Effect Of Sustained Virological Response Research Articles

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.

Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.

Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores. Methods: We included consecutive CHC patients treated with DAA and followed up with them for three years. Outcomes were changes from baseline (before DAA) in ASCVD and FIB-4 scores, measured at the end of treatment, 12-, 24-, and 36-months follow-up. Results: In total, 91 patients with CHC were finally included (median age: 66 years (IQR = 58–72 years); 43% females). Median follow-up was 2 years (1–3 years) and all patients reached SVR. The ASCVD score did not significantly change from baseline (Mean = 17.2%, 95% CI 14.1, 20.3), but the FIB-4 score significantly decreased at any time-point by an average of 0.8 (95% CI 0.78, 0.82, p < 0.001). Elevated FIB-4 scores at one (β = 1.16, p < 0.001) and three years (β = 2.52, p < 0.001) were associated with an increased ASCVD score. Clinically, two participants- with non-decreasing FIB-4 scores after treatment- had acute coronary syndrome at the end of treatment and one year follow-up, respectively. Conclusions: In our study, we found that FIB-4 and ASCVD scores exhibited a positive correlation irrespective of time-point after treatment. Larger studies are essential to further investigate the utility of FIB-4 scores in cardiovascular risk assessment.

Effect of sustained virological response after direct-acting antivirals on liver fibrosis in patients with chronic HCV infection

BackgroundDirect-acting antivirals (DAAs) have revolutionized the therapy of HCV infection with higher sustained virological response (SVR) rates. Fibrosis regression after achieving SVR to DAA remains to be evaluated in chronic hepatitis C patients. One of the main inquiries here is what occurs with liver fibrosis after achieving a SVR, albeit the current DAA was not intended to be antifibrotic. Liver biopsy was replaced by various non-invasive methods, like FIB4 score and fibroscan. The aim of the study was to evaluate the impact of SVR following DAAs on liver fibrosis in chronic HCV patients.ResultsFive hundred of 1170 F4 treated patients (42.7%) improved and became 190 F3, 90 F2, and 220 F1. Also, 40 of 60 F3 patients improved and became 10 F2 and 30 F1. Also, 350 of 1230 treated patients (28.4%) transited from significant fibrosis (≥F3) to non-significant fibrosis (≤F2). There was a significant improvement of FIB-4 (p<0.001) in the improved group after DAAs were proved by liver stiffness measurement.ConclusionTreatment of chronic HCV with DAAs is associated with regression of liver fibrosis as about 28% of patients improved from significant fibrosis (≥F3) to non-significant fibrosis (≤F2) after treatment.

Effect of different direct-acting antiviral regimens for treatment of nondiabetic hepatitis C virus\u2013infected Egyptian patients on insulin resistance and sensitivity

BackgroundThe association between hepatitis C virus (HCV), insulin resistance (IR), and metabolic syndrome has been extensively investigated. Direct-acting antivirals (DAAs) have a high sustained virologic response (SVR) rate, reaching > 90%. The effect of SVR after DAA treatment on metabolic parameters and IR in nondiabetic patients could be an important factor in the patient’s long-term outcome. The aim of the study is to evaluate the impact of different DAA regimens on IR and sensitivity in naïve chronic HCV-infected nondiabetic patients (before and after 12 weeks of treatment).MethodsThis prospective cohort study was conducted on 100 HCV-infected Child A nondiabetic patients eligible for DAA treatment in the Department of Gastroenterology and Hepatology, Ain Shams University, and Kobry El-Kobba Military Hospital among patients attending the outpatient clinic.Patients were categorized into four groups according to the HCV regimens they received for 12 weeks.All patient were subjected to the following tests before and 12 weeks after treatment: HCV quantitative PCR, Fibroscan, fasting insulin level (using insulin quantitative test kit), fasting and postprandial blood glucose (PPG), lipid profile, liver enzymes, BMI, and waist circumference.ResultsAll patients achieved SVR at 12 weeks. In all treatment groups, lab was assessed before and after treatment, the 2-h PPG, high-density lipoprotein, and low-density lipoprotein levels showed statistically significant increases, whereas triglyceride, fasting glucose, hemoglobin A1C, and fasting plasma insulin levels showed statistically significant decreases. The homeostasis model assessment of insulin resistance (HOMA-IR) exhibited statistically significant decreases, whereas the quantitative insulin sensitivity check index (QUICKI) and Matsuda index showed statistically significant increases, across the four groups.ConclusionsDAA treatment in naïve nondiabetic HCV-infected patients affects metabolic profile and insulin resistance/sensitivity, with similar effect among different DAA regimens.

Effect of Sustained Virological Response with Direct Acting Antiviral Agents on Insulin Resistance in Patients with Chronic HCV Infection

Abstract Background Infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. Liver disease is not the only problem caused by chronic HCV infection; many extra-hepatic complications such as insulin resistance (IR) can be associated with HCV infection as well. Objective To assess the effect of sustained virological response on insulin resistance in patients with chronic hepatitis C infection. Patients and methods This study was conducted in New Cairo Viral Hepatitis Treatment Center (NCVHTC), in the period between December 2017 and December 2018. The current study was conducted on 46 enrolled HCV patients with type 2 Diabetes Mellitus (T2DM). Fasting Insulin (FI) and fasting blood glucose (FBG) as well as lipid profile were assessed in all patients at three time points; before treatment, at the end of treatment (EOT) and 12 weeks after the EOT. Results Despite using 4 different DAA regimens, all patients achieved SVR regardless of the regimen used. As a measurement of IR, HOMA-IR was calculated at the three time points using FI &amp; FBG, it was found that HOMA-IR decreased significantly at the EOT; however, when calculated at week 12 after EOT, the reduction of HOMA-IR was not significant compared to the baseline levels. on the other hand, total cholesterol &amp; LDL increased at the EOT and continued to increase at 12 weeks after the EOT. Conclusion Improvements in IR and glycemic control were not statistically significant after achieving sustained virologic response (SVR) with DAAs in patients with chronic HCV infection. Changes in the lipid profile such as an increase in the levels of total cholesterol and LDL can be expected after treatment with DAAs.

The effect of hepatitis C virologic clearance on cardiovascular disease biomarker lipoprotein-associated phospholipase A2 and its relation to serum lipids

BackgroundChronic hepatitis C virus (HCV) infection has been linked to cardiovascular disease (CVD). However, CVD risk prediction in chronic HCV-infected patients is problematic as the prevalence of different cardiac biomarkers in these patients is currently unknown. Serum lipids, which are routinely used in traditional CVD risk scores, may underestimate CVD risk in these patients, while non-hepatically produced biomarkers, including lipoprotein-associated phospholipase A2 (Lp-PLA2), may better reflect CVD risk. In this study, we aimed to evaluate the effect of sustained virologic response (SVR) on CVD risk, predicted by Lp-PLA2 mass in comparison with serum lipid levels.ResultsNinety chronic HCV-infected patients were enrolled in this study. Serum Lp-PLA2 mass was measured before and after HCV treatment via direct-acting antivirals and compared with the changes in serum lipids and Framingham risk score (FRS). The Lp-PLA2 level was categorized into high (>235 ng/ml) or low predicted CVD risk (≤235 ng/ml). Mean Lp-PLA2 mass significantly decreased from 322.37 ± 79.15 ng/ml to 263.79 ± 51.804 ng/ml with SVR, and the number of high-risk patients significantly dropped from 82.22 to 60% after treatment. Total cholesterol, low-density lipoprotein, and high-density lipoprotein levels were low/optimal at baseline (170 ± 40.34 mg/dl, 71.98 ± 24.12 mg/dl, and 48.43 ± 6.79 mg/dl) and significantly increased with SVR (195.66 ± 55.68 mg/dl, 103.24 ± 46.57 mg/dl, and 53.91 ± 8.67 mg/dl). According to FRS, only 30% of patients were moderate/high risk at baseline and insignificantly declined to 28.89% post-treatment.ConclusionLp-PLA2 may be a better predictor of CVD risk in chronic HCV-infected patients. Furthermore, SVR may reduce hepatic inflammation and consequently CVD risk.

The impact of direct-acting antiviral treatment on glycemic homeostasis in patients with chronic hepatitis C.

There is robust epidemiological evidence suggesting the link of chronic hepatitis C virus (HCV) infection with type 2 diabetes mellitus (DM). Viral clearance achieved by direct acting antiviral agents (DAAs) has been associated to significant improvements in glycometabolic control but data on the long-term effect of sustained virological response (SVR) on diabetic disease are limited. The aim of this review is to evaluate the influence of SVR after DAA-based therapy on insulin resistance (IR) and DM incidence in non-diabetic patients, on the glycemic homeostasis in diabetic patients and on their long-term hepatic and metabolic outcomes. An electronic search of Embase, PubMed, MEDLINE, Ovid and the Cochrane Database of Systematic Reviews was performed for papers regarding the effect of DAA-induced SVR on the glycometabolic control and clinical outcomes of HCV-positive diabetic patients up to September 30, 2020. Among non-diabetic patients, a significant reduction in the risk of IR and DM was reported by the vast majority of the studies; the glycometabolic control significantly improved in diabetic patients during and immediately after the end of antiviral treatment. However, whether this beneficial effect is long lasting is still matter of debate. Furthermore, at variance with data obtained during the Interferon era, DM does not seem to be an unfavorable predictive factor of hepatocellular carcinoma in cured patients. A favorable influence of DAA-induced SVR on IR and DM incidence and on glycemic control is reported by several studies. However, the long-term biochemical, metabolic and clinical impact of this endocrine benefit remains largely unknown.

Successful Antiviral Therapy Reduces Risk of Schizophrenia Among Chronic Hepatitis C Patients: A Nationwide Real-World Taiwanese Cohort (T-COACH).

BackgroundChronic hepatitis C (CHC) has been associated with major psychoses, and interferon (IFN)-based therapy may cause psychiatric sequelae. We aimed to evaluate the effects of sustained virological response (SVR) on the incidence of major psychoses in a nationwide Taiwanese CHC cohort. MethodsFifteen thousand eight hundred thirty-six CHC Taiwanese who received IFN-based therapy were enrolled between 2003 and 2015. Of those, 12 723 patients were linked to the National Health Insurance Research Databases for the incidence of major psychoses. Death before major psychoses was considered a competing risk.ResultsTwenty-four patients developed new-onset major psychoses during 67 554 person-years (3.6 per 10 000 person-years), including 16 affective psychoses, 7 schizophrenia, and 1 organic psychotic condition. The incidence of major psychoses and affective psychoses did not differ between the SVR and non-SVR groups. The 10-year cumulative incidence of schizophrenia were significantly higher in the non-SVR than in SVR patients (0.14% vs 0.04%, P = .036). Cox subdistribution hazards showed that SVR and older age were associated with a significantly lower risk of schizophrenia (hazard ratio = 0.18 and 0.17). Sustained virological response was associated with decreased incidence of schizophrenia and majorly observed among patients with age <45 (P = .02). ConclusionsSuccessful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.

The impact of SVR from direct-acting antiviral- and interferon-based treatments for HCV on hepatocellular carcinoma risk.

We evaluated the effect of sustained virologic response (SVR) from direct-acting antiviral (DAA)- and interferon-based treatments on hepatocellular carcinoma (HCC) risk in a large population-based cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets. Patients were followed from the end of HCV treatment to HCC, death or 31 December 2016. We assessed HCC risk among those who did and did not achieve SVR by treatment type using proportional hazard models. Of 12776 eligible individuals, 3905 received DAAs while 8871 received interferon-based treatments, followed for a median of 1.0 [range: 0.6-2.7] and 7.9 [range: 4.4-17.1] years, respectively. A total of 3613 and 6575 achieved SVR with DAAs- and interferon-based treatments, respectively. Among DAAs-treated patients, HCC incidence rate was 6.9 (95%CI: 4.7-10.1)/1000 person yr (PY) in SVR group (HCC cases: 26) and 38.2 (95%CI: 20.6-71.0) in the no-SVR group (HCC cases: 10, P<.001). Among interferon-treated individuals, HCC incidence rate was 1.8 (95%CI: 1.5-2.2) in the SVR (HCC cases: 99) and 13.9 (95%CI: 12.3-15.8) in the no-SVR group (HCC cases: 239, P<.001). Compared with no-SVR from interferon, SVR from DAA- and interferon-based treatments resulted in significant reduction in HCC risk (adjusted subdistribution hazard ratio (adjSHR) DAA=0.30, 95%CI: 0.19-0.48 and adjSHR interferon=0.2, 95%CI: 0.16-0.26). Among those with SVR, treatment with DAAs compared to interferon was not associated with HCC risk (adjSHR=0.93, 95%CI: 0.51-1.71). In conclusion, similar to interferon era, DAA-related SVR is associated with 70% reduction in HCC risk.

Ledipasvir/Sofosbuvir in Adolescents With Chronic Hepatitis C Genotype 4 With and Without Hematological Disorders: Virological Efficacy and Impact on Liver Stiffness.

Egypt has the highest prevalence of hepatitis C virus (HCV) infection. Anti-HCV antibodies were detectable in 3% of children in Upper Egypt. Our aim was to evaluate the efficacy of ledipasvir/sofosbuvir for chronic HCV genotype 4 in adolescents with/without hematological disorders and to determine the effect of sustained virological response (SVR) on liver stiffness. Sixty-five adolescents were recruited. There were 3 patient groups: group 1, 44 treatment-naive without hematological disorders; group 2, 6 previously treated; and group 3, 15 treatment-naive with hematological disorders. All patients received sofosbuvir 400 mg/ledipasvir 90 mg per day for 12 weeks. Serum HCV RNA levels were measured before treatment, at week 12, and at 12 weeks after the end of treatment (SVR12). Liver stiffness and the aspartate aminotransferase-platelet ratio index (APRI) score were estimated at baseline and at SVR12. SVR12 was 100%. At SVR12, there was a significant improvement in liver stiffness in all groups. The APRI score showed significant improvements in groups 1 and 3 (P < .001 and P = .004, respectively). The treatment was well tolerated, with minimal and self-limited side effects. Treatment of chronic HCV in adolescents using ledipasvir/sofosbuvir was effective, with a cure rate (at SVR12) of 100%. Significant improvement in liver stiffness was found in all groups.

Long-term outcome of hepatocellular carcinoma occurrence, esophageal varices exacerbation, and mortality in hepatitis C virus-related liver cirrhosis after interferon-based therapy.

The long-term effects of sustained virologic response (SVR) to antiviral therapy on the risk of liver complications, such as exacerbation of esophageal varices (EV), hepatocellular carcinoma (HCC), malignant lymphoma, and liver-related and overall death in hepatitisC virus (HCV)-infected patients with liver cirrhosis are not fully known. These risks were evaluated during long-term follow up of 457 patients with HCV-related Child-Pugh ClassA liver cirrhosis without history of HCC. The respective cumulative 5- and 10-year rates of EV exacerbation were 2.0% and 3.1%. Multivariate analysis identified the presence of EVs, thrombocytopenia at baseline. and alcohol intake as significant independent predictors of EV exacerbation before and after SVR. The cumulative 5- and 10-year rates of HCC were 6.8% and 10.2%, respectively. Male sex and the presence of EV were significant independent determinants of HCC before and after SVR. Although the cumulative 5-year HCC recurrence rate was 49.4%, the overall survival rate since HCC was 73.6% at 5years. The overall survival rates since SVR were 98.7% and 93.6% at 5 and 10years, respectively. Progression of HCC was the most frequent all-cause mortality, but none of the patients died of liver decompensation. Male sex and Fibrosis-4 index of ≥3.0 after SVR were significant and independent predictors of mortality. Patients with HCV remain at risk of HCC for >10years after achieving SVR, and HCC is the most common cause of mortality. We recommend long-term surveillance of cirrhotic patients with HCV, even after achieving SVR.

Aminopyrine breath test predicts liver-related events and death in HCV-related cirrhosis on SVR after DAA therapy.

In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13 C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation - defined as Child A6 (N=22, 44%) or previous decompensation (N=7, 14%) - or Child B cirrhosis (N=21, 42%) eligible for DAA-based antiviral therapy. ABT was performed at baseline and 12weeks after the end of antiviral therapy. Patients received sofosbuvir-based regimens. Aminopyrine breath test was available for all 50 patients at baseline. The 120' cumulative dose was directly associated at regression analysis only with albumin levels (P=.001). ABT was available at follow-up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2months (range 12.2-32.1months). Lower Ʌ ABT - defined as changes of 120' cumulative dose from FUW12 to baseline - (HR 0.97, 95% CI 0.94-0.99; P=.02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16-310.3; P=.03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of Ʌ ABT was good (0.87, 95% CI 0.75-0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver-related events/death (P<.001). In patients with advanced HCV cirrhosis who achieve SVR with DAA, Ʌ ABT assists in assessing the residual likelihood of liver-related events and deaths after viral cure.

Impact of HCV treatment in patients with advanced hepatocellular carcinoma on sorafenib.

e15645 Background: Hepatocellular carcinoma (HCC) is the 4th leading cause of global cancer deaths. In North America, HCC is most commonly caused by Hepatitis C virus (HCV). Direct acting antivirals (DAAs) have dramatically increased sustained virologic response (SVR) rates for HCV. Studies of DAAs in early stage HCC have had conflicting results on HCC outcomes. A small Asian study of 58 advanced HCC patients treated with sorafenib demonstrated SVR improved survival, but whether the same effect occurs in North American patients is unknown. Methods: Inclusion criteria for this retrospective study were: biopsy or clinically proven advanced incurable HCC, sorafenib treatment at Princess Margaret Cancer Centre between January 1 2008-June 30 2018 and a history of HCV. Survival was analyzed using the Kaplan Meier method and a cox proportional hazards model was fit to determine the effect of SVR on OS. Results: 93 patients were included with a median duration of sorafenib therapy of 3 months. 89% were ECOG 0-1 and 96% were BCLC-C (See table 1). Of those receiving antivirals, 95% were given before sorafenib. Overall, SVR was achieved in 23 (50%) patients. Median OS of patients achieving SVR vs not in SVR was 10.3 vs 8.9 months respectively (HR 0.67, 95% CI 0.36-1.24, p = 0.20). Median PFS was 6.4 vs 5.0 months in patients with or without SVR (HR 0.66, 95% CI 0.39-1.13, p = 0.13). There was no significant difference between mean dose of sorafenib or discontinuation due to toxicity in patients by SVR status. Conclusions: Antiviral therapy with SVR lead to a non-statistically significant improvement in OS in patients with Child-Pugh A-B liver disease, advanced HCC treated with sorafenib and HCV. These results should be validated in larger data-sets. [Table: see text]

The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection.

Direct-acting anti-viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. Of the 45260 patients treated with DAA with mean follow-up of 2.01years, 41711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR)=0.23; 95% CI 0.10-0.56), glomerulonephritis (aHR=0.61; 95% CI 0.41-0.90) and lichen planus (aHR=0.46; 95% CI 0.30-0.70), but not for non-Hodgkin's lymphoma (aHR=0.86; 95% CI 0.52-1.43) or diabetes (aHR=0.98; 95% CI 0.81-1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR=0.33; 95% CI 0.11-1.03). Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non-Hodgkin's lymphoma or diabetes.

Evaluating Flexible Modeling of Continuous Covariates in Inverse-Weighted Estimators.

Correct specification of the exposure model is essential for unbiased estimation in marginal structural models with inverse-probability-of-treatment weights. However, although flexible modeling is commonplace when estimating effects of continuous covariates in outcome models, its use is less frequent in estimation of inverse probability weights. Using simulations, we assess the accuracy of the treatment effect estimates and covariate balance obtained with different exposure model specifications when the true relationship between a continuous, possibly time-varying covariate Lt and the logit of the probability of exposure is nonlinear. Specifically, we compare 4 approaches to modeling the effect of Lt when estimating inverse probability weights: a linear function, the covariate-balancing propensity score, and 2 easy-to-implement flexible methods that relax the assumption of linearity: cubic regression splines and fractional polynomials. Using data from 2 empirical studies, we compare linear exposure models with flexible exposure models to estimate the effect of sustained virological response to hepatitis C virus treatment on the progression of liver fibrosis. Our simulation results demonstrate that ignoring important nonlinear relationships when fitting the exposure model may provide poorer covariate balance and induce substantial bias in the estimated exposure-outcome associations. Analysts should routinely consider flexible modeling of continuous covariates when estimating inverse-probability-of-treatment weights.

Sustained Virological Response Is Associated with a Decreased Risk of Posttransplant Diabetes Mellitus in Liver Transplant Recipients with Hepatitis C-Related Liver Disease.

Posttransplant diabetes mellitus (PTDM), an increasingly recognized complication of solid organ transplantation, is associated with increased morbidity and mortality following liver transplantation (LT). Hepatitis C virus (HCV) infection is a consistent and modifiable risk factor for PTDM. Prior studies have demonstrated improvement in glucose metabolism following sustained virological response (SVR). However, the effect of SVR on the incidence of PTDM has not been previously investigated in a large cohort of LT recipients. We performed a single-center retrospective cohort study of LT recipients with HCV from January 1, 2010 to June 30, 2015 to compare the risk of sustained posttransplant diabetes mellitus (s-PTDM) prior to and following SVR. SVR was treated as a discrete time varying exposure. The s-PTDM was defined as de novo diabetes mellitus following LT of a >6-month duration. Univariate and multivariate Cox proportional hazards models were used to compare crude and adjusted time to s-PTDM prior to and following SVR. There were 256 eligible LT recipients analyzed. Median follow-up was 41.2 months. Overall, 31 (12.1%) and 178 (69.5%) patients achieved SVR prior to LT and following LT, respectively. During follow-up, 71 (27.7%) patients developed s-PTDM. The incidence of s-PTDM was greatest in the first year after LT. After adjustment for potential confounders, SVR was associated with a significantly reduced risk of s-PTDM (HR, 0.40; P = 0.048). In conclusion, eradication of HCV is independently associated with a reduced incidence of s-PTDM. This benefit appears to be most influenced by pre-LT SVR and persists throughout the post-LT period. Given the association between PTDM and posttransplant morbidity and mortality, these data provide another motivator for pre-LT or early post-LT treatment of HCV.

Impression of direct-acting antiviral agents in the treatment of recurrent hepatocellular carcinoma related to chronic hepatitis C

The treatment of chronic hepatitis C has gradually entered into the era of direct-acting antiviral agents (DAAs) from the era of pegylated interferon-α combined with ribavirin, which has a high curative effect, good tolerability, and complete patient-friendly oral form of administration. Sustained virologic response (SVR) acquired by pegylated interferon-α plus ribavirin therapy has been widely recognized by scholars in reducing the recurrence of primary liver cancer and liver cancer, especially in cirrhotic patients. The clinical application time of DAAs is short and its report is inconsistent with the increase or decrease of primary liver cancer and liver cancer recurrence. Simultaneously, the effect of SVR in people with hepatocellular carcinoma on DAAs seems to be different from those in patients without hepatocellular carcinoma. This article reviews some of the existing reports in order to increase the understanding of DAAs and liver cancer and serve the long-term benefit of clinical treatment.

The Best of Both Worlds: Impact of Remission of Hepatitis C on Glycemic Control in Patients With Type II Diabetes

Introduction: Globally, chronic hepatitis C (CHC) is one of the major causes of chronic liver disease and cirrhosis. CHC is characterized by a high prevalence of metabolic derangements (HCADS- hepatitis C-associated dysmetabolic syndrome) that contributes to high morbidity and mortality. CHC is associated with higher risk of type 2 diabetes (T2DM) which is thought to due to hepatic insulin resistance induced by high levels of proinflammatory cytokines tumor necrosis factor- alfa (TNF-α) and Interleukin (IL-6). Thus, with sustained virological response (SVR) resulting in lower levels of proinflammatory cytokines, insulin resistance and glycemic control should improve. There are no published studies on the effect of SVR in patients with CHC using the new oral direct acting anti-viral (DAA) agents on glycemic control. We hypothesized that achieving an SVR using DAAs in the treatment of CHC would improve glycemic control in patients with T2DM. Methods: We performed a proof of concept study at a single center through a retrospective chart review of patients with CHC and T2DM who achieved SVR with DAAs. The primary endpoint was change in HbA1c. We also looked at other factors that could contribute to changes in HbA1c. Results: We found 180 patients with the diagnosis of CHC from 2014 through 2016, 12 had T2DM. DAAs resulted in SVR in 6 of these 12 patients with T2DM. The mean HbA1C was 9.9% before treatment, which decreased to 6.1% after SVR. Lifestyle or weight changes were not observed. Conclusion: There are numerous reports of higher risk of DM2 and insulin resistance with CHC, the impact of SVR with anti HCV therapy is largely unknown. This is the first observation of a significant improvement in HbA1c with SVR in CHC using DAAs. More importantly, a decrease in HbA1c occurred despite decrease in the anti-diabetic therapy. The improved glycemic control is likely due to SVR and not due to DAAs as this effect was sustained even after the therapy was stopped. Larger prospective trials are required to establish concrete association of SVR with improvement in glycemic control.Table: Table. Patient data

Effects of All-Oral Anti-Viral Therapy on HVPG and Systemic Hemodynamics in Patients With Hepatitis C Virus-Associated Cirrhosis

Patients with hepatitis C virus-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH. We performed a multicenter prospective study of 226 patients with hepatitis C virus-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain. The portal pressure gradient was determined based on HVPG at baseline and 24 weeks after therapy; patients also underwent right-heart catheterization and LSM at these time points. Primary outcomes were effects of SVR on the hepatic, pulmonary, and systemic hemodynamics; factors related to HVPG ≥10% reduction and to CSPH persistence; and whether LSMs can rule out the presence of CSPH after SVR. Most patients (75%) had esophageal varices, 21% were Child-B, and 29% had at least 1 previous episode of liver decompensation. Overall, HVPG decreased from 15 (IQR: 12-18) before treatment to 13 (10-16) mmHg after SVR (reduction of 2.1 ± 3.2 mmHg; P<.01). However, CSPH persisted in 78% of patients. HVPG decreased by 10% or more from baseline in 140 patients (62%). Baseline level of albumin below 3.5 g/dL was the only negative factor associated with an HVPG reduction of 10% or more. LSM decreased from 27 (20-37) kPa before treatment to 18 (14-28) kPa after SVR (P < .05). One third of patients with a reduction in LSM to below 13.6 kPa after SVR still had CSPH. A higher baseline HVPG and a lower decrease in LSM after treatment were associated with persistence of CSPH after SVR. Systemic hemodynamics improved after SVR. Interestingly, pulmonary hypertension was present in 13 patients at baseline and 25 after SVR, although only 3 patients had increased pulmonary resistance. In a multicenter prospective study of patients with hepatitis C virus-associated cirrhosis, an SVR to all-oral therapy significantly reduced HVPG, compared with before treatment. Nevertheless, CSPH persists in most patients despite SVR, indicating persistent risk of decompensation. In this population, changes in LSM do not correlate with HVPG and cut-off values are not reliable in ruling out CSPH after SVR.

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...