HCV Eradication Research Articles

Safety and efficacy of HCV eradication during etanercept treatment for severe psoriasis

Treatment of severe psoriasis in HCV positive patients is challenging, because several psoriasis medications have a toxic effect on the liver, and interferon alpha, used to treat hepatitis, can induce worsening of psoriatic lesions. TNF-alpha inhibitors seem to be a safe and effective option in HCV positive psoriatic patients, but there are concerns about long-term safety, impact on liver fibrosis progression and risk of immune-mediated liver injury. With regard to HCV treatment, new direct-acting antiviral therapies (DAA) seem to be extremely effective, with minimal side effects, but little is known about possible interactions with other medications, particularly with biologics. We report the case of a psoriatic patient, in treatment with Etanercept, who needed to undergo HCV eradication with Daclastavir and Sofosbuvir because of worsening liver fibrosis due to chronic hepatitis C. The present treatment produced excellent results in terms of HCV eradication and control of psoriatic lesions, without side effects.

Long-Term Outcomes of Patients With HCV-Associated Cryoglobulinemic Vasculitis After Virologic Cure

Patients with hepatitis C virus-associated cryoglobulinemic vasculitis (HCV-CV) have high rates of clinical remission after treatment with direct-acting antivirals (DAAs), but circulating cryoglobulins persist, and vascular disorders reappear in some patients shortly after DAA treatment ends. We performed a prospective study to assess the long-term clinical and immune system effects of HCV eradication with DAAs in 46 patients with HCV-CV and 42 asymptomatic patients with circulating cryoglobulins. A median of 24 months after DAA treatment (range, 17-41 months), 66% of patients with HCV-CV and 70% of asymptomatic patients with circulating cryoglobulins had an immunologic response, with comparable reductions in cryocrit from 2.6% to 0% (P < .05). However, 20% of patients still had positive test results for cryoglobulins after DAA therapy. Among patients with HCV-CV, 42 (91%) had a clinical response, in that their Birmingham Vasculitis Activity Score (version 3) decreased from 7 to 0 (P < .01). Nevertheless, within 2 years after a sustained viral response to DAA therapy, 5 patients with HCV-CV (11%, 4 with cirrhosis) had relapses of vasculitis that included severe organ damage and death.

Shear wave elastography predicts hepatocellular carcinoma risk in hepatitis C patients after sustained virological response.

AimTo evaluate the relationship between fibrosis and HCC after sustained virological response (SVR) to treatment for chronic hepatitis C (HCV).MethodsThis single-center study retrospectively evaluated 196 patients who achieved SVR after HCV infection. The associations of risk factors with HCC development after HCV eradication were evaluated using univariate and multivariate Cox proportional hazards regression models.ResultsAmong the 196 patients, 8 patients (4.1%) developed HCC after SVR during a median follow-up of 26 months. Multivariate analyses revealed that HCC development was independently associated with age of ≥75 years (risk ratio [RR] = 35.16), α- fetoprotein levels of ≥6 ng/mL (RR = 40.30), and SWE results of ≥11 kPa (RR = 28.71).ConclusionsOur findings indicate that SWE may facilitate HCC surveillance after SVR and the identification of patients who have an increased risk of HCC after HCV clearance.

FRI-371 - Impact of curative HCC history on the development of HCC after the eradication of HCV by DAA therapy in patients with HCV infection

FRI-371 - Impact of curative HCC history on the development of HCC after the eradication of HCV by DAA therapy in patients with HCV infection

FRI-418 - Development of hepatocellular carcinoma following HCV eradication by direct-acting antivirals: Real-life experience from Japanese multicenter cohort

FRI-418 - Development of hepatocellular carcinoma following HCV eradication by direct-acting antivirals: Real-life experience from Japanese multicenter cohort

FRI-368 - Long-term immunological and clinical impact of HCV eradication with direct acting antivirals in patients with HCV-associated cryoglobulinemia vasculitis

FRI-368 - Long-term immunological and clinical impact of HCV eradication with direct acting antivirals in patients with HCV-associated cryoglobulinemia vasculitis

Long-term impact of HCV eradication after all-oral therapy in patients with clinical significant portal hypertension

Long-term impact of HCV eradication after all-oral therapy in patients with clinical significant portal hypertension

FRI-370 - The impact of HCV eradication by IFN-free regimens on the transition of precancerous hepatic nodules to HCC: a prospective observational study

FRI-370 - The impact of HCV eradication by IFN-free regimens on the transition of precancerous hepatic nodules to HCC: a prospective observational study

Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in HIV and HCV: Strategies in the DAA Era.

The purpose of this review is to summarize the prevalence and clinical implications of the isolated anti-HBc serologic profile in HIV-infected individuals. We highlight the rare but important issue of HBV reactivation in the setting of HCV therapy and describe an approach to management. The isolated anti-HBc pattern, a profile that most often indicates past exposure to HBV with waning anti-HBs immunity, is found commonly in HIV-infected individuals, particularly those with HCV. Some large cohort studies demonstrate an association with advanced liver disease, while others do not. Conversely, meta-analyses have found an association between occult HBV infection (a component of the isolated anti-HBc pattern) and advanced liver disease and hepatocellular carcinoma in HIV-uninfected individuals. In HIV-uninfected individuals with anti-HBc positivity, HBV reactivation has been reported in patients receiving HCV therapy. This phenomenon is likely the result of disinhibition of HBV with HCV eradication. In HIV-infected patients, the long-term liver outcomes associated with the isolated anti-HBc pattern remain to be fully elucidated, supporting the need for large cohort studies with longitudinal follow-up. HBV reactivation during HCV DAA therapy has been well-described in HIV-uninfected cohorts and can inform algorithms for the screening and management of the isolated anti-HBc pattern in this population.

Race/ethnicity and insurance status disparities in access to direct acting antivirals for hepatitis C virus treatment

Despite availability of highly effective direct acting antivirals (DAA), barriers in access to these therapies limit our ability to achieve HCV eradication. We aim to evaluate overall rates and predictors of HCV treatment across four community-based health-care systems focusing on race/ethnicity and insurance-specific disparities. We retrospectively evaluated all adults with chronic HCV at four health care systems from 1 January 2011 to 28 February 2017, which included a large proportion of ethnic minorities, two safety-net systems, and a broad payer mix across four states. Overall and stratified HCV treatment rates were calculated using Kaplan-Meier methods. Multivariate logistic regression models evaluated for predictors of receiving treatment. Among 29,544 chronic HCV patients (60.5% male, 38.4% black, 8.8% Hispanic, 18.7% Medicaid, 25.9% Medicare, 22.5% private/commercial), overall annual treatment rates were stable from 2011 (0.5%) to 2013 (2.0%), but increased from 2014 (4.8%) to 2017 (16.9%) after availability of DAAs. While similar treatment rates were observed by sex, significantly lower odds of treatment were observed in Hispanics (OR 0.48, 95% CI 0.39-0.60, p < 0.001) compared to non-Hispanic whites and among those with Medicaid (OR 0.21, 95% CI 0.20-0.24, p < 0.001) compared to commercially insured patients. Among our cohort of 29,544 chronic HCV patients, we observed significant improvements in HCV treatment rates after the availability of DAAs in 2014, but overall treatment rates remained <20% in 2017. The lowest rates of treatment were seen among Hispanics and those with Medicaid or indigent care insurance, which is concerning given these are particularly vulnerable populations.

Hepatitis C virus eradication by direct antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis

Introduction/aim: We aimed to assess whether HCV eradication by direct antiviral agents (DAA)-based therapies improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis.

HCV eradication by DAA improves glucose tolerance and reduces post-load insulin resistance in cirrhotic patients with genotype 1

HCV eradication by DAA improves glucose tolerance and reduces post-load insulin resistance in cirrhotic patients with genotype 1

The impact of antiviral therapy on hepatocellular carcinoma epidemiology.

The development of nucleos(t)ide analogs and direct antiviral agents has revolutionized the management of chronic infection with HBV and HCV, respectively. These regimens allow to expand treatment to virtually all infected, including those with poor hepatic reserve and those with severe comorbidities. As a result, permanent suppression of HBV and eradication of HCV has been achieved in almost all treated patients, resulting in substantial clinical benefits. In several cohorts, these successes have translated into a reduction of the incidence of hepatocellular carcinoma that was more frequently observed in patients with less advanced hepatitis, whereas liver cancer was more often associated with male gender, cirrhosis, alcohol abuse and diabetes.

Follow-up of sustained virological responders with hepatitis C and advanced liver disease after interferon/ribavirin-free treatment.

The introduction of direct-acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long-term durability of viral eradication after successful DAA therapy are scarce. To evaluate the long-term success of viral eradication in patients with advanced fibrosis or cirrhosis treated with DAAs. Five hundred and fifty-one patients with advanced fibrosis (n=158) or cirrhosis (CPS-A:317,CPS-B/C:76) and SVR after interferon and ribavirin-free DAA therapy treated between October 2013 and April 2016 were studied with a median follow-up of 65.6 (13.0-155.3) weeks. Only patients without hepatocellular carcinoma (HCC) at baseline and without liver transplantation were included. Twelve patients (2.2%) died during follow-up: the mortality rate was 0.6% in F3, 2.2% in CPS-A and 5.3% in CPS-B/C patients (P=.08). During follow-up 36 patients with cirrhosis (9.1%) developed a liver related event, including 16 with de-novo HCC (4.1%). Seven patients were transplanted at a median of 9.7 (range 3.8-21.7) months after EOT. History of decompensation was significantly associated with liver related events during follow-up (HR 7.9; 95% CI 2.7-22.6; P<.001), and with mortality (HR 5.5; 95% CI 1.5-20.2, P=.01). Eradication of HCV by DAA therapy was durable irrespective of the DAA combination used. Most of the cured patients had an excellent long-term clinical prognosis. Nevertheless, the risk of new occurrence of HCC remains worrisome and thus regular surveillance is obligatory even after clinical stabilization and improvement of the patient.

Safety and Efficacy of Ledipasvir/Sofosbuvir on Hepatitis C Eradication in HCV/ HIV Co-infected Patients

Introduction: There are few published data on the experience of FDA-approved oral combination of ledipasvir/sofosbuvir in HIV/HCV co-infected patients. The aim of this study is to evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with HCV and HIV co-infection in an urban HIV clinic center in Orlando.Figure: Demographic Characteristics of the Patients at Baseline.Figure: Antiviral regimen.Methods: A retrospective study was performed in patients co-infected with HIV-1 and HCV who were treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 weeks from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Figure: Response during and after Therapy.Results: Of the 40 patients enrolled, 55% were black, 22.5 % had been previously treated for HCV, and 25 % had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5 %) had a sustained virologic response at 12 weeks after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b.One patient with HCV genotype 3a was included and achieved SVR12 successfully. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7(17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5 %), fatigue (10%), and diarrhea (2.5%). Conclusion: This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well-tolerated HCV treatment option that does not require modification for many of the common HIV ART. HIV virologic rebound during the treatment emphasized the importance of closely monitoring HIV RNA level while treating HCV.

HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma

It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk. We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA + IFN vs. IFN-only) and HCC risk. We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29; 95% CI 0.23-0.37), DAA + IFN (AHR 0.48; 95% CI 0.32-0.73) or IFN-only (AHR 0.32; 95% CI 0.28-0.37). Receipt of a DAA-only or DAA + IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen. DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN. It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.

Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review.

Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing chronic liver disease in 170 million people worldwide. Recent data has identified HCV infection as a risk factor for subclinical and clinical cardiovascular disease (CVD), but these data have been mixed and whether HCV is an independent risk factor for development of CVD remains controversial. In this review, we present the literature regarding the association of HCV with subclinical and clinical CVD and the possible underlying mechanisms leading to increased CVD among those infected with HCV. HCV infection leads to increased CVD via direct and indirect mechanisms with chronic inflammation, endothelial dysfunction and direct invasion of the arterial wall cited as possible mechanisms. Our review showed that HCV infection, particularly chronic HCV infection, appears to lead to increased subclinical CVD most consistently and potentially also to increased clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore, the majority of studies evaluating the impact of HCV therapy on CVD morbidity and mortality showed an improvement in subclinical and clinical CVD endpoints in patients who were successfully treated and achieved sustained viral suppression. These results are of particular interest following the development of new direct antiviral agents which have made HCV eradication simple and feasible for many more patients globally, and in doing so may possibly reduce CVD morbidity and mortality in those with chronic HCV infection.

Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study.

Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the probability of HCC early recurrence from DAA starting by Kaplan-Meier method. Eighty-six per cent of patients were in Child-Pugh class A and 76% of patients were BCLC A. Almost all patients (96%) achieved sustained virological response. Twenty-four HCC recurrences were observed, with nodular or infiltrative pattern in 83% and 17% of patients, respectively. The 6-, 12- and 18-month HCC recurrence rates were 12%, 26.6% and 29.1%, respectively. Main tumour size and history of prior HCC recurrence were independent risk factors for HCC recurrence by Cox multivariate model. Probability of HCC early recurrence in patients who had HCC previously cured remains high, despite HCV eradication by DAAs. Risk was comparable but not higher to that reported in literature in DAA-untreated patients. Previous HCC recurrence and tumour size can be used to stratify the risk of HCC early recurrence. Further studies are needed to assess impact of DAAs on late recurrence and mortality.

The outcomes of glucose abnormalities in chronic hepatitis C patients receiving interferon-free direct antiviral agents

Direct-acting antiviral agents (DAAs) have been widely used for chronic hepatitis C (CHC) treatment recently. The characteristics of glucose abnormalities after DAAs therapy however, remain elusive. We aimed to elucidate the mutual impact between treatment response and parameters of glucose abnormalities after DAAs therapy in CHC patients. CHC patients who received DAAs therapy were recruited. The primary outcome measurements were their insulin resistance (IR) and beta-cell function assessed by the homeostasis model assessment (HOMA) method before treatment and at end-of-follow-up (EOF). Sixty-five CHC patients (19 males, mean age = 59.8 ± 10.3 years) were consecutively enrolled. They included 47 (72.3%) patients of genotype-1 infection. The treatment regimens among patients were sofosbuvir in 30 patients, paritaprevir-ritonavir/ombitasvir/dasabuvir in 23 patients, and asunaprevir/daclatasvir in 12 patients respectively. The overall sustained virological response rate was 98.5%. The mean IR at EOF was 2.6 ± 1.8, which was not significantly different from baseline level (2.7 ± 2.9, P = 0.75). There was a significant improvement of beta-cell function at EOF compared to baseline (107.7 ± 86.8 to 86.7 ± 44.5, P = 0.05). The amelioration of beta-cell function at EOF was significantly observed among 23 patients of high baseline IR (166.7 ± 111.3 of baseline vs 105.7 ± 48.2 of EOF, P = 0.04). Six (60%) of the 10 pre-diabetic patients at baseline achieved a normoglycemic state at EOF. Successful eradication of HCV by DAAs might improve glucose abnormalities in CHC patients, particularly among those who had high IR.

Risk of HBV Reactivation in Patients Infected with HBV/HCV Treated with DAA

: The exact number of HBV/HCV co-infected patients is unknown. In many cases of HBV/HCV co-infection, HCV inhibits replication of HBV. After treatment and eradication of the dominant virus, the other one may then become active. The overall dominant effect appears to be hepatitis C over hepatitis B. Therefore, when planning treatment for eradication of HCV, the risk of HBV reactivation should be taken into account. In interferon-based therapies of patients with HBV/HCV co-infection, some cases of HBV reactivation without hepatitis were observed because IFN is effective against both viruses. In contrast, DAA treatment of hepatitis C in HBV/HCV co-infection is not well established. Currently, no clinical trials have been published regarding treatment of HBV/HCV co-infected patients with HCV DAA therapy. There is several research on HCV DAA therapy in HBV/HCV co-infection, which describes cases of HBV reactivation during and after DDA therapy for HCV. Result of the first available studies demonstrated that patients with HBV/HCV co-infection treated with DAA against HCV should be monitored for HBV reactivation during and after DAA treatment, even though HBV may be inactive at the time of treatment initiation.