SVR-24 Achievement Two weeks After Sofosbuvir and Daclatasvir overdose Assumption in an HCV Infected Patient With Genotype 3

BACKGROUND: Presently, DAA are the best choice to treat chronic HCV infection. SVR24 is usually achieved in more than 90% of patients with 8 to 24 weeks of therapy. HCV genotype 3 (GT3) has been associated with increased rates of steatosis, fibrosis, and hepatocellular carcinoma. For GT3 HCV infection, the best DAA combinations treatment are Sofosbuvir/Velpatasvir and Sofosbuvir plus Daclatasvir, although the latter only is currently available in Italy. CASE DESCRIPTION: A 51-years-old Pakistani man came to our attention because of positive Quantiferon test with normal chest radiography. In 1993 he presented nodal tuberculosis (TB) treated with 6 months therapy with unspecified drugs. He had been in Italy for 6 years without speaking or understanding Italian, thus a cultural mediator was needed for medical interview and examination. Although the patient was symptom-free, laboratory analyses showed persistent increased transaminases and bilirubin and chronic HCV infection was detected. Moreover, laboratory (blood tests) and instrumental  (abdominal and chest CT-scan, colonoscopy with biopsy, esophagogastroduodenoscopy, liver biopsy) examinations, were undertaken to evaluate if liver disease was caused by HCV itself or if there was a concomitant extrapulmonary TB infection. Enteric TB was diagnosed. In order to reduce liver toxicity, antiviral therapy was started. Owing to the moderate fibrosis (liver biopsy: Ishak score: 9, stage: 3; Metavir score: 2. Fibroscan: Metavir score: F2-F3), the best combination therapy among those available (Table 1), resulted to be Sofosbuvir 400 mg daily plus Daclatasvir 60 mg daily without Ribavirin for 12 weeks tests were performed to check the possible effects of a Daclatasvir overdose. LDH, CPK and CK-MB resulted abnormally increased and according with standard guidelines. Thanks to cultural mediator support, the patient was informed about the correct assumption of each drug per day according to standard guidelines: A therapy with Sofosbuvir 400 mg, 1 tablet once daily plus Daclatasvir 60 mg, 1 tablet once daily was started. The patient returned to our Institution 13 days after for a programmed visit and we learned he had assumed an overdose of Daclatasvir  (3 tablets daily) stopping the drug 9 days after. Although the patient didn’t complain symptoms, blood antiviral therapy was stopped. Overall, the patient assumed Daclatasvir 60 mg 3 times daily for 9 days and Sofosbuvir 400 mg for 15 days. He didn’t assume any other treatment for HCV infection nor for intestinal TBC. HCV viremia was checked after 4, 12 and 24 weeks and resulted always negative. CONCLUSIONS: The described case is clinically relevant because of the peculiar outcome. Achievement of SVR24 was not expected at all after only 15 days of DAA assumption. One only report described a patient with GT1b infection in whom SVR24 was achieved after 17-days treatment with Daclatasvir plus Asunaprevir. Moreover, very few data are available regarding an eventual short-duration therapy in GT3 infected patients (Table 2). The favourable outcome in our patient has been obtained with a three fold increase dose that may have caused biochemical alteration and faster HCV suppression. If confirmed on a large number of cases, these data could serve to further investigate that the shorter dose effects of DAA could potentially reduce times and costs of their treatment in patients with chronic HCV infection.