Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis

Yang, Yong‐Yu; Xie, Li; Zhang, Ning‐Ping; Zhou, Detang; Liu, Tao-Tao; Wu, Jian

doi:10.1038/s41401-022-00860-3

Cited by 31 publications

(32 citation statements)

References 94 publications

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“…The etiology of HCC is likely multifactorial and it is plausible that HCC might results from alterations in lipid metabolism, cell lipotoxicity, insulin resistance, and oxidative stress since subjects with non-alcoholic fatty liver disease (NAFLD) are at high risk of development and progression of HCC [ 5 , 6 ]. At present, the non-alcoholic steatohepatitis (NASH) and obesity represent, at least in developed countries, the most important cause of HCC, and probably in the next future they could become the main cause for developing HCC [ 7 ] as well as alcohol abuse, that strongly interacts with other causes of liver damage [e.g. hepatitis B (HBV) and C (HCV)], worsening the progression of the disease and the development of HCC [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression

Cabiati

Gaggini

Simone

et al. 2022

Clin Exp Metastasis

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Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. The study aimed to perform a data mining analysis of the expression and regulatory role of key genes in HCC to reveal novel potential biomarkers of diagnosis prognosis, or progression since their availability is still almost lacking. Starting from data of our cohort of patients (HCV-positive HCC pts undergoing liver transplantation (LR, n = 10) and donors (LD, n = 14), deeply analyzed previously, in which apelin, osteopontin, osteoprotegerin, NOTCH-1, CASP-3, Bcl-2, BAX, PTX3, and NPTX2 were analyzed, we applied statistical analysis and in-silico tools (Gene Expression Profiling Interactive Analysis, HCCDB database and GeneMania, UALCAN) to screen and identify the key genes. Firstly, we performed a stepwise regression analysis using our mRNA-datasets which revealed that higher expression levels of apelin and osteopontin were positively associated with the HCC and identified that the most consistently differentially expressed gene across multiple HCC expression datasets was only OPN. This comprehensive strategy of data mining evidenced that OPN might have a potential function as an important tumor marker-driven oncogenesis being associated with poor prognosis of HCC patients.

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Section: Introductionmentioning

confidence: 99%

Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression

Cabiati

Gaggini

Simone

et al. 2022

Clin Exp Metastasis

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“…Regarding the pharmacotherapy for NASH, several biological pathways critical for glycolipid and bile acid metabolism, inflammation, hepatocellular damage (oxidative stress) and liver fibrosis have been explored as drug targets. Pharmaceutical agents, including modulators of farnesoid X receptor, peroxisome proliferator-activated receptors (PPARs), fibroblast growth factor, acetyl-CoA carboxylase (ACC), and apoptosis signal-regulating kinase 1 (ASK1), have been shown to exhibit some positive effects against NAFLD/NASH with various limitations in multiple clinical trials[ 6 ]. Thus, there is still an unmet clinical need to identify and validate novel targets for the treatment of NAFLD/NASH.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, targets outside the liver broaden potential approaches to ameliorate NAFLD (Figure 1 ). The drugs in phase II/III clinical trials were extensively discussed in a recently published review[ 6 ]. In the present review, we summarize recent findings that not only provide new insights into the mechanisms of NAFLD development but also explore the possibility of treating NAFLD by targeting novel signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Emerging novel targets for nonalcoholic fatty liver disease treatment: Evidence from recent basic studies

Wang¹,

Zhang²,

Guan³

2023

World J Gastroenterol

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Nonalcoholic fatty liver disease (NAFLD), a leading chronic disease worldwide, affects approximately a quarter of the global population. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD and is more likely to progress to liver fibrosis than simple steatosis. NASH is also identified as the most rapidly growing cause of hepatocellular carcinoma. Although in the past decade, several phase II/III clinical trials have shown promising results in the use of novel drugs targeting lipid synthase, farnesoid X receptor signaling, peroxisome proliferator-activated receptor signaling, hepatocellular injury, and inflammatory signaling, proven pharmaceutical agents to treat NASH are still lacking. Thus, continuous exploration of the mechanism underlying the pathogenesis of NAFLD and the identification of novel therapeutic targets remain urgent tasks in the field. In the current review, we summarize studies reported in recent years that not only provide new insights into the mechanisms of NAFLD development but also explore the possibility of treating NAFLD by targeting newly identified signaling pathways. We also discuss evidence focusing on the intrahepatic targets involved in the pathogenesis of NAFLD as well as extrahepatic targets affecting liver metabolism and function.

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“…The increasing prevalence of pediatric NAFLD is closely associated with the potential for progression to advanced liver disease/cirrhosis and cardiometabolic syndrome in adulthood, resulting in a significant economic burden to society. However, to date, no treatment has been registered for NAFLD for either adults ( 6 ) or children ( 7 ), and as of now, the treatment of pediatric NAFLD represents a major challenge.…”

Section: Introductionmentioning

confidence: 99%

“…6 parameters, and qSteatosis just 3 parameters, in the respective models. Fibrosis and steatosis components were strongly correlated with NASH CRN (P < 0.001) (Supplementary Tables 1-…”

mentioning

confidence: 99%

Developing a New qFIBS Model Assessing Histological Features in Pediatric Patients With Non-alcoholic Steatohepatitis

et al. 2022

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BackgroundThe evolution of pediatric non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is associated with unique histological features. Pathological evaluation of liver specimen is often hindered by observer variability and diagnostic consensus is not always attainable. We investigated whether the qFIBS technique derived from adult NASH could be applied to pediatric NASH.Materials and Methods102 pediatric patients (<18 years old) with liver biopsy-proven NASH were included. The liver biopsies were serially sectioned for hematoxylin-eosin and Masson trichrome staining for histological scoring, and for second harmonic generation (SHG) imaging. qFIBS-automated measure of fibrosis, inflammation, hepatocyte ballooning, and steatosis was estabilshed by using the NASH CRN scoring system as the reference standard.ResultsqFIBS showed the best correlation with steatosis (r = 0.84, P < 0.001); with ability to distinguish different grades of steatosis (AUROCs 0.90 and 0.98, sensitivity 0.71 and 0.93, and specificity 0.90 and 0.90). qFIBS correlation with fibrosis (r = 0.72, P < 0.001) was good with high AUROC values [qFibrosis (AUC) > 0.85 (0.85–0.95)] and ability to distinguish different stages of fibrosis. qFIBS showed weak correlation with ballooning (r = 0.38, P = 0.028) and inflammation (r = 0.46, P = 0.005); however, it could distinguish different grades of ballooning (AUROCs 0.73, sensitivity 0.36, and specificity 0.92) and inflammation (AUROCs 0.77, sensitivity 0.83, and specificity 0.53).ConclusionIt was demonstrated that when qFIBS derived from adult NASH was performed on pediatric NASH, it could best distinguish the various histological grades of steatosis and fibrosis.

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Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis

Cited by 31 publications

References 94 publications

Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression

Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression

Emerging novel targets for nonalcoholic fatty liver disease treatment: Evidence from recent basic studies

Developing a New qFIBS Model Assessing Histological Features in Pediatric Patients With Non-alcoholic Steatohepatitis

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