Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

Zhang, Jianbin; Lin, Shuangzhe; Jiang, Daozhuo; Li, Mengting; Chen, Yuanwen; Li, Jun; Fan, Jian‐Gao

doi:10.1111/liv.14369

Cited by 53 publications

(45 citation statements)

References 127 publications

(257 reference statements)

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“…In the human HSC line LX-2, PAX6 binds to the promoter of the GLI1 gene, thereby promoting fibrogenic activities and proliferation ( Li C. et al, 2020 ). In the same cell line, GLI1 was further shown to be integrated in a complex network of Wnt/β-catenin, which regulates cellular contraction ( Zhang F. et al, 2020 ). However, the significance of GLI1 positive perivascular mesenchymal stem-like cells for liver fibrogenesis is still unknown.…”

Section: Cellular Mediators Of Hepatic Fibrosismentioning

confidence: 99%

Cellular Mechanisms of Liver Fibrosis

et al. 2021

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The liver is a central organ in the human body, coordinating several key metabolic roles. The structure of the liver which consists of the distinctive arrangement of hepatocytes, hepatic sinusoids, the hepatic artery, portal vein and the central vein, is critical for its function. Due to its unique position in the human body, the liver interacts with components of circulation targeted for the rest of the body and in the process, it is exposed to a vast array of external agents such as dietary metabolites and compounds absorbed through the intestine, including alcohol and drugs, as well as pathogens. Some of these agents may result in injury to the cellular components of liver leading to the activation of the natural wound healing response of the body or fibrogenesis. Long-term injury to liver cells and consistent activation of the fibrogenic response can lead to liver fibrosis such as that seen in chronic alcoholics or clinically obese individuals. Unidentified fibrosis can evolve into more severe consequences over a period of time such as cirrhosis and hepatocellular carcinoma. It is well recognized now that in addition to external agents, genetic predisposition also plays a role in the development of liver fibrosis. An improved understanding of the cellular pathways of fibrosis can illuminate our understanding of this process, and uncover potential therapeutic targets. Here we summarized recent aspects in the understanding of relevant pathways, cellular and molecular drivers of hepatic fibrosis and discuss how this knowledge impact the therapy of respective disease.

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Section: Cellular Mediators Of Hepatic Fibrosismentioning

confidence: 99%

Cellular Mechanisms of Liver Fibrosis

et al. 2021

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“…NAFLDrelated lipotoxicity can generate excessive reactive oxygen species through endocytoplasmic reticulum stress and the mitochondrial respiratory chain, leading to oxidative damage of DNA and other biological macromolecules, which also serves as a key process involved in HCC pathogenesis as well. 26 All of the above risk factors may independently and collectively increase the risk of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Considering non‐alcoholic fatty liver disease (NAFLD) as the main hepatic manifestation of obesity, NAFLD‐mediated exacerbation of inflammatory injury and fibrogenesis in HBV infection maybe another possible reason. NAFLD‐related lipotoxicity can generate excessive reactive oxygen species through endocytoplasmic reticulum stress and the mitochondrial respiratory chain, leading to oxidative damage of DNA and other biological macromolecules, which also serves as a key process involved in HCC pathogenesis as well 26 . All of the above risk factors may independently and collectively increase the risk of HCC.…”

Section: Discussionmentioning

confidence: 99%

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy

Fan¹,

Niu²,

Ma³

et al. 2021

Aliment Pharmacol Ther

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Summary Background Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB). Aim To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy. Methods We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body‐mass index (BMI). Central obesity was evaluated by waist circumference, waist‐to‐hip ratio and waist‐to‐height ratio. Results A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5‐year cumulative incidence of HCC was 2.9%. Waist‐to‐height ratio performed better in predicting HCC development than BMI, waist circumference or waist‐to‐hip ratio. Patients with central obesity (defined as waist‐to‐height ratio >0.5) had significantly higher 5‐year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist‐to‐height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12‐3.13, P = 0.017). Conclusions Central obesity, evaluated by the waist‐to‐height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.

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“…Especially, Huang et al pointed that the current infection of CHB groups had a lower prevalence than past infection ( 4 ). However, the mechanistic role of HBV infection in NAFLD pathogenesis remained unclear ( 22 ). Some researchers attributed the association to adiponectin, which exhibited anti-inflammatory roles and could alleviate steatosis function ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Incidence of Non-alcohol Fatty Liver Disease in Chronic Hepatitis B Population in Southeast China: A Community-Based Study

Zheng

et al. 2021

Front. Med.

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Background: To investigate the prevalence and incidence of non-alcohol fatty liver disease (NAFLD) in a community-based chronic hepatitis B (CHB) population from Southeast China and evaluate the association between NAFLD and metabolic factors, viral factors, and underlying chronic diseases.Methods: CHB patients were recruited in 2012 and followed up from 2017 to 2019 in Zhejiang, China. NAFLD prevalence of the last visit and NAFLD incidence were calculated. Potential risk factors, including metabolic and viral factors, were also evaluated using Logistic or Cox regression models.Results: NAFLD prevalence of the last visit in 2019 was estimated at 26.76%. Waist circumference, body mass index (BMI), triglyceride (TG), low-density lipoprotein (LDL), and diabetes mellitus (DM) were found as associated factors. In subgroups analysis, HBV infection types were also identified as a risk factor in the non-diabetic population. HBeAg-negative hepatitis and immunotolerant had lower NAFLD prevalence than past CHB infection. NAFLD incidence was estimated at 22.63/1,000 person-years after 1,634.74 person-years of follow-up. Waist circumference, TG, LDL, and alkaline phosphatase (ALP) were identified as associated factors.Conclusion: The NAFLD prevalence and incidence in our study were slightly lower than previous reports from East Asia. Health education and healthy living habits were extremely important in reducing the NAFLD burden. Metabolic factors, history of DM, and viral factors were associated with NAFLD in CHB patients.

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Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

Cited by 53 publications

References 127 publications

Cellular Mechanisms of Liver Fibrosis

Cellular Mechanisms of Liver Fibrosis

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy

Prevalence and Incidence of Non-alcohol Fatty Liver Disease in Chronic Hepatitis B Population in Southeast China: A Community-Based Study

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