Fibrosis Evaluation by Transient Elastography in Patients With Long-Term Sustained HCV Clearance

BACKGROUND: Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy. OBJECTIVES: Measuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting. PATIENTS AND METHODS: We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4). RESULTS: TE was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in 28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed since achieving SVR was 36 months (range: 18-77, SD¬¬:18). Stratifying patients according to the histological stage assessed before treatment, a clear-cut gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P = 0.001). Overall, 86 patients had lower values of LS than the expected LS values according to Metavir-stage. At multivariate logistic analysis γ-GT and histological steatosis were independently associated with persistence of higher values of LS. CONCLUSION: Long term responders to IFN-based therapies have lower LS values than those who are untreated and still viraemic. High levels of γ-GT and liver steatosis, all markers of insulin resistance, may hamper reduction of liver stiffness after HCV-clearance

Clinical and laboratory findings associated with severe scrub typhus

<p>Abstract</p> <p>Background</p> <p>Scrub typhus is a mite-borne bacterial infection of humans caused by <it>Orientia tsutsugamushi </it>that causes a generalized vasculitis that may involve the tissues of any organ system. The aim of this study was to identify factors associated to severe complications from scrub typhus.</p> <p>Methods</p> <p>We conducted this prospective, case-control study on scrub typhus patients who presented to the Department of Internal Medicine at Chosun University Hospital between September, 2004 and December, 2006. Cases were 89 scrub typhus patients with severe complications and controls were 119 scrub typhus patients without severe complications.</p> <p>Results</p> <p>There were significant differences in the absence of eschar, white blood cell (WBC) counts, hemoglobin, albumin, serum creatinine, fibrinogen, C-reactive protein (CRP), and active partial thromboplastin time (aPTT) between the two groups. Multivariate analysis demonstrated that only the following four factors were significantly associated with the severe complications of scrub typhus: (1) age ≥ 60 years (odd ratio [OR] = 3.13, <it>P </it>= 0.002, confidence interval [CI] = 1.53-6.41), (2) the absence of eschar (OR = 6.62, <it>P </it>= 0.03, CI = 1.22-35.8, (3) WBC counts > 10, 000/mm3 (OR = 3.6, <it>P </it>= 0.001, CI = 1.65-7.89), and (4) albumin ≤ 3.0 g/dL (OR = 5.01, <it>P </it>= 0.004, CI = 1.69-14.86).</p> <p>Conclusions</p> <p>Our results suggest that clinicians should be aware of the potential for complications, when scrub typhus patients are older (≥ 60 years), presents without eschar, or laboratory findings such as WBC counts > 10, 000/mm3, and serum albumin level ≤ 3.0 g/dL. Close observation and intensive care for scrub typhus patients with the potential for complications may prevent serious complications with subsequent reduction in its mortality rate.</p

Genetic structure of Miscanthus sinensis and Miscanthus sacchariflorus in Japan indicates a gradient of bidirectional but asymmetric introgression

Unilateral introgression from diploids to tetraploids has been hypothesized to be an important evolutionary mechanism in plants. However, few examples have been definitively identified, perhaps because data of sufficient depth and breadth were difficult to obtain prior to the advent of affordable high-density genotyping. Throughout Japan, tetraploid Miscanthus sacchariflorus and diploid M. sinensis are common, and occasionally hybridize. In this study, we characterized 667 M. sinensis and 78 M. sacchariflorus genotypes from Japan using 20,704 SNPs and ten plastid microsatellites. Similarity of SNP genotypes between diploid and tetraploid M. sacchariflorus indicated that the tetraploids originated via autopolyploidy. Structure analysis indicated a gradient of introgression from diploid M. sinensis into tetraploid M. sacchariflorus throughout Japan; most tetraploids had some M. sinensis DNA. Among phenotypically M. sacchariflorus tetraploids, M. sinensis ancestry averaged 7% and ranged from 1-39%, with introgression greatest in southern Japan. Unexpectedly, rare (~1%) diploid M. sinensis individuals from northern Japan were found with 6-27% M. sacchariflorus ancestry. Population structure of M. sinensis in Japan included three groups, and was driven primarily by distance, and secondarily by geographic barriers such as mountains and straits. Miscanthus speciation is a complex and dynamic process. In contrast to limited introgression between diploid M. sacchariflorus and M. sinensis in northern China, selection for adaptation to a moderate maritime climate likely favored cross-ploidy introgressants in southern Japan. Our results will help guide the selection of Miscanthus accessions for the breeding of biomass cultivars.Office of Science - Biological and Environmental Research, U.S. Department of Energy [Project ID 0017582]Energy Biosciences InstituteOpe

Telbivudine combination with adefovir versus adefovir monotherapy in HBeAg-positive chronic hepatitis B (CHB) patients with lamivudine resistance

Background/Aims: A large proportion of patients fail lamivudine treatment and guidelines recommend switching to nucleotides or add-on therapy. The aim of this report is to evaluate the efficacy and safety of the switch to adefovir (ADV) monotherapy versus telbivudine (LDT) plus adefovir in CHB patients with confirmed YMDD mutation with prior lamivudine treatment. Methods: 150 HBeAg positive patients were planned to be included into an open label randomized 96-week trial evaluating ADV versus ADV + LDT. The study was terminated early due to difficulties enrolling patients into the ADV monotherapy arm. However, 42 patients were randomized 1:1 (91% Korean). Results: Median treatment duration was 48 weeks and 20 patients per arm completed 48 weeks of treatment. HBV DNA decline at week 24 was higher in the combination arm versus ADV monotherapy arm: -6.7 versus -5.0 log10 copies/ml (baseline ADV + LDT:10.3; ADV:10.1 log10 copies/ml). At week 48, HBV DNA decline by -7.4 (ADV + LDT) and -4.9 (ADV) log10 copies/ml, with 38.5% (5/13) and 0% (0/9) of patients, respectively, achieving undetectable HBV DNA (300 copies/ml). Virologic breakthrough occurred in 0% (0/21) of ADV + LDT and 9.6% (2/21) of ADV patients. HBeAg loss was achieved in one patient per arm at week 24 and in 23.1% (3/13) and 0% (0/9) at week 48 in the ADV+LDT versus ADV groups. The safety profile was similar in both treatment arms with 16 AEs reported per group. ALT flares (AASLD criteria) occurred in one patient per arm, increased creatine phosphokinase was reported in 3/21 patients ADV + LDT and 1/21 ADV arm, but all were grade 1/2. One case of musculoskeletal pain and parasthesia each occurred in the combination arm. Conclusion: In these 42 patients with established YMDD resistance on lamivudine treatment, the switch to the combination of telbivudine and adefovir showed better outcomes compared with adefovir alone, and both had a similar safety profile

Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B

BACKGROUND: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. DESIGN: We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. RESULTS: At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (0.05). The serum mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were -5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were -4.65, -4.55 and -4.67, respectively (p>0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1%) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. CONCLUSIONS: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.link_to_subscribed_fulltex