Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.status: publishe

Symptomatic Acute Hepatitis C in Egypt: Diagnosis, Spontaneous Viral Clearance, and Delayed Treatment with 12 Weeks of Pegylated Interferon Alfa-2a

The aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously.Patients with symptomatic acute hepatitis C were recruited from two "fever hospitals" in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 microg/week).Between May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%-43.2%]) at three months and 41.5% (95%CI [33.0%-51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4-6 months after onset of symptoms was 15/17 = 88.2% (95%CI [63.6%-98.5%]).Spontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C

SARS-CoV-2 serological profile in healthcare professionals of a Southern Italy hospital

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the first coronavirus that has caused a pandemic. Assessing the prevalence of anti-SARS-CoV-2 in healthcare worker groups offers a unique opportunity to study the correlation between seroconversion and immunization because of their occupational exposure and a higher risk of contagion. The study enrolled 3242 asymptomatic employees of “Policlinico Riuniti”, Foggia. After the first screening, we collected sequential serum samples for up to 23 weeks from the same subjects. In order to perform a longitudinal follow-up study and get information about the titration of IgG levels, we analyzed data from subjects (33) with at least two consecutive serological IgG—positive tests; 62 (1.9%; 95% CI: 1.4–2.3) tested positive for at least one anti-SARS-CoV-2 antibody. The seroprevalence was lower in the high-risk group 1.4% (6/428; 95% CI: 0.5–2.6) vs. the intermediate-risk group 2.0% (55/2736; 95% CI: 1.5–2.5). Overall, within eight weeks, we detected a mean reduction of –17% in IgG levels. Our data suggest a reduction of about 9.27 AU/mL every week (R2 = 0.35, p = 0.0003). This study revealed the prevalence of SARS-CoV-2 antibodies among Foggia’s hospital healthcare staff (1.9%). Moreover, the IgG level reduction suggests that the serological response fades fast in asymptomatic infections

Identification of na\uefve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin

Background & Aims The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. Methods In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. Results Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637-7.101), low (80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. Conclusions A consistent subset of na\uefve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin. \ua9 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B

BACKGROUND: After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants. METHODS: The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced. RESULTS: Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers. CONCLUSIONS: Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children

The Jurassic–Cretaceous depositional and tectonic evolution of the southernwestern margin of the Neotethys Ocean, Northern Oman and United Arab Emirates

The concept that the autochthonous, parautochthonous and allochthonous Permian–Cretaceous sequences in the United Arab Emirates (UAE) and Oman record the transition from platform, slope to basin sedimentation within the southern part of Neotethys has been fundamental to the interpretation of the geological history of the region. The results of a major geological mapping programme of the UAE, carried out by the British Geological Survey for the Federal Government of the UAE, coupled with the detailed examination of key sections within northern Oman has led to a re-evaluation of the geological evolution of this region. This detailed study has led to a greater appreciation of the sedimentology and depositional setting of the sediments laid down along the northeastern Arabian continental margin during the Jurassic to Cretaceous, allowing a more refined model of Neotethys Ocean basin evolution to be established. The model charts the progressive breakup of the Arabian continental margin and closure of Neotethys during the mid to late Cretaceous and is divided into three main stages: Stage 1—Initial rifting and formation of the Neotethys Ocean, followed by a prolonged period of stable, passive margin sedimentation which extended from the Permian to Late Jurassic times; Stage 2—Uplift and erosion of the shelf margin during the Late Jurassic to Early Cretaceous, coincident with increased carbonate-clastic sedimentation in the outer ramp, distal slope and basinal areas; Stage 3—Increased instability during the Late Cretaceous leading to the breakup of the platform margin and foreland basin sedimentation accompanying the obduction of the Oman-UAE ophiolite. Data obtained for the upper part of the platform and platform margin to slope successions has revealed that the topography of the “shelf”-slope-basinal margin was more subdued than previously thought, with this more gentle ramp margin morphology persisting until early to mid-Cretaceous times when the platform margin started to become unstable during ophiolite obduction. The thrust-repeated allochthonous sedimentary rocks of the Hamrat Duru Group were deposited on the outer platform margin/lower slope rise to basinal plain of this basin margin and includes the dismembered remains of two turbidite fan systems which fed carbonate-rich detritus into deeper parts of the ocean. A re-evaluation of the chert-rich sequences, previously equated with deposition on the abyssal plain of Neotethys, has led to the conclusion that they may record sedimentation at a much shallower level within a starved ocean basin, possibly in a mid-ramp (above storm wave base) to outer ramp setting. A marked change in basin dynamics occurred during the mid-Cretaceous leading to the development of a shallow ramp basin margin in Oman with terrestrial to shallow marine sedimentary rocks interdigitating with red siliceous mudstones. By contrast, the contemporaneous succession in the Dibba Zone of the UAE indicates considerable instability on a steep shelf break. This instability is recorded by the presence of several major olistostrome deposits within the Aruma Group of the UAE which are thought to have been generated in advance of the rapidly obducting Oman-UAE ophiolite

Hepatitis B Therapy in Pregnancy

All decisions about initiating, continuing, or stopping therapy of the hepatitis B virus (HBV) during pregnancy must include an analysis of the risks and benefits for mother and fetus. The trimester of the pregnancy and the stage of the mother’s liver disease are important factors. Treatment in the third trimester may be initiated to aid in preventing perinatal transmission, which appears to be most pronounced in mothers with high viral loads. Consideration of initiating treatment in the third trimester should occur after a high viral load is documented in the latter part of the second trimester, to allow adequate time for initiation of antiviral therapy with significant viral suppression before delivery. This discussion should include the topic of breastfeeding, because it is generally not recommended while receiving antiviral therapy. Currently, lamivudine and tenofovir appear to be the therapeutic options with the most reasonable safety data in pregnancy