Impact Of Sustained Virological Response Research Articles

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

Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: impact of a sustained virological response.

Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma (HCC). A sustained virological response (SVR) is associated with improved outcomes, however, its impact on different ethnic groups is unknown. To evaluate ethnic differences in the natural history of CHC and the impact of SVR. We conducted a cohort study of 8039 consecutive adult CHC patients seen at two medical centres in California between January 1997 and June 2016. Individual chart review confirmed CHC diagnosis. Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was independently associated with increased cirrhosis (adjusted HR 1.37, CI, confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13-1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic ethnicity was no longer independently associated with cirrhosis (adjusted HR 1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01, CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall survival among the ethnicities by SVR status. Hispanic and Asian ethnicity was independently associated with increased cirrhosis and HCC risk. Achieving an SVR eliminates the ethnic disparity in liver disease progression and overall survival between Hispanic and Asian vs Caucasian CHC patients.

Impact of sustained virological response to chronic hepatitic C antiviral therapy on new onset diabetes mellitus type 2 after controlling for metabolic syndrome

The high cost associated with antiviral treatment for chronic hepatitis C virus (HCV) infection mandates further investigation in the context of preventing complications such as type 2 diabetes mellitus (DM2)....

Impact of direct-acting antiviral agents-induced SVR on the long-term burden of hepatocellular carcinoma in chronic hepatitis C cirrhosis.

230 Background: Sustained virological response (SVR) has been associated with decreased morbidity and mortality from hepatitis C virus (HCV) infection. Data are sparse, however, about the long-term benefits of direct-acting antiviral agents (DAAs) in terms of risk reduction for hepatocellular carcinoma (HCC). We estimate the impact of SVR on the HCC incidence in the DAA era when SVR is achieved nearly universally even in patients with advanced fibrosis and cirrhosis. Methods: We constructed a Markovian model of 50-year-old patients with compensated HCV cirrhosis (n=1,000) to model the incidence of HCC over 20-years of follow-up. We compared 2 cohorts: 1) SVR following DAA therapy and 2) no SVR (natural history). In the latter, HCC would develop at an annual rate of 4.2% and patients would die as a result of end stage liver disease (ESLD) according to their MELD (=6 at baseline). In the former, MELD score would not increase, the HCC risk would decrease and, in some patients, cirrhosis would regress. Results: The table summarizes the 20-year outcome in the two cohorts. In the cohort without SVR, HCC would occur in 33% and 63% would die of ESLD. In the SVR cohort, the proportion of HCC would increase to 37% as the number of subjects at HCC risk would increase, as a result of a dramatic reduction in deaths from ESLD. In the univariate sensitivity analyses, the cumulative HCC incidence was mainly influenced by the rate at which the risk of HCC is decreased after SVR, followed by the change in cirrhosis regression rate. Conclusions: Although HCC risk would decrease after SVR in a given individual patient with cirrhosis, on the population level, highly effective DAA therapy may lead to a paradoxical increase in the burden of HCC. These data underscore the important of (1) HCC surveillance in patients with cirrhosis even after SVR and (2) DAA intervention before cirrhosis develops. [Table: see text]

SAT-223 - Impact of sustained virological response with DAAs in patients with compensated HCV cirrhosis and endoscopic esophageal varices study

SAT-223 - Impact of sustained virological response with DAAs in patients with compensated HCV cirrhosis and endoscopic esophageal varices study

FRI-067 - Impact of sustained virological response to interferon therapy for chronic hepatitis C on recurrence and long-term survival in patients with hepatocellular carcinoma

FRI-067 - Impact of sustained virological response to interferon therapy for chronic hepatitis C on recurrence and long-term survival in patients with hepatocellular carcinoma

FRI-198 - The impact of sustained virological response on long term risk of decompensated cirrhosis: the BC hepatitis testers cohort

FRI-198 - The impact of sustained virological response on long term risk of decompensated cirrhosis: the BC hepatitis testers cohort

HCV eradication does not impact gut dysbiosis or systemic inflammation in cirrhotic patients.

Eradication of hepatitis C virus (HCV) is increasing but its residual impact on the pro-inflammatory milieu in cirrhosis, which is associated with gut dysbiosis, is unclear. To define the impact of sustained virological response (SVR) on gut dysbiosis and systemic inflammation in HCV cirrhosis patients. Cirrhotic out-patients with HCV with/without SVR (achieved >1 year prior) and age-matched healthy controls underwent serum and stool collection. Serum was analysed for IL-6, TNF-α and endotoxin while stool microbiota analysis was performed using multitagged pyrosequencing. Microbial comparisons were made using UNIFRAC and cirrhosis dysbiosis ratio (lower score indicates dysbiosis). Comparisons were performed between cirrhotics with/without SVR and controls vs. cirrhotic patients. A total of 105 HCV cirrhotics and 45 age-matched healthy controls were enrolled. Twenty-one patients had achieved SVR using pegylated interferon + ribavrin a median of 15 months prior. No significant differences on demographics, cirrhosis severity, concomitant medications or diabetes were seen between cirrhotics with/without SVR. There was no significant difference in overall microbiota composition (UNIFRAC P = 0.3) overall or within specific microbial families (cirrhosis dysbiosis ratio median 1.3 vs. 1.0, P = 0.45) between groups with/without SVR. This also extended towards IL-6, TNF-α and endotoxin levels. Both cirrhosis groups, however, had significant dysbiosis compared to healthy controls [UNIFRAC P = 0.01, cirrhosis dysbiosis ratio (1.1 vs. 2.9, P < 0.001)] along with higher levels of endotoxin, IL-6 and TNF-α. Gut dysbiosis and a pro-inflammatory systemic milieu, are found in HCV cirrhosis regardless of SVR. This persistent dysbiosis could contribute towards varying rates of improvement after HCV eradication in cirrhosis.

Su1449 Impact of Sustained Virological Response on MELD Score in Patients With Chronic Hepatitis C Related Decompensated Cirrhosis

Su1449 Impact of Sustained Virological Response on MELD Score in Patients With Chronic Hepatitis C Related Decompensated Cirrhosis

PGI36 - The Cost Effectiveness of Peginterferon Alfa and Ribavirin for the Treatment of Hepatitis C in Children and Young People

OBJECTIVES: To assess the cost-effectiveness of peginterferon ?-2a and peginterferon ?-2b in combination with ribavirin compared to best supportive care (BSC), for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3 to 17 years. METHODS: A Markov state-transition economic model of chronic HCV in children and young people was developed that extrapolated the impact of sustained virological response (SVR) on life expectancy, quality-adjusted life expectancy and lifetime costs. The model was adapted from one previously developed for adults. A systematic review was conducted of the clinical effectiveness of the treatments, and the health related quality of life for patients with hepatitis C. Uncertainty was explored through probabilistic and deterministic sensitivity analyses. RESULTS: Seven studies were identified that were relatively small and of generally poor quality. Estimates of SVR were similar for for peginterferon ?-2a (60%) and peginterferon ?-2b (58%) was similar, whilst the SVR for no treatment was assumed to be zero. From this model, peginterferon alfa (?-2a or ?-2b) in combination with ribavirin was more effective and cheaper than BSC. Sensitivity analyses suggest that the results were generally robust to all changes to the structural assumptions and input parameters. The model results were most sensitive to changes to the discount rate, time horizon, SVR and baseline fibrosis of the cohort. CONCLUSIONS: Treatment of children and young people with peginterferon alfa (?-2a or ?-2b) and ribavirin may be an effective therapy. Peginterferon alfa (?-2a or ?-2b) in combination with ribavirin is cost-effective compared with BSC. However, the available evidence is of poor quality. The views expressed in this paper are those of the authors and do not necessarily represent the views or policies of the UK HTA programme or Department of Health.

S1263 Predictors of Sustained Virological Response Among Patients With Hepatitis C Post OLT and the Impact of Sustained Virological Response on Mortality

G A A b st ra ct s to 4. Prior constitutional symptoms were present in 14%, and 38% were asymptomatic. Acute icteric feature was seen in 47%. Twelve patients had cirrhosis and were transplanted (57%). One had spontaneous remission and 1 died of liver failure. Remaining 7 patients achieved remission (43%) following treatment with steroid and azathioprine. Relapse on maintenance treatment was 28%. In group 2, the mean age was 38+14 years, female to male ratio was 30 to 7. Prior constitutional symptoms were present in 70% and 11% were asymptomatic. These parameters were significantly different between the groups (p<0.05). Acute icteric feature was seen in 19%. Twelve patients (32%) were transplanted. Eight had spontaneous remission. Remaining 17 patients achieved remission (41%) following treatment. Relapse on maintenance treatment was 59%. Conclusions: Elderly patients with AIH are more often asymptomatic or have less constitutional symptoms. AIH in elderly is usually an advanced disease at presentation than in younger patients. Relapse of AIH after remission is less common in the elderly. 1. Distinctive phenotype and treatment outcome of AIH in elderly. Hepatology 43:532, 2006

499 The impact of sustained virological response (SVR) on health-related quality of life (HRQL) in patients with chronic hepatitis C (CHC) and persistently normal ALT levels (PNALT) treated with peginterferon alfa-2A (PEGASYS®) and ribavirin (COPEGUS®)

499 The impact of sustained virological response (SVR) on health-related quality of life (HRQL) in patients with chronic hepatitis C (CHC) and persistently normal ALT levels (PNALT) treated with peginterferon alfa-2A (PEGASYS®) and ribavirin (COPEGUS®)