Recombinant HCV Core, Nonstructural Protein 3, Nonstructural Protein 4

Reactivation of hepatitis B virus (HBV) in HBV surface antigen (HBsAg)-positive patients treated with cytotoxic chemotherapy is well known. HBV reactivation in patients with HBV and hepatitis C virus (HCV) coinfection caused by direct-acting antiviral (DAA) therapy has also recently been reported. We report a case of acute hepatitis B in a patient with HCV infection after DAA therapy. An 83-year-old woman was referred for chronic hepatitis C. She was infected with HCV genotype 1b and negative for HBsAg at baseline. She received daclatasvir and asunaprevir therapy, and HCV became negative at 4 weeks and remained negative until 6 months after the end of DAA therapy. Acute hepatitis B developed 5 months after ending DAA therapy. Genome sequencing revealed the subgenotype as B1, and the serological subtype as adr. T118 K mutation at the S region as an immune escape mutant was identified. These virologic features led to HBV reactivation. The presence of hepatitis B core antibody or HBs antibody was not determined before DAA therapy, so prior HBV infection status was unclear. This case is speculated to represent HBV reactivation in a patient with previously resolved HBV induced by DAA therapy, based on virologic analysis and clinical status. The risk might be very low, but DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. When acute hepatitis emerges in patients who have received DAA therapy for HCV, HBV reactivation should be considered to allow early initiation of anti-HBV therapy.

Background Whereas 72% of hepatitis C virus (HCV)-infected people worldwide live in low- and middle-income countries (LMICs), only 6% of them have been diagnosed. Innovative technologies for HCV diagnosis provide opportunities for developing testing strategies more adapted to resource-constrained settings. However, studies about their economic feasibility in LMICs are lacking. Methods Adopting a health sector perspective in Cameroon, Cote-d'Ivoire, and Senegal, a decision tree model was developed to compare 12 testing strategies with the following characteristics: a one-step or two-step testing sequence, HCV-RNA or HCV core antigen as confirmative biomarker, laboratory or point-of-care (POC) tests, and venous blood samples or dried blood spots (DBS). Outcomes measures were the number of true positives (TPs), cost per screened individual, incremental cost-effectiveness ratios, and nationwide budget. Corresponding time horizon was immediate, and outcomes were accordingly not discounted. Detailed sensitivity analyses were conducted. Findings In the base-case, a two-step POC-based strategy including anti-HCV antibody (HCV-Ab) and HCV-RNA testing had the lowest cost, euro8.18 per screened individual. Assuming a lost-to-follow-up rate after screening > 1.9%, a DBS-based laboratory HCV-RNA after HCV-Ab POC testing was the single un-dominated strategy, requiring an additional cost of euro3653.56 per additional TP detected. Both strategies would require 8-25% of the annual public health expenditure of the study countries for diagnosing 30% of HCV-infected individuals. Assuming a seroprevalence > 46.9% or a cost of POC HCV-RNA < euro7.32, a one-step strategy based on POC HCV-RNA dominated the two-step POC-based strategy but resulted in many more false-positive cases. Conclusions POC HCV-Ab followed by either POC- or DBS-based HCV-RNA testing would be the most cost-effective strategies in the study countries. Without a substantial increase in funding for health or a dramatic decrease in assay prices, HCV testing would constitute an economic barrier to the implementation of HCV elimination programs in LMICs.