Research Papers

@article{LI2016,
title = {Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus–coinfected Individuals From 2001 to 2014: A Multicohort Study},
author = {Gjærde LI and Shepherd L and Jablonowska E and Lazzarin A and Rougemont M and Darling K and Battegay M and Braun D and Martel-Laferriere V and Lundgren JD and Rockstroh JK and Gill J and Rauch A and Mocroft A and Klein MB and Peters L},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996136/},
doi = {10.1093/cid/ciw380},
year = {2016},
date = {2016-06-15},
journal = {Clinical Infectious Diseases},
abstract = {Background. While liver-related deaths in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)–coinfected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We describe the epidemiology of HCC and other liver events in a multicohort collaboration of HIV/HCV–coinfected individuals.

Methods. We studied HCV antibody-positive adults with HIV in the EuroSIDA study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios.

Results. Our study comprised 7229 HIV/HCV–coinfected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval [CI], 1.3, 2.0) and 8.6 (95% CI, 7.8, 9.5) cases per 1000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI, 4%, 19%) and decreased 4% for other liver events (95% CI, 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. Older age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events.

Conclusions. In HIV/HCV–coinfected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.},
keywords = {Cohort study, HCV, Hepatocellular carcinoma, HIV, Liver disease},
pubstate = {published},
tppubtype = {article}
}

@article{Costiniuk2016,
title = {Tobacco Smoking Is Not Associated With Accelerated Liver Disease in Human Immunodeficiency Virus-Hepatitis C Coinfection: A Longitudinal Cohort Analysis},
author = {Cecilia T. Costiniuk and Laurence Brunet and Kathleen C. Rollet-Kurhajec and Curtis Cooper and Sharon Walmsley and M. John Gill and Valérie Martel-Laferriere and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27047987},
doi = {10.1093/ofid/ofw050},
year = {2016},
date = {2016-03-04},
journal = {Open Forum Infectious Diseases},
abstract = {Background.  Tobacco smoking has been shown to be an independent risk factor for liver fibrosis in hepatitis C virus (HCV) infection in some cross-sectional studies. No longitudinal study has confirmed this relationship, and the effect of tobacco exposure on liver fibrosis in human immunodeficiency virus (HIV)-HCV coinfected individuals is unknown. Methods.  The study population consisted of participants from the Canadian Co-infection Cohort study (CTN 222), a multicenter longitudinal study of HIV-HCV coinfected individuals from 2003 to 2014. Data were analyzed for all participants who did not have significant fibrosis or end-stage liver disease (ESLD) at baseline. The association between time-updated tobacco exposure (ever vs nonsmokers and pack-years) and progression to significant liver fibrosis (defined as an aspartate-to-platelet ratio index [APRI] ≥1.5) or ESLD was assessed by pooled logistic regression. Results.  Of 1072 participants included in the study, 978 (91%) had ever smoked, 817 (76%) were current smokers, and 161 (15%) were previous smokers. Tobacco exposure was not associated with accelerated progression to significant liver fibrosis nor with ESLD when comparing ever vs never smokers (odds ratio [OR] = 1.06, 95% confidence interval [CI], 0.43-1.69 and OR = 1.20, 95% CI, 0.21-2.18, respectively) or increases in pack-years smoked (OR = 1.05, 95% CI, 0.97-1.14 and OR = 0.94, 95% CI, 0.83-1.05, respectively). Both time-updated alcohol use in the previous 6 months and presence of detectable HCV ribonucleic acid were associated with APRI score ≥1.5. Conclusions.  Tobacco exposure does not appear to be associated with accelerated progression of liver disease in this prospective study of HIV-HCV coinfected individuals.},
keywords = {Cohort study, HCV, HIV, Liver disease, Tobacco},
pubstate = {published},
tppubtype = {article}
}

@article{Brunet2013,
title = {Marijuana Smoking Does Not Accelerate Progression of Liver Disease in HIV–Hepatitis C Coinfection: A Longitudinal Cohort Analysis},
author = {Laurence Brunet and Erica E. M. Moodie and Kathleen C. Rollet-Kurhajec and Curtis Cooper and Sharon Walmsley and Martin Potter and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23811492},
doi = {10.1093/cid/cit378},
year = {2013},
date = {2013-09-14},
journal = {Clinical Infectious Diseases},
volume = {57},
number = {5},
pages = {663-670},
abstract = {BACKGROUND:
Marijuana smoking is common and believed to relieve many symptoms, but daily use has been associated with liver fibrosis in cross-sectional studies. We aimed to estimate the effect of marijuana smoking on liver disease progression in a Canadian prospective multicenter cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected persons.
METHODS:
Data were analyzed for 690 HCV polymerase chain reaction positive (PCR-positive) individuals without significant fibrosis or end-stage liver disease (ESLD) at baseline. Time-updated Cox Proportional Hazards models were used to assess the association between the average number of joints smoked/week and progression to significant liver fibrosis (APRI ≥ 1.5), cirrhosis (APRI ≥ 2) or ESLD.
RESULTS:
At baseline, 53% had smoked marijuana in the past 6 months, consuming a median of 7 joints/week (IQR, 1-21); 40% smoked daily. There was no evidence that marijuana smoking accelerates progression to significant liver fibrosis (APRI ≥ 1.5) or cirrhosis (APRI ≥ 2; hazard ratio [HR]: 1.02 [0.93-1.12] and 0.99 [0.88-1.12], respectively). Each 10 additional joints/week smoked slightly increased the risk of progression to a clinical diagnosis of cirrhosis and ESLD combined (HR, 1.13 [1.01-1.28]). However, when exposure was lagged to 6-12 months before the diagnosis, marijuana was no longer associated with clinical disease progression (HR, 1.10 [0.95-1.26]).
CONCLUSIONS:
In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection. A slight increase in the hazard of cirrhosis and ESLD with higher intensity of marijuana smoking was attenuated after lagging marijuana exposure, suggesting that reverse causation due to self-medication could explain previous results.},
keywords = {Cannabis, Cohort study, HCV, HIV, Liver disease},
pubstate = {published},
tppubtype = {article}
}

@article{Vali2010,
title = {HCV-specific T cells in HCV/HIV Co-infection show elevated frequencies of dual Tim-3/PD-1 expression that correlate with liver disease progression},
author = {Bahareh Vali and R. Brad Jones and Ali Sakhdari and Prameet M. Sheth and Kiera Clayton and Feng-Yun Yue and Gabor Gyenes and David Wong and Marina B. Klein and Sahar Saeed and Erika Benko and Colin Kovacs and Rupert Kaul and Mario A. Ostrowski},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20623550},
doi = {10.1002/eji.201040340},
year = {2010},
date = {2010-09-01},
journal = {European Journal of Immunology},
volume = {40},
number = {9},
pages = {2493-2505},
abstract = {Co-infection of HCV with HIV has been associated with more rapid progression of HCV-related disease. HCV-specific T-cell immune responses, which are essential for disease control, are attenuated in co-infection with HIV. T-cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) expression in T-cell exhaustion during HCV/HIV co-infection. We show that in HCV/HIV co-infection, both total and HCV-specific T cells co-express Tim-3 and PD-1 in significantly higher frequencies, compared with HCV mono-infection. Co-expression of these two markers on HCV-specific CD8(+) T cells positively correlated with a clinical parameter of liver disease progression. HCV-specific CD8(+) T cells showed greater frequencies of Tim-3/PD-1 co-expression than HIV-specific CD8(+) T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim-3 or PD-1 pathways restored both HIV- and HCV-specific CD8(+) T-cell expansion in the blood of co-infected individuals. These data demonstrate that co-expression of Tim-3 and PD-1 may play a significant role in HCV-specific T-cell dysfunction, especially in the setting of HIV co-infection.},
keywords = {HIV-HCV co-infection, Liver disease, T-cell exhaustion},
pubstate = {published},
tppubtype = {article}
}