Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Abstract

ObjectiveTo evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART).DesignRetrospective analysis of a prospective cohort study.SettingItalian HIV care centers participating to the ICONA Foundation cohort.ParticipantsTreatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up.MethodsCox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD.ResultsThree-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45–3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4>3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4>3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART.ConclusionsThe FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.

Liver fibrosis progression and clinical outcomes are intertwined

“…These findings were previously demonstrated both in HIV mono-infected patients and in HCV-coinfected patients. [15,20–23] Our data confirm that viro-immunological parameters may have a role in LF progression. A cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses.…”

“…Despite a recent study found that noninvasive markers are not optimal, [20] these markers were already validated for estimating LF [13] and predicted hepatic decompensation and death in cohorts of patients. [4,15] For these reasons, the European Association for the Study of the Liver (EASL) provided specific guidelines for the use of these scores in clinical practice. [12] Second, in dealing with a possible effect of antiretroviral drugs, we did not try to disregard the impact of individual compounds because of the risk of introducing biases when statistical analysis is “forced” to provide such levels of details given the fact that combination of drugs are prescribed.…”

“…[11,12] Some of these methods, such as the fibrosis-4 (FIB-4) index, are based on serum biomarkers, reflect with acceptable accuracy the degree of LF and are significant predictors of hepatic decompensation and liver-related deaths both in HIV mono-infected and in those with positive HCV antibodies. [13–15] …”

“…Second, an important limitation of the current prognostic models is that patients with positive anti-HCV antibodies (HCV-Ab) are selected, without consideration of HCV-RNA (in some cases, patients have spontaneously eradicated HCV), and this may have confounded risk estimates associated with other variables tested. [15] In conclusion, there is a need for more studies conducted in HIV-infected patients with confirmed HCV coinfections (assessed through positive HCV-RNA) to explore whether FIB-4 plays a role as a predictor of clinical evolution and survival in relationship with HIV-related variables and occurrence of AIDS and non-AIDS-related events.…”

The Role of Current and Historical Alcohol Use in Hepatic Fibrosis Among HIV-Infected Individuals

“…The Fibrosis-4 (FIB-4) index, derived from age, liver aminotransferases and platelet count, is more widely available than biopsy, and has been shown to predict liver-related events and death in patients with chronic hepatitis C virus infection (HCV), HIV and HIV/HCV co-infection (9–12). …”