4 New HCV ABSTRACTS

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Clin Infect Dis. 2011 Jan 31. [Epub ahead of print]

Patterns and Characteristics of Hepatitis C Transmission Clusters among

HIV-Positive and HIV-Negative Individuals in the Australian Trial in Acute

Hepatitis C.

s GV, Pham ST, Hellard M, Grebely J, Zhang L, Oon A, Marks P, van Beek I,

Rawlinson W, Kaldor JM, Lloyd A, Dore GJ, White PA; on behalf of the ATAHC Study

Group.

National Centre in HIV Epidemiology and Clinical Research.

Abstract

Background. Injecting drug users remain the population at greatest risk of

acquiring hepatitis C virus (HCV) infection, although a recent increase in cases

of sexually transmitted HCV infection has been observed among human

immunodeficiency virus (HIV)-infected individuals. The extent to which these

separate epidemics overlap is unknown. Methods. The Australian Trial in Acute

Hepatitis C (ATAHC) enrolled 163 individuals (29% of whom were HIV infected)

with recent HCV infection. E1/HVR1 sequences were used to construct phylogenetic

trees demonstrating monophyletic clusters or pairs, and viral epidemic history

and phylogeography were assessed using molecular clock analysis. Individual

clusters were characterized by clinical and demographic characteristics.

Results. Transmission through injection drug use occurred for 73% of subjects,

with sexual transmission occurring for 18% (92% of whom were HIV infected).

Among 112 individuals with available E1/HVR1 sequences, 23 (20%) were infected

with a strain of HCV identical to that of another subject, comprising 4

homologous clusters and 3 monophyletic pairs, the majority of which (78%) were

HIV infected. Clusters contained individuals with both injection drug

use-related and sex-related acquisition, and in all clusters (except for 1

female HIV-uninfected pair), individuals identified as men who have sex with

men, irrespective of HIV status. Conclusions. This large unique study of

HIV-infected and HIV-uninfected individuals with recently acquired HCV infection

demonstrates that clustering is common in the HIV-infected population and that

it occurred almost invariably among men who have sex with men, irrespective of

the actual mode of acquisition. These findings suggest the coexistence of both

injection drug use and sexual risk behaviors for individuals in the same social

networks and have implications for the development of public health messages.

Clinical trial registration. NCT00192569.

PMID: 21282185 [PubMed - as supplied by publisher]

Related citations

2.Clin Infect Dis. 2011 Jan 31. [Epub ahead of print]

Incident Hepatitis C Virus Infection among US HIV-Infected Men Enrolled in

Clinical Trials.

LE, Holubar M, Wu K, Bosch RJ, Wyles DL, JA, Mayer KH, Sherman KE,

Tashima KT.

Department of Medicine, Brown University, Providence, Rhode Island.

Abstract

Background. Outbreaks of sexually transmitted hepatitis C virus (HCV) infection

have been reported among human immunodeficiency virus (HIV)-infected men who

have sex with men in Europe, Australia, and New York. Whether this is occurring

across the United States is unknown. Methods. We determined incidence of HCV

infection during 1996-2008 among male participants of the AIDS Clinical Trial

Group Longitudinal Linked Randomized Trials cohort, a long-term study of

HIV-infected persons randomized into selected US-based clinical trials. We

evaluated associations with self-reported injection drug use (IDU), time-varying

CD4(+) cell count, and HIV RNA level with use of multivariate Poisson

regression. No sexual or non-IDU risk factor data was available. Results. A

total of 1830 men had an initial negative HCV antibody test result and at least

1 subsequent HCV antibody test result, contributing >7000 person-years. At the

time of the initial negative HCV antibody test result, 94% of men were receiving

highly active antiretroviral therapy (HAART) and 6% reported current or prior

IDU. Thirty-six seroconverted, with overall incidence of .51 cases per 100

person-years (95% confidence interval, .36-.70). Mean age at seroconversion was

46 years. Seroconversion was associated with IDU (25% of seroconverters reported

IDU history vs 5% of nonseroconverters; P < .001), whereas 75% (n = 27) of

seroconverters reported no IDU (incidence, 2.67 cases per 100 person-years among

IDUs, .40 cases per 100 person-years among non-IDUs). Seroconversion was

associated with HIV RNA level >400 copies/mL (44% at time of antibody positivity

vs 21% at time of last negative antibody test result; P = .02) but not with

CD4(+) cell count. Conclusions. Incident HCV infection occurs in HIV-infected

men involved in US HIV therapeutic trials, primarily through nonparenteral

means, despite engagement in care and HAART. HCV antibody development was not

related to immune status but was associated with inadequate HIV suppression.

At-risk HIV-infected persons should have access to HCV surveillance.

PMID: 21282184 [PubMed - as supplied by publisher]

Gut. 2011 Jan 26. [Epub ahead of print]

Hepatic fatty acid translocase CD36 upregulation is associated with insulin

resistance, hyperinsulinaemia and increased steatosis in non-alcoholic

steatohepatitis and chronic hepatitis C.

Miquilena-Colina ME, Lima-Cabello E, Sánchez-Campos S, García-Mediavilla MV,

Fernández-Bermejo M, Lozano-Rodríguez T, Vargas-Castrillón J, Buqué X, Ochoa

B, Aspichueta P, González-Gallego J, García-Monzón C.

University Hospital Santa Cristina, Instituto de Investigación Sanitaria

Princesa, Madrid, Spain.

Abstract

Background Fatty acid translocase CD36 (FAT/CD36) mediates uptake and

intracellular transport of long-chain fatty acids in diverse cell types. While

the pathogenic role of FAT/CD36 in hepatic steatosis in rodents is well-defined,

little is known about its significance in human liver diseases. Objective To

examine the expression of FAT/CD36 and its cellular and subcellular distribution

within the liver of patients with non-alcoholic fatty liver disease (NAFLD) and

chronic hepatitis C virus (HCV) infection. Patients 34 patients with

non-alcoholic steatosis (NAS), 30 with non-alcoholic steatohepatitis (NASH), 66

with HCV genotype 1 (HCV G1) and 32 with non-diseased liver (NL). Methods

Real-time PCR and western blot analysis were used to assess hepatic FAT/CD36

expression. Computational image analysis of immunostained liver biopsy sections

was performed to determine subcellular distribution and FAT/CD36 expression

index. Results Compared with NL, hepatic mRNA and protein levels of FAT/CD36

were significantly higher in patients with NAS (median fold increase 0.84 (range

0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and

0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and

0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and

0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly

located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1

with steatosis. A significant correlation was observed between hepatic FAT/CD36

expression index and plasma insulin levels, insulin resistance (HOMA-IR) and

histological grade of steatosis in patients with NASH (r=0.663, r=0.735 and

r=0.711, respectively) and those with HCV G1 with steatosis (r=0.723, r=0.769

and r=0.648, respectively). Conclusions Hepatic FAT/CD36 upregulation is

significantly associated with insulin resistance, hyperinsulinaemia and

increased steatosis in patients with NASH and HCV G1 with fatty liver.

Translocation of this fatty acid transporter to the plasma membrane of

hepatocytes may contribute to liver fat accumulation in patients with NAFLD and

HCV.

PMID: 21270117 [PubMed - as supplied by publisher]

Hepatology. 2011 Feb;53(2):596-603. doi: 10.1002/hep.24098. Epub 2011 Jan 10.

Serum chemokine CXC ligand 10 (CXCL10) predicts fibrosis progression after liver

transplantation for hepatitis C infection.

Berres ML, Trautwein C, Schmeding M, Eurich D, Tacke F, Bahra M, Neuhaus P,

Neumann UP, Wasmuth HE.

Medical Department III, University Hospital Aachen, Aachen, Germany.

Abstract

The recurrence of liver fibrosis after liver transplantation (LT) for hepatitis

C virus (HCV) infection is responsible for graft loss and patient mortality.

Although the contribution of the immune system to fibrosis recurrence is

anticipated, systematic studies evaluating immune parameters as predictive

markers of allograft fibrosis are lacking. The infiltration of immune cells into

the graft is governed by chemokines. Here we assessed the predictive value of

serum levels of chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10,

CXCL11, and chemokine (C-C motif) ligand 2 (CCL2)] with respect to fibrosis

recurrence after LT in 90 HCV-infected organ recipients. Chemokines were

determined within the first and third years after LT and were correlated with

histological fibrosis progression in protocol biopsy samples at 1, 3, 5, and 7

years (median follow-up = 3 years). The association of chemokines with fibrosis

progression was assessed by univariate and multivariate analyses and by

regression analysis. The results for the analyzed chemokines showed that CXCL10

levels in the first year after LT were strongly associated with early fibrosis

recurrence (P = 0.005) independently of risk confounders (including the donor

age, HCV viral load, HCV genotype, acute rejection, and inflammatory activity).

As assessed by regression analysis, a CXCL10 serum level ≤ 140 pg/mL was

significantly predictive of the absence of F2 fibrosis (P = 0.001), whereas a

level ≤ 220 pg/mL early after LT predicted the absence of F3 fibrosis during

follow-up (P = 0.035). Conclusion: CXCL10 is an independent biomarker of the

recurrence of significant fibrosis after LT for HCV infection. These results

might guide patients' care after transplantation and help us to select optimal

candidates for antiviral therapy post-LT. (HEPATOLOGY 2011;53:596-603).

Copyright © 2010 American Association for the Study of Liver Diseases.

PMID: 21274880 [PubMed - in process]