Association of nonalcoholic fatty liver disease and liver cancer

Schulz, Perla; Ferreira, Fábio Gonçalves; Nascimento, Maria de Fátima Araujo; Vieira, Andréa; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

doi:10.3748/wjg.v21.i3.913

Cited by 24 publications

(25 citation statements)

References 40 publications

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“…Today, NAFLD is becoming the leading cause of chronic liver disease, afflicting 25% of adults in the United States. Although liver metastasis can occur in CRC patients without NAFLD, a recent large prospective human cohort analyzing 2,715 CRC patients with liver metastasis as well as other retrospective studies have suggested that the patients with NAFLD have an increased risk of liver metastasis and for the recurrence of liver metastasis after resection, when compared with patients without NAFLD . Moreover, higher recurrence rate of liver metastasis in patients with fibrosis have also been reported in recent studies .…”

Section: Discussionmentioning

confidence: 89%

“…Previous animal studies have demonstrated that high‐fat diet (HFD)‐induced NAFLD promotes the tumor growth of CRC and PDAC liver metastasis . Large prospective and retrospective human cohorts have demonstrated that cancer patients with NAFLD have increased risk of liver metastasis and for recurrence after resection of liver metastasis compared with patients without NAFLD . The increased prevalence of obesity and NAFLD will likely increase the occurrence of liver metastasis.…”

mentioning

confidence: 99%

“…However, liver macrophages as well as tumor‐associated macrophages (TAMs) could promote a pro‐metastatic niche formation in the liver, likely by polarizing to M2 macrophage, to enhance the growth of metastatic tumor cells that survived the initial tumoricidal attack. Inflammatory, fibrotic, and fatty liver microenvironment enhances liver tumor growth . Indeed, in a NAFLD condition, CD4 + T cells are depleted and tumor surveillance is impaired, which promotes hepatocellular carcinoma (HCC) growth .…”

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confidence: 99%

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NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

Ohashi¹,

Wang

Yang

et al. 2019

Hepatology

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Nonalcoholic fatty liver disease (NAFLD) enhances the growth and recurrence of colorectal cancer (CRC) liver metastasis. With the rising prevalence of NAFLD, a better understanding of the molecular mechanism underlying NAFLD‐associated liver metastasis is crucial. Tumor‐associated macrophages (TAMs) constitute a large portion of the tumor microenvironment that promotes tumor growth. NOD‐like receptor C4 (NLRC4), a component of an inflammasome complex, plays a role in macrophage activation and interleukin (IL)‐1β processing. We aimed to investigate whether NLRC4‐mediated TAM polarization contributes to metastatic liver tumor growth in NAFLD. Wild‐type and NLRC4‐/‐ mice were fed low‐fat or high‐fat diet for 6 weeks followed by splenic injection of mouse CRC MC38 cells. The tumors were analyzed 2 weeks after CRC cell injection. High‐fat diet–induced NAFLD significantly increased the number and size of CRC liver metastasis. TAMs and CD206‐expressing M2 macrophages accumulated markedly in tumors in the presence of NAFLD. NAFLD up‐regulated the expression of IL‐1β, NLRC4, and M2 markers in tumors. In NAFLD, but not normal livers, deletion of NLRC4 decreased liver tumor growth accompanied by decreased M2 TAMs and IL‐1β expression in tumors. Wild‐type mice showed increased vascularity and vascular endothelial growth factor (VEGF) expression in tumors with NAFLD, but these were reduced in NLRC4‐/‐ mice. When IL‐1 signaling was blocked by recombinant IL‐1 receptor antagonist, liver tumor formation and M2‐type macrophages were reduced, suggesting that IL‐1 signaling contributes to M2 polarization and tumor growth in NAFLD. Finally, we found that TAMs, but not liver macrophages, produced more IL‐1β and VEGF following palmitate challenge. Conclusion: In NAFLD, NLRC4 contributes to M2 polarization, IL‐1β, and VEGF production in TAMs, which promote metastatic liver tumor growth.

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Section: Discussionmentioning

confidence: 89%

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confidence: 99%

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confidence: 99%

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NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

Ohashi¹,

Wang

Yang

et al. 2019

Hepatology

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“…The application of such patches during the surgical intervention could allow avoiding intraportal MSC injection that may cause embolization and be lethal for patients who have undergone massive hepatectomy. Moreover, there is an emerging evidence of hepatocellular carcinoma in noncirrhotic NAFLD and NAFLD prevalence in patients with hepatic metastases from colorectal cancer is high (Schulz et al, ). Therefore, the number of patients requiring liver surgery is increasing in parallel with NAFDL.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells seeded on a human amniotic membrane improve liver regeneration and mouse survival after extended hepatectomy

Despeyroux

Duret

Gondeau

et al. 2017

J Tissue Eng Regen Med

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Liver failure remains the leading cause of post-operative mortality after hepatectomy. This study investigated the effect of treatment with allogenic mesenchymal stem cells (MSCs) on survival and liver regeneration 48 hr and 7 days after 80% hepatectomy in C57Bl/6 mice. To optimize their biodistribution, MSCs were grown on acellular human amniotic membranes (HAM) and applied as a patch on the remnant liver. This approach was compared with MSC infusion and HAM patch alone. Hepatectomized mice without any treatment were used as control group. Survival rate was calculated and biological and histopathological parameters were analysed to monitor liver function and regeneration. MSCs grown on HAM retained their ability to proliferate, to differentiate into osteoblasts and adipocytes and to respond to pro-inflammatory stimuli. Extended hepatectomy (80%) led to liver failure that resulted in death within 72 hr in 76% of mice. MSC infusion showed an early but transitory positive effect on survival. MSC/HAM patches stimulated regeneration and significantly improved survival rate (54% vs. 24% in the control group at 7 days). They also decreased the severity of hepatectomy-induced steatosis, suggesting a modulation of lipid metabolism in hepatocytes. MSCs were still present on HAM at Days 2 and 7 posthepatectomy. In conclusion, engineered tissue constructs that combine MSCs and HAM improve survival and liver regeneration after 80% hepatectomy in mice. These encouraging results pave the way to potential clinical application.

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“…Intracellular deposition of lipid leads to oxidative stress in hepatocytes and also induces cytokine‐mediated injury (Parola & Robino, ). An elevated level of cytokines and macrophages in systemic circulation remodels the extracellular matrix and leads to a more lethal condition like inflammation, fibrosis, and HCC (Decaris et al, ; Schulz et al, ).…”

Section: Introductionmentioning

confidence: 99%

Curcuma longaandTrigonella foenum graecum‐enriched nutrient mixture from germinatedMacrotyloma uniflorumandVigna radiateameliorate nonalcoholic fatty liver diseases in rats

et al. 2020

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The prevalence of nonalcoholic fatty liver is increasing due to modern lifestyle. Germinated and dehulled Macrotyloma uniflorum and Vigna radiate were shown to have enhanced nutrients. Curcuma longa and Trigonella foenum graecum were proven hepatoprotective.The supplementation of the nutrient herbal mixture to the MCD diet‐induced steatosis shows reduced hepatic fat accumulation and lipid profile, and liver injury markers in serum also reserved in normal. Increased serum albumin in the treatment group indicates that the liver function is enhanced than that of steatosis. The supplementation of the herbal mixture has preserved the hepatic antioxidant. Zymographic analysis of matrix metalloproteinase, western blot determination of α‐SMA, and histological evolution (H&E, Sirius red) depicted reduced fibrosis and reveled management of hepatic stellate cells in quiescent form. The present study concludes that the herbal mixture has reduced hepatocyte fat accumulation in steatotic animals, and curtailed the oxidative stress, further it prevents the progression of steatohepatitis. Practical applications Fatty liver diseases can be treated by modulating the diet composition such as consuming food rich in the nutrient herbal mixture. In this study, the nutrient mixture was made with dynamic food processing techniques such as germination, dehulling, and milling to augment the nutritional contents. Besides, Macrotyloma uniflorum, Vigna radiate, Curcuma longa, and Trigonella foenum graecum were used to improve the medicinal value and antioxidant. This formulation could target the various stages of NAFLD. This study revealed that the nutrient herbal mixture reduces the steatosis of the liver and curtailed the progression of steatohepatitis from hepatic steatosis. Since the edible foodstuff was used to make the nutrient mixture, it has excellent clinical application.

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Association of nonalcoholic fatty liver disease and liver cancer

Abstract: NAFLD is more common in patients with liver metastases caused by colorectal cancer.

Cited by 24 publications

References 40 publications

NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

Mesenchymal stem cells seeded on a human amniotic membrane improve liver regeneration and mouse survival after extended hepatectomy

Curcuma longaandTrigonella foenum graecum‐enriched nutrient mixture from germinatedMacrotyloma uniflorumandVigna radiateameliorate nonalcoholic fatty liver diseases in rats

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