Research Papers

@article{N2021,
title = {Liver Fibrosis in Human Immunodeficiency Virus (HIV)-Hepatitis C Virus (HCV) Coinfection Before and After Sustained Virologic Response: What Is the Best Noninvasive Marker for Monitoring Regression?},
author = {N, Kronfli; J, Young; S, Wang; J, Cox; S, Walmsley; M, Hull; C, Cooper; V, Martel-Laferriere; A, Wong; N, Pick; MB, Klein; Canadian Coinfection Cohort Study Investigators.},
url = {https://academic.oup.com/cid/article/73/3/468/5854053?login=false},
doi = {10.1093/cid/ciaa702},
year = {2021},
date = {2021-08-02},
journal = {Clinical Infectious Diseases},
abstract = {Background: Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in human immunodeficiency virus (HIV)-HCV coinfected patients.

Methods: Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least 1 pre- and posttreatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modeled using a generalized additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent body mass index, binge drinking, and detectable HIV RNA.

Results: Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -.05, .12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -.06, .01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: .36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -.80, -.31) after SVR.

Conclusions: TE should be the preferred noninvasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.},
keywords = {APRI, Fibrosis regression, HIV-HCV coinfection, Sustained virologic response, Transient elastography},
pubstate = {published},
tppubtype = {article}
}

@article{Kronfli2020,
title = {Liver fibrosis in HIV-Hepatitis C virus (HCV) co-infection before and after sustained virologic response: what is the best non-invasive marker for monitoring regression?},
author = {Nadine Kronfli and Jim Young and Shouao Wang and Joseph Cox and Sharon Walmsley and Mark Hull and Curtis Cooper and Valerie Martel-Laferriere and Alexander Wong and Neora Pick and Marina B Klein and Canadian Co-infection Cohort Study Investigators},
url = {https://pubmed.ncbi.nlm.nih.gov/32504083/},
doi = {10.1093/cid/ciaa702},
year = {2020},
date = {2020-06-05},
journal = {Clinical Infectious Diseases},
abstract = {Background: Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in HIV-HCV coinfected patients.

Methods: Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least one pre- and post-treatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modelled using a generalised additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent BMI, binge drinking and detectable HIV RNA.

Results: Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -0.05, 0.12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -0.06, 0.01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: 0.36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -0.80, -0.31) after SVR.

Conclusions: TE should be the preferred non-invasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.},
keywords = {APRI, Fibrosis regression, HIV-HCV co-infection, Sustained virologic response, Transient elastography},
pubstate = {published},
tppubtype = {article}
}

@article{A2019,
title = {Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis},
author = {Benmassaoud A and Nitulescu R and Pembroke T and Halme AS and Ghali P and Deschenes M and Wong P and Klein MB and Sebastiani G},
url = {https://pubmed.ncbi.nlm.nih.gov/30561558/},
doi = {10.1093/cid/ciy1082},
year = {2019},
date = {2019-09-27},
journal = {Clinical Infectious Diseases},
abstract = {Background: Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown.

Methods: HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status.

Results: A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%).

Conclusions: HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.},
keywords = {HCC surveilance, HIV, Liver-related events, Occult cirrhosis, Transient elastography},
pubstate = {published},
tppubtype = {article}
}

@article{T2017,
title = {Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis},
author = {Pembroke T and Deschenes M and Lebouché B and Benmassaoud A and Sewitch M and Ghali P and Wong P and Halme A and Vuille-Lessard E and Pexos C and Klein MB and Sebastiani G},
url = {https://pubmed.ncbi.nlm.nih.gov/28527666/},
doi = {10.1016/j.jhep.2017.05.011},
year = {2017},
date = {2017-10-01},
journal = {Journal of Hepatology},
abstract = {Background & aims: Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear.

Methods: The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression.

Results: A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection.

Conclusion: HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.},
keywords = {Controlled attenuation parameter, Hepatic steatosis, HIV mono-infection, HIV-HCV co-infection, Incidence, Liver fibrosis, Liver stiffness, Prevalence, Transient elastography},
pubstate = {published},
tppubtype = {article}
}