hepatic and biliary disorders
Hepatitis C, Chronic
Treatment of Chronic Hepatitis C
Direct-acting antiviral drugs (See also the American Association for the Study of Liver Disease [AASLD]–Infectious Disease Society of America [IDSA] practice guidelinesRecommendations for Testing, Managing, and Treating Hepatitis CandWhen and in Whom To Initiate HCV Therapy.) For chronic hepatitis C, treatment is recommended for all patients, except those with a short life expectancy due to comorbid conditions that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy. The goal of treatment is permanent elimination of HCV RNA (ie, SVR), which is associated with permanent normalization of aminotransferase levels and cessation of histologic progression. Treatment results are more favorable in patients with less fibrosis than in patients with cirrhosis. is no longer considered first-line and is used only in certain alternative regimens. Currently, all patients are treated with direct-acting antivirals (DAAs) that affect specific HCV targets, such as proteases or polymerases (see also HCV genotype 1 and Interferon-based treatment regimens are no longer used to treat chronic hepatitis C, andribavirinis used only in certain alternative regimens. DAAs are not used as single drugs but are used in specific combinations to maximize efficacy. Current recommendations for HCV treatment are evolving rapidly.Hepatitis C Guidance 2019 Update: AASLD–IDSA recommendations for testing, managing, and treating hepatitis C virus infectionavailable online, are updated frequently. Decompensated cirrhosis due to hepatitis C is the most common indication for Liver Transplantation in the US. HCV recurs almost universally in the graft. Before the use of DAAs, patient and graft survival was less favorable than when transplantation is done for other indications. However, when DAAs are used, the SVR rate in patients who have had a liver transplant exceeds 95% whether they have cirrhosis or not. Because SVR rates are so high, transplantation of hepatitis C–positive organs is being done increasingly, particularly among recipients who are also hepatitis C–positive, thus expanding the pool of potential donors. If the recipient and donor are hepatitis C–positive, treatment can be postponed until after transplantation. As a result, an unnecessary pretransplantation course of treatment can be avoided. Regimens ofsofosbuvir/velpatasvir,elbasvir/grazoprevir, orglecaprevir/pibrentasvirare now considered to have a good safety profile and are effective in patients with end-stage kidney disease, including dialysis patients. Treatment of hepatitis C in patients with decompensated cirrhosis should be done in consultation with hepatologists, ideally in a liver transplant center. HCV regimens that include protease inhibitors (those drugs with the ending of -previr) should not be used in patients with decompensated cirrhosis because levels of protease inhibitors are increased in patients with hepatic dysfunction. Hepatitis B reactivation resulting in liver failure and death has been reported during or after HCV treatment with DAAs. Therefore, all patients with hepatitis C being treated with DAAs should be checked for evidence of chronic or prior hepatitis B; tests should include all of the following: Hepatitis B surface antigen (HBsAg) Hepatitis B surface antibody (anti-HBs) IgG antibody to hepatitis B core (IgG anti-HBc) Patients with chronic hepatitis B or evidence of prior hepatitis B should be monitored for reactivation during and after HCV treatment, and Treatment should be considered during the course of HCV treatment. Genotype 1 is more resistant to traditional treatment with dual therapy with pegylated interferon-alpha plusribavirinthan other genotypes. However, now with the use of interferon-free regimens of direct-acting antivirals (DAAs), the rate of SVR has increased from<50% to≥95%. First-line regimensforHCV genotype 1include Ledipasvir/sofosbuvir Elbasvir/grazoprevir Velpatasvir/sofosbuvir Glecaprevir/pibrentasvir Fixed-dose combination of ledipasvir 90 mg/sofosbuvir400 mg is given orally once a day for 8 to 12 weeks depending on history of prior treatment, pretreatment viral load, and degree of liver fibrosis. Fixed-dose combination of elbasvir 50 mg/grazoprevir 100 mg is given orally once a day, with or withoutribavirin500 to 600 mg orally twice a day, for 12 to 16 weeks depending on history of prior treatment, degree of liver fibrosis, and, in patients with genotype 1a, the presence or absence of baseline NS5A resistance–associated variants to elbasvir. Fixed-dose combination of velpatasvir 100 mg/sofosbuvir400 mg is given orally once a day for 12 weeks. Fixed-dose combination of glecaprevir 300 mg/pibrentasvir 120 mg is given orally once a day for 8 to 16 weeks, depending on history of prior treatment and degree of liver fibrosis. Ribavirinis usually well-tolerated but commonly causes anemia due to hemolysis; dosage should be decreased if hemoglobin decreases to<10 g/dL (100 g/L).Ribavirinis teratogenic in both men and women, requiring contraception during treatment and for 6 months after treatment is completed. Forgenotype 2, one of the following combinations is recommended: Fixed-dose combination ofsofosbuvir400 mg/velpatasvir 100 mg once a day for 12 weeks Fixed-dose combination of glecaprevir 300 mg/pibrentasvir 120 mg once a day for 8 to 12 weeks, depending on history of prior treatment and degree of liver fibrosis ( Treatment references ) Forgenotype 3, first-line treatments include Fixed-dose combination ofsofosbuvir400 mg/velpatasvir 100 mg once a day for 12 weeks Fixed-dose combination of glecaprevir 300 mg/pibrentasvir 120 mg once a day for 8 to 16 weeks, depending on history of prior treatment and degree of liver fibrosis Forgenotype 4,first-line treatments include Fixed-dose combination of ledipasvir 90 mg/sofosbuvir400 mg orally once a day for 12 weeks Fixed-dose combination of elbasvir 50 mg/grazoprevir 100 mg orally once a day for 12 weeks Fixed-dose combination of velpatasvir 100 mg/sofosbuvir400 mg once a day for 12 weeks Fixed-dose combination of glecaprevir 300 mg/pibrentasvir 120 mg once a day for 8 to 12 weeks, depending on degree of liver fibrosis Forgenotypes 5 and 6,first-line treatments include Fixed-dose combination of ledipasvir 90 mg/sofosbuvir400 mg orally once a day for 12 weeks Fixed-dose combination of velpatasvir 100 mg/sofosbuvir400 mg once a day for 12 weeks Fixed-dose combination of glecaprevir 300 mg/pibrentasvir 120 mg once a day for 8 to 12 weeks, depending on degree of liver fibrosis 1.Bourlière M, Gordon SC, Flamm SL, et al:Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection.N Engl J Med376 (22):2134-2146, 2017. doi: 10.1056/NEJMoa1613512 2.Asselah T, Kowdley KV, Zadeikis N, et al: Efficacy ofglecaprevir/pibrentasvirfor 8 or 12 weeks in patients with hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis.Clin Gastroenterol Hepatol16 (3):417-426, 2018. doi: 10.1016/j.cgh.2017.09.027 