Rare Birds in North America: Acute Hepatitis C Cohorts

TY - JOUR

T1 - Rare Birds in North America

T2 - Acute Hepatitis C Cohorts

AU - Cox, Andrea L.

AU - Page, Kimberly

AU - Bruneau, Julie

AU - Shoukry, Naglaa H.

AU - Lauer, Georg M.

AU - Kim, Arthur Y.

AU - Rosen, Hugo R.

AU - Radziewicz, Hank

AU - Grakoui, Arash

AU - Fierer, Daniel S.

AU - Branch, Andrea D.

AU - Kaplan, David E.

AU - Chang, Kyong Mi

N1 - Funding Information: Studies of this cohort focus on understanding the mechanisms governing cytotoxic T-cell escape, 18 the importance of CD4 + T-cell help, 19 characterization of T-cell thresholds associated with recovery, 19 the suppressive function of regulatory T cells in the early stages of infection, 20 dysregulation of interleukin-7Ra and persistence, 21 and the innate immune response, particularly of natural killer and natural T cells. 22 Collaborations have been established with the Massachusetts General Hospital/Broad Institute and The Johns Hopkins University groups to address novel questions utilizing this rare population of individuals. Work with this cohort has been funded by NIH RO1 DK60590 Funding Information: Histopathology studies on this cohort showed that fibrogenesis occurred early and was markedly accelerated in this group of subjects 27 : 17 of the first 20 biopsies, performed at a median of 4.3 months after the first noted increase in ALT levels, revealed stage 2 (of 4, Scheuer scale) fibrosis, a much greater number than reported in patients who acquired HCV infection before HIV infection. Age and male gender may contribute to this rapid fibrosis progression, but no other known risk factors for fibrosis explain these findings. Treatment with pegylated interferon and weight-based ribavirin during the acute phase resulted in a 70% sustained viral response rate. Early spontaneous clearance occurred in approximately 15% of patients, but was not related to the occurrence of symptomatic hepatitis. Ongoing work centers on understanding factors contributing to the accelerated fibrosis progression, maximizing treatment response, and characterizing factors that are contributing to this ongoing outbreak of acute HCV infection among HIV-infected men who have sex with men in New York City. Investigators of the Philadelphia Cohort collaborate in this study to characterize early immunologic responses in HIV-infected patients. The work with this cohort has been funded by NIH DA016156 and DK066939. Funding Information: Acute hepatitis C is diagnosed by a combination of clinical and serologic findings, including documented HCV seroconversion and/or spontaneous viremic fluctuations in patients with recent increases in liver enzymes without other causes of liver diseases as recently described. 24 Patients are asked a series of questions to identify the potential source, timing, and circumstance of HCV inoculation. With patient's consent, relevant clinical laboratory measures are communicated to the patient and the primary hepatologist for clinical decisions—to be made at the discretion of each patient's primary clinical provider with the patient. Active follow-up is maintained by the research coordinator; blood samples are collected to monitor the clinical and virologic course as well as immunologic parameters (particularly the adaptive immune response). Studies of this cohort have resulted in a number of observations regarding the relevance of antiviral effector and regulatory T-cell, as well as neutralizing antibody, responses in patients with acute hepatitis C. 24,25 Moreover, studies are examining the relevance of immune inhibitory or costimulatory molecules in HCV immune pathogenesis. 26 The work with this cohort has been funded by the National Institutes of Health (NIAID, RO-1 AI47519) and the WW Smith Charitable Foundation. Funding Information: Based on data from this cohort, researchers hope to understand correlates of the innate and adaptive immune responses to the outcome of HCV during the acute phase and early interferon therapy, 8 as well as the impact of acute HCV infection and antiviral treatment on the behaviors and quality of life of active IDUs who have access to IDU-targeted health services. 9 The work with this cohort was supported by grants from the Canadian Institutes for Health Research (CIHR) (MOP-74524, MOP-74581, MOP-84451), Fonds de la Recherche en Santé du Quebec (FRSQ) (FRSQ-12428), and the FRSQ-AIDS and Infectious Disease Network (SIDA-MI). Funding Information: The work with this cohort has been funded by NIH DA016156 and DK066939. Funding Information: In this cohort, the researchers study T-cell functional deficits and the role of coinhibitory receptors such as PD-1 in regulating HCV-specific immune responses. 23 Clinicians at the Atlanta VA collaborate in research to better understand the immune response to HCV and host determinants of infection outcome. We acknowledge the support from the Grand Challenges in Global Health Initiative, EVC/CFAR Flow Cytometry Core P30 AI050409, Cancer Research Institute Investigator Award (AG), the Yerkes Research Center Base Grant RR-00165, and the Public Health Service [K08 AI072191 (HR), AI070101 (AG)].

PY - 2009/1

Y1 - 2009/1

UR - https://www.scopus.com/pages/publications/59849089441

U2 - 10.1053/j.gastro.2008.11.049

DO - 10.1053/j.gastro.2008.11.049

M3 - Editorial

C2 - 19059257

AN - SCOPUS:59849089441

SN - 0016-5085

VL - 136

SP - 26

EP - 31

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -