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The study aimed to determine adjusted all‐cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age‐ and sex‐matched persons from the general population. We used nationwide registers to identify persons aged ≥18 years with chronic HBV infection in 2002–2017 in Denmark and included 10 age‐ and sex‐matched controls for each. Follow‐up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause‐specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow‐up of 7.7 years (range 0.0–15.5), 315 (5%) persons with—and 1525 (2%) without—chronic HBV infection died. The adjusted all‐cause MRR was 1.5 (95% CI 1.2–2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6–17.7]), external causes (MRR 3.3 [2.5–4.7]), endocrine disease (MRR 3.2 [1.8–5.4]), genitourinary disease (MRR 3.2 [1.2–7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2–2.0]). In conclusion, this study showed an increased all‐cause mortality in persons with chronic HBV infection in comparison with age‐ and sex‐matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma). [ABSTRACT FROM AUTHOR]

Direct‐acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance‐associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment‐failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral‐titre data were compared between the two patient groups, and HCV full‐length open reading frame deep‐sequencing was performed. The proportion of HCV NS5A‐RASs at baseline was higher in treatment‐failure (82%) than matched SVR patients (25%) (p =.0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment‐failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B‐substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3‐helicase and NS5A‐domain‐III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs. [ABSTRACT FROM AUTHOR]