Sustained Virological Response Group Research Articles

Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection who had received direct-acting antiviral therapy.

The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied. We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated. Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group). The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

Treatment of HCV with direct-acting antivirals on reducing mortality related to extrahepatic manifestations: a large population-based study in British Columbia, Canada

HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality. The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders. Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2-32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9-30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1-8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18-0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78-84%). Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health. This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Comparison of postoperative outcomes in cases achieving sustained virological response with direct-acting antiviral and interferon therapy.

The effect of direct-acting antiviral agents (DAAs) on hepatocellular carcinoma (HCC) recurrence after curative hepatectomy remains uncertain. This retrospective study aimed to evaluate the effect of sustained virological response (SVR) with DAAs or interferon (IFN) therapy on recurrence and overall survival (OS) after hepatectomy. We enrolled 593 patients who underwent curative resections between January 2010 and December 2017. Among them, 186 achieved SVR before hepatectomy: a total of 51 (27.4%) in the DAA-SVR group and 132 (72.6%) in the IFN-based SVR group. SVR before hepatectomy was an independent predictor of OS, and the 5-year OS rate was significantly higher in the SVR group than that in the non-SVR group (82.2% vs. 63.9%). There were no significant differences in the recurrence rates or OS between DAA and IFN treatments in achieving SVR before hepatectomy, regardless of poor hepatic function in the DAA therapy group. There was no significant difference in OS and recurrence-free survival (RFS) between the preoperative SVR achieved with DAA and IFN groups in this study, although liver function was significantly worse at the time of surgery in the DAA group compared to the IFN group.

Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: a retrospective cohort study.

Low-level viremia (LLV), a special case of poor response to antiviral therapy, has become a focus of liver disease research; however, most studies have focused on poor response to antiviral therapy, and little attention has been paid to LLV. Therefore, this study aimed to investigate the factors influencing LLV in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) monotherapy. Clinical data of CHB patients receiving ETV treatment for at least 1year at the outpatient department of the Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were collected. Patients were divided into LLV (180 cases) and sustained virological response (SVR) groups (337 cases) according to the hepatitis B virus (HBV) DNA load at the end of the observation period. Demographic features and laboratory markers were also examined. Univariate and multivariate logistic regression analyses were performed to examine factors influencing LLV in patients receiving long-term ETV monotherapy. Significant differences were noted between the LLV and SVR groups in terms of age, sex, presence or absence of cirrhosis, HBeAg positivity rate, baseline HBV DNA load, and baseline HBsAg level before treatment. Multivariate logistic regression analysis showed that baseline HBeAg status, HBV DNA load, and HBsAg quantification were pretreatment risk factors for LLV in long-term ETV antiviral therapy. CHB patients with a high HBV DNA load, high HBsAg quantification, and positive HBeAg results tend to have a high risk of LLV despite long-term ETV antiviral treatment and should be dynamically monitored.

Expression Profiling of the Tripartite Motif Family Genes in Chronic Hepatitis C Patients.

Hepatitis C virus (HCV) is one of the most prevalent pathogens which causes significant morbidity and mortality in 2% of the world's population. Several interferon-stimulated genes (ISGs) are involved in HCV clearance by interacting with the viral proteins. Among these ISGs, the tripartite motif (TRIM) family genes are elevated during HCV infection. This study aims to evaluate the expression of three TRIM family genes in chronic hepatitis C patients, distributed among different groups, including TRIM11, TRIM14, and TRIM25. A total of 242 participants were recruited in this study, including 182 infected patients, 37 naïve individuals, and 23 control individuals. Out of 182 infected patients, 100 achieved sustained virologic response (SVR), 61 achieved rapid virologic response (RVR), and 21 patients developed hepatocellular carcinoma (HCC), showing no response to the given treatments. Our results indicate highest expression levels of TRIM mRNA transcripts in the RVR group with the highest increase of 7.5 folds in TRIM25, 6.68 folds in TRIM14, followed by the data from patients of the SVR group. The elevation was also evident in other groups, i.e., SVR and HCC, in different patterns among all the three TRIM genes. In addition to elevation in expression levels, a linear correlation is observed between the TRIM mRNAs and viral loads of HCV. These results showed the potential role of TRIM family genes in HCV restriction.

Transcriptional Analysis of TP53 Gene in Chronic Hepatitis C Patients Treated with Sofosbuvir, Daclatasvir, Pegylated Interferon, and Ribavirin.

Hepatitis C virus (HCV) is a major public health problem that affects more than 170 million people globally. HCV is a principal cause of hepatocellular carcinoma (HCC) around the globe due to the high frequency of hepatitis C infection, and the high rate of HCC is seen in patients with HCV cirrhosis. TP53 is considered as a frequently altered gene in all cancer types, and it carries an interferon response element in its promoter region. In addition to that, the TP53 gene also interacts with different HCV proteins. HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene that lower the expression of this gene in HCV patients and leads to HCC development. In this study, we examined the transcriptional analysis of the TP53 gene in HCV-infected patients administered with different combinations of antiviral therapies including sofosbuvir + daclatasvir, sofosbuvir + ribavirin, and pegylated interferon + ribavirin. This study included 107 subjects; 15 treated with sofosbuvir + daclatasvir, 58 treated with sofosbuvir + ribavirin, 11 treated with interferon + ribavirin, 8 untreated, 10 HCC patients, and 5 were healthy controls. Total RNA was extracted from the PMBCs of HCV infected patients and reverse transcribed into cDNA using a gene specific reverse primer. The expression level of TP53 mRNA was analyzed using quantitative PCR. The expression of TP53 mRNA was notably upregulated in rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) groups as compared to non-responders and naïve groups. The expression of TP53 mRNA was seen high in HCC as compared to control groups. Additionally, it has been demonstrated that sofosbuvir + daclatasvir treatment stimulates significant elevation in TP53 gene expression as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. This study indicates that the TP53 gene expression is highly upregulated in RVR, EVR, and SVR groups as compared to control groups. Moreover, sofosbuvir + daclatasvir therapy induces significant rise in TP53 mRNA expression levels as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. According to these results, it can be concluded that sofosbuvir + daclatasvir plays a significant role in preventing HCV patients from developing severe liver complications as compared to other administered therapies. This study is novel as no such type of study has been conducted previously on the expression of TP53 in local HCV-infected population treated with different combinations of therapies. This study is helpful for the development of new therapeutic strategies and for improving existing therapies.

Direct-Acting Antivirals Reduce the De Novo Development of Esophageal Varices in Patients with Hepatitis C Virus Related Liver Cirrhosis.

The real-world benefits of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) remain unclear in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). This is a retrospective cohort study evaluating all patients with Child-Pugh class A HCV-related LC during 2013 to 2020 in the Chang Gung Medical System. A total of 215 patients fit the inclusion criteria and were enrolled. Of them, 132 (61.4%) patients achieved DAA induced-SVR and 83 (38.6%) did not receive anti-viral treatment. During a median follow-up of 18.4 (interquartile range, 10.1-30.9) months, the 2-year incidence of de novo EV occurrence was 8 (7.0%) in the SVR group and 7 (12.7%) in the treatment-naïve group. Compared to the treatment-naïve group, the SVR group was associated with a significantly lower incidence of EV occurrence (adjusted hazard ratio [aHR]: 0.47, p = 0.030) and a significantly lower incidence of EV progression (aHR: 0.55, p = 0.033). The risk of EV progression was strongly correlated with the presence of baseline EV (p &lt; 0.001). To the best of our knowledge, this is the first study to demonstrate that DAA-induced SVR is associated with decreased risk of de novo EV occurrence and progression in the real world.

HCV Core-antigen Assay as an Effective Alternative to HCV RNA Quantification in Patients With Hepatitis C.

Hepatitis C virus (HCV) core antigen (Ag) test has been increasingly applied as an effective alternative to conventional molecular tests allowing rapid and affordable diagnosis, which is of paramount relevance to achieve global elimination of HCV infection. ARCHITECT® HCV Ag test was evaluated in comparison with HCV RNA quantification test (CAP/CTM) to calculate its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and to determine their correlation level. Its performance, according to low and high viral load values and in different treatment stages [during treatment (T), at the end of the therapeutic protocol (EOT) and when sustained virological response (SVR) was evaluated]. In total, 145 samples were included. Considering CAP/CTM, the sensitivity, specificity, PPV and NPV of the HCV-Ag test were 88.9%, 99.1%, 97.0% and 96.4%, respectively, and the correlation among tests was high (r=0.890), with only five discordant results. A decrease in sensitivity was found for low viral load values (<1,000 IU/ml), but the opposite was verified for high viral concentrations (≥1,000 IU/ml). A good agreement was verified for the T and EOT groups (k=0.789 and k=0.638) and an excellent agreement in the SVR group (k=1.000). HCV-Ag seems to be an effective alternative that can be routinely combined with other faster and more accessible tests (e.g., HCV antibody tests) for the identification of new HCV infections in suspected patients, eventually reserving the molecular techniques for samples with discordant results.

Persistent epigenetic alterations in transcription factors after a sustained virological response in hepatocellular carcinoma.

The risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis. Whole-genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort. The coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non-tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes. This study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence.

Direct-Acting Antiviral Therapy for Hepatitis C Virus in Patients with BCLC Stage B/C Hepatocellular Carcinoma.

The benefits of hepatitis C virus (HCV)eradication for hepatocellular carcinoma (HCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B/C remain uncertain. In this hospital-based cohort study, all HCV-infected patients with BCLC stage B/C HCC during the period January 2017 to March 2021 were retrospectively screened, with 97 patients who had completed direct-acting antiviral (DAA) therapy being enrolled for final analysis. In total, the sustained virological response (SVR) rate was 90.7%. In logistic regression analysis, progressive disease (PD) to prior tumor treatments was significantly associated with SVR failure (odds ratio 5.59, 95% CI 1.30-24.06, p = 0.021). Furthermore, the overall survival (OS) rate was significantly higher in the SVR group than that in the non-SVR group (1-year OS: 87.5% vs. 57.1%, p = 0.001). SVR was found to be an independent factor related to OS (hazard ratio 8.42, 95% CI 2.93-24.19, p = 0.001). However, even upon achieving SVR, the OS rates in BCLC stage C or Child-Pugh stage B patients remained poor. In BCLC stage B/C HCC, DAA could achieve a high SVR rate except in those patients with PD to prior HCC treatments. SVR was related to improvements in OS; therefore, DAA therapy should be encouraged for patients diagnosed without a short life expectancy.

Hepatocellular carcinoma incidence in chronic hepatitis C patients according to sustained virological response (SVR) with interferon‐based therapies and baseline characteristics

AbstractIntroductionHepatocellular carcinoma (HCC) is the second most common cause of cancer‐related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC‐associated HCC in the next decades.AimTo assess the HCC incidence in relation to interferon (IFN)‐based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.MethodsWe retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH‐University Hospital of Vienna before the introduction of direct‐acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.ResultsOur study included 2134 patients, who were treated or not treated with IFN‐based antiviral treatment and had long‐term follow‐up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow‐up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0‐2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non‐SVR and no‐treatment group as compared with SVR patients: 12.4% vs 1.9%, P &lt; .0001, 7.3% vs 1.9%, P &lt; .0001. In multivariate analysis, lower platelet count (odds ratio‐OR = ‐0.1, 95% CI: 0.15‐0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59‐8.17), ALBI grade &gt;=2 (OR = 2.3, 95% CI: 1.0‐5.3) for the non‐SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha‐fetoprotein values (OR = 10.2, 95% CI: 2.2‐47.9).ConclusionThe achievement of SVR significantly reduces the risk for HCC occurrence during long‐term follow‐up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more advanced liver disease. These risk factors should be considered in decision‐making of HCC surveillance in this settling.

Determination of Risk Factors Associated with the Failure of 12 Weeks of Direct-Acting Antiviral Therapy in Patients with Hepatitis C: A Prospective Study.

Introduction Direct-acting antivirals (DAAs) have significantly improved the efficacy and tolerability of the treatment of hepatitis C virus (HCV). However, studies conducted on actual patients with the aim of predicting the risk associated with treatment failure are lacking. Methods Our study enrolled 334 new HCV patients and assessed the effectiveness of treatment and predicted the risk of failure to achieve sustained virological response (SVR) by developing a multiple logistic model. Our study compared the variables between the two groups, those who did (group 0, n = 239) and did not achieve SVR (group 1, n = 95). Results The cure rate of HCV at 12th week in our study was 71.56%. We found that advanced cirrhosis, HCV genotype, HBV coinfection, rapid virological response (RVR), fibrosis index (FIB-4) score, serum levels of AST, ALP, hemoglobin, and viral load before treatment were prognostic factors associated with rate of failure to achieve SVR at week 12 of DAA therapy. In the multiple logistic model, eight significant predictors including advanced cirrhosis status, HCV genotype, RVR, AST/ALP levels, FIB-4 score, and viral load before treatment predicted the risk of failure with excellent model performance (area under the receiver operating characteristic curve (AUCROC) [95% CI] =0.986 (0.971-0.999)). RVR and advanced cirrhosis were the two strongest predictors with odd ratios (95% CI) =9.72 (2.8, 39.28) and 51.54 (6.39, 139.82), respectively. Conclusion The multiple logistic regression model included significant factors to estimate the probability of failure to achieve SVR, which could improve HCV treatment strategy.

Low Incidence of Hepatocellular Carcinoma after Antiviral Therapy in Patients with Chronic Hepatitis C and Hemophilia.

Background: Hepatocellular carcinoma (HCC) rarely develops in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). We assessed the incidence of HCC in CHC patients with hemophilia after treatment with pegylated interferon plus ribavirin (PegIFN/RBV) and direct-acting antivirals (DAAs). Methods: Patients (n = 202) were enrolled between March 2007 and July 2019. A total of 139 patients were treated with PegIFN/RBV (genotype 1, n = 98; genotype 2, n = 41). Sixty-three patients were treated with DAAs (genotype 1, n = 44; genotype 2, n = 19). The cumulative incidence rates of HCC were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: For genotype 1, SVR was achieved in 78.6% (77/98) and 90.9% (40/44) of patients in the PegIFN/RBV and DAAs groups, respectively. For genotype 2, SVR was achieved in 95.1% (39/41) and 94.7% (18/19) of patients in the PegIFN/RBV and DAAs groups, respectively. Six HCC cases were identified. The cumulative incidence of HCC was 4.1% at 14 years in PegIFN/RBV and 1.7% at 5 years in DAAs. The 14-year cumulative incidence of HCC was 1.9% in the SVR group and 21.7% in the no-SVR group in the PegIFN/RBV group (p < 0.001). Conclusions: Treatment with PegIFN/RBV led to stable SVR and a low incidence of HCC. Although the follow-up period was short, DAAs led to more stable SVR than PegIFN/RBV and a low incidence of HCC in CHC patients with hemophilia.

Hepatitis C virus eradication prolongs overall survival in hepatocellular carcinoma patients receiving molecular-targeted agents.

The aim of this multicenter retrospective study was to evaluate the impact of the eradication of hepatitis C virus (HCV) on the clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with molecular-targeted agents (MTAs). Among 877 patients who received any MTA as first-line systemic therapy for HCC between June 2009 and March 2019, 569 patients with HCV-related HCC were enrolled in this retrospective study. Of these, 109 patients achieved sustained virological response (SVR) before starting MTA. After propensity score matching, the clinical outcomes of 109 patients in the SVR group and 109 patients in the non-SVR group were compared. The median time to progression in the SVR group (7.8months) was similar to that in the non-SVR group (5.6months) (p = 0.212). The median time to treatment failure in the SVR group (5.3months) was longer than that in the non-SVR group (2.8months) (p = 0.059), and post-progression survival and overall survival in the SVR group were significantly longer than those in the non-SVR group (12.0months vs 7.2months; p = 0.039, and 18.1months vs 11.3months; p = 0.019). At the end of first-line MTA therapy, the albumin-bilirubin (ALBI) score in the SVR group ( - 2.25) was significantly lower than that in the non-SVR group ( - 2.10) (p = 0.008). The eradication of HCV before MTA therapy maintained liver function and led to a prolonged treatment period and improved overall survival of HCV-related HCC patients. We should not overlook the benefits of HCV eradication in HCC patients.

Mac-2-Binding Protein Glycosylation Isomer as a Novel Predictor of Hepatocellular Carcinoma Recurrence in Patients with Hepatitis C Virus Eradication

Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) can recur even after achievement of a sustained virologic response (SVR). Mac-2-binding protein glycosylation isomer (M2BPGi) is a newly identified biomarker correlated with liver fibrosis. This study aimed to clarify outcomes for patients with an SVR and to assess the prognostic value of M2BPGi. This single-center retrospective study analyzed patients who underwent surgical resection for primary HCV-related HCC between 2008 and 2018. The study enrolled 81 patients whose M2BPGi could be evaluated after an SVR. The relationship between liver fibrosis-related factors and scores (including M2BPGi) and HCC recurrence, was evaluated. Of the 81 patients, 57 (70.4%) with HCV-related HCC obtained an SVR, whereas 24 patients (29.6%) did not. The patients with an SVR had a significantly more favorable recurrence-free survival (RFS) than the patients with no SVR (P < 0.0001, log-rank). Among the SVR groups, M2BPGi predicted a shorter RFS after hepatic resection with a higher degree of accuracy than other markers and scores in the SVR group. The high-M2BPGi group had worse liver function, RFS, and overall survival (OS) (P = 0.0014 and 0.0006,log-rank, respectively). In the multivariate analysis, high M2BPGi was significantly associated with worse RFS and OS. Even after achievement of an SVR, the risk of HCC recurrence cannot be eliminated. Measurement of M2BPGi after an SVR can be applied for risk stratification in the assessment of patients with HCV-related HCC.

From the Editor’s desk…

From the Editor’s desk…

Effect of direct-acting antiviral drugs for hepatitis C virus on hepatic fibrosis and glycemic control in type 2 diabetes mellitus

General background Hepatitis C virus (HCV) is a major cause of chronic liver disease, resulting in end-stage liver disease and hepatocellular carcinoma. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia. Not only does HCV increases type 2 diabetes mellitus (T2DM) risk but it also worsens its control and is associated with increased prevalence of diabetes complications. There is interacting relationship between HCV, T2DM, and the degree and severity of liver fibrosis (FIB) and that T2DM is potentially preventable or controllable by curing HCV infection. Our study aimed to evaluate the effect of eradication of HCV by direct-acting antivirals on the glycemic control, indicated by glycated hemoglobin, and liver FIB, indicated by FIB-4 score. Patients and methods We enrolled in our study 200 patients with chronic hepatitis C (with compensated liver function) and T2DM, who were treated with direct-acting antiviral drugs for 12 weeks, and we followed up their fasting blood sugar, glycated hemoglobin %, and FIB-4 score at the beginning of treatment, at the end of treatment, and then after 3 months. Results Overall, 95% of the patients achieved sustained virological response (SVR) and 5% did not (NSVR). Moreover, 80% from SVR achieved improved glycemic control versus only 10% in NSVR. On the contrary, 80.5% of SVR exhibited decrease (improvement) in FIB-4 score versus 70% in NSVR, but the reduction of FIB-4 was more significant in SVR group. Moreover, there was a statistically significant relationship between improved glycemic control and improvement of FIB-4 score. Conclusion Eradication of HCV was significantly associated with improvement of glycemic control and FIB-4 score. Improvement of glycemic control occurred along with improvement of FIB-4 score after eradication of HCV.

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study

We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, Canada. We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality. Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 [96%], no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3-3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths= 552), 86.5/1,000 PY among the no-SVR group (deaths= 96), and 99.2/1,000 PY among the untreated group (deaths= 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality. DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs. We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.