GT1 of HCV is the most common genotype at worldwide and subgenotype 1b is most predominant in Europe and Eastern Asia as well as in Taiwan.9,10 Infection with HCV is usually asymptomatic (50% to 90% of cases), with only a minority of patients presenting with symptomatic AHC, while fulminant liver failure is rare. According to a study of 1053 patients with AHC, the case-fatality rate was reported as 5/100025 and the clinical event occurs more frequently in the cases of HCV superinfection among HBV carriers.26,27 For this patient, no history of underlying liver disease could be traced and the reasons responsible for his fulminant course except old age remains to be clarified.
HCV infection is predominantly transmitted by exposure to blood or body fluids. The patient had not received any blood transfusion during his life and he also denied ingesting herbal medicine or over-the-counter drugs. He had visited two local clinics for one time each near his residence in the countryside of northern Taiwan, where he received intravenous drugs and fluid infusions to relieve his common cold symptoms during July and August 2017. No other possible routes of infection were found. Given the time window of anti-HCV seroconversion, therefore, we thought that AHC may have been transmitted through recent nonsterile needle injection.
At the time of admission to our hospital, the patient presented with deteriorated direct-type predominant hyperbilirubinemia. Antiviral therapy was strongly indicated due to significant hepatic decompensation accompanied with a very high HCV RNA load. IFN-based or protease inhibitor containing all oral DAAs regimens should not be chosen due to evidence of liver failure. Therefore, we selected SOF, a nucleotide NA5B polymerase inhibitor, and DCV, a NS5A inhibitor, as treatment regimen plus RBV 600 mg/day as therapeutic regimen in accordance with his genotype results. After all oral DAAs therapy, patient’s subjective symptoms and liver function began to improve. Viral kinetics showed a significant decline of HCV RNA and a more than 2 log10 IU/mL reduction of RNA level was observed after one week of therapy. The HCV RNA level was 70 IU/mL in week 4 and became undetectable (<15 IU/mL) by week 8 and remained so thereafter. During the treatment period, the patient responded well to the therapy and he had no obvious symptoms or abnormal laboratory results that may have been due to DAA or RBV-related adverse events. After completion of 12 weeks of all oral DAAs and post-treatment follow up, he achieved biochemical normalization and SVR12.
Currently, evidence regarding IFN-free DAAs therapy for AHC is still limited and mainly derived from HIV-infected individuals. According to literature reports, rates of SVR12 for compensated AHC range from 21% to 60% with 6 weeks of SOF and RBV, may reach 53% to 92% by 12 weeks of SOF and RBV.20–22 Rates of SVR12 ranges from 93% after 4 weeks of therapy with SOF plus ledipasvir up to 77% to 100% with 6 weeks therapy of SOF plus ledipasvir.23,24 Therefore, the European Association for the Study of the Liver (EASL) recommends a combination of SOF and an NS5A inhibitor such as ledipasvir, DCV, or velpatasvir for 8 weeks for AHC-infected patients, which may be prolonged to 12 weeks for patients with AHC and HIV coinfection and/or a baseline HCV RNA level >1 million IU/mL (6.0 log10 IU/mL).28 The American Association for the Study of Liver Diseases (AASLD) recommends the same type and duration of DAA therapy for CHC as AHC infection.15
To date, this is the first case report using SOF and DCV plus a low dose of RBV for 12 weeks for monoinfected AHC with significant hepatic decompensation and extremely high HCV RNA level (3.51 × 107 IU/mL). The RBV dose was adjusted to 600 mg/day as the patient had decreased creatinine clearance (52.3 mL/min). The patient responded well to our treatment and no obvious adverse effects were reported during or after the antiviral therapy. As optimal treatment guidelines including treatment duration and DAA combinations in AHC patients are not well established yet, more studies focusing on IFN-free DAA combinations for AHC patients with or without HIV infection remain necessary to address these important issues.
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