Over time evaluation of glycaemic control in direct-acting antiviral-treated hepatitis C virus/diabetic individuals with chronic hepatitis or with cirrhosis.

BACKGROUND: Data concerning the impact of hepatitis C virus (HCV) cure on type 2 diabetes mellitus (T2DM) are controversial. The aim of the study was to evaluate the effects of anti-HCV direct-acting antiviral (DAA) treatments on long-term glucose control in HCV/T2DM patients with chronic hepatitis C (CHC) or with cirrhosis. METHODS: One hundred and eighty-two consecutive HCV/T2DM patients who achieved a viral clearance by DAA treatment were enrolled. Seventy or 182 of them had CHC, and 112 had cirrhosis. Clinical, biochemical and instrumental parameters were recorded at baseline and at 48, 96 and 120 weeks (48w, 96w and 120w, respectively) after stopping DAA therapy. RESULTS: At baseline, the overall study population had a mean of glycated haemoglobin (HbA1c) value of 7.2% (ranging from 5 to 11.2), without any significant differences between CHC and cirrhosis [7.1 and 7.2, respectively]. Evaluation over time of HbA1c variations showed a significant improvement of glucose control at all post-treatment time points compared with baseline in CHC patients (P = .001). In cirrhotic patients, a significant decrease of HbA1c levels was only found when comparing HbA1c values between baseline and 48w time-point (P = .001), whereas this improvement disappeared at both 98w and 120w (P = .8 and P = .3, respectively). Multivariate logistic regression analysis showed that patients with chronic hepatitis have a 2.5 (CI 1.066-5.945) times greater chance of achieving an improvement of glycaemic values than patients with liver cirrhosis (P = .035). CONCLUSION: DAA-based HCV cure induces a significant and persistent amelioration of glycaemic control in HCV/diabetic patients with chronic hepatitis, whereas cirrhotic HCV/diabetic subjects have only a transient benefit from the virus elimination.

Mortality rates and risk factors in 1412 Japanese patients with decompensated hepatitis C virus-related cirrhosis: a retrospective long-term cohort study.

BACKGROUND: Hepatitis C virus is the leading cause of liver cirrhosis and hepatocellular carcinoma in Japan. We aimed to examine the long-term (> 20 years) mortality and hepatocellular carcinoma rates and associated risk factors in 1412 Japanese patients with decompensated hepatitis C virus-related cirrhosis (Child-Pugh B or C). METHODS: Cumulative survival and hepatocellular carcinoma rates were determined using Kaplan-Meier analysis. Independent risk factors were identified by multivariate analysis. A two-tailed P-value of < 0.05 was considered significant. RESULTS: The patients were followed up for a median of 2 years (range 0.5-24.2 years). In total, 62.3%, 41.7%, 4.7%, and 68.3% of the patients had a history of hepatocellular carcinoma, ascites, hepatic encephalopathy, and esophageal varices, respectively. The 1-, 5-, 10-, and 20-year cumulative overall survival rates in the total cohort was 74.9%, 29.0%, 9.1%, and 1.4%, respectively. The 1-, 3-, 5-, and 10-year cumulative survival rates for patients without hepatocellular carcinoma were 93.1%, 54.4%, 18.2%, and 4.0%, respectively, and the corresponding cumulative post-decompensation hepatocellular carcinoma rates were 14.0%, 31.6%, 46.1%, and 66.2%, respectively. The independent risk factors for mortality were older age, Child-Pugh C cirrhosis, the presence of hepatocellular carcinoma, low estimated glomerular filtration rate, low serum sodium level, low platelet count, and high γ-glutamyl transferase and α-fetoprotein levels for all patients and older age, Child-Pugh C cirrhosis, and low estimated glomerular filtration rate for patients without hepatocellular carcinoma. Overall, 1035 patients (73.3%) died; the causes of death were liver failure with/without hepatocellular carcinoma, pneumonia, sepsis, cardiovascular disease, and non-hepatocellular carcinoma malignancies. The corresponding morality rates per person-year were 133.4, 59.9, 10.9, 10.6, 9.0, and 5.2, respectively. CONCLUSIONS: Among Japanese patients with decompensated hepatitis C virus-related cirrhosis, hepatocellular carcinoma is associated with poor prognosis. Our results highlight the importance of managing liver-related events, including hepatocellular carcinoma, in these patients.

Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population.

BACKGROUND & AIMS: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. METHODS: The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age- and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population. RESULTS: Overall, 28/181 patients followed-up for a median period of 9.6years (range 1-25years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3-94.8) and 62.9% (95% CI, 45.9-75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR=1.00 (95% CI, 0.72-1.35), with an SMR for non-SVR patients of 3.85 (95% CI, 3.43-4.30), for untreated of 3.01 (95% CI, 2.64-3.42) and for decompensated of 6.70 (95% CI, 5.39-8.22). CONCLUSIONS: Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable.

Management of HCV patients with cirrhosis with direct acting antivirals.

In recent years, several studies have clearly shown that sustained virological response (SVR) achieved by interferon-based therapies may delay or reduce the risk of hepatocellular carcinoma, liver decompensation and all-causes of mortality in all categories of patients with HCV-related cirrhosis, a condition characterized by a wide heterogeneity of clinical features, especially in patients with compensated disease. Unfortunately, the advanced fibrosis stage has been shown to be associated with poor SVR rates and poor tolerance with Peg-interferon and ribavirin. Therefore, on the basis of its risk/efficacy evaluation, most patients are considered to be ineligible for antiviral therapy with these molecules. Recently, improvement in the knowledge of the HCV life-cycle, has resulted in the rapid development of many direct-acting antivirals (DAAs). Two first generation DAAs, boceprevir (BOC) and telaprevir (TVR), have been approved, and more than 40 new small molecules are still in development. However, only a few individuals with compensated cirrhosis were included in the phase III studies assessing the safety and efficacy of BOC or TVR in naïve and chronic hepatitis C genotype 1 patients in whom treatment had failed, and patients with either decompensation or end-stage liver disease were excluded. Therefore, the information available in these patients, which have shown significantly lower SVR compared with patients with mild to moderate fibrosis, are not fully reliable. In addition, in real practice, some studies that have not yet been fully published have shown that triple therapy with these two molecules was associated with low SVR and high serious adverse events (SAEs).

Severe Stenosis of Mitral Bioprosthetic Valve Thrombosis in a Patient with HCV-Related Cirrhosis and Duodenal Variceal Bleeding: The Deadly Triad.

Bioprosthetic valve thrombosis (BPVT) is considered a relatively rare but life-threatening clinical entity. Thus, there is the need of high clinical suspicion in order to make a timely diagnosis and related appropriate therapeutic interventions. In this regard, the management of BPVT is high risk, whatever the option taken (surgery and/or systemic fibrinolysis). The presence of severe comorbidities-as decompensated cirrhosis-further complicates the clinical decision-making process, calling for a patient-tailored integrated multidisciplinary approach. We report a challenging case of a 45-year-old patient with mitral bioprosthetic valve thrombosis and hepatitis C virus (HCV)-related cirrhosis complicated by active duodenal variceal bleeding.

Methylation of tumour suppressor genes RUNX3, RASSF1A and E-Cadherin in HCV-related liver cirrhosis and hepatocellular carcinoma.

Background: HCV infection is related to aberrant methylation of several genes. RASSF1A, E-Cadherin and RUNX3 are tumour suppressor genes that may be inactivated by hypermethylation in many tumours including hepatocellular carcinoma (HCC). We hypothesized that methylation is a diagnostic biomarker for HCC in patients with HCV-related liver cirrhosis.Methods: We recruited 207 cases of HCV-related liver cirrhosis, 193 HCC patients and 53 healthy controls. Methylation-specific polymerase chain reaction for detection of circulating hypermethylated RASSF1A, E-Cadherinand RUNX3. Alpha fetoprotein (AFP) was measured by commercial immunoassay.Results: Significant hypermethylation of the three genes was found in the HCC group compared to both cirrhosis and healthy groups (P < 0.001), whereas no significant difference in hypermethylation was found between cirrhosis and healthy groups (P = 0.17, 0.50 and 0.14, respectively). No significant links were found between hypermethylated RASSF1A, E-Cadherin and RUNX3 and stages of Barcelona Clinic of Liver Cancer score (P =0.21, 0.63 and 0.98, respectively). No significant associations were found between AFP value and hypermethylated genes in cirrhosis and HCC groups (P = 0.82) except with E-Cadherin in HCC (P = 0.02). In multiple regression analysis, RASSF1A and E-Cadherin were predictors of HCC within cirrhosis cases, but only E-Cadherin was an independent risk factor for prediction of HCC in cases with low AFP (P = 0.01).Conclusions: The presence of hypermethylated serum RASSF1A, E-Cadherin and RUNX3 is linked to HCC in patients with HCV-related cirrhosis. Only E-Cadherin is an independent risk factor for prediction of HCC with low AFP. These findings may be of diagnostic value.

Chronic Hepatitis C-Related Cirrhosis Hospitalization Cost Analysis in Bulgaria.

OBJECTIVE: HCV infection is a leading cause of chronic liver disease with long-term complications-extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital "Queen Joanna-ISUL" for 3-year period (2012-2014). METHODS: It is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital "Queen Joanna-ISUL" for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy) were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF), hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal-Wallis, and Friedman tests were used for statistical processing. RESULTS: 76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839) with an average cost per patient 4,577 BGN (€2,340). Statistically significant correlation was observed between the total cost per patient from the different payers' perspective and the Child-Pugh cirrhosis score. CONCLUSION: HCV-related cirrhosis is resource demanding and sets high direct medical costs as it is related with increased hospitalizations and complications acquiring additional treatment.