Fibrosis-4 index predicts mortality in HIV/HCV co-infected patients receiving combination antiretroviral therapy in rural China

Chen, Xiaochen; Liu, Xing; Tang, Renhai; Ye, Runhua; Yang, Yuecheng; Yao, Shitang; Wang, Jibao; Ding, Yingying; Duan, Song; He, Na

doi:10.5582/bst.2018.01299

Cited by 5 publications

(5 citation statements)

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“…(34,35) The association we found between HCV clearance and all-cause mortality has already been documented in chronic HCV patients, (36) with a magnitude very similar to the one we found. In line with our findings, FIB-4, a marker of fibrosis, was previously associated with all-cause (37) and liverrelated (38) mortality in coinfected patients. As advanced fibrosis may lead to cirrhosis, liver failure, and portal hypertension, we suggest that the relationship we found between elevated FIB-4 and mortality may be mediated through liver-related mortality.…”

Section: Discussionsupporting

confidence: 92%

Elevated Fatty Liver Index as a Risk Factor for All‐Cause Mortality in Human Immunodeficiency Virus–Hepatitis C Virus–Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study)

et al. 2020

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Background and Aims Human immunodeficiency virus (HIV)–hepatitis C virus (HCV)–coinfected patients are at high risk of metabolic complications and liver‐related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV–HCV‐coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on Aids and Viral Hepatitis CO13 HEPAVIH cohort (983 patients, 4,432 visits), we tested whether elevated FLI (≥60) was associated with all‐cause mortality. Approach and Results After multiple adjustment, individuals with FLI ≥ 60 had almost double the risk of all‐cause mortality (adjusted hazard ratio [95% confidence interval], 1.91 [1.17‐3.12], P = 0.009), independently of the following factors: HCV cure (0.21 [0.07‐0.61], P = 0.004), advanced fibrosis (1.77 [1.00‐3.14], P = 0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82‐15.69], P < 10−3), history of indirect clinical signs of cirrhosis (2.80 [1.22‐6.41], P = 0.015), and HIV Centers for Disease Control and Prevention clinical stage C (2.88 [1.74‐4.79], P < 10−3). Conclusions An elevated FLI (≥60) is a risk factor for all‐cause mortality in HIV–HCV‐coinfected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct‐acting antivirals, these findings encourage the more systematic use of noninvasive steatosis biomarkers to help identify coinfected patients with higher mortality risk.

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Section: Discussionsupporting

confidence: 92%

Elevated Fatty Liver Index as a Risk Factor for All‐Cause Mortality in Human Immunodeficiency Virus–Hepatitis C Virus–Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study)

et al. 2020

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“…The primary outcomes of interest were HCC, overall mortality, and liver-related mortality in 21[ 11 , 13 - 15 , 29 - 44 , 49 ], 12[ 3 , 12 , 17 - 24 , 38 , 46 ], and 10[ 16 , 18 , 20 , 21 , 25 , 27 , 28 , 45 , 47 , 48 ] studies, respectively. Twelve studies selected HD or a compound of LREs as relevant outcome(s)[ 12 , 17 - 21 , 23 , 24 , 26 , 38 , 43 , 46 ]. Characteristics of all the studies are summarized in Table 1 and .…”

Section: Resultsmentioning

confidence: 99%

“…However, taken individually, any NIT showed statistically significant positive associations and predictive values for their respective outcomes. The HRs and AUROCs of NITs and liver-related outcomes are summarized in Tables 4 and 5 [ 12 , 16 - 21 , 23 - 28 , 38 , 43 , 45 - 48 ].…”

Section: Resultsmentioning

confidence: 99%

Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis

Yongpisarn¹,

Thimphitthaya²,

Laoveeravat³

et al. 2021

WJH

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BACKGROUND Liver fibrosis leads to liver-related events in patients with chronic hepatitis C (CHC) infection. Although non-invasive tests (NITs) are critical to early detection of the development of liver fibrosis, the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies. AIM To determine the prognostic value of NITs for risk stratification in CHC patients. METHODS The protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019128176). The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25, 2020. We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma, decompensation, or mortality. Pooled hazard ratios (HR) and area under the receiver operating characteristic (AUROC) for each NIT were estimated using a random effects model. Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response (SVR), treatment with either pegylated interferon and ribavirin or direct acting antiviral, Eastern or Western countries, and different cutoff points. RESULTS The present meta - analysis included 29 cohort studies, enrolling 69339 CHC patients. Fibrosis-4 (FIB-4) index, aspartate aminotransferase to platelet ratio (APRI) score, and liver stiffness measurement (LSM) were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48 [95% confidence interval (CI): 1.91-3.23, I 2 = 96%], 4.24 (95%CI: 2.15-8.38, I 2 = 20%) and 7.90 (95%CI: 3.98-15.68, I 2 = 52%) and AUROCs of 0.81 (95%CI: 0.73-0.89, I 2 = 77%), 0.81 (95%CI: 0.75-0.87, I 2 = 68%), and 0.79 (95%CI: 0.63-0.96, I 2 = 90%), respectively. Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22 (95%CI: 2.32-4.47, I 2 = 80%). Pooled adjusted HRs for post-treatment with SVR FIB-4, APRI, and LSM were 3.01 (95%CI: 0.32-28.61, I 2 = 89%), 9.88 (95%CI: 2.21-44.17, I 2 = 24%), and 6.33 (95%CI: 2.57-15.59, I 2 = 17%), respectively. Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55 (95%CI: 1.47-21.02, I 2 = 36%). Pooled AUROCs for po...

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“…Liver complications including liver fibrosis, cirrhosis and ESLD have emerged as an important concern of non-AIDS-defining morbidity and mortality among PLWH in China, especially among those who are coinfected with HCV and/or hepatitis B virus (HBV) [16,20,21] . In the present study, 54.8% of HIV/HCV coinfected patients had advanced liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Profiling Circulating Inflammation and Microbial Translocation Biomarkers Associated with Advanced Liver Fibrosis in HIV/HCV Coinfected Persons

Chen¹,

Liu²,

Duan³

et al. 2020

Preprint

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Background: HIV/HCV coinfection leads to accelerated liver fibrosis, in which microbial translocation and systemic inflammation might play important roles. This study aimed to provide an extensive profile of plasma microbial translocation and inflammation biomarkers associated with advanced liver fibrosis among HIV/HCV coinfected patients.Methods:This cross-sectional study recruited 343 HIV/HCV coinfected patients on combination antiretroviral therapy (cART) from a rural prefecture of Yunnan province in Southwest China. Plasma concentrations of sCD14 and 27 cytokines/chemokines were assayed, and were compared against advanced or mild levels of liver fibrosis.Results: Of the 343 HIV/HCV coinfected patients, 188 (54.8%) had severe or advanced liver fibrosis (FIB-4 >3.25). Patients with advanced liver fibrosis (FIB-4 >3.25 vs. FIB-4 ≤3.25) had higher plasma levels of IL-1β, IL-6, IL-7, IL-9, IL-12, IL-15, IL-17, GM-CSF, IFN-γ, TNF-α, IL-4, IL-10, IL-13, FGF-basic and MCP-1. Multivariable logistic regression models showed that advanced liver fibrosis was associated with increased plasma level of IL-1β, IL-6, IL-7, IL-12, IL-17, GM- CSF, IFN-γ, IL-4, IL -10, MCP-1, Eotaxin and FGF-basic, with FGF-basic remained to be positively and significantly associated with advanced liver fibrosis after Bonferroni correction for multiple comparisons (aOR=1.82; 95%CI: 1.26-2.66; p=0.002). Plasma sCD14 was also significantly associated with advanced liver fibrosis (aOR=1.14; 95%CI: 1.01-1.30; p=0.048).Conclusions: HIV/HCV coinfected patients are living with high prevalence of advanced liver fibrosis which coexists with a mixture of elevated plasma inflammation and microbial translocation biomarkers. The significant associations of advanced liver fibrosis with FGF-basic and sCD14 may reveal pathogenic mechanisms and potential clinical intervention targets of liver fibrosis in HCV/HIV coinfection.

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Fibrosis-4 index predicts mortality in HIV/HCV co-infected patients receiving combination antiretroviral therapy in rural China

Cited by 5 publications

References 32 publications

Elevated Fatty Liver Index as a Risk Factor for All‐Cause Mortality in Human Immunodeficiency Virus–Hepatitis C Virus–Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study)

Elevated Fatty Liver Index as a Risk Factor for All‐Cause Mortality in Human Immunodeficiency Virus–Hepatitis C Virus–Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study)

Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis

Profiling Circulating Inflammation and Microbial Translocation Biomarkers Associated with Advanced Liver Fibrosis in HIV/HCV Coinfected Persons

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