Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16–152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta −2.37, p <.001). Also, platelet count (HR 0.99, beta-0.01, p =.007) and albumin value (HR 0.26, beta −1.36 p =.001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p <.001). Presence of diabetes (HR 3.45, beta 1.24, p =.014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease

Disease outcomes after DAA-induced SVR: Data from the resist-HCV cohort

Background and aims: Large scale, real life data on the long term course of liver disease after HCV clearance obtained with DAAs are still scanty, and the separate effects on hepatic and non-hepatic causes of death still unclear. Method: We evaluated 4147 patients (mean age: 65.7 ± 11.5 years, 57.6% males) included in the prospective RESIST-HCV cohort who started DAAs treatment in 22 centres between March 2015 and April 2017. All patients were follow after SVR to register liver-related and unrelated outcomes. The primary endpoint was the evaluation of survival since starting DAAs. Cox regression analysis was used to assess the predictors of liver-related and unrelated death. Results: Patients were observed for a median of 50 weeks (range: 1–199), 934 (22.5%) had diagnosis of chronic hepatitis (F3 in >90%), 2851 (68.7%) had Child A cirrhosis and 362 (8.7%) had Child B cirrhosis. Overall, 3766 patients (90.8%) achieved SVR while 381 patients (9.2%) were HCV-RNA positive at the last control. Fifty-five patients (1.3%) died during the observation: 25 of them died for liver related causes and 30 for unrelated causes (16: cardiovascular disease, 6: sepsis, 8: other). The lack of SVR was associated with an increased incidence of overall mortality in comparison to patients with SVR (hazard ratio [HR]; 28.9; 95% confidence interval [CI]: 16.5–50.8; p < 0.001) and death from liver-related and unrelated causes (HR: 18.5, 95%CI: 8.2–41.3; p < 0.001 and HR: 45.5; 95%CI: 19.3–107.4; p < 0.001 respectively). By multivariate Cox regression analysis lack of SVR (HR: 14.9, 95%CI: 6.3–35.1; p < 0.001) and Child B cirrhosis (HR: 29.4, 95%CI: 3.8–223.9; p < 0.001) were independently related with liver mortality. Independent predictors of liver-unrelated mortality were no SVR (HR: 41.77, 95%CI: 17.30–100.87; p < 0.001), Child B cirrhosis (HR: 3.00, 95%CI: 1.36–6.22; p = 0.006), BMI (HR: 0.89, 95%CI: 0.81–0.98, p = 0.023) and diabetes (HR: 2.38, 95%CI: 1.13–5.00, p = 0.022). Conclusion: In this real world setting using a variety of DAA regimens SVR reduced overall mortality and risk of liver-related and unrelated deaths at all stages of disease, nut mostly in Child A cirrhosis. The effect on cardiovascular deaths, which is evident also in the pre-cirrhotic stages deserves further follow up and investigation

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background & Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. Results: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI 0.17–0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR 0.70; 95% CI 0.44–1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR 0.32; 95% CI 0.13–0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00–0.19; p <0.001), HCC recurrence (HR 0.25; 95% CI 0.11–0.57; p <0.001) and hepatic decompensation (HR 0.12; 95% CI 0.02–0.38; p = 0.02). Conclusions: In patients with HCV-related cirrhosis who had been successfully treated for early HCC, DAAs significantly improved OS compared with No DAA treatment. Lay summary: We aimed to determine whether direct-acting antivirals (DAAs) significantly improve overall survival in patients with hepatitis C virus-related compensated cirrhosis and a first diagnosis of hepatocellular carcinoma (HCC) which has been successfully treated with curative resection or ablation. Using propensity-score matched patients, we found that DAAs improved overall survival and reduced the risk of hepatic decompensation. However, the risk of HCC recurrence was not significantly reduced

Direct acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background &amp; aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) after successful treatment of early hepatocellular carcinoma (HCC) has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We enrolled prospectively 163 consecutive patients with HCV-related cirrhosis and at first diagnosis of early Barcelona Clinic Liver Cancer (BCLC) 0/A HCC who had achieved a complete radiologic response after curative resection or ablation, subsequently treated with DAAs. DAA-untreated patients from ITA.LI.CA. cohort (n = 328) served as controls. After propensity-score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. Results: In DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in DAA group compared with No DAA group (hazard ratio [HR] = 0.39; 95% confidence Interval [CI] = 0.17–0.91, p = 0.03). HCC recurrence was not significantly different between DAA and No DAA groups (HR = 0.70; 95%CI = 0.44–1.13, p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in DAA group compared with No DAA group (HR = 0.32; 95%CI = 0.13-0.84, p = 0.02). In DAA group, sustained virologic response was a significant predictor of overall survival (HR 0.02, 95%CI 0.00–0.19, p &lt; 0.001), HCC recurrence (HR 0.25, 95%CI 0.11–0.57, p &lt; 0.001) and hepatic decompensation (HR 0.12, 95%CI 0.02-0.38, p = 0.02). Conclusions: In patients with HCV-related cirrhosis and previous successful treatment of early HCC, DAAs significantly improved OS compared with No DAA treatment

Factors enhancing treatment of hepatitis C virus\u21d3infected italian people who use drugs: The CLEO-GRECAS experience

INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P &lt; 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P &lt; 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/ velpatasvir; odds ratio: 3.126; P 5 0.000) and belonging to the SerDs group (odds ratio: 2.356; P 5 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs

Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents

Background &amp; Aims: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. Methods: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. Results: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P &lt;.001). Seventy-eight patients (3.5%) developed HCC during a mean follow-up of 14 months (range = 6–24 months). At 1 year after exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh class B with an SVR and 12.4% of patients with no SVR (P &lt;.001 by log-rank test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval = 1.12–2.82, P =.015), platelet count below 120 × 109/L (hazard ratio = 3.89, 95% confidence interval = 2.11–7.15, P &lt;.001), and absence of an SVR (hazard ratio = 3.40, 95% confidence interval = 1.89–6.12, P &lt;.001) were independently associated increased risk for HCC. The mean interval from exposure to DAAs to an HCC diagnosis was 9.8 months (range = 2–22 months) and did not differ significantly between patients with (n = 64, 9.2 months) and without (n = 14, 12.0 months) an SVR (P =.11). A larger proportion of patients with an SVR had a single HCC lesion (78% vs 50% without an SVR; P =.009) or an HCC lesion smaller than 3 cm (58% vs 28% without an SVR; P =.07). Conclusions: In an analysis of data from a large prospective study of patients with hepatitis C virus–associated compensated or decompensated cirrhosis, we found that the SVR to DAA treatment decreased the incidence of HCC over a mean follow-up of 14 months