Real‐world impact following initiation of interferon‐free hepatitis C regimens on liver‐related outcomes and all‐cause mortality among patients with compensated cirrhosis

Abstract

Few studies have investigated clinical outcomes among patients with cirrhosis who were treated with interferon (IFN)‐free direct‐acting antiviral (DAA). We aimed to quantify treatment impact on first decompensated cirrhosis hospital admission, first hepatocellular carcinoma (HCC) admission, liver‐related mortality and all‐cause mortality among a national cohort of cirrhotic patients. Through record linkage between Scotland's HCV Clinical Database and inpatient/day‐case hospitalization and deaths records, a study population comprising chronic HCV‐infected patients with compensated cirrhosis and initiated on IFN‐free DAA between 1 March 2013 and 31 March 2018 was analysed. Cox regression evaluated the association of each clinical outcome with time‐dependent treatment status (on treatment, responder, nonresponder or noncompliant), adjusting for patient factors including Child‐Pugh class. Among the study population (n = 1073) involving 1809 years of follow‐up, 75 (7.0%) died (39 from liver‐related causes), 47 progressed to decompensated cirrhosis, and 28 developed HCC. Compared with nonresponders, treatment response (96% among those attending their 12 weeks post‐treatment SVR test) was associated with a reduced relative risk of decompensated cirrhosis (hazard ratio [HR] = 0.14; 95% CI: 0.05‐0.39), HCC (HR = 0.17; 95% CI: 0.04‐0.79), liver‐related death (HR = 0.13; 95% CI: 0.05‐0.34) and all‐cause mortality (HR = 0.30; 95% CI: 0.12‐0.76). Compared with responders, noncompliant patients had an increased risk of liver‐related (HR = 6.73; 95% CI: 2.99‐15.1) and all‐cause (HR = 5.45; 95% CI: 3.07‐9.68) mortality. For HCV patients with cirrhosis, a treatment response was associated with a lower risk of severe liver complications and improved survival. Our findings suggest additional effort is warranted to address the higher mortality among the minority of cirrhotic patients who do not comply with DAA treatment or associated RNA testing.

Residual risk of liver disease after hepatitis C virus eradication

“…In the retrospective analysis of clinical trials of patients with HCV-associated decompensated cirrhosis treated with sofosbuvir-based regimens, SVR was associated with a significant reduction in the risk of transplantation or death (HR 0.12; 95% CI 0.04-0.38). 24 Real-world cohorts 8,16,25 have confirmed this significant reduction in the risk of liver-related death: in the HEPATHER prospective cohort, patients with SVR showed a yearly incidence of liver-related mortality of 0.36% (vs. 0.96% in non-SVR). In patients with cirrhosis, the respective rates were 0.64% vs. 1.57%.…”

“…Patients with low MELD scores on a liver transplant list can even be delisted, [3][4][5] although the clinical improvement may not necessarily persist, and patients may still develop ascites or hepatocellular carcinoma (HCC), to the point of facing the risk of relisting or death. [5][6][7] A Scottish, real-world, hospital-based linkage study 8 reported an 86% reduction in the risk of decompensation in patients who achieved SVR compared to those who did not, while none of 457 patients cured of HCV developed decompensation 10 years after SVR in a study from Japan. 9 Hepatocellular carcinoma Interferon (IFN)a-induced SVR has repeatedly been associated with a significantly reduced risk of developing HCC, including in patients who have received prior ablative treatment for HCC.…”

Impact of viral eradication by direct‐acting antivirals on the risk of hepatocellular carcinoma development, prognosis, and portal hypertension in hepatitis C virus‐related compensated cirrhosis patients

“…10 Recent reports have shown that achievement of SVR by DAA therapy is associated with reduction in HCC development risk 11 and improvement of prognosis in patients with compensated liver cirrhosis. 12 Liver cirrhosis patients also often have complications due to portal hypertension, such as esophagogastric varices (EGV) and portosystemic encephalopathy. Until now, little information has been available about the evolution and management of portal hypertension after SVR.…”

“…Progression of liver fibrosis is strongly associated with HCC development after HCV eradication 10 . Recent reports have shown that achievement of SVR by DAA therapy is associated with reduction in HCC development risk 11 and improvement of prognosis in patients with compensated liver cirrhosis 12 …”

Noninvasive Risk Stratification After HCV Eradication in Patients With Advanced Chronic Liver Disease

“…Interferon (IFN)-free therapies for chronic hepatitis C (CHC) are highly effective, achieving sustained virologic response (SVR; i.e., HCV-cure) in almost all patients with advanced chronic liver disease (ACLD) (1). Although SVR ameliorates portal hypertension (PH) in the majority of ACLD patients treated with IFN-free regimens (2)(3)(4)(5), a considerable proportion still remains at risk for hepatic decompensation (6)(7)(8). Thus, risk stratification concepts to facilitate personalized follow-up (FU) in these patients are urgently needed and currently a matter of debate.…”