Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir

BACKGROUND: Tenofovir (TDF) is an adenosine nucleotide analogue that has been approved for the treatment of HIV-1 infection. It also shows activity against hepatitis B virus (HBV) in patients with or without lamivudine (LAM)-associated mutations. Development of clinical or virological HBV breakthrough during TDF therapy has not been reported so far. The aim of this study was to analyse the HBV polymerase (pol) from HIV/HBV-coinfected patients with detectable serum levels of HBV DNA during treatment with TDF for longer than 6 months. METHODS: The HBV pol was sequenced from 43 patient's serum before and during TDF therapy. Phenotypic analyses were performed using HBV replication-competent plasmids carrying unique mutations selected under TDF therapy. RESULTS: Mean exposure to LAM was 35.3 +/- 27.5 months and to TDF 11.2 +/- 6.7 months. Genotypic analyses from 21 of the patients revealed LAM-associated mutations, and a further two patients developed a novel mutation, rtA194T, along with LAM-resistance-associated mutations. Phenotypic analyses revealed that constructs harbouring rtA194T combined with rtL180M and rtM204V displayed an over 10-fold increase in the IC50 for TDF compared with the wild type. CONCLUSION: The selection of HBV mutations in HBV/HIV-coinfected patients failing TDF therapy is an unlikely event within the first 12 months of treatment. However, HBV from two of the 43 patients treated with TDF for more than 12 months was found to contain one novel mutation located distal to the catalytic site of the HBV pol. In vitro, rtA194T conferred a reduced susceptibility to TDF in the presence of LAM-associated mutations.     

Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals

BACKGROUND: Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic. METHODS: Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of hepatitis C infection with pegylated interferon (peg-IFN) therapy. RESULTS: Early treatment resulted in sustained virological response in 61% of patients. Peg-IFN alone showed similar treatment response rates and lower incidence of anaemia compared with peg-IFN+ribavirin combination therapy. Higher treatment response rates were observed in patients treated over 48 weeks compared with 24 weeks. CONCLUSIONS: Treatment of hepatitis C in HIV-positive individuals in the acute phase of infection leads to high rates of sustained virological response. Optimal time and mode of therapy have yet to be defined.     

Iron,HCV and the liver

Ｉｒｏｎ,ＨＣＶａｎｄｔｈｅｌｉｖｅｒＫ．Ｐ．ＭａｉｅｒＳｕｂｊｅｃｔｈｅａｄｉｎｇｓＩｒｏｎ;ｈｅｐａｔｉｔｉｓＣｖｉｒｕｓ;ｌｉｖｅｒ;ｈｅｐａｔｉｔｉｓＣＩＲＯＮＩｒｏｎｓｅｒｖｅｓａｓａｎｅｓｅｎｔｉａｌｍｅｔａｌｆｏｒｔｈｅｓｕｒｖｉｖａｌ...     

Choice of jumping strategy in two standard jumps,squat and countermovement jump-effect of training background or inherited preference?

Six male subjects, three professional ballet dancers and three elite volleyball players, performed maximal vertical jumps from 1) a static preparatory position (squat jump), 2) starting with a countermovement (countermovement jump) and 3) a specific jump for ballet and for volleyball, respectively. The jumps were recorded on highspeed film (500 Hz) combined with registration of ground reaction forces, and net joint moments were calculated by inverse dynamics. The purpose was to investigate the choice of strategy in two standard jumps, squat jump and countermovement jump. The volleyball jump was performed with a sequential strategy and the ballet jump was performed with a simultaneous strategy. In the two standard jumps, the choice of strategy was individual and not related to training background. This was additionally confirmed in a test of seven ballet dancers and seven volleyball players.     

Novel method of intraoperative liver tumour localisation with indocyanine green and near-infrared imaging

INTRODUCTIONFluorescence imaging (FI) with indocyanine green (ICG) is increasingly implemented as an intraoperative navigation tool in hepatobiliary surgery to identify hepatic tumours. This is useful in minimally invasive hepatectomy, where gross inspection and palpation are limited. This study aimed to evaluate the feasibility, safety and optimal timing of using ICG for tumour localisation in patients undergoing hepatic resection.METHODSFrom 2015 to 2018, a prospective multicentre study was conducted to evaluate feasibility and safety of ICG in tumour localisation following preoperative administration of ICG either on Day 0–3 or Day 4–7.RESULTSAmong 32 patients, a total of 46 lesions were resected: 23 were hepatocellular carcinomas (HCCs), 12 were colorectal liver metastases (CRLM) and 11 were benign lesions. ICG FI identified 38 (82.6%) lesions prior to resection. The majority of HCCs were homogeneous fluorescing lesions (56.6%), while CLRM were homogeneous (41.7%) or rim-enhancing (33.3%). The majority (75.0%) of the lesions not detected by ICG FI were in cirrhotic livers. Most (84.1%) of ICG-positive lesions detected were < 1 cm deep, and half of the lesions ≥ 1 cm in depth were not detected. In cirrhotic patients with malignant lesions, those given ICG on preoperative Day 0−3 and Day 4−7 had detection rates of 66.7% and 91.7%, respectively. There were no adverse events.CONCLUSIONICG FI is a safe and feasible method to assist tumour localisation in liver surgery. Different tumours appear to display characteristic fluorescent patterns. There may be no disadvantage of administering ICG closer to the operative date if it is more convenient, except in patients with liver cirrhosis.