Hepatic steatosis in patients with HIV-Hepatitis C Virus coinfection: is it associated with antiretroviral therapy and more advanced hepatic fibrosis?

<p>Abstract</p> <p>Background and aims</p> <p>Patients with HIV and hepatitis C virus (HCV) coinfection are at increased risk of developing hepatic steatosis. The aims of this study were to assess the prevalence of steatosis in a cohort with HIV-HCV coinfection, and to determine an association, if any, between steatosis, antiretroviral therapy (ART), and advanced hepatic fibrosis.</p> <p>Patients and methods</p> <p>HIV-HCV coinfected patients were retrospectively identified from the HIV clinic. ART was classified as none, nucleoside reverse transcriptase inhibitors (NRTIs) only, highly active antiretroviral therapy (HAART) only, and sequential therapy (initial NRTIs followed by HAART). Fibrosis stage and necroinflammation grade were assessed by the modified HAI (Ishak) scoring method. Steatosis was graded as 0–3.</p> <p>Results</p> <p>Sixty patients were identified. The overall prevalence of hepatic steatosis was 58%. Those that received HAART only had a lower prevalence of steatosis (41%) compared to those on NRTIs only (70%) or sequential therapy (82%). Independent predictors of hepatic steatosis were absence of HAART only therapy, OR 2.9, p = 0.09, and presence of cirrhosis, OR 4.6, p = 0.044. Forty five percent of the patients had advanced fibrosis (fibrosis stage ≥ 3). NI grade (OR 1.9, p = 0.030), and steatosis grade (OR 3.6, p = 0.045), were independent predictors of advanced fibrosis.</p> <p>Conclusion</p> <p>Hepatic steatosis is associated with more advanced hepatic fibrosis in the HIV-HCV coinfected population. HAART only therapy (rather than NRTIs only or sequential therapy) appears to be associated with a lower prevalence of hepatic steatosis. This may be one of the mechanisms by which HAART could attenuate hepatic fibrosis in such a cohort.</p

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The Role of Liver Fibrosis Assessment in the Management of Patients with Chronic Hepatitis B Infection: Lessons Learned from a Single Centre Experience

Background & Aims. Assess the clinical utility of the Prati criteria and normal ALT (<40 IU/L) in a cohort of patients with chronic hepatitis B infection (CHB). Methods. Serology, radiology, and histology were obtained in 140 patients with CHB. Results. HBeAg+ group: 7 patients (7/56−12% HBeAg+ group) misclassified as “immunotolerant”, with HBV DNA > 6 log copies/ml and normal ALT, who in fact had moderate/severe fibrosis on liver biopsy. HBeAg− group: 10 patients with normal ALT and moderate/severe fibrosis on liver biopsy; 4 of these patients had >3 log copies/ml HBV DNA levels and 6 patients misclassified as “inactive carriers” with negative HBV DNA levels normal ALT and moderate/severe fibrosis (6/84−7% HBeAg− group). Two male HBeAg+ and three male HBeAg− patients with ALT between 20 and 30 IU/L and moderate/severe fibrosis on liver biopsy would have been further mischaracterised using the Prati criteria for normal ALT. Age and ethnic group were more important predictors of moderate/severe fibrosis in multivariate analysis. Conclusion. HBeAg status, age, ethnic origin with longitudinal assessment of LFTs and viral load should be studied in patients with “normal ALT” at the upper end of normal range (ALT 20–40 IU/L) to appropriately classify patients and identify patients for liver fibrosis assessment to inform treatment decisions

Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men

&lt;b&gt;Objective&lt;/b&gt; An epidemic of acute hepatitis C virus (HCV) infection in HIV-positive men-who-have-sex-with-men (MSM) is emerging in Europe, Australia and the USA. The aim of this study was to characterise the natural history of primary HCV in this setting and to assess host and viral factors which predict spontaneous clearance.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; This prospective longitudinal cohort study was carried out in 112 HIV-positive patients who were followed in a single centre (the St Mary's Acute HCV Cohort). Plasma and peripheral blood mononuclear cells (PBMCs) were obtained at monthly intervals for 3 months and at 3-monthly intervals thereafter for a median of 45 months (IQR=29–69 months). The primary end point was spontaneous clearance of HCV. Cox regression was used to assess the impact of clinical and virological variables on outcome, including liver function, CD4 count, rate of HCV RNA decline, T cell response and clonal sequence evolution within the HCV E2 envelope gene.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; 15% of patients cleared HCV spontaneously, while 85% progressed towards chronicity. The latter group included a significant proportion of ‘fluctuating’ progressors (37.5%), in whom a fall followed by a rise (&gt;1 log10) in viraemia was observed. This was associated with superinfection with new HCV strains and partially effective T cell responses. Spontaneous clearance was strongly associated with a 2.2 log10 viral load drop within 100 days of infection (HR=1.78; p&#60;0.0001), elevated bilirubin (≥40 μmol/l; HR=5.04; p=0.006), elevated alanine aminotransferase (ALT; ≥1000 IU/ml; HR=2.62; p=0.048) and baseline CD4 count ≥650×106/l (HR=2.66; p=0.045), and only occurred in patients with genotype 1 infection. Evolution to spontaneous clearance occurred in patients with low viral diversity in the presence of an early multispecific T cell response.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Spontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses

A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery:the BARIACT project

BackgroundBariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials-the BARIACT Study.Methods and findingsOutcomes identified from systematic reviews and patient interviews informed a questionnaire survey. Patients and health professionals were surveyed three times and asked to rate the importance of each item on a 1-9 scale. Delphi methods provided anonymised feedback to participants. Items not meeting predefined criteria were discarded between rounds. Remaining items were discussed at consensus meetings, held separately with patients and professionals, where the COS was agreed. Data sources identified 2,990 outcomes, which were used to develop a 130-item questionnaire. Round 1 response rates were moderate but subsequently improved to above 75% for other rounds. After rounds 2 and 3, 81 and 14 items were discarded, respectively, leaving 35 items for discussion at consensus meetings. The final COS included nine items: "weight," "diabetes status," "cardiovascular risk," "overall quality of life (QOL)," "mortality," "technical complications of the specific operation," "any re-operation/re-intervention," "dysphagia/regurgitation," and "micronutrient status." The main limitation of this study was that it was based in the United Kingdom only.ConclusionsThe COS is recommended to be used as a minimum in all trials of bariatric and metabolic surgery. Adoption of the COS will improve data synthesis and the value of research data. Future work will establish methods for the measurement of the outcomes in the COS

Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002

BACKGROUND: Although diet and activity are key factors in the obesity epidemic, laboratory studies suggest that endocrine disrupting chemicals may also affect obesity. METHODS: We analyzed associations between six phthalate metabolites measured in urine and body mass index (BMI) and waist circumference (WC) in National Health and Nutrition Examination Survey (NHANES) participants aged 6–80. We included 4369 participants from NHANES 1999–2002, with data on mono-ethyl (MEP), mono-2-ethylhexyl (MEHP), mono-n-butyl (MBP), and mono-benzyl (MBzP) phthalate; 2286 also had data on mono-2-ethyl-5-hydroxyhexyl (MEHHP) and mono-2-ethyl-5-oxohexyl (MEOHP) phthalate (2001–2002). Using multiple regression, we computed mean BMI and WC within phthalate quartiles in eight age/gender specific models. RESULTS: The most consistent associations were in males aged 20–59; BMI and WC increased across quartiles of MBzP (adjusted mean BMI = 26.7, 27.2, 28.4, 29.0, p-trend = 0.0002), and positive associations were also found for MEOHP, MEHHP, MEP, and MBP. In females, BMI and WC increased with MEP quartile in adolescent girls (adjusted mean BMI = 22.9, 23.8, 24.1, 24.7, p-trend = 0.03), and a similar but less strong pattern was seen in 20–59 year olds. In contrast, MEHP was inversely related to BMI in adolescent girls (adjusted mean BMI = 25.4, 23.8, 23.4, 22.9, p-trend = 0.02) and females aged 20–59 (adjusted mean BMI = 29.9, 29.9, 27.9, 27.6, p-trend = 0.02). There were no important associations among children, but several inverse associations among 60–80 year olds. CONCLUSION: This exploratory, cross-sectional analysis revealed a number of interesting associations with different phthalate metabolites and obesity outcomes, including notable differences by gender and age subgroups. Effects of endocrine disruptors, such as phthalates, may depend upon endogenous hormone levels, which vary dramatically by age and gender. Individual phthalates also have different biologic and hormonal effects. Although our study has limitations, both of these factors could explain some of the variation in the observed associations. These preliminary data support the need for prospective studies in populations at risk for obesity.National Institutes of Environmental Health Sciences (R21ES013724

Hepatitis B virus infection in HIV-positive individuals in the UK collaborative HIV cohort (UK CHIC) study.

Hepatitis B virus (HBV) infection is an increasingly important cause of morbidity and mortality in HIV-infected adults. This study aimed to determine the prevalence and incidence of HBV in the UK CHIC Study, a multicentre observational cohort

The prevention and management of viral hepatitis

In this review we will discuss advances in the primary and secondary prevention of viral hepatitis and the treatment for chronic viral hepatitis.</p

Acute HCV in HIV positive men : viral evolution and cellular immune responses

Background: The natural history of early HCV infection has been only partially characterised previously, as primary infection is usually asymptomatic. An emerging epidemic of acute HCV virus (HCV) infection in HIV-positive men in Europe, Australia and the USA has allowed the recruitment of new cohorts of patients with early HCV. We aimed to describe the natural history of virus evolution and cellular immune responses in a rare cohort of acute HCV infected HIV-positive patients in order to identify key determinants of spontaneous clearance. Methods: 110 patients were recruited and followed at 1-3 monthly intervals for a median period of 3 years. HCV E2 envelope, NS5B polymerase and NS5A genes were amplified at multiple time points using PCR and cloning techniques from plasma, liver and lymphocytes. A library of 2295 HCV E2 sequences were available for analysis .The functional immune response was assessed by ELISpot and flow cytometry. Results: 14% of patients cleared HCV spontaneously while 86% progressed towards chronicity. Three patterns of infection were observed based on viral load dynamics; spontaneous clearance (SC) and 2 patterns of progression; plateau (PV) and fluctuating viraemia (FV). SC was associated with a >1.7log10 viral load drop within 100 days of infection (OR=2.76; p=<0.001), slow viral diversification of the envelope E2 gene and the emergence of an early multi-specific T-cell response. PV was associated with positive selection within E2 and rapid viral diversification. Superinfection with new HCV strains (40% of the cohort), delayed T-cell responses and the presence of HCV within lymphocytes were all associated with FV. CD4+ responses were particularly important in defining the final outcome of infection. Conclusions: Spontaneous clearance of acute HCV in HIV-positive men can be predicted by rapid decline in viral load, low viral diversity and T-cell response. Key words: HIV, HCV, HVR-1EThOS - Electronic Theses Online ServiceGBUnited Kingdo