Once-daily treatment with glecaprevir-pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157 .).

Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66-82% with 24-48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.

Mannose-binding lectin (MBL) is a C-type lectin produced mainly by the liver that binds to a wide range of pathogens. Polymorphisms at the promoter and exon 1 of the MBL2 gene are responsible for low serum levels of MBL and have been associated with an increased risk of infections. We prospectively analyzed 95 liver transplant recipients. Well-known functionally relevant polymorphisms of the MBL2 gene of the liver donor were examined by gene sequencing. Infectious events were collected prospectively. No differences in the incidence of infections were found according to the donor MBL2 genotypes. Survival was lower in patients receiving a liver graft from a donor with an exon 1 MBL2 variant genotype, and they had higher infection-related mortality (50% versus 14%, P = 0.040). No differences were found according to other polymorphisms involving the promoter and 5'-untranslated region. When we analyzed bacterial infection episodes, we found that patients receiving a liver from a donor with an exon 1 variant genotype had a higher incidence of septic shock (46% versus 11%, P = 0.004). Independent variables associated with graft or patient survival were as follows: receiving a graft from a donor with an exon 1 MBL2 variant genotype [adjusted hazard ratio (aHR), 9.64; 95% confidence interval (CI), 2.59-36.0], the Model for End-Stage Liver Disease score (aHR, 1.14; 95% CI, 1.05-1.23), and bacterial infections (aHR, 11.1; 95% CI, 2.73-44.9). Liver transplantation from a donor with a variant MBL2 exon 1 genotype was associated with a worse prognosis, mainly because of infections of higher severity.

Current NAFLD management is rapidly evolving, and new pathophysiology-based therapies are expected to be introduced in the near future. All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease, diabetes and cardiovascular events.

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Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC.

Key Points Question What is the efficacy of a high-dose vaccine schedule compared with standard dosage for hepatitis B virus (HBV) revaccination in patients living with HIV? Findings In this randomized clinical trial including 107 adults at a single HIV and hepatology clinic in Chile, 72% of patients receiving a high dose of HBV vaccine achieved serological response as compared with 51% in the standard-dose group. Higher and longer-lasting hepatitis B surface antibody titers were seen in the high-dose group as well. Meaning These results suggest that a high-dose regimen may be superior to a standard-dose schedule for HBV revaccination to achieve seroprotection in patients living with HIV.

OBJECTIVE:The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS:A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS:The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8% Ϯ 3% in yr 1, 11% Ϯ 4% in yr 2, and 13% Ϯ 4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS:In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries. (Am J Gastroenterol 2000;95: 50 -56.