• Humans
• Hepatic Stellate Cells/metabolism
• HIV Infections/complications
• HIV Infections/metabolism
• HIV Infections/virology
• HIV Infections/immunology
• Coinfection
• Hepacivirus/physiology
• Hepatitis C/metabolism
• Hepatitis C/virology
• Hepatitis C/complications
• Hepatitis C/immunology
• Coculture Techniques
• Jurkat Cells
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Liver Cirrhosis/virology
• Liver Cirrhosis/etiology
• Cytokines/metabolism
• Bystander Effect
• Hepatocytes/metabolism
• Hepatocytes/virology
• HIV/physiology
• Oxidative Stress
• Cell Communication
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/metabolism
• Extracellular Matrix/metabolism

• HIV
• alcohol
• cause-specific
• cohort
• hepatitis C virus
• mortality

• Adult
• Humans
• Hepacivirus
• Cause of Death
• Coinfection/epidemiology
• Coinfection/complications
• Hepatitis C/complications
• Hepatitis C/epidemiology
• Cohort Studies
• HIV Infections/complications
• HIV Infections/drug therapy
• HIV Infections/epidemiology

• Wellcome Trust
• U01 AA026209 NIAAA NIH HHS
• U01 AA026230 NIAAA NIH HHS
• 222770/Z/21/Z Wellcome Trust
• Alberta Health
• European Regional Development Fund
• Gilead Sciences
• Institut National de la Santé et de la Recherche Médicale
• Janssen Pharmaceuticals
• Merck Sharp and Dohme
• Ministère des Affaires Sociales et de la Santé
• Ministerie van Volksgezondheid, Welzijn en Sport
• Ministerio de Sanidad, Política Social e Igualdad
• National Institute for Health Research
• National Institute on Alcohol Abuse and Alcoholism
• Stichting HIV Monitoring
• Swiss National Science Foundation
• U.S. Department of Veterans Affairs
• VHA Office of Research and Development
• ViiV Healthcare
• Wellcome Trust

• Adult
• Humans
• HIV Infections/complications
• HIV Infections/drug therapy
• Hepacivirus
• Antiviral Agents/therapeutic use
• Treatment Outcome
• Hepatitis C/complications
• Hepatitis C/drug therapy
• Morbidity
• Hepatitis C, Chronic/complications
• Coinfection

• U01 AA026209 NIAAA NIH HHS
• U01 AA026224 NIAAA NIH HHS
• U01 AA026230 NIAAA NIH HHS

• Circulating MicroRNA
• Coinfection/virology
• HIV Infections/complications
• HIV-1
• Hepacivirus
• Hepatitis C/complications
• Humans
• Liver Cirrhosis/diagnosis

HIV infection exacerbates the prognosis of HCV infection, with a faster progression of hepatitis. Hepatic fibrosis is the major disruption of the hepatic tissue architecture characterized by anarchic deposition and excess of the extracellular matrix. The objective of this study was to evaluate hepatic fibrosis in HIV/HCV co-infected individuals as compared to HCV mono-infected.

A total of 97 participants (mean age 60.2 ± 14.3 years and 0.76 male/female sex ratio) was enrolled in a study conducted in Yaoundé, Cameroon from November 2018 to January 2019. Liver fibrosis was assessed by the APRI score (Aspartate Aminotransferase or AST/Platelet Ratio Index) which identifies the stage of fibrosis as classified by the Metavir system (F0 to F4). CD4 counts and plasmatic HIV viral load of HIV/HCV co-infected individuals were determined and the correlation between hepatic fibrosis and immuno-virological status established. Statistical analysis was done using Microsoft Excel 2016 and EpiInfo7 software.

A high proportion (63.6%) of HIV/HCV co-infected participants had an abnormal AST level: 73.6 ± 45.8 IU/L as compared to 58.5 ± 39.3 IU/L (59.3%) among HCV mono-infected participants. The frequency of thrombocytopenia was 63.6% with a mean platelet count of 137 ± 50 ×  10³ IU/L in HIV/HCV co-infected participants as compared to 176 ± 67 × 10³ IU/L in HCV mono-infected participants (38.4%). The progression of hepatic fibrosis in participants with clinically significant fibrosis: F2, F3 and F4 was higher among HIV/HCV co-infected and the mean APRI score was 1.7 ± 1.4 versus 1 ± 0.8 among HCV mono-infected (26.7%). All participants (100%) with detectable HIV viral load had clinically significant fibrosis compared to 33.4% in those with undetectable HIV viral load (p = 0.55). Only 42.9% participants with CD4 >  500 cells/μL had clinically significant fibrosis (p = 0.72) while 100% participants with CD4 <  200 cells/μL had clinically significant fibrosis (p = 0.58).

A high level of AST combined with thrombocytopenia (APRI score > 1.5) is an indicator of hepatic fibrosis in HIV/HCV co-infected individuals. Because of its non-invasive and less costly nature, the APRI score can be a suitable biomarker to monitor hepatic fibrosis in HIV/HCV co-infected individuals in resource constrained settings.

• APRI score
• HIV/HCV co-infection
• Liver fibrosis
• Resource constrained settings
• Thrombocytopenia

• Fibrosis
• Hepatitis B virus
• Hepatitis C virus
• Human immunodeficiency virus
• Stiffness
• Treatment

• Antiviral Agents/therapeutic use
• Coinfection/drug therapy
• Coinfection/epidemiology
• Coinfection/pathology
• Coinfection/virology
• Comorbidity
• Disease Progression
• Drug Therapy, Combination
• HIV/immunology
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• HIV Infections/pathology
• HIV Infections/virology
• Hepacivirus/immunology
• Hepatitis B/drug therapy
• Hepatitis B/epidemiology
• Hepatitis B/pathology
• Hepatitis B/virology
• Hepatitis B virus/immunology
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C/pathology
• Hepatitis C/virology
• Humans
• Liver/pathology
• Liver/virology

• K01 AA026864 NIAAA NIH HHS
• R24 OD018546 NIH HHS

The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study.

HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates.

1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4–49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2–6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders.

Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

• Adult
• Antiviral Agents/therapeutic use
• Coinfection/diagnostic imaging
• Coinfection/drug therapy
• Coinfection/mortality
• Elasticity Imaging Techniques
• Female
• France
• HIV Infections/diagnostic imaging
• HIV Infections/drug therapy
• HIV Infections/mortality
• Hepatitis C, Chronic/diagnostic imaging
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/mortality
• Humans
• Liver/diagnostic imaging
• Male
• Middle Aged
• Mortality
• Proportional Hazards Models
• Prospective Studies
• Risk Factors
• Sustained Virologic Response

• Aging
• Cancer
• Coinfection
• HIV
• HPV
• Liver disease
• Viral hepatitis

Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake.

We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness.

Liver stiffness ranged from 3.0–34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated.

Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations.

• Ageing
• Antiretroviral therapy
• Bayesian model averaging
• Elasticity imaging techniques
• HIV
• Lipodystrophy
• Liver fibrosis

Ukraine’s injecting drug use-driven HIV epidemic is among the most severe in Europe with high burden of HCV co-infection. HIV/HCV co-infected individuals are at elevated risk of HCV-related morbidity, but little is known about burden of liver disease and associated factors in the HIV-positive population in Ukraine, particularly among women.

Characteristics of 2050 HIV-positive women enrolled into the Ukrainian Study of HIV-infected Childbearing Women were described by HCV serostatus. Aspartate transaminase (AST) to platelet ratio (APRI) and FIB-4 scores were calculated and exact logistic regression models fitted to investigate factors associated with significant fibrosis (APRI >1.5) among 762 women with an APRI score available.

Of 2050 HIV-positive women (median age 27.7 years, IQR 24.6-31.3), 33% were HCV co-infected (79% of those with a history of injecting drug use vs 23% without) and 17% HBsAg positive. A quarter were on antiretroviral therapy at postnatal cohort enrolment. 1% of the HIV/HCV co-infected group had ever received treatment for HCV. Overall, 24% had an alanine aminotransferase level >41 U/L and 34% an elevated AST (53% and 61% among HIV/HCV co-infected). Prevalence of significant fibrosis was 4.5%; 2.5% among 445 HIV mono-infected and 12.3% among 171 HIV/HCV co-infected women. 1.2% had a FIB-4 score >3.25 indicating advanced fibrosis. HCV RNA testing in a sub-group of 56 HIV/HCV co-infected women indicated a likely spontaneous clearance rate of 18% and predominance of HCV genotype 1, with one-third having genotype 3 infection. Factors associated with significant fibrosis were HCV co-infection (AOR 2.53 95%CI 1.03-6.23), history of injecting drug use (AOR 3.51 95%CI 1.39-8.89), WHO stage 3-4 HIV disease (AOR 3.47 95%CI 1.51-7.99 vs stage 1-2 HIV disease) and not being on combination antiretroviral therapy (AOR 3.08 95%CI 1.23-7.74), adjusted additionally for HBV co-infection, smoking and age.

Most HIV/HCV co-infected women had elevated liver enzymes and 12% had significant fibrosis according to APRI. Risk factors for liver fibrosis in this young HIV-positive population include poorly controlled HIV and high burden of HCV. Results highlight the importance of addressing modifiable risk factors and rolling out HCV treatment to improve the health outcomes of this group.

• APRI
• Combination antiretroviral therapy
• Eastern Europe
• FIB-4
• HIV
• Hepatitis C
• Liver fibrosis
• Ukraine
• Women

HIV co-infection exacerbates hepatitis C disease, increasing the risk of cirrhosis and hepatitis C-related mortality. Combination antiretroviral therapy (cART) is the current standard treatment for co-infected individuals, but the impact of cART and antiretroviral (ARV) monotherapy on liver disease in this population is unclear. We aimed to assess the effect of cART and ARV monotherapy on liver disease progression and liver-related mortality in individuals co-infected with HIV and chronic hepatitis C.

A systematic review with meta-analyses was conducted. MEDLINE and EMBASE bibliographic databases were searched up to September 2015. Study quality was assessed using a modified Newcastle-Ottawa scale. Results were synthesised narratively and by meta-analysis.

Fourteen observational studies were included. In analyses that adjusted for potential confounders, risk of liver-related mortality was significantly lower in patients receiving cART (hazard ratio/odds ratio 0.31, 95 % CI 0.14 to 0.70). Results were similar in unadjusted analyses (relative risk 0.40, 95 % CI 0.29 to 0.55). For outcomes where meta-analysis could not be performed, results were less consistent. Some studies found cART was associated with lower incidence of, or slower progression of liver disease, fibrosis and cirrhosis, while others showed no evidence of benefit. We found no evidence of liver-related harm from cART or ARV monotherapy compared with no HIV therapy.

cART was associated with significantly lower liver-related mortality in patients co-infected with HIV and HCV. Evidence of a positive association between cART and/or ARV monotherapy and liver-disease progression was less clear, but there was no evidence to suggest that the absence of antiretroviral therapy was preferable.

The online version of this article (doi:10.1186/s41124-016-0015-7) contains supplementary material, which is available to authorized users.

• Anti-retroviral agents
• HIV
• Hepatitis C
• Meta-analysis
• Systematic review

Transient elastography (TE) data in HIV-HBV co-infection are lacking. The majority of this cohort had mild-moderate fibrosis, however over 28% of those with >1 TE showed liver fibrosis regression and the prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7 to 20.4%) over a median 31 months

Background. Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment.

Methods. We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined.

Results. The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%–20.4%) over a median of 31 months.

Conclusions. The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression.

• HIV-HBV coinfection
• antiretroviral therapy
• fibrosis
• transient elastography

• HIV coinfection
• alanine aminotransferase
• aspartate aminotransferase
• hepatitis C virus
• liver fibrosis

• HIV/HCV co-infection
• liver fibrosis
• transient elastometry