD 2018 Hepatitis B Guidance, Tenofovir alafenamide (Vemlidy )

21 Pegylated-interferon α MOA: acts as cytokine with antiproliferative, antiviral, immunomodulatory effects 180 mcg SQ weekly for 48 weeks Seroconversion 20-31%; sustained response 65% No worries for development of resistance Factors predictive of poor response: High HBV DNA and ALT levels at therapy start Higher histologic scores Interferon alpha-2b. Micromedex Solutions. Truven Health Analytics, Inc. AASLD 2018 Hepatitis B Guidance, 2018.

22 Pegylated interferon α ADRs: Flu-like symptoms Thrombocytopenia, bone marrow depression Depression, anxiety (must screen prior to starting treatment) Thyroid dysfunction Risk of triggering hepatic flares and/or precipitating hepatic decompensation Contraindications: autoimmune disease, uncontrolled psychiatric illness, uncontrolled seizures, cytopenias, severe cardiac disease, decompensated cirrhosis, pregnancy Interferon alpha-2b. Micromedex Solutions. Truven Health Analytics, Inc.

23 Entecavir (Baraclude ) Treatment naïve: 0.5 mg PO QD Lamivudine resistant or decompensated liver disease: 1 mg PO QD Avoid in lamivudine-resistant HBV due to 50% resistance rate at 5 years Tenofovir preferred in both lamivudine-resistance, decompensated cirrhosis Resistance rate 3% at 96 weeks; 67-90% achieve undetectable HBV DNA ADRs: nausea, dizziness, headache, fatigue Entecavir. Micromedex Solutions. Truven Health Analytics, Inc. AASLD 2018 Hepatitis B Guidance, No Major Drug Interactions Renal Dose Adjust

24 Viread. Micromedex Solutions. Truven Health Analytics, Inc. Vemlidy. Micromedex Solutions. Truven Health Analytics, Inc. AASLD 2018 Hepatitis B Guidance, Tenofovir (Viread, Vemlidy ) Tenofovir disoproxil fumarate: 300 mg PO QD ADRs: Nephrotoxicity, decreased bone mineral density Tenofovir alafenamide: 25 mg PO QD Major drug interactions with anticonvulsants ADRs: Increased triglyercides, LDL, and HDL levels Less nephrotoxicity, bone mineral affects than other formulation Very low resistance rates; 80-95% achieve undetectable HBV DNA Cross-resistance to adefovir since both target adenosine Renal Dose Adjust

25 Second Line Treatment Options Nucleoside Analogs Lamivudine (Epivir-HBV ) Adefovir (Hepsera ) Telbivudine (Tyzeka ) AASLD 2018 Hepatitis B Guidance, 2018.

26 Lamivudine (Epivir-HBV ) No Major Drug Interactions Approved for HIV and HBV treatment 100 mg PO QD for minimum of 1 year (optimal duration unknown) Higher dose needed for HIV Seroconversion 16-21% after 1 year High rates of resistance Unavoidable and increases with each year of treatment 20% at 1 year, 40% at 2 years, 70% at 3 years Renal Dose Adjust May be beneficial in HIV co-infected patients as part of antiretroviral therapy regimen Lamivudine. Micromedex Solutions. Truven Health Analytics, Inc. AASLD 2018 Hepatitis B Guidance, 2018.

27 Adefovir (Hepsera ) No Major Drug Interactions Useful in lamivudine-resistant HBV as part of combination regimen Replaced by tenofovir which is a more potent and effective monotherapy 10 mg PO QD Up to 25% of patients have minimal to no virus suppression at recommended dosing Higher doses associated with nephrotoxicity 0% resistance at 1 year; 29% after 5 years Renal Dose Adjust Adefovir. Micromedex Solutions. Truven Health Analytics, Inc. AASLD 2018 Hepatitis B Guidance, 2018.

28 Telbivudine (Tyzeka ) No longer available in the United States Slightly more potent antiviral effect than lamivudine and adefovir High rate of cross-resistance to lamivudine 4.4% resistance rate at 1 year; 22% at 2 years Not recommended as first line Risk of myopathy, peripheral neuropathy, upper respiratory infections Telbivudine. Micromedex Solutions. Truven Health Analytics, Inc. AASLD 2018 Hepatitis B Guidance, 2018.

29 Prevention Minimize exposure risk Immunization 3 dose series (0, 1, 6 months) Who should be vaccinated? All infants, unvaccinated children <19 years old People at risk by sexual, percutaneous, or blood exposure International travelers to endemic areas HCV or HIV infection Chronic liver disease People who are incarcerated Anyone desiring protection from HBV Viral Hepatitis. Centers for Disease Control and Prevention.

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