New Drugs for NASH and HIV Infection: Great Expectations for a Great Need

Guaraldi, Giovanni; Maurice, James; Marzolini, Catia; Monteith, Kenneth Marc; Milić, Jovana; Tsochatzis, Emmanuel; Price, Jennifer; Ingiliz, Patrick; Lemoine, Maud; Sebastiani, Giada

doi:10.1002/hep.31177

Cited by 16 publications

(17 citation statements)

References 70 publications

(58 reference statements)

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“…However, at present, there are limited pharmacokinetic data on this drug in the human body, which needs further study ( Ratziu et al, 2016 ). On 11 May 2020, Genfit announced that in its phase III trial of Elafibranor in the treatment of NASH, the drug failed to significantly improve patients’ NASH histological symptoms, and in some cases, exacerbated hepatic fibrosis compared to placebo ( Guaraldi et al, 2020 ; Shen and Lu, 2021 ). A total of 1070 patients with NASH were randomized (2:1) to receive Elafibranor 120 mg/day or a placebo ( Guaraldi et al, 2020 ; Shen and Lu, 2021 ).…”

Section: Elafibranor (Gft505)mentioning

confidence: 99%

New Drugs for Hepatic Fibrosis

et al. 2022

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The morbidity and mortality of hepatic fibrosis caused by various etiologies are high worldwide, and the trend is increasing annually. At present, there is no effective method to cure hepatic fibrosis except liver transplantation, and its serious complications threaten the health of patients and cause serious medical burdens. Additionally, there is no specific drug for the treatment of hepatic fibrosis, and many drugs with anti-hepatic fibrosis effects are in the research and development stage. Recently, remarkable progress has been made in the research and development of anti-hepatic fibrosis drugs targeting different targets. We searched websites such as PubMed, ScienceDirect, and Home-ClinicalTrials.gov and found approximately 120 drugs with anti-fibrosis properties, some of which are in phase Ⅱ or Ⅲ clinical trials. Additionally, although these drugs are effective against hepatic fibrosis in animal models, most clinical trials have shown poor results, mainly because animal models do not capture the complexity of human hepatic fibrosis. Besides, the effect of natural products on hepatic fibrosis has not been widely recognized at home and abroad. Furthermore, drugs targeting a single anti-hepatic fibrosis target are prone to adverse reactions. Therefore, currently, the treatment of hepatic fibrosis requires a combination of drugs that target multiple targets. Ten new drugs with potential for development against hepatic fibrosis were selected and highlighted in this mini-review, which provides a reference for clinical drug use.

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Section: Elafibranor (Gft505)mentioning

confidence: 99%

New Drugs for Hepatic Fibrosis

et al. 2022

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“…We discarded sequencing adapters, mapped miRNAs to the reference human genome and assessed the RNA biotypes for each sample with the programs: cutadapt [18], STAR [19] and featureCounts [3,20], respectively. Data were stored with miRBase [21], and sRNAbench [22] was used for the identification of miRNAs (canonical and isomiR variants).…”

Section: Mirna Sequence Analysismentioning

confidence: 99%

Circulating microRNA signatures that predict liver fibrosis progression in patients with HIV-1/hepatitis C virus coinfections

Franco

Buccione

Tural

et al. 2021

Aids

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Objective: The lack of available biomarkers for diagnosing and predicting different stages of liver disease with a noninvasive strategy is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific microRNAs (miRNAs) may be significantly altered in patients with liver injury, including those with HIV type 1 (HIV-1) infections.Design/methods: Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 patients with HIV-1/hepatitis C virus (HCV) coinfections that did not exhibit liver fibrosis at the time of sampling.Results: A total of 1065 different miRNAs were identified. After a mean of 10.3 years, 26 out of the 46 patients developed liver fibrosis (stage F2-4) and 20 remained without signs of liver fibrosis (stage F0-1). We identified a signature of seven miRNAs: 100-5p, 192-5p, 99a-5p, 122-5p, 125b-2-3p, 1246 and 194-5p, which were highly correlated with progression to liver fibrosis. These seven miRNAs detected liver fibrosis progression with an area under the curve (AUC) of 0.910-0.806. Two miRNAs, 100-5p and 192-5p, which displayed the best AUC values, yielded a sensitivity of 88% and a specificity of 85% for detecting liver fibrosis progression. Conclusion:Our results demonstrated that circulating miRNA levels had potential in predicting liver fibrosis progression before the clinical detection of liver fibrosis or significant clinical signs, such as elevated liver transaminases or platelets. Thus, our results might facilitate predictions of liver injury progression in patients with HIV-1-infections.

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“…This pathway could help the case-finding of at-risk PWH who will benefit from specialist referral for secondary fibrosis assessment, such as TE examination. The identification of PWH at a high risk for liver fibrosis is of paramount importance considering that there is no pharmacologic treatment for NAFLD-associated liver fibrosis and that PWH are excluded from most ongoing global clinical trials for NASH [53]. Future studies should focus on the longitudinal and long-term effects of the large-scale application of these models of care.…”

Section: Discussionmentioning

confidence: 99%

Two-Tier Care Pathways for Liver Fibrosis Associated to Non-Alcoholic Fatty Liver Disease in HIV Mono-Infected Patients

Sebastiani

Milić

Cervo

et al. 2022

JPM

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(1) Background: Developing strategies to identify significant liver fibrosis in people with HIV (PWH) is crucial to prevent complications of non-alcoholic fatty liver disease (NAFLD). We aim to investigate if five simple serum biomarkers applied to PWH can optimize a care pathway to identify significant liver fibrosis defined by transient elastography (TE). (2) Methods: A two-tier fibrosis pathway was applied to three prospective cohorts of PWH undergoing TE with CAP. NAFLD was diagnosed as a controlled attenuation parameter ≥ 248 dB/m. Five simple fibrosis biomarkers (FIB-4 < 1.3, BARD score 0–1, NAFLD fibrosis score < −1.455, AST:ALT ratio < 0.8 and APRI < 0.5) were applied as first-tiers to exclude significant liver fibrosis. We determined the decrease in referral for TE that would have occurred based on biomarker assessment and the discordance between low simple fibrosis biomarkers and high TE (≥7.1 kPa), indicating significant liver fibrosis. (3) Results: Of the 1749 consecutive PWH, 15.1% had significant liver fibrosis by TE and 39.1% had NAFLD. The application of the fibrosis biomarkers as first tiers would have resulted in a decrease in TE referrals between 24.9% (BARD score) and 86.3% (APRI). The lowest discordance rate was with NAFLD fibrosis score (8.5%). After adjustments, BMI (odds ratio (OR) 1.12, 95% CI: 1.08–1.17) and triglycerides (OR 1.26, 95% CI: 1.11–1.44) were independent predictors of discordance for APRI < 0.5 and TE ≥ 7.1. The performance of the two-tier pathways was similar in PWH with and without NAFLD. (4) Conclusions: Implementing a two-tier pathway could save a substantial proportion up of TE examinations, reducing costs and helping resource optimization in HIV care. Patients with metabolic risk factors for NAFLD and low fibrosis biomarker may still be considered for TE referral.

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New Drugs for NASH and HIV Infection: Great Expectations for a Great Need

Cited by 16 publications

References 70 publications

New Drugs for Hepatic Fibrosis

New Drugs for Hepatic Fibrosis

Circulating microRNA signatures that predict liver fibrosis progression in patients with HIV-1/hepatitis C virus coinfections

Two-Tier Care Pathways for Liver Fibrosis Associated to Non-Alcoholic Fatty Liver Disease in HIV Mono-Infected Patients

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