Liver fibrosis progression and clinical outcomes are intertwined

Focà, Emanuele; Fabbiani, Massimiliano; Prosperi, Mattia; Quiros-Roldan, Eugenia; Castelli, Francesco; Maggiolo, F; Filippo, Elisa Di; Giambenedetto, Simona Di; Gagliardini, Roberta; Saracino, Annalisa; Pietro, Massimo Di; Gori, Andrea; Sighinolfi, Laura; Pan, Angelo; Postorino, Maria Concetta; Torti, Carlo

doi:10.1097/md.0000000000004091

Cited by 20 publications

(5 citation statements)

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“…Also, higher levels of serum glucose were associated with clinical events. These findings are not unexpected because it is well known that life-style factors, such as nutritional habits, alcohol abuse, intravenous drug use or smoking exert an important role for the risk of clinical events even in HIV infected patients [ 27 , 36 – 39 ]. So, we confirm that targeted interventions to correct these modifiable risk factors should be prioritized in HIV infected patients to reduce risk of clinical events even when more “metabolic friendly” regimens are prescribed.…”

Section: Discussionmentioning

confidence: 84%

“…The Fib-4 score is a reliable marker of liver fibrosis progression and clinical events in HIV infected patients [ 26 , 27 ]. Indeed, we also found a statistically significant association of higher Fib-4 scores with the composite clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Lastly, among proposed serum non-invasive biomarkers of liver fibrosis, the Fib-4 score has been validated both in HIV/HCV co-infected and in HIV mono-infected patients and it was a reliable driver of both liver fibrosis progression and clinical events [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in the Italian MASTER cohort

et al. 2017

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BackgroundAtazanavir (ATV) not boosted by ritonavir (uATV) has been frequently used in the past for switching combination antiretroviral therapy (cART). However, the clinical outcomes and predictors of such strategy are unknown.MethodsAn observational study was carried out on the Italian MASTER, selecting HIV infected patients on cART switching to an uATV-containing regimen. Baseline was set as the last visit before uATV initiation. In the primary analysis, a composite clinical end-point was defined as the first occurring of any condition among: liver, cardiovascular, kidney, diabetes, non AIDS related cancer or death events. Incidence of AIDS events and incidence of composite clinical end-point were estimated. Kaplan-Meier and multivariable Cox regression analysis were used to assess predictors of the composite clinical end-point.Results436 patients were observed. The majority of patients were males (61.5%) and Italians (85.3%), mean age was 42.7 years (IQR: 37.7–42), the most frequent route of transmission was heterosexual intercourse (47%), followed by injection drug use (25%) and homosexual contact (24%); the rate of HCV-Ab positivity was 16.3%. Patients were observed for a median time of 882 days (IQR: 252-1,769) under uATV. We recorded 93 clinical events (3 cardiovascular events, 20 kidney diseases, 33 liver diseases, 9 non AIDS related cancers, 21 diabetes, 7 AIDS events), and 19 deaths, accounting for an incidence of 3.7 (composite) events per 100 PYFU. At multivariable analysis, factors associated with the composite clinical end-point were intravenous drug use as risk factor for HIV acquisition vs. heterosexual intercourses [HR: 2.608, 95% CI 1.31–5.19, p = 0.0063], HIV RNA per Log10 copies/ml higher [HR: 1.612, 95% CI 1.278–2.034, p < 0.0001], number of switches in the nucleoside/nucleotide (NRTI) backbone of cART (performed to compose the uATV regimen under study or occurred in the past) per each more [HR: 1.085, 95% CI 1.025–1.15, p = 0.0051], Fib-4 score per unit higher [HR: 1.03, 95% CI 1.018–1.043, p < 0.0001] and Neutrophil/lymphocytes ratio (NLR inflammation score) per Log10 higher [HR: 1.319, 95% CI 1.047–1.662, p = 0.0188].ConclusionsIntravenous drug users with high HIV RNA, high Fib-4 levels and more heavily exposed to antiretroviral drugs appeared to be more at risk of clinical events. Interestingly, high levels of inflammation measured through NLR, were also associated with clinical events. So, these patients should be monitored more strictly.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in the Italian MASTER cohort

et al. 2017

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“…Hypertension was defined as two consecutive measurements of blood pressure more than 140/90 mmHg; dyslipidaemia as elevated total or low-density lipoprotein (LDL) cholesterol or low high-density lipoprotein (HDL) cholesterol using ATPIII classification; type 2 diabetes mellitus (T2DM) as fasting serum glucose levels more than 126 mg/dl or HbA1C more than 6.5%; chronic kidney disease (CKD) as an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m 2 calculated using the CKD-Epi equation; osteoporosis in postmenopausal women and men aged at least 50 years as a bone mass index (BMD) T -score of −2.5 or less, and in premenopausal women and men aged less than 50 years as a BMD Z -score of −2 or less in addition to a fragility fracture; chronic obstructive pulmonary disease (COPD) as postbronchodilator spirometric forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) less than 0.70. Liver cirrhosis was defined through noninvasive assessment with either serum biomarkers (FIB-4) [14] or transient elastography, and cancers including both AIDS and non-AIDS defining conditions. Multimorbidity was defined as presence at least three comorbidities in the same individual.…”

Section: Methodsmentioning

confidence: 99%

Dolutegravir is not associated with weight gain in antiretroviral therapy experienced geriatric patients living with HIV

Guaraldi

Calza

Milić

et al. 2021

Aids

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The aim of this study was to explore weight gain in people with HIV (PWH) at least 65 years of age who switch to a DTG based regimen (DTG-s) vs. remaining INSTI-naive (INSTI-n) on stable ART.Methods: This was a longitudinal prospective study of PWH from the GEPPO cohort. At the beginning of the observational period, participants were INSTI-naives (INSTI-n). During follow-up, they were divided in two groups: INSTI-n vs. dolutegravir-switchers (DTG-s) with no further change in ART. Body weight was assessed at baseline and at last follow-up visit. Significant weight gain was defined as an increase at least 5% of baseline weight from the first to the last visit. ART regimens were collected at each patients' visit. Kaplan-Meier curves were drawn to assess time to reach a weight gain more than 5%.Results: Out of 568 PWH (83.1% men, median age 69.5 years), 427 (75%) were INSTIn and 141 (25%) DTG-s. After an average follow-up of 2.6 (AE0.8) years, no significant change in body weight was observed both among INSTI-n [delta weight ¼ 0.02 (AE7.5), P ¼ 0.633] and DTG-s [delta weight ¼ À0.04 (AE5.2), P ¼ 0.755]. Weight gain was also not significantly different between study groups (9.3% in INSTI-n and 15.1% in DTG-S: P ¼ 0.175). No significant differences in time to achieve a weight gain greater or equal than 5% of baseline weight emerged in INSTI-n vs. DTG-s (P ¼ 0.93), two-drug regimens (2DR) vs. three-drug regimens (3DR) (P ¼ 0.56) or TAF vs. TDF (P ¼ 0.56).

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“…NRTIs are the best studied drugs as far as LF is concerned ( Table 2 ). In two large studies of HIV/HCV co-infected patients, the use of NRTIs was correlated with a worsening of LF, a higher risk of liver decompensation and increased mortality, while in another similar study from McGovern et al, the use of NRTIs, and especially DDI and d4T, were linked to liver steatosis and fibrosis [ 83 , 84 , 85 ].…”

Section: Nucleoside Reverse Transcriptase Inhibitors (Nrtis)mentioning

confidence: 99%

Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?

Bakasis

Ανδρουτσάκος

2021

Cells

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After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. HIV itself may lead to liver damage and subsequent liver fibrosis (LF) through multiple pathways. Apart from HIV, viral hepatitis, alcoholic and especially non-alcoholic liver diseases have been implicated in liver involvement among PLWH. Another well known cause of hepatotoxicity is ART, raising clinically significant concerns about LF in long-term treatment. In this review we present the existing data and analyze the association of LF with all ART drug classes. Published data derived from many studies are to some extent controversial and therefore remain inconclusive. Among all the antiretroviral drugs, nucleoside reverse transcriptase inhibitors, especially didanosine and zidovudine, seem to carry the greatest risk for LF, with integrase strand transfer inhibitors and entry inhibitors having minimal risk. Surprisingly, even though protease inhibitors often lead to insulin resistance, they do not seem to be associated with a significant risk of LF. In conclusion, most ART drugs are safe in long-term treatment and seldom lead to severe LF when no liver-related co-morbidities exist.

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Liver fibrosis progression and clinical outcomes are intertwined

Abstract: Supplemental Digital Content is available in the text

Cited by 20 publications

References 30 publications

Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in the Italian MASTER cohort

Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in the Italian MASTER cohort

Dolutegravir is not associated with weight gain in antiretroviral therapy experienced geriatric patients living with HIV

Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?

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