Liver Fibrosis Is Associated With Corrected QT Prolongation During Ledipasvir/Sofosbuvir Treatment for Patients With Chronic Hepatitis C

Abstract

Combination treatment of ledipasvir and sofosbuvir (LDV/SOF) is first‐line treatment for patients with chronic hepatitis C genotype 1 in the United States, Europe, and Japan. However, the influence of LDV/SOF on the cardiovascular system is poorly characterized. A total of 470 chronic hepatitis C patients who started LDV/SOF treatment between September 2015 and February 2016 at nine hospitals in Japan were prospectively enrolled in this study. Corrected QT (QTc) prolongation was defined as a QTc interval ≥450 milliseconds. The sustained virologic response rate was 96.0% (451/470), and the discontinuance rate due to adverse effects was 0.9% (4/470). Among 395 patients whose electrocardiogram was evaluated over time and compared with baseline, the QTc interval was significantly prolonged during treatment and returned to baseline levels 12 weeks after the end of treatment. Twenty‐four of 376 patients with baseline QTc intervals <450 milliseconds experienced on‐treatment QTc prolongation. Higher aspartate aminotransferase‐to‐platelet ratio index scores (≥0.76; odds ratio, 4.375; P = 0.005) and longer QTc intervals (≥416 milliseconds; odds ratio, 4.823; P = 0.003) at baseline were significantly associated with on‐treatment QTc prolongation on multivariate analysis. Patients with cirrhosis showed significantly longer QTc intervals than those without cirrhosis during treatment but not at baseline, and they developed on‐treatment QTc prolongation at a higher rate than patients without cirrhosis. No cardiovascular events occurred, except for 1 patient who developed paroxysmal supraventricular tachycardia. Conclusion: Newly developed QTc prolongation was observed in 6.4% of Japanese patients during treatment and was associated with more advanced fibrosis. (Hepatology Communications 2018; 00:000‐000)

Prediction model for hepatocellular carcinoma occurrence in patients with hepatitis C in the era of direct‐acting anti‐virals

“…The development of direct-acting anti-virals (DAAs) has led to a high rate of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) infection. [1][2][3] The incidence rates of hepatocellular carcinoma (HCC) occurrence among patients who achieved SVR by DAA treatment were 1.1%-1.9% at 1 year and 1.9%-4.1% at 2 years. [4][5][6][7] The HCC incidence rate was lower in patients who achieved SVR by DAA treatment than in those who did not achieve SVR.…”

Hepatocellular carcinoma occurrence does not differ between interferon‐based and interferon‐free treatment with liver histological assessment

“…Antiviral treatments for patients infected with hepatitis C virus (HCV) have dramatically changed since direct‐acting antivirals (DAAs) were introduced. Sustained virologic response (SVR) rates of ≥90% could be achieved even in clinical practice . Treatments with DAAs enable us to achieve high SVR rates for patients with more advanced liver disease and of older ages who were difficult to treat in the era of interferon (IFN)‐based treatment …”

“…Sustained virologic response (SVR) rates of ≥90% could be achieved even in clinical practice. [1][2][3] Treatments with DAAs enable us to achieve high SVR rates for patients with more advanced liver disease and of older ages who were difficult to treat in the era of interferon (IFN)-based treatment. [4][5][6] Among those treated with IFN-based treatments, the cumulative rate of hepatocellular carcinoma (HCC) occurrence is higher in non-SVR patients than in SVR patients.…”

Clinical outcomes of direct‐acting antiviral treatments for patients with hepatitis C after hepatocellular carcinoma are equivalent to interferon treatment

“…1,2 In recent years, IFN-free direct-acting antiviral (DAA) treatment enabled the achievement of high SVR in patients with HCV, including those who had a history of HCC treatment. [3][4][5][6] Regarding the impact of antiviral treatment on HCC recurrence, for IFN treatment, the HCC recurrence rate was lower in SVR patients than in non-SVR patients. 1,7,8 Regarding DAA treatment, early HCC recurrence was reported after the initiation of DAA treatment.…”

“…IN THE ERA of interferon (IFN) treatment, the sustained virologic response (SVR) rate of antiviral treatment for patients with hepatitis C virus (HCV) after hepatocellular carcinoma (HCC) treatment was low, and patients who received previous HCC treatment were difficult to treat 1,2 . In recent years, IFN‐free direct‐acting antiviral (DAA) treatment enabled the achievement of high SVR in patients with HCV, including those who had a history of HCC treatment 3–6 . Regarding the impact of antiviral treatment on HCC recurrence, for IFN treatment, the HCC recurrence rate was lower in SVR patients than in non‐SVR patients 1,7,8 .…”