HCV Eradication Research Articles

Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus.

Hepatitis C virus (HCV) infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral (DAA) agents is associated with improved glycemic control in patients with diabetes. We identified 2,435 patients with diabetes who underwent interferon-free and ribavirin-free DAA-based antiviral treatment for HCV in the national Veterans Affairs health care system. Changes in average hemoglobin A1c (HbA1c) level and use of antidiabetic medications 1 year before and after antiviral treatment were compared between patients who achieved sustained virologic response (SVR) and those who did not. Among patients with elevated baseline HbA1c, the drop in HbA1c associated with antiviral treatment was greater in those who achieved SVR (0.98%) than in those who sustained treatment failure (0.65%) (adjusted mean difference 0.34, P = 0.02). Use of antidiabetic medications decreased more in patients who achieved SVR than in those who sustained treatment failure, especially for the use of insulin, which dropped significantly from 41.3% to 38% in patients achieving SVR compared with a slight increase from 49.8% to 51% in those who sustained treatment failure. DAA-based eradication of HCV is associated with improved glycemic control in patients with diabetes as evidenced by decreased mean HbA1c and decreased insulin use. These endocrine benefits of SVR provide additional justification for considering antiviral treatment in all patients with diabetes.

Outcomes from a large 10 year hepatitis C treatment programme in people who inject drugs: No effect of recent or former injecting drug use on treatment adherence or therapeutic response.

Background and aimsPeople who inject drugs (PWID) are historically viewed as having “difficult to treat” hepatitis C disease, with perceived inferior treatment adherence and outcomes, and concerns regarding reinfection risk. We evaluated for differences in treatment adherence and response to Peginterferon-alfa-2a/Ribavirin (Peg-IFNα/RBV) in a large urban cohort with and without a history of remote or recent injection drug use.MethodsPatient data was retrospectively reviewed for 1000 consecutive patients—608 former (no injecting drug use for 6 months of therapy), 85 recent (injecting drug use within 6 months) PWID, and 307 non-drug users who were treated for chronic hepatitis C with Peg-IFNα/RBV. The groups were compared for baseline characteristics, treatment adherence, and outcome.ResultsThere was no significant difference in treatment non-adherence between the groups (8.4% in PWID vs 6.8% in non-PWIDs; RR = 1.23, CI 0.76–1.99). The overall SVR rate in PWID (64.2%) was not different from non-PWIDs (60.9%) [RR = 1.05, 95% CI 0.95–1.17]. There was no significant difference in SVR rates between the groups controlling for genotype (48.4% vs 48.4% for genotype 1; 74.9 vs 73.3% for genotype 3). Former and recent PWID had similar adherence rates.ConclusionsPWID have comparable treatment adherence and SVR rates when compared to non-drug users treated with Peg-IFNα/RBV. These data support a public health strategy of HCV treatment and eradication in PWID in the DAA era.

On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C.

Background and aimsInterferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs.MethodsWe conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor.ResultsWe found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92).ConclusionsOn-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection

ObjectiveLipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the...

Effective Treatment With Daclatasvir and Asunaprevir in Kidney Transplant Patients Infected With Hepatitis C Virus: A Report of Two Cases

BackgroundHepatitis C virus (HCV) infection is known to affect long-term patient and graft survivals after kidney transplantation (KT). Recently, combination therapy with the use of 2 oral direct-acting antivirals, daclatasvir (DCV) and asunaprevir (ASV) reportedly showed a high rate of HCV eradication. We report the safety and efficacy of DCV and ASV therapy in 2 KT patients. MethodsThe safety and viral responses were investigated in a prospective study of KT patients infected with HCV genotype 1. Two patients received 60 mg DCV once daily plus 100 mg ASV twice daily for 24 weeks. ResultsA 69-year-old woman and a 57-year-old man underwent DCV and ASV therapy for 24 weeks. In both cases, the HCV genotype was 1b. Case 1 had undergone KT twice and had received treatment with pegylated interferon and ribavirin. She received DCV and ASV therapy 12 years after the 2nd KT, and had undetectable virus after only 6 weeks of treatment and at 24 weeks after the end of treatment (SVR24). The post-transplantation immunosuppressive therapy at that time comprised tacrolimus, mycophenolate mofetil, and prednisolone. The other case, after failure of interferon treatment, received DCV and ASV therapy 27 years after his KT and achieved SVR24. His immunosuppressive regimen at that time was mizoribine and prednisolone. DCV and ASV therapy did not affect renal graft function or tacrolimus blood concentrations. ConclusionsDCV and ASV therapy had high antiviral effect and a low rate of adverse events in KT patients.

Treatment of Hepatitis C Virus (HCV) Genotype 1 Disease.

The landscape of therapeutic options for HCV infection has dramatically changed with the approval of all-oral direct-acting antiviral (DAA) regimens. DAAs target important steps in the HCV viral life cycle, resulting in higher response rates and fewer adverse events than were afforded with interferon and ribavirin, the prior standard of care. The achievement of sustained virologic response (SVR) rates in excess of 90% with use of DAA regimens has not only translated into HCV eradication for the hundreds of thousands treated but is also anticipated to decrease the incidence of major complications associated with chronic HCV infection. Additionally, the favorable side effect profile of DAAs has made HCV therapy feasible in difficult-to-treat populations, including those with previous exposure to interferon and ribavirin, cirrhosis, decompensated liver disease, HIV and HCV co-infection, and severe renal dysfunction/end stage renal disease. Given this tremendous progress, all patients infected with HCV infection should be treated.

Management of Cirrhotic Patients After Successful HCV Eradication

Chronic hepatitis C (HCV) is a hepatotropic virus which, when untreated, can lead to progressive inflammation and fibrosis resulting in cirrhosis, hepatocellular carcinoma (HCC), and decompensations related to end-stage liver disease. The relatively recent introduction of all oral, interferon-free, direct-acting antiviral medications against HCV has transformed the management of these patients. Previous treatment regimens were prolonged, poorly tolerated, and frequently did not result in cure. Current therapies achieve sustained viral response (SVR) in the vast majority of patients including those with decompensated liver disease; a previously challenging population to treat. These successes will result in significant numbers of cirrhotic patients requiring management after SVR. Although many complications of cirrhosis are improved in this setting, regular follow-up of HCC, esophageal varices, and other sequelae of cirrhosis will be necessary. This chapter will review the management of cirrhosis in HCV patients achieving cure.

Chronic Hepatitis C Treatment : A Systematic Review

Background: Chronic hepatitis C (CHC) infection affects almost 3% of the global population and can lead to cirrhosis, liver failure, and hepatocellular carcinoma in a significant number of those infected. Thus, there is a complelling need to develop and introduce new therapeutics with a direct-acting antiviral effect in order to target various stages of the HCV lifecycle for HCV eradication without concomitant interferon. Study Objective: to provide treatment recommendations for chronic HCV for specialists and generalists based on published evidence. Methods: A literature search of Web of Science, Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, Google Scholar, and Oaister was conducted from 1990 to 2016, records were filtered according to the Inclusion criteria and 27 hits were yielded. Results: Hepatitis C virus genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin because of the shorter duration of therapy and high rates of SVR (89%-90%). Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 (SVR, 79%-86%). Patients with HCV genotypes 2 and 3 should receive therapy with sofosbuvir + ribavirin alone (SVR for genotype 2, 12 weeks’ duration: 82%-93%; SVR for genotype 3, 24 weeks’ duration, 80%-95%). Patients with HIV-HCV coinfection and patients with compensated cirrhosis (ie, cirrhosis but preserved synthetic liver function) should receive the same treatment as HCV-monoinfected patients. Conclusion: A growing body of evidence suggests that recently developed HCV combined treatment modalities have transformed chronic HCV into a routinely curable disease being relatively available and well tolerated ,which can potentially reduce the need for liver transplantation and reduce HCV-related mortality. Treatment protocol for genotype1 is based on a combined regimen of Pegylated interferons with ribavirin and sofosbuvir or simeprevir while Sofosbuvir with ribavirin alone should be used to treat patients infected with HCV genotypes 2 and 3. Patients coinfected with human immunodefiency virus and HCV genotype 1 should be treated for HCV with pegylated interferons, ribavirin, and sofosbuvir by a physician with experience in treating this particular group of patients and familiar with potential drug interactions.

OC.13.1: Eradication of HCV in Patients Awaiting Liver Transplantation does not Increase Drop-Out Due to HCC Progression

OC.13.1: Eradication of HCV in Patients Awaiting Liver Transplantation does not Increase Drop-Out Due to HCC Progression

Effect of Treatment with Direct Acting Antiviral on Glycemic Control in Patients with Diabetes Mellitus and Chronic Hepatitis C

Introduction and aim. The effect of the new direct acting antiviral drugs (DAAs) for chronic hepatitis C (HCV) on glycemic control is unknown.Materials and methods. We conducted a retrospective cohort study of patients who were treated for chronic HCV with direct-acting antiviral medications at a single academic institution between May 2013 and April 2016. Univariate analysis was performed comparing subjects pre- and post-treatment.Results. One hundred seventy-five consecutive adult patients were treated for chronic HCV and met enrollment criteria. The majority (80.8%) were genotype 1 and overall cohort sustained virologic response at week 12 (SVR12) was 97.8%. Thirty-one (18.5%) had diabetes mellitus (DM); twenty-six had pre- and post-treatment HbA1c values. Of these, 76.9% were male and 61.5% had cirrhosis. Ninety-six percent were prescribed sofosbuvir-based therapy and all but one (96.8%) achieved SVR12. Three patients were started on treatment despite meeting the definition for poorly controlled DM (HbA1c > 9 mg/dL). There was no significant difference when comparing pre-treatment (7.36 mg/dL, 95% CI 6.55-8.16) to post-treatment HbA1c (7.11 mg/dL, 95% CI 6.34-7.88, p = 0.268). Thirty-one percent of subjects required dose escalation or the initiation of insulin based therapy during treatment.Discussion. Although chronic HCV is associated with exacerbation of insulin resistance, our results showed HbA1c to be unaffected by eradication of chronic HCV with DAA in diabetic patients with and without cirrhosis. Paradoxically, almost 1/3 of patients required escalation of anti-diabetic therapy during treatment. Long-term studies are warranted to understand the relationship between HCV viral eradication and insulin metabolism.

Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response

BackgroundNovel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts.MethodsThis post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493).ResultsWe observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens.ConclusionThis is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR.

Eradication of HCV in patients awaiting liver transplantation does not increase drop-out due to HCC progression

Eradication of HCV in patients awaiting liver transplantation does not increase drop-out due to HCC progression

Sustained virological response by direct antiviral agents in HCV leads to an early and significant improvement of liver fibrosis.

Direct antiviral agents (DAA) demonstrated high efficacy among HCV-infected patients in registered trials. Nevertheless, the impact of these therapies on liver stiffness measurement (LSM) and liver functionality in 'real-life' is not well-known. The aim of the present study was to evaluate the sustained virological response (SVR) impact on LSM and clinical parameters of DAA-therapy on a real-life population of HCV patients with F3/F4 fibrosis. A total of 749 HCV genotype 1-4 patients with F3/F4 hepatitis undergoing antiviral therapy were consecutively enrolled in four centres of hepatology in Italy. Clinical, biochemical and imaging data were collected at the baseline (T0), at the end of treatment (EoT) and after 12 weeks (SVR12). Out of 749 patients, 69.7% were F4 and 30.3% were F3. SVR12 was reached in 97.5%. LSM significantly decreased from T0 to EoT (P<0.001), whereas, it did not from EoT to SVR12 (P= not significant). Moreover, in F4 no significant differences were found in Child and MELD between T0, EoT and SVR12 (P= not significant). At the univariate analysis of clinical and liver parameters, baseline high glucose (P<0.005), type 2 diabetes (P<0.001), low alanine aminotransferase (ALT; P<0.001), low platelets (P<0.005), and the presence of esophageal varices (EV; P<0.001) were found to be associated with a lack of a significant EoT LSM improvement. At multiple regression, ALT (P<0.05), diabetes (P<0.005) and EV (P<0.05) were inversely associated with significant LSM reduction. Virological response to DAA is associated with fibrosis regression and recovery of liver functionality and this can be detected as early as EoT. HCV eradication is associated with a rapid and significant clinical improvement that lasts over time and seems to be negatively influenced by diabetes and EV.

Longterm Evaluation of Hemoglobin A1c Following Hepatitis C Therapy in Patients with and without HIV Co-infection

BackgroundHistorically, eradication of HCV with interferon-based treatments was linked with decreased incidence of diabetes. While viral clearance with direct acting agents (DAAs) may be associated with acute decreases in fasting glucose levels and hemoglobin A1c (HbA1c), there remains a need for larger prospective studies to address the longterm impact of sustained viral response (SVR) achieved with DAAs on glucose metabolism.MethodsProspective longitudinal cohort study of 251 subjects with chronic HCV (100% genotype 1a/b, 31% HIV+, 17% diabetes) evaluated pre- and post-DAA therapy with median follow-up of 28 mos. Change in HbA1c, glucose, lipid and transaminase levels were compared based on SVR, HIV, diabetes status and fibrosis stage.ResultsThere was no difference in change in HbA1c between subjects who achieved SVR (n = 241) compared with those who did not. Mean change in HbA1c did not differ from zero (−0.022 ± 0.53%) for those with SVR. Further, when subjects were grouped based on HIV, diabetes or fibrosis stage, there were no significant differences in changes in HbA1c or glucose following SVR. Subjects with HIV had smaller reductions in transaminase values (change ALT −33.3 ± 51 IU/L HIV+ vs. −47.8 ± 45 IU/L HIV-, P = 0.0007). Following SVR, total and LDL cholesterol increased (P = 0.0002 and P = 0.0003, respectively) whereas triglyceride levels decreased (P = 0.008). A greater proportion of subjects (7%) started or increased medication therapy for diabetes following SVR compared with the percentage who decreased diabetes therapy (3%). There was a statistically significant positive correlation between change in BMI and change in HbA1c (r=0.17, P = 0.006).ConclusionThe current study failed to identify sustained benefits in glucose or HbA1c in HCV treated patients, irrespective of HIV, diabetes or fibrosis stage. HIV infection blunted improvements in transaminase levels related to SVR. While HbA1c did not improve with HCV clearance, alterations in lipids were identified that warrant further investigation.Disclosures C. Gross, Merck: stock holder, Own stock; Pfizer: stock holder, Own stock; JohnsonandJohnson: stock holder, Own stock

The Effect of Hepatitis C Virus Eradication with New Direct Acting Antivirals on Glucose Homeostasis in Non-Diabetic Egyptian Patients

Introduction: Chronic hepatitis C (HCV) infection and Diabetes Mellitus (DM) are common health problems in Egypt. HCV treatment by the new Direct Acting Antiviral (DAA) drugs gives hope to eradicate HCV. However, its effect on glucose homeostasis is not studied. Aim: Study of glucose homeostasis before and after treatment of HCV infected patients with DAA drugs. Subjects and methods: Eighty patients chronically infected with HCV, diagnosed by quantitative PCR, were subjected to physical examination and anthropometric measurements. In addition, FBS, fasting insulin, CBC, bilirubin, AST, ALT, Serum Albumin and serum creatinine were assessed at the beginning of the study. HOMA-IR, β cell %, BMI and e GFR were calculated. All patients received DAA drugs ± ribavirin for 3 months. All parameters were reassessed at End of Treatment (EOT). Results: FBS, Hb, AST, ALT and Platelet count were reduced at EOT. Serum bilirubin, fasting insulin and HOMAIR were significantly increased at EOT. No significant difference as regarding body weight, serum creatinine, e GFR or β cell function. Correlation between insulin resistance at EOT with all basal and EOT measurements showed only a significant positive correlation with basal bilirubin. Conclusion: Although eradication of HCV by DAA drugs improves glycemic control, it is associated with increased IR. Basal serum bilirubin can predict the development of IR. However, this predictive value is lost with viral eradication by DAA.

SAT-269 - Drop-out rate due to HCC progression is not affected by HCV eradication with DAAs in patients awaiting liver transplantation

SAT-269 - Drop-out rate due to HCC progression is not affected by HCV eradication with DAAs in patients awaiting liver transplantation

PS-032 - HCV eradication reduces the occurrence of major adverse cardiovascular events in hepatitis C cirrhotic patients: data from the prospective ANRS CO12 CirVir cohort

PS-032 - HCV eradication reduces the occurrence of major adverse cardiovascular events in hepatitis C cirrhotic patients: data from the prospective ANRS CO12 CirVir cohort

Platelet Count Increase Seen with Ledipasvir-Sofosbuvir Combination Treatment of Chronic Hepatitis C in Patients with Thrombocytopenia

Background: Thrombocytopenia (TCP) is commonly seen in chronic Hepatitis C (HCV). Ledipasvir-sofosbuvir (LDV/SOF) is a novel, fixed-dose anti-HCV combination that has shown high sustained virologic response (SVR) rates. However, since much remains to be learned about the natural history of TCP following LDV/SOF treatment, we set out to examine platelet (PLT) counts in thrombocytopenic patients with chronic HCV before, during, and after treatment with LDV/SOF.Methods: This is an IRB-approved, retrospective study of patients diagnosed with chronic HCV who received LDV/SOF between November 2014 and April 2016 at the Washington DC Veterans Affairs Medical Center. Patients who had PLT counts less than or equal to 150 x 109/L for at least 6 months prior to treatment andcompleted therapy with LDV/SOF were included. Patients diagnosed with heparin-induced TCP; disseminated intravascular coagulation; medication-induced TCP; sepsis; as well as those who received PLT transfusion or thrombopoietic agents were excluded. PLT counts were collected at baseline (within 6 months prior to the start of therapy), during treatment, and throughout the follow-up period until the last follow-up, initiation of a new HCV medication, liver transplant, or death. Patients were categorized into 3 groups: mild TCP (100-150 x 109/L), moderate (50-99 x 109/L), and severe (<50 x 109/L). Paired t-test was used to compare pre-treatment, on-treatment (week 4), and the last measured PLT counts. Multivariate regression analysis was used to determine the baseline variables associated with improvement in PLT counts. All registered PLT counts from the start of therapy were included in repeated measurement analyses to assess the evolution of PLTs over time.Results: Inclusion criteria were met in 244 patients (median age 64, 98% male, 88.9% African American). HCV genotypes were 1a (77.4%) and 1b (22.6%). The median follow-up from treatment start was 13 months. Treatment duration was 8 weeks (13.9%), 12 weeks (69.7%), or 24 weeks (16.4%), all at the fixed dose of LDV 90 mg and SOF 400 mg once daily. SVR at 12 weeks (SVR12) was attained in 159 patients (65.2%) while 67 patients (27.5%) had a documented undetectable viral load earlier than 12 weeks from treatment completion with no further testing. Eight patients (3.3%) failed treatment and 10 (4.1%) were lost-to-follow-up. The mean pre-treatment PLT count was 114 x 109/L (22-150). The on-treatment and last measured PLT counts were significantly higher than the baseline PLT count (129 x 109/L, p<0.001 and 144 x 109/L, p<0.001 respectively). The increase from the on-treatment to the last measured PLT count was also statistically significant (p=0.008). The last measured PLT counts were on average 32.8 ± 66.7% higher than the baseline and 31.6% of patients had normal last measured PLT counts. The increase in PLT count was observed for all three TCP groups: mild (73.4%): from 129 x 109/L at baseline to 149 x 109/L during treatment (p<0.001) to 160 x 109/L after (p=0.045); moderate (24.2%): from 75 x 109/L before to 89 x 109/L during (p=0.004) to 112 x 109/L after (p=0.027); severe (2.5%): from 38 x 109/L before to 64 x 109/L during (p=0.003) to 97 x 109/L after (p=0.234). Multivariate regression analysis was performed including the following variables: age; gender; HCV genotype; baseline PLT count, albumin, bilirubin, and AST/ALT; history of severe alcohol abuse; HIV coinfection; Hepatitis B coinfection; presence of splenomegaly; presence of cirrhosis; treatment duration and reaching SVR12. It showed that reaching SVR12 is associated with a faster increase in PLT count (p=0.022). Repeated measurement analyses showed a gradual and linear increase in PLT counts from the start of therapy for the entire cohort (p<0.001) as well as in every TCP group: mild (p<0.001), moderate (p=0.001) and severe (p=0.015).Conclusion: LDV/SOF is associated with an increase in PLT counts in chronic HCV patients with TCP. This desired effect becomes apparent even before the conclusion of therapy. It is thus tempting to correlate the increase in PLT count with LDV/SOF-associated quick eradication of HCV soon after treatment initiation. Whether that is due to elimination of HCV-associated bone marrow suppression and autoimmune TCP or other not yet known mechanisms, these results are tantalizing but would require longer follow-up. Larger prospective studies are needed to ascertain these results and uncover potential mechanisms. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly patients infected with HCV genotype 1B

Anti-hepatitis C virus (HCV) therapy by interferon (IFN)-free regimen with oral direct-acting antiviral drugs are tolerable in aged patients, with fewer adverse effects than IFN-based therapies. We investigated the efficacy and tolerability of an IFN-free anti-HCV therapy in extremely aged patients, as well as the survival benefit of sustained virologic response (SVR). Following IFN-free therapy with daclatasvir and asunaprevir, tolerability and SVR rate were compared between 115 HCV genotype 1-infected patients aged 80years or older, 151 patients in their 70s (⩾70 and <80years), and 115 patients under the age of 70. One-year mortality and morbidity in patients aged ⩾80years were compared between SVR patients and propensity score-matched patients with persistent HCV infection. The SVR rate was 96.5% in patients ⩾80years, comparable to that in patients aged ⩾70 and <80years (95.4%) and patients aged <70years (93.9%). There were no differences in treatment discontinuation rate (2.6%, 1.3%, and 0.9%, respectively). One-year mortality was significantly lower in SVR patients (2.7%) than in patients with persistent HCV infection (15.3%, p=0.0016). Whereas 1-year mortality due to liver-related diseases was 8.1% in patients with persistent HCV infection who were aged ⩾80years, no SVR patients died from liver diseases within 1-year after the end of therapy. IFN-free therapy for HCV infection was associated with high tolerability and antiviral efficacy, even in patients aged ⩾80years. In addition, there seemed to be a survival benefit from the eradication of HCV in this population. IFN-free therapy with oral direct-acting antiviral drugs (daclatasvir and asunaprevir) for HCV infection showed similar tolerability and antiviral efficacy in patients aged ⩾80years as in younger patients (patients aged ⩾70 and <80years and patients aged <70years), with an SVR rate over 90% and no severe adverse effects. There was a survival benefit from the eradication of HCV even in patients aged ⩾80years.

Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.