The Current Status of Granulocyte-Colony Stimulating Factor to Treat Acute-on-Chronic Liver Failure.

Patients with acute-on-chronic liver failure (ACLF) have a devastating prognosis and therapeutic options are limited. Granulocyte-colony stimulating factor (G-CSF) mobilizes immune and stem cells and possess immune-modulatory and proregenerative capacities. In this review, we aim to define the current evidence for the treatment with G-CSF in end-stage liver disease. Several smaller clinical trials in patients with different severity grades of end-stage liver disease have shown that G-CSF improves survival and reduces the rate of complications. Adequately powered multicenter European trials could not confirm these beneficial effects. In mouse models of ACLF, G-CSF increased the toll-like receptor (TLR)-mediated inflammatory response which led to an increase in mortality. Adding a TLR4 signaling inhibitor allowed G-CSF to unfold its proregenerative properties in these ACLF models. These data suggest that G-CSF requires a noninflammatory environment to exert its protective properties.

12 Weeks of a Ribavirin-Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation.

Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor ± RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a sustained virological response 12 weeks after the end of treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3, 21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups of patients according to their treatment and duration: SOF + NS5A without RBV for 12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47 patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%, and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment failure. Under multivariate analysis, factors such as fibrosis stage, previous treatment, HCV genotype, and baseline HCV viral load did not influence SVR12 rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001). CONCLUSION: SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000).

Left gastric vein embolization during TIPS placement for acute variceal bleeding has no effect on bleeding recurrence: Results of a multicenter study.

PURPOSE: The purpose of this study was to evaluate whether concomitant left gastric vein embolization (LGVE) during transjugular intrahepatic portosystemic shunt (TIPS) for acute variceal hemorrhage could reduce the risk of bleeding recurrence. MATERIAL AND METHOD: A national multicenter observational study was conducted in 14 centers between January 2019 and December 2020. All cirrhotic patients who underwent TIPS placement for acute variceal bleeding were included. During TIPS procedure, size of left gastric vein (LGV), performance of LGVE, material used for LGVE and portosystemic pressure gradient (PPG) before and after TIPS placement were collected. A propensity score for the occurrence of LGVE was calculated to assess effect of LGVE on rebleeding recurrence at six weeks and one year. RESULTS: A total of 356 patients were included (mean age 57.3 ± 10.8 [standard deviation] years; 283/356 [79%] men). Median follow-up was 11.2 months [interquartile range: 1.2, 13.3]. The main indication for TIPS was pre-emptive TIPS (162/356; 46%), rebleeding despite secondary prophylaxis (105/356; 29%), and salvage TIPS (89/356; 25%). Overall, 128/356 (36%) patients underwent LGVE during TIPS procedure. At six weeks and one year, rebleeding-free survival did not differ significantly between patients who underwent LGVE and those who did not (6/128 [5%] vs. 15/228 [7%] at six weeks, and 11/128 [5%] vs. 22/228 [7%] at one year, P = 0.622 and P = 0.889 respectively). A total of 55 pairs of patients were retained after propensity score matching. In patients without LGVE, the rebleeding rate was not different from those with LGVE (3/55 [5%] vs. 4/55 [7%], P > 0.99, and 5/55 [9%] vs. 6/55[11%], P > 0.99, at six weeks and one year respectively). Multivariable analysis identified PPG after TIPS placement as the only predictor of bleeding recurrence (hazard ratio = 1.09; 95% confidence interval: 1.02-1.18; P = 0.012). CONCLUSION: In this multicenter national real-life study, we did not observe any benefit of concomitant LGVE during TIPS placement for acute variceal bleeding on bleeding recurrence rate.

Safety of TNF inhibitors in rheumatic disease in case of NAFLD and cirrhosis.

The management of inflammatory rheumatic diseases has substantially changed in recent years, as has the profile of patients. The advent of biotherapies has been a revolution in rheumatology and the impact of co-morbidities in the management of these patients is now becoming increasingly important. Metabolic syndrome (MetS) is one of the most frequent comorbidities, and hepatic complications of MetS are not uncommon. MetS is responsible for Non-alcoholic fatty liver disease (NAFLD), characterized by excessive hepatic fat accumulation. In extreme cases, progression to cirrhosis is possible. NAFLD ranks among the top three indications for liver transplantation. We review available data on the safety, especially the risk of infections, of TNF inhibitors (TNFi) in case of NAFLD and in case of liver cirrhosis, in patients with rheumatic disease. In cases of NAFLD without severe fibrosis, available data are reassuring and tend to show a beneficial effect of TNFi on hepatic tissue. In case of cirrhosis, data are conflicting. Further large, well-designed studies are needed to explore this specific issue.