Hepatic inflammatory responses in liver fibrosis

Hammerich, Linda; Tacke, Frank

doi:10.1038/s41575-023-00807-x

Cited by 134 publications

(68 citation statements)

References 256 publications

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“…2 Numerous studies have identified increased liver fat content, cellular injury and hepatic inflammation as the key drivers associated with fibrosis progression in NASH patients. 3 On the other hand, a recent study has suggested that there is a causal relationship between liver fat accumulation and fibrosis progression, independent of disease activity. 4 However, such histologic hallmarks of NASH, including steatosis, lobular inflammation and hepatocellular ballooning have been reported to diminish when patients have further progressed to advanced liver fibrosis or cirrhosis, also termed burnt-out NASH.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have identified increased liver fat content, cellular injury and hepatic inflammation as the key drivers associated with fibrosis progression in NASH patients 3 . On the other hand, a recent study has suggested that there is a causal relationship between liver fat accumulation and fibrosis progression, independent of disease activity 4 .…”

Section: Introductionmentioning

confidence: 99%

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Low liver fat in non‐alcoholic steatohepatitis‐related significant fibrosis and cirrhosis is associated with hepatocellular carcinoma, decompensation and mortality

Lee,

Huang,

Bettencourt

et al. 2023

Aliment Pharmacol Ther

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SummaryBackgroundProgression to cirrhosis in non‐alcoholic steatohepatitis (NASH) is associated with a decrease in liver fat. However, the prognostic significance of liver fat content in NASH‐related significant fibrosis and cirrhosis is unclear.AimTo investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH‐related significant fibrosis and cirrhosis.MethodsIn this meta‐analysis of individual participant data, 456 patients with both magnetic resonance elastography (MRE) and MRI‐derived protein density fat fraction (MRI‐PDFF) were enrolled, and 296 patients with longitudinal follow‐up were analysed. MRE combined with fibrosis‐4 (MEFIB‐index), and MRI‐PDFF were used to measure liver fibrosis and fat, respectively. MEFIB‐negative, MEFIB‐positive+ MRI‐PDFF ≥5% and MEFIB‐positive+ MRI‐PDFF <5% were defined as no significant liver fibrosis, NASH with significant fibrosis and higher liver fat content, and NASH with significant fibrosis and low liver fat content groups, respectively. The primary outcome was hepatic decompensation, HCC and death.ResultsThe rates of decompensation, HCC and mortality were highest in the NASH with significant fibrosis and low liver fat group (33%, 17% and 17%, respectively), followed by the NASH with significant fibrosis and higher liver fat group (18%, 13% and 13% respectively), and lowest in the no significant fibrosis (MEFIB‐negative) group (0%, 1% and 2% respectively). In multivariable‐adjusted analysis, low liver fat content was strongly associated (HR = 42.2 [95% CI: 7.5–235.5, p < 0.0001]) with HCC, decompensation and death. Sensitivity analyses for patients with cirrhosis (MRE ≥5 kPa) determined consistent findings.ConclusionsLow liver fat content in patients with burnt‐out NASH‐related significant fibrosis and cirrhosis is associated with an increase in hepatic decompensation, HCC and mortality.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low liver fat in non‐alcoholic steatohepatitis‐related significant fibrosis and cirrhosis is associated with hepatocellular carcinoma, decompensation and mortality

Lee,

Huang,

Bettencourt

et al. 2023

Aliment Pharmacol Ther

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“…Liver fibrogenesis is a highly dynamic process of aberrant wound‐healing and scar tissue formation, which is in principle reversible at early fibrosis stages and even cirrhotic states depending on the disease aetiology 1,18 . Interestingly, in the current issue of Liver International Dr. Manka and coworkers not only identified an upregulation of fibrosis‐related genes in TRα −/− MEFs but also observed TGFβ induced migration and increased aberrant wound‐healing responses 10 .…”

Section: Figurementioning

confidence: 99%

Cell type‐specific actions of thyroid hormones in nonalcoholic steatohepatitis and liver fibrosis

Puengel,

Tacke

2024

Liver International

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“…4 The liver is an important site in inflammatory responses with a quantity of innate and adaptive immune cells. 5 Inflammation is an adaptive response for pathogen clearance and tissue repair. 6 It is generally known that inflammatory reaction plays a crucial role in liver repair and recover from damage.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The liver is an important site in inflammatory responses with a quantity of innate and adaptive immune cells . Inflammation is an adaptive response for pathogen clearance and tissue repair .…”

Section: Introductionmentioning

confidence: 99%

Nanozymes with Broad-Spectrum Scavenging of Reactive Oxygen Species (ROS) Alleviate Inflammation in Acute Liver Injury

Wang,

Yuan,

Shen

et al. 2024

ACS Materials Lett.

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Reactive oxygen species (ROS) related oxidative stress causes an inflammatory storm and massive hepatocyte necrosis in acute liver injury (ALI). Necrotic hepatocytes trigger an irreversible secondary injury mediated by the innate immune system, potentially leading to liver failure or even death. Therefore, antioxidant therapies may be hepatoprotective. Herein, we have reported novel metal−phenolic nanozymes (CA-Mn NPs) with broad-spectrum ROS scavenging ability. CA-Mn NPs inhibited hepatocyte apoptosis and prevented the recruitment of inflammatory monocytes through antioxidant mechanism in vitro. Meanwhile, CA-Mn NPs suppressed cell apoptosis and the levels of inflammatory factors in carbon tetrachloride (CCl 4 )-induced ALI mice. We further focused on the anti-inflammatory mechanisms of CA-Mn NPs and found that the Nrf2-Keap1 signaling pathway was upregulated and the NF-κB p65 pathway was downregulated. Besides, CA-Mn NPs restored the autophagic function and converted the M1 type macrophages to the M2 type. RNA sequencing also confirmed that CA-Mn NPs regulate the expression of apoptotic, autophagic, and inflammatory genes. Overall, the clearance of ROS by CA-Mn NPs prevented inflammation and apoptosis in ALI mice, providing new insights for the development of therapeutic strategies.

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Hepatic inflammatory responses in liver fibrosis

Cited by 134 publications

References 256 publications

Low liver fat in non‐alcoholic steatohepatitis‐related significant fibrosis and cirrhosis is associated with hepatocellular carcinoma, decompensation and mortality

Low liver fat in non‐alcoholic steatohepatitis‐related significant fibrosis and cirrhosis is associated with hepatocellular carcinoma, decompensation and mortality

Cell type‐specific actions of thyroid hormones in nonalcoholic steatohepatitis and liver fibrosis

Nanozymes with Broad-Spectrum Scavenging of Reactive Oxygen Species (ROS) Alleviate Inflammation in Acute Liver Injury

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