Interferon-based Antiviral Therapy Research Articles

Protective effect of interferon-based antiviral therapy on risk of bipolar disorder in patients with hepatitis C Virus infection: A nationwide longitudinal study

Background: A recent study has shown the beneficial effects of interferon (IFN)-based antiviral therapy (AVT) in reducing the risk of newly diagnosed depression among patients with hepatitis C virus (HCV) infection. But whether IFN-based AVT reduces the risk of bipolar disorder remains unknown. Methods: This is a retrospective study based on the Taiwan National Health Insurance Research Database. From enrollment to the end of 2013, 24,240 patients with HCV infection (4473 treated with IFN-based AVT and 19,767 without such treatment) as well as 96,960 age- and sex-matched controls were included in this study. Time-dependent Cox regression models were used to study the differences in risk of newly-diagnosed bipolar disorder between patients being treated with and without IFN-based AVT and the control participants. Results: Patients with HCV infection who had not yet received IFN-based AVT (hazard ratio = 4.86, 95% confidence interval = 1.87–12.66, p = 0.001), but not those who were receiving IFN-based AVT (1.69, 0.94 - 30.50, nonsignificance) and those who completed the IFN-based AVT (1.77, 0.69 - 4.54, nonsignificance), were significantly more to be diagnosed with bipolar disorder compared with the control group. Conclusion: Our study supports the temporal association between HCV infection and subsequent bipolar disorder, further suggesting that the optimal AVT to eradicate HCV may be associated with a reduced risk of incident bipolar disorder later in life.

Hepatitis C-associated late-onset schizophrenia: a nationwide, population-based cohort study.

Background:Whether infection with the hepatitis C virus (HCV) causes schizophrenia — and whether the associated risk reverses after anti-HCV therapy — is unknown; we aimed to investigate these topics.Methods:We conducted a nationwide, population-based cohort study using the Taiwan National Health Insurance Research Database (TNHIRD). A diagnosis of schizophrenia was based on criteria from the International Classification of Diseases, 9th revision (295.xx).Results:From 2003 to 2012, from a total population of 19 298 735, we enrolled 3 propensity-score-matched cohorts (1:2:2): HCV-treated (8931 HCV-infected patients who had received interferon-based therapy for ≥ 6 months); HCV-untreated (17 862); and HCV-uninfected (17 862) from the TNHIRD. Of the total sample (44 655), 82.81% (36 980) were 40 years of age or older. Of the 3 cohorts, the HCV-untreated group had the highest 9-year cumulative incidence of schizophrenia (0.870%, 95% confidence interval [CI] 0.556%–1.311%; p < 0.001); the HCV-treated (0.251%, 95% CI 0.091%–0.599%) and HCV-uninfected (0.118%, 95% CI 0.062%–0.213%) cohorts showed similar cumulative incidence of schizophrenia (p = 0.33). Multivariate Cox analyses showed that HCV positivity (hazard ratio [HR] 3.469, 95% CI 2.168–5.551) was independently associated with the development of schizophrenia. The HCV-untreated cohort also had the highest cumulative incidence of overall mortality (20.799%, 95% CI 18.739%–22.936%; p < 0.001); the HCV-treated (12.518%, 95% CI 8.707%–17.052%) and HCV uninfected (6.707%, 95% CI 5.533%–8.026%) cohorts showed similar cumulative incidence of mortality (p = 0.12).Limitations:We were unable to determine the precise mechanism of the increased risk of schizophrenia in patients with HCV infection.Conclusion:In a population-based cohort (most aged ≥ 40 years), HCV positivity was a potential risk factor for the development of schizophrenia; the HCV-associated risk of schizophrenia might be reversed by interferon-based antiviral therapy.

Association between hepatitis C virus infection and subsequent chronic inflammatory skin disease.

Hepatitis C virus (HCV) infection is associated with several cutaneous manifestations, including lichen planus and psoriasis. However, its association with other chronic inflammatory skin diseases (CISD) remains largely unknown. The aim of this study was to investigate the association between HCV infection and CISD. Participants were recruited from the National Health Insurance Research Database in Taiwan. Altogether 23509 patients with HCV infection and 94036 matched controls were included to assess the risk of CISD. A Cox regression model was used for the analyses. Compared with controls, patients with HCV infection had an adjusted hazard ratio (aHR) of 6.34 (95% confidence interval [CI], 5.30-7.58) for CISD after adjustment for potential confounders. Regarding individual CISD, patients with HCV infection had a significantly increased risk of developing lichen planus, psoriasis, vitiligo, alopecia areata, and cutaneous lupus erythematosus. Interferon-based antiviral therapy (IFN-based AVT) was significantly associated with a decreased risk of CISD (aHR=0.42; 95% CI, 0.28-0.64). Patients with HCV infection had a significantly increased risk of CISD, while IFN-based AVT was associated with a decreased risk. These findings suggest monitoring of CISD in patients with HCV infection.

Sorafenib use in hepatitis B virus- or hepatitis C virus-related hepatocellular carcinoma: A propensity score matching study.

Sorafenib is the recommended first-line treatment option for patients with advanced hepatocellular carcinoma (HCC). Hepatitis C virus (HCV)-related advanced HCC (HCV-HCC) seemed to have a better response than hepatitis B virus (HBV)-related HCC (HBV-HCC) in sorafenib use, but it was undetermined. Hence, we aimed to investigate the effect of sorafenib between HBV-HCC and HCV-HCC patients in Taiwan. From August 2012 to December 2016, 575 consecutive advanced HCC patients received sorafenib under the reimbursement of Taiwan national health insurance in our hospital. Radiologic assessment was performed at a 2-month interval. Those patients with tumor progression or liver function deterioration were disallowed for further sorafenib use. Patients with HBV or HCV infection were, retrospectively, enrolled and followed till December 2018. There were 277 (62.4%) HBV-HCC patients and 167 (37.6%) HCV-HCC patients. Before sorafenib, 192 (69.3%) HBV-HCC patients who had used nucleoside analogs (NAs) for HBV management, whereas only 5 (3%) HCV-HCC patients received interferon-based antiviral therapy. Overall survival (OS) of HCV-HCC patients was significantly superior to HBV-HCC patients without NAs (8.8months vs. 4.9months, p= 0.006), but was noninferior to HBV-HCC patients with NAs (8.8months vs. 10.7months, p= 0.54). Using propensity score matching, progression-free survival (2.0months vs. 2.1months, p= 0.374) and OS (10.5months vs. 9.6months, p= 0.746) between HBV-HCC and HCV-HCC groups were not different. Antiviral therapy might increase survival benefits of advanced HBV-HCC patients underwent sorafenib use, leading to a comparable OS to HCV-HCC patients in Taiwan.

Metabolic and cardiovascular complications after virological cure in hepatitis C: What awaits beyond.

The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers’ clinical practice.

Managing display of authors if there are too many

In patients with cirrhosis and hepatitis C virus (HCV) it has been hard to define the benefit of sustained virologic response (SVR) on patients survival because of selection bias and other confounding factors in studies. To overcome this, researchers studied 796 patients with HCV-related cirrhosis treated with interferon-based antiviral therapy and compared them with age […]

Screening for Hepatitis C Virus Infection in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance A 2013 review for the US Preventive Services Task Force (USPSTF) of hepatitis C virus (HCV) screening found interferon-based antiviral therapy associated with increased likelihood of sustained virologic response (SVR) and an association between achieving an SVR and improved clinical outcomes. New direct-acting antiviral (DAA) regimens are available. Objective To update the 2013 review on HCV screening to inform the USPSTF. Data Sources Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through February 2019, with surveillance through September 2019. Study Selection Randomized clinical trials (RCTs) and nonrandomized treatment studies of HCV screening and DAA therapy; cohort studies on screening, antiviral therapy, and the association between an SVR after antiviral therapy and clinical outcomes. Data Extraction and Synthesis One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures Mortality, morbidity, quality of life, screening and treatment harms, and screening diagnostic yield. Results Eight RCTs of DAA therapy vs placebo or an outdated antiviral regimen, 48 other treatment studies, and 33 cohort studies, with a total of 179 230 participants, were included. No study evaluated effects of HCV screening vs no screening. One new study since the 2013 review (n = 5917) found similar diagnostic yield of risk-based screening (sensitivity, 82%; number needed to screen to identify 1 HCV case, 15) and birth cohort screening (sensitivity, 76%; number needed to screen, 29), assuming perfect implementation. Ten open-label studies (n = 3292) reported small improvements in some quality-of-life and functional outcomes (eg, less than 3 points on the 0 to 100 36-Item Short Form Health Survey physical and mental component summary scales) after DAA treatment compared with before treatment. Two cohort studies (n = 24 686) found inconsistent associations of antiviral therapy vs no therapy with risk of hepatocellular carcinoma. Forty-nine treatment studies (n = 10 181) found DAA regimens associated with pooled SVR rates greater than 95% across genotypes, and low short-term rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%). An SVR after antiviral therapy was associated with decreased adjusted risk of all-cause mortality (13 studies, n = 36 986; pooled hazard ratio [HR], 0.40 [95% CI, 0.28-0.56) and hepatocellular carcinoma (20 studies, n = 84 491; pooled HR, 0.29 [95% CI, 0.23 to 0.38]) vs no SVR. Conclusions and Relevance Direct evidence on the effects of HCV screening on clinical outcomes remains unavailable, but DAA regimens were associated with SVR rates greater than 95% and few short-term harms relative to older antiviral therapies. An SVR after antiviral therapy was associated with improved clinical outcomes compared with no SVR.

Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis

HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT). We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies. Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1-9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5-5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4-12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69-0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62-7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82-8.59) had higher reinfection rates. HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment. Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population - reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.

Antiviral Therapy in Patients With Chronic Hepatitis C Is Associated With a Reduced Risk of Parkinsonism

The risk of parkinsonism after antiviral treatment against chronic hepatitis C (CHC) is unclear. To investigate the association between CHC and parkinsonism and the efficacy of antiviral therapy. Using the National Health Insurance Research Database of Taiwan from 2004 to 2012, patients with and without CHC, patients receiving pegylated interferon-based antiviral therapy, and those without such therapy were matched by age, gender, and comorbidities by propensity scores and followed for new diagnoses of parkinsonism and Parkinson's disease (PD). Multivariable Cox proportional hazards regression analyses were performed. Overall, 49,342 patients with CHC were matched with 49,342 non-CHC patients. After adjustment for confounding factors, there was a significantly increased risk (31%) of parkinsonism (hazard ratio [HR] 1.306; 95% confidence interval [CI], 1.208-1.412) in those with CHC and the risk of parkinsonism requiring anti-Parkinson medication (HR 1.323; 95% CI, 1.214-1.441). Furthermore, 23,647 untreated CHC patients were matched with 23,647 patients receiving antiviral therapy. Patients receiving antiviral therapy had a significantly lower risk of developing parkinsonism (38%; HR 0.618; 95% CI, 0.498-0.765) and a reduced risk of parkinsonism requiring anti-Parkinson medication (HR 0.651; 95% CI, 0.515-0.823). In sensitivity analyses, antiviral therapy significantly reduced the risk of parkinsonism and PD after adjustment for detection, selection, disease latency biases, and competing mortality. Our results suggest successful antiviral therapy associates with a reduced risk of hepatitis C virus-related parkinsonism compared with those with treatment failure. CHC infection is associated with an increased risk of parkinsonism or PD. Antiviral therapy against CHC is associated with a reduced risk of parkinsonism or PD. © 2019 International Parkinson and Movement Disorder Society.

Association of Antiviral Therapy With Risk of Parkinson Disease in Patients With Chronic Hepatitis C Virus Infection

Epidemiologic evidence suggests that hepatitis C virus (HCV) could be a risk factor for Parkinson disease (PD), but treatment for HCV infection has never been considered in these studies; hence, the association between antiviral therapy and PD incidence has remained unclear. Understanding this association may help in developing strategies to reduce PD occurrence. To identify the risk of PD development in patients with HCV infection receiving antiviral treatment and in patients not receiving this treatment. This cohort study obtained claims data from the Taiwan National Health Insurance Research Database. Adult patients with a new HCV diagnosis with or without hepatitis per International Classification of Diseases, Ninth Revision, Clinical Modification codes and anti-PD medications from January 1, 2003, to December 31, 2013, were selected for inclusion. After excluding participants not eligible for analysis, the remaining patients (n = 188 152) were categorized into treated and untreated groups according to whether they received antiviral therapy. Propensity score matching was performed to balance the covariates across groups for comparison of main outcomes. This study was conducted from July 1, 2017, to December 31, 2017. Development of PD was the main outcome. A Cox proportional hazards regression model was used to compare the risk of PD, and the hazard ratio (HR) was calculated at 1 year, 3 years, and 5 years after the index date and at the end of the cohort. A total of 188 152 patients were included in the analysis. An equal number (n = 39 936) and comparable characteristics of participants were retained in the treated group (with 17 970 female [45.0%] and a mean [SD] age of 52.8 [11.4] years) and untreated group (with 17 725 female [44.4%] and a mean [SD] age of 52.5 [12.9] years) after matching. The incidence density of PD was 1.00 (95% CI, 0.85-1.15) in the treated group and 1.39 (95% CI, 1.21-1.57) per 1000 person-years in the untreated group. The advantage of antiviral therapy reached statistical significance at the 5-year follow-up (HR, 0.75; 95% CI, 0.59-0.96), and this advantage continued to increase until the end of follow-up (HR, 0.71; 95% CI, 0.58-0.87). Evidence suggested that the PD incidence was lower in patients with chronic HCV infection who received interferon-based antiviral therapy; this finding may support the hypothesis that HCV could be a risk factor for PD.

Eltrombopag enables initiation and completion of pegylated interferon/ribavirin therapy in Japanese HCV-infected patients with chronic liver disease and thrombocytopenia.

To investigate the efficacy of eltrombopag for the treatment of thrombocytopenia in patients with chronic hepatitis C, a phase II, single-arm, open-label study with a 9-week pre-antiviral phase was conducted, followed by a 48-week antiviral phase and a 24-week follow-up phase. The proportion of patients who achieved a platelet count threshold, the proportion of patients who maintained a platelet count >50,000/µl, sustained virological response (SVR) rates and safety parameters were evaluated. Of the 45 enrolled patients (median age, 59 years; median platelet count, 63,000/µl; 98% with Child-Pugh class A), 43 (96%) achieved the platelet count threshold during the pre-antiviral phase. A total of 13 patients (29%) experienced ≥1 adverse event (AE), of which headache and vomiting were the most common, and 41 patients (mostly receiving eltrombopag 12.5 mg or 25 mg) entered the antiviral phase, of which 36 (88%) maintained the platelet count threshold; no patient platelet count decreased below 25,000/µl. Nine patients (22%) achieved an SVR at the 24-week follow-up. Grade ≥3 AEs occurred in 25 patients (61%). A total of 8 serious AEs occurred in five patients (12%). No mortality, thromboembolic events (TEEs), or cataract progression were reported. Eltrombopag increased the platelet count in chronic hepatitis C virus-infected patients with cirrhosis and thrombocytopenia and enabled them to initiate and complete interferon-based antiviral therapy (NCT01636778; first submitted: July 05, 2012).

Impact of direct-acting antivirals on early recurrence of HCV-related HCC: Comparison with interferon-based therapy

It remains controversial whether direct-acting antivirals (DAAs) accelerate the recurrence of hepatitis C-related hepatocellular carcinoma (HCC) after curative therapy. This study aimed to evaluate HCC recurrence after DAA treatment of chronic hepatitis C. We enrolled patients with a history of successful radiofrequency ablation treatment for hepatitis C-related HCC who received antiviral therapy with DAAs (DAA group: 147 patients) or with interferon (IFN)-based therapy (IFN group: 156 patients). We assessed HCC recurrence rates from the initiation of antiviral therapy using the Kaplan-Meier method and evaluated risk factors for HCC recurrence by multivariate Cox proportional hazard regression analysis. The recurrence pattern was categorized as follows: intrahepatic recurrence with a single tumor <2 cm (stage 0), a single tumor or up to 3 tumors ≤3 cm (stage A), multinodular (stage B), and extrahepatic metastasis or macrovascular invasion (stage C). The recurrence rates at 1 and 2 years were 39% and 61% in the IFN group and 39% and 60% in the DAA group, respectively (p = 0.43). Multivariate analysis identified higher lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, a history of multiple HCC treatments, and a shorter interval between HCC treatment and initiation of antiviral therapy as independent risk factors for HCC recurrence. HCC recurrence in stage 0, A, B, and C was found in 56 (41%), 60 (44%), 19 (14%), and 1 (0.7%) patients in the IFN group and 35 (44%), 32 (40%), 11 (14%), and 2 (2.5%) patients in the DAA group, respectively (p = 0.70). HCC recurrence rates and patterns after initiation of antiviral therapy did not differ between patients who received IFN-based therapy and DAA therapy. We detected no significant difference in early hepatocellular carcinoma (HCC) recurrence rates and patterns between patients who received interferon-based and direct-acting antiviral therapy after HCC treatment. High lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, short recurrence-free period, and a history of multiple HCC treatments were independent risk factors for early HCC recurrence after the initiation of antiviral therapy.

Characterization of Hepatitis C Virus IRES Quasispecies - From the Individual to the Pool.

Hepatitis C virus (HCV) is a single-stranded positive-sense RNA virus from the genus Hepacivirus. The viral genomic +RNA is 9.6 kb long and contains highly structured 5′ and 3′ untranslated regions (UTRs) and codes for a single large polyprotein, which is co- and post-translationally processed by viral and cellular proteases into at least 11 different polypeptides. Most of the 5′ UTR and an initial part of the polyprotein gene are occupied by an internal ribosome entry site (IRES), which mediates cap-independent translation of the viral proteins and allows the virus to overcome cellular antiviral defense based on the overall reduction of the cap-dependent translation initiation. We reconsidered published results concerning a search for possible correlation between patient response to interferon-based antiviral therapy and accumulation of nucleotide changes within the HCV IRES. However, we were unable to identify any such correlation. Rather than searching for individual mutations, we suggest to focus on determination of individual and collective activities of the HCV IRESs found in patient specimens. We developed a combined, fast, and undemanding approach based on high-throughput cloning of the HCV IRES species to a bicistronic plasmid followed by determination of the HCV IRES activity by flow cytometry. This approach can be adjusted for measurement of the individual HCV IRES activity and for estimation of the aggregate ability of the whole HCV population present in the specimen to synthesize viral proteins. To detect nucleotide variations in the individual IRESs, we used denaturing gradient gel electrophoresis (DGGE) analysis that greatly improved identification and classification of HCV IRES variants in the sample. We suggest that determination of the collective activity of the majority of HCV IRES variants present in one patient specimen in a given time represents possible functional relations among variant sequences within the complex population of viral quasispecies better than bare information about their nucleotide sequences. A similar approach might be used for monitoring of sequence variations in quasispecies populations of other RNA viruses in all cases when changes in primary sequence represent changes in measurable and easily quantifiable phenotypes.

Immunosuppressive and antiviral treatment of hepatitis C virus-associated glomerular disease: A long-term follow-up.

The evidence in the medical literature on the treatment of hepatitis C virus-associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety. We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus-associated glomerular disease. In the first phase of the study, patients with hepatitis C virus-associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively). We enrolled 25 consecutive patients with hepatitis C virus-associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after treatment ended, sustained viral response12). The mean (±standard deviation) proteinuria decreased from 2.61 ± 1.01 at baseline to 1.71 ± 1.43 (g/day) at sustained viral response 48, p = 0.031; microscopic hematuria and serum cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively, after sustained viral response by direct-acting antivirals. Adverse events occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin-related anemia requiring blood transfusions (no drop-outs). After sustained viral response by direct-acting antivirals, immunosuppressive and immunomodulatory agents were initiated in clinical relapsers ( n = 2) and nonresponders ( n = 3) with some benefit. Among patients on interferon-based regimens ( n = 12), viral response (sustained viral response 24) and dropout rates were 58% (7/12) and 33% (4/12), respectively. After sustained viral response by interferon-based therapy, clinical relapsers ( n = 3) were successfully managed with immunosuppressive agents in two patients. Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus-related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.

The prevalence of occult hepatitis B in chronic hepatitis C patients treated with interferon-based antiviral therapy

Background and study aimsOccult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders. Patients and MethodsThis retrospective cross-sectional study was conducted in CHC patients who had previously received IFN-based antiviral therapy. Serum samples of 100 HBsAg negative CHC patients were tested for HBV DNA, anti-HBc IgG, anti-HBs, ALT and AST. The presence of OBI was compared between 50 IFN responders and 50 IFN non-responders. Patients with a history of previous HBV infection, patients with evidence of cirrhosis and patients who had received IFN therapy within the last one year were excluded from the study. ResultsAnti-HBc IgG positivity was determined in 53% of the patients. HBV DNA positivity, indicating OBI was determined in 1 (1%) patient. This patient was anti-HBc IgG positive, anti-HBs negative, ALT and AST levels were normal. The HBV DNA and anti-HBc IgG positivity rates were higher in the non-responder group than in the responder group, but the difference was not statistically significant (p = 0.31 and p = 0.07 respectively). ConclusionAccording to the results of this study, the prevalence of OBI is lower than expected amongst CHC patients in Turkey and it may not be necessary to apply routine screening to IFN non-responders for OBI infection before DAA therapy. However, there is a need for multicentre studies with larger patient series.

Expert opinion on managing chronic HCV infection in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) has been identified as an extrahepatic manifestation of chronic HCV infection. Conversely, in the context of chronic HCV infection, T2DM can accelerate the course of HCV-induced liver disease leading to increased risk of fibrosis, cirrhosis and hepatocellular carcinoma. The presence of T2DM negatively impacts the efficacy of interferon-based antiviral therapy, but real-world data with high-efficacy direct-acting antiviral therapies suggest high viral clearance rates in T2DM patients. In HCV-infected individuals, viral eradication is associated with a reduced risk of de novo T2DM in non-diabetic patients and beneficial metabolic changes in patients with T2DM, highlighting the importance of antiviral treatment and physician awareness of this association.

Hepatocellular Carcinoma Occurrence and Recurrence after Antiviral Treatment in HCV-Related Cirrhosis. Are Outcomes Different after Direct Antiviral Agents? A Review.

Hepatitis C virus (HCV) infection is one of the major causes of hepatocellular carcinoma (HCC) worldwide. In the last decades, several studies have showed a lower rate of HCC occurrence or recurrence in patients with HCV-related cirrhosis after interferon-based antiviral therapies compared to untreated controls, even without reaching viral clearance. Unfortunately, interferon regimens could only yield viral clearance in approximately half of the patients. The recent development of new all-oral regimens with direct-acting antivirals (DAAs) has radically improved the cure rate to above 90%. In respect to these findings, many would have thought that interferon-free regimens would decrease the development and recurrence of HCC. Literature data have unexpectedly reported high rates of both the occurrence and recurrence of HCC after therapy with DAAs. However, it is probably too early to express some concerns. More recent data showed that both occurrence and recurrence of HCC are decreased by the DAAs. Interferon-free therapy is definitely not without limits. Together with the initial thoughts of an increased risk of HCC, these may lead to an unwanted restricted access to interferon-free regimens in specific subpopulations. This issue should be settled as soon as possible because millions of hepatitis C patients are and will be using DAAs in the present and future. Our purpose is to review the existing literature and to offer a more precise and rational interpretation of the existing data.

Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

Background/AimsLong-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.MethodsCHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment.Results131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54–62) years with median estimated duration of infection 33-years (IQR 29–38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12–17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p = 0.0001). SVR was independently associated with protection from liver fibrosis progression after adjustment for other variables including baseline ALT (p = 0.011), duration of HCV infection and mode of acquisition.ConclusionHCV eradication is associated with lower rates of liver fibrosis progression. The data support early treatment to prevent long-term liver complications of HCV infection.

Hepatocellular Carcinoma after Achievement of Sustained Viral Response with Daclatasvir and Asunaprevir in Patients with Chronic Hepatitis C Virus Infection

Background: Interferon-based antiviral therapies against hepatitis C virus (HCV) infection have been shown to reduce the incidence of hepatocellular carcinoma (HCC) in patients with sustained viral response (SVR). Recently, direct-acting antivirals (DAAs) have been proven to be much more effective in achieving SVR than interferon-based therapies. However, whether DAAs can efficiently prevent the occurrence of HCC after SVR remains controversial. To clarify this issue, we analyzed the clinical features of patients in whom HCC developed after achievement of SVR with DAAs for chronic HCV infection. Summary: Among patients who achieved SVR with daclatasvir and asunaprevir (n = 100), HCC developed in 17 patients (HCC group; n = 17) and did not develop in 83 patients (non-HCC group; n = 83) during a mean observation period of 15 months. A multivariate Cox proportional hazards analysis identified past history of HCC and male sex as significant risk factors for the emergence of HCC after DAAs. Sixteen cases with HCC after DAAs were in the very early or early stage (16/17, 94.1%), and one case was in the advanced stage (1/17, 5.9%) with portal venous tumor thrombus. Radiofrequency ablation and/or transarterial chemoembolization were performed in most cases as curative therapy (16/17, 94.1%). Key Messages: SVR by DAAs did not completely prevent the occurrence of HCC. However, even if HCC did develop after SVR, curative anticancer therapy was applicable in most cases.

The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection

Background and aimChronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited.MethodsWe conducted a...