Table 3.
HBV Reactivation in HCV-Infected Patients Receiving DAA therapy
| Cohort | DAAs | N | Cohort | Other outcomes: ALT elevation, clinical illness, HBsAg appearance | HBV DNA elevation | Hepatic Decompensation, liver transplant, death | Reference |
|---|---|---|---|---|---|---|---|
| Retrospective evaluation of veterans receiving DAAs from VA | SOF/SIM LDV/SOF OBV/PTV/r+DSV EBR/GRZ SOF/VEL |
N=62,290 | HBsAg+ (n=377) Isolated anti-HBc+ (n=7295) |
HBsAg+: 6/8 with HBV DNA elevation with ALT elevation Isolated anti-HBc: 0 of 390 tested had appearance of HBsAg |
HBsAg+: n=8 with HBV DNA >1000 IU/ml from BL Isolated anti-HBc: 4 of 173 tested had elevated HBV DNA, 1 with HBV DNA >1000 IU/ml from baseline |
Not reported | Belperio Hepatol 2017 |
| Meta-analysis of HCV patients receiving DAA vs IFN containing therapy* | DAAs IFN |
28 studies (chronic HCV pts with overt and occult HBV N=779) | HBsAg+ HBsAg(−) and HBV DNA+ |
ALT elevation: HBsAg+: 12.2 % DAA 0% IFN HBsAg(-) and HBV DNA+: 2 case reports DAA 0 IFN |
HBsAg+: 12.2% DAA 14.5% IFN HBsAg(-) and HBV DNA+: 3 case reports DAA 0 IFN |
Not reported | Chen Hepatol 2017 |
| Prospective observational cohort study, China | LDV/SOF DAC/SOF Viekira Pak |
N=327 | HBsAg+ (n=10) Occult HBV (n=124) |
HBsAg+: 30% with hepatitis associated with HBV reactivation Occult HBV: 0% |
Not reported | N=2 with jaundice or liver failure | Wang CGH 2017 |
| Retrospective cohort study; Taiwan/Korea | SOF/LDV | N=173 | Anti-HBc + (n=103) | 1 had grade 3 ALT elevation at wk 3 (up from grade 2 at BL) | 2 with HBV DNA detectable | Sulkowski CID 2016 | |
| Prospective cohort study (Taiwan) | IFN-free DAAs | 93 (12 HBsAg+, 81 HBsAg negative) | Anti-HBc + | 16.7% HBsAg+ 0 HBsAg- |
Liu Open Forum Infect Dis 2017 | ||
| Reported cases to FDA FAERS | Viekira Pak/RBV DCV/ASV SIM/SOF SIM/SOF/RBV SOF/RBV LDV/SOF SIM/PEG/RBV DCV/ASV DCV/SOF/RBV LDV/SOF/RBV |
N=29 | HBsAg+(n=13) Anti-HBc+(n=6) HBV DNA+ (n=9) |
8/29 (29%) with clinical illness | % not reported | Decompensated liver failure in 3 patients 2 deaths 1 liver transplant |
Bersoff-Matcha Ann Intern Med 2017 |
| Prospective observational study; New Zealand | SOF/LDV | N=8 | HBsAg+ | 0 with clinical flare | 7/8 with HBV DNA elevation | None | Gane Antivir Ther 2016 |
| Case study | SOF/SIM | 1 | NA | ALT increased from 62 IU/L before DAAs to 1495 IU/L | Increased HBV DNA from 2.3 IU/mL before DAAs to 22 million after | Hepatic decompensation (jaundice) | Collins Clin Infect Dis 2015 |
| Case study | LDV/SOF | 1 | NA | ALT elevation | From undetectable before DAAs to 8.9 log IU/mL after DAAs | Hepatic decompensation | De Monte J Clin Virol 2016 |
| Case report | LDV/SOF | 1 | OBI: HBV DNA in HBsAg- patients | ALT elevation/hepatitis after DAA termination | Increased HBV DNA | NA | Fabbri BMC Infect Dis 2017 |
| Case report | Prev IFN/RBV SIM/SOF/RBV |
1 | NA | ALT elevation after DAA initiation | Increased HBV DNA | Fulminant hepatic failure requiring liver transplant | Ende J Med Case Rep 2015 |
| Case study | DAC/ASV | 1 | NA | ALT elevation after DAA initiation | Increased HBV DNA | Acute liver failure (treated with entecavir), recovered | Hayashi Clin J Gastroenterol 2016 |
| Case study | SOF/RBV | 1 | NA | ALT elevation after DAA initiation | Increased HBV DNA | Hepatic flare then treated with tenofovir | Madonia Liver Int 2016 |
*
11 studies included in meta-analysis did not have a clear definition for HBV reactivation but are included under HBV DNA elevation