In This Article

Editor's Note: Based on presentations delivered at The Liver Meeting 2015—the 66th Annual Meeting of the American Association for the Study of Liver Diseases—this is the final installment of a three-part series on hepatitis C and discusses the benefits associated with its successful treatment, including improved quality of life and a reduction in liver-related and all-cause mortality. The long-term adverse consequences of the infection (eg, end-stage liver disease [ESLD] and hepatocellular carcinoma [HCC]) and the potential for drug resistance are also reviewed, along with a glimpse into what the future holds in terms of treatment. Part 1 reviewed the prevalence, screening methods, and access and barriers to care; and Part 2 focused on novel therapeutic strategies directed against the infection.

Reported Outcomes

Reduced Work

Hepatitis C virus (HCV) is associated with significant impairment in health-related quality of life (HRQOL) and other patient-reported outcomes (PROs). Additionally, patients with HCV are known to have reduced work productivity, both in terms of presenteeism (ie, impairment in work productivity while working) and absenteeism (ie, productivity loss due to absence from work).[1] Of 4121 patients with HCV who completed four pretreatment PRO questionnaires, 60% reported that they were currently employed and that their work productivity was impaired, resulting in substantial costs to society. The most important drivers of work productivity and its components were impairment of physical aspects of HRQOL.

Sofosbuvir and Ledipasvir Improve Outcomes

Younossi and colleagues[2] assessed the impact of the fixed-dose combination of ledipasvir and sofosbuvir (LDV/SOF) on the PROs of patients coinfected with HCV genotype 1 and HIV. A sustained virologic response at 12 weeks (SVR12) was achieved in 96% of these patients, whereas only 76% of patients who were treated with SOF and ribavirin (RBV) achieved SVR12. PRO scores improved significantly both during treatment and after achieving SVR when compared with baseline measures and vs the RBV-containing regimen.

Effect of Treatment on the Metabolic Syndrome

Pedersen and colleagues[3] evaluated the effect of therapy with direct-acting antiviral agents (DAAs) on components of the metabolic syndrome. Concomitant metabolic syndrome components in patients with HCV prior to treatment were hypertension (39%), diabetes (17%), and hyperlipidemia (15%). For the entire cohort, end-of-treatment response was 98%, with 79% going on to achieve SVR12. Significant reductions in each of the various components were noted. Changes in systolic and diastolic blood pressure in the entire cohort were observed, but only those who achieved SVR12 demonstrated sustained changes.

Treatment Outcomes and Hospitalization Rates

HCV is associated with high all-cause hospitalization rates. Successful treatment of the infection results in reduced morbidity and mortality. Teshale and colleagues[4] reported that for patients with HCV who were treated in the pre-DAA era, all-cause hospitalization rates were cut by approximately half after SVR. Among those who achieved SVR, hospitalization rates declined across all ages, sexes, races, income levels, types of insurance, and stages of liver disease.

Regression of Advanced Fibrosis or Cirrhosis

SVR has also been associated with a reduced rate of hepatic decompensation, reduced risk for HCC, and reduced liver-related mortality. Crissien and colleagues[5] conducted a retrospective chart review of patients who were treated for HCV. Of the patients with cirrhosis at baseline, 53% demonstrated improvement by FibroScan, with a median time to improvement of 2.8 years after SVR. Of the subjects who had advanced fibrosis, 67% demonstrated improvement within a median of 2.0 years. Sex, body mass index (BMI), age, and HCV genotype were not associated with improvement or worsening of baseline liver disease.

The demonstrated improvement by FibroScan scores correlated with reported changes in liver stiffness measured by transient elastography (TE), as reported by Bourlière and colleagues,[6] who explored changes in liver stiffness and a correlated novel fibrosis marker (sLOXL2) in cirrhotic patients with an SVR after SOF/LDV-based therapy. At baseline, the median liver stiffness by TE was 17.5 kPa, and the median sLOXL2 was 146 pg/mL. At SVR24, 80% of patients had a decline in liver stiffness. The estimated fibrosis category improved in 39%, was stable in 60%, and worsened in 0.7% of patients. In a multivariate model adjusting for BMI, model for end-stage liver disease (MELD) score, platelets, and baseline liver stiffness, improvement in the fibrosis category was more common in patients with higher platelet counts and lower liver stiffness at baseline.

Screening and Surveillance for HCC

A retrospective Veterans Affairs (VA) cohort study[7] of patients with HCV who were treated with pegylated interferon and RBV from 1999 to 2009 demonstrated an HCC incidence rate of 3.27/1000 patient-years in those who attained an SVR vs 13.2/1000 in those without SVR attainment. Predictors of HCC after SVR were cirrhosis at the time of SVR, Hispanic ethnicity, and the presence of diabetes.

Nagaoki and colleagues[8] also assessed risk factors for the development of HCC in 2262 consecutive patients with HCV after successful interferon-based eradication of HCV. During the observation period, 3% of patients developed HCC. The median period from HCV eradication to HCC development was 37 months, and the cumulative rates of developing HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified age ≥ 60 years, male sex, advanced fibrosis stage, and tumor marker alpha-fetoprotein value ≥ 10 ng/mL at 1 year as significant independent risk factors for HCC development after HCV eradication.

Impact of SVR on Liver-Related Outcomes

The impact of SVR achievement on long-term hepatic outcomes in patients with cirrhosis, especially those who are Child-Pugh B or C, was reported by Saxena and colleagues.[9] They compared the liver-related events in a cohort of patients with HCV genotype 1 with varying severity of cirrhosis who achieved SVR with patients who did not achieve SVR or untreated matched controls. Achieving HCV cure among patients with compensated and decompensated cirrhosis significantly reduced the frequency of liver-related outcomes, including portal hypertensive complications and liver transplant or death.

Cause of Death in Patients Who Achieved SVR

During 2006-2012, a total of 2314 deaths occurred in a cohort of patients with HCV. Of these, 3% were patients known to have achieved an SVR.

Xu and colleagues[10] described the stage of liver disease at the time of SVR and the timing and cause of death in patients after SVR. Overall, 5% of SVR patients died vs 16% of non-SVR patients (P<.001). The mean time from SVR date to death was 4.9 years. The age of death was similar to patients who died without SVR, with most deaths occurring at an age younger than 60 years. Of the 71 deaths that occurred in patients after SVR, 21% had liver cancer. Thus, although mortality among patients who had achieved SVR was lower, premature death and liver cancer can still occur and may be related to the late stage of liver disease at the time of treatment and achievement of SVR.

Bruden and colleagues[11] used liver biopsy to determine the development of ESLD, HCC, and liver-related death in patients with HCV. Of 412 persons undergoing liver biopsy, 68% had mild or moderate fibrosis, 21% had severe fibrosis, and 10% had cirrhosis. Within 5 years of biopsy, 5% of persons with mild or moderate fibrosis had developed ESLD compared with 16% and 45% of persons with severe fibrosis and cirrhosis. HCC developed in 1.0%, 1.1%, and 13% of persons with mild or moderate fibrosis, severe fibrosis, and cirrhosis, respectively. Five years after biopsy, 0.5% of persons with mild or moderate fibrosis had suffered a liver-related death compared with 5% of persons with severe fibrosis and 16% of persons with cirrhosis. Thus, among persons with cirrhosis, almost half developed ESLD within 5 years after liver biopsy, and over 10% developed HCC or had liver-related death. For prevention of HCC, liver-related death, and ESLD in the short term, HCV therapy can be targeted toward those with the greatest risk for severe sequelae after biopsy.

Of note, statin use was associated with a decreased risk of developing HCC in patients with cardiovascular risk factors. In a report by Nyberg and colleagues,[12] statin use had a strong protective effect after adjustment of clinical and sociodemographic characteristics.


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