Effects of direct-acting antiviral agents on lipid and glucose profile in HCV patients with type 2 diabetes: A real-life Italian experience.

OBJECTIVES: Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct-acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages. METHODS: T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan. RESULTS: In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low-density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients. CONCLUSIONS: HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed.

Management of intermediate-stage hepatocellular carcinoma in the elderly with transcatheter arterial chemoembolization failure: Retreatment or switching to systemic therapy?

BACKGROUND: Transcatheter Arterial chemoembolization (TACE) is the first-line option for the intermediate-stage hepatocellular carcinoma. Guidelines do not define the number of TACE sessions to be repeated before stopping treatment and switching to sorafenib. METHODS: We retrospectively analysed 76 patients aged ≥65 years who were treated by multiple TACE sessions (re-TACE group; N = 36 patients) or one TACE session followed by sorafenib (TACE/Sorafenib group; N = 40 patients). The primary outcome was the overall survival (Kaplan-Meier analysis and log-rank test). RESULTS: Median overall survival was 320 days (range: 70-420 days) in re-TACE subgroup and 285 days (range: 50-368 days) in TACE/Sorafenib subgroup without significant differences between the two groups (log-rank test P = .72; HR = 0.87; 95% IC 0.41-1.87). The survival rate at one year was 43.6% and 32% in the re-TACE and in the TACE/sorafenib groups (P = .12), respectively. Subgroup analysis by gender, number of nodules at baseline and etiology of liver cirrhosis was performed but no differences were found. No statistical difference was observed in the frequency of side effects, but sorafenib was associated with severe diarrhoea in most patients requiring dose reduction. CONCLUSION: In our study including HCC patients aged ≥65 years, no differences in survival rate and side effects were found between patients Retreated with further TACE sessions and patients with treatment stage migration to sorafenib after first TACE failure. We included in our analysis a small study population; therefore, larger prospective studies are needed to confirm these findings.

Direct-acting antivirals restore systemic redox homeostasis in chronic HCV patients.

Chronic hepatitis C therapy has completely changed in the last years due to the availability of direct-acting antivirals (DAAs). Removing the virus may be not enough since chronic infection deeply modifies immune system and cellular metabolism along decades of inflammation. Oxidative stress plays a significant role in maintaining systemic inflammation during chronic HCV infection. Other than removing the virus, effective therapy could counteract oxidative stress. This study investigated the impact of DAA treatment on circulating markers of oxidative stress and antioxidant defence in a cohort of patients affected by chronic hepatitis C. To this, an observational study on 196 patients who started therapy with DAA for HCV-related hepatitis was performed. Patients were assessed at baseline, 4 weeks after the initiation of therapy (4wks), at the end of treatment (EoT), and 12 weeks after the EoT (SVR12). Circulating oxidative stress was determined by measuring serum hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and 8-hydroxydeoxyguanosine (8-OHdG). Antioxidant status was evaluated by measuring the enzymatic activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in peripheral blood mononuclear cells. We observed a reduction of serum 8-OHdG at 4wks, while the circulating level of both HNE- and MDA-protein adducts diminished at EoT; all these markers persisted low at SVR12. On the other side, we reported an increase in the enzymatic activity of all the antioxidant enzymes in PBMC at EoT and SVR12. Taking into account circulating 8-OHdG and antioxidant enzyme activities, patients with high fibrosis stage were those that had the most benefit from DAA therapy. To conclude, this study indicates that treatment with DAAs improves the circulating redox status of patients affected by chronic hepatitis C. This positive impact of DAA therapy may be related to its effectiveness on cutting down viremia and pro-inflammatory markers.

Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma.

: Metabolic reprogramming is critically involved in the development and progression of cancer. In particular, lipid metabolism has been investigated as a source of energy, micro-environmental adaptation, and cell signalling in neoplastic cells. However, the specific role of lipid metabolism dysregulation in hepatocellular carcinoma (HCC) has not been widely described yet. Alterations in fatty acid synthesis, ß-oxidation, and cellular lipidic composition contribute to initiation and progression of HCC. The aim of this review is to elucidate the mechanisms by which lipid metabolism is involved in hepatocarcinogenesis and tumour adaptation to different conditions, focusing on the transcriptional aberrations with new insights in lipidomics and lipid zonation. This will help detect new putative therapeutic approaches in the second most frequent cause of cancer-related death.

Two-Dimensional Shear Wave Elastography versus Transient Elastography: A Non-Invasive Comparison for the Assessment of Liver Fibrosis in Patients with Chronic Hepatitis C.

In recent years, several non-invasive methods have been developed for staging liver fibrosis in patients with chronic hepatitis C. A 2D-Shear wave elastography (SWE) technique has been recently introduced on the EPIQ 7 US system (ElastQ), but its accuracy has not been validated in patients with chronic hepatitis C virus (HCV) infection. We enrolled 178 HCV patients to assess their liver fibrosis stage with ElastQ software using transient elastography as a reference standard. The best cut-off values to diagnose ³ F2, ³ F3, and F4 were 8.15, 10.31, and 12.65 KPa, respectively. Liver stiffness values had a positive correlation with transient elastography (r = 0.57; p < 0.001). The area under the receiver operating characteristics (AUROC) was 0.899 for ³ F2 (moderate fibrosis), 0.900 for ³ F3 (severe fibrosis), and 0.899 for cirrhosis. 2D-SWE has excellent accuracy in assessing liver fibrosis in patients with chronic hepatitis C and an excellent correlation with transient elastography.

Risk of Statin-Induced Hypertransaminasemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia. PATIENTS AND METHODS: We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration. RESULTS: Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; P<.001). Atorvastatin showed the highest odds (OR 2.66; 95% CI, 1.74-4.06; P<.001) followed by rosuvastatin (OR 1.35; 95% CI, 1.06-1.70; P=.01) and lovastatin (OR 1.53; 95% CI, 1.03-2.28; P=.04). Pravastatin, fluvastatin, and simvastatin yielded no statistically different odds compared with placebo. CONCLUSIONS: A dose-dependent risk of developing hypertransaminasemia occurs in patients taking atorvastatin, rosuvastatin, and lovastatin.