Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

Mikolašević, Ivana; Filipec-Kanižaj, Tajana; Mijić, Maja; Jakopčić, Ivan; Milić, Sandra; Hrstić, Irena; Sobočan, Nikola; Stimac, Davor; Burra, Patrizia

doi:10.3748/wjg.v24.i14.1491

Cited by 109 publications

(107 citation statements)

References 100 publications

(247 reference statements)

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“…NASH is predicted to be a leading cause of transplantation for both pediatric and adult liver diseases in the near future 9 , therefore it becomes essential and important to identify its pathological mechanisms and therapeutic targets, other than lifestyle changes. Our study for the first-time reports that Rebaudioside A improves diet-induced NASH and hepatic fibrosis, possibly through improving ER stress, insulin sensitization, pancreatic autonomic innervation and microbiome composition.…”

Section: Discussionmentioning

confidence: 99%

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Xi¹,

Bhattacharjee²,

Salazar-González³

et al. 2020

Sci Rep

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Sugar-sweetened beverage consumption is a known independent risk factor for nonalcoholic steatohepatitis (NASH). Non-caloric sweeteners (NCS) are food additives providing sweetness without calories and are considered safe and/or not metabolized by the liver. The potential role of newer NCS in the regulation of NASH, however, remain unknown. Our study aimed to determine the impact of newer NCS including Rebaudioside A and sucralose on NASH using high fat diet induced obesity mouse model by substituting fructose and sucrose with NCS in the drinking water. We characterized the phenotype of NCS-treated obesity and investigated the alterations of hepatic function and underlying mechanisms. We found that NCS have no impact on weight gain and energy balance in high fat diet induced obesity. However, in comparison to fructose and sucrose, Rebaudioside A significantly improved liver enzymes, hepatic steatosis and hepatic fibrosis. Additionally, Rebaudioside A improved endoplasmic reticulum (ER) stress related gene expressions, fasting glucose levels, insulin sensitivity and restored pancreatic islet cell mass, neuronal innervation and microbiome composition. We concluded that Rebaudioside A significantly ameliorated murine NASH, while the underlying mechanisms requires further investigation. Current treatment strategies for nonalcoholic steatohepatitis (NASH) have focused on lifestyle management of modifiable risk factors, through a combination of diet and exercise 1-3. Potential therapeutic targets for NASH intersect with the complex pathogenesis of NASH including hepatic steatosis from the imbalance of lipogenesis and free fatty acid (FFA) promoting inflammatory response and fibrosis progression 4,5. However, despite pharmaceutical agents currently in advanced stages of clinical testing 6-8 , NASH is on track predicted to become the main reason for liver transplant in the very near future 9. Therefore, it is essential to continue to explore novel NASH therapies. Sugar sweetened beverages are now well acknowledged to have severe consequences on human health. Consequently, non-caloric sweeteners (NCS) such as aspartame, sucralose, saccharin, and Rebaudioside A have increased in popularity and usage. However, there is a limited evidence for the benefits of frequent consumption of NCS sugar substitutes. This is especially true for the most recent addition Rebaudioside A, that is an extract of the stevia leaf that provides sweetness without calories 10. Interestingly, recent literature has reported that Rebaudioside A may in fact play a role in glucose metabolism and has even been reported to improve post-prandial glucose-insulin index 11 , and its consumption may result in weight loss in mice fed a high fat diet 12. These observations suggest a potential role for Rebaudioside A on glucose metabolism in general, and on liver function and NASH in particular. The well-known interactions between human health, diet and intestinal microbiota are based on the involvement of the microbiome in metabolism and immunity, which also par...

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Section: Discussionmentioning

confidence: 99%

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Xi¹,

Bhattacharjee²,

Salazar-González³

et al. 2020

Sci Rep

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“…N onalcoholic fatty liver disease (NAFLD) is the leading cause of liver enzyme abnormalities in the developed world (1) and a major cause for liver transplantation. (2) Patients with NAFLD are at risk for metabolic comorbidities, such as cardiovascular disease, cerebrovascular events, and diabetes. (3,4) Moreover, patients with steatohepatitis are at risk for liver-related morbidity and mortality.…”

mentioning

confidence: 99%

Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

et al. 2018

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Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non‐Hodgkin lymphoma (NHL). In this retrospective case‐control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R‐CHOP) or R‐CHOP + etoposide (EPOCH‐R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3‐ to 6‐month intervals and reviewed for steatosis. Patients with de novo steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow‐up 53 months), 25 (10%) developed de novo steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m2; P = 0.014) and hyperlipidemia (12% versus 2%; P = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m2 (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls (P = 0.003). Etoposide‐containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; P < 0.001) despite similar baseline risk factors. Conclusion: The recovery period from NHL chemotherapy appears to be a “hot spot” for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.

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“…Table (1) shows that the rs738409 PNPLA3 C allele was higher in normal controls (70%) compared to (55%) in obese FL group (p = 0.083), while the rs738409 PNPLA3 G allele was higher in obese FL group (45%) compared to (30%) in normal controls (p = 0.083). The (wild type) CC genotype was higher in normal controls (40%) compared to (25%) in obese FL group while homozygous mutant GG genotype was (15%) in obese FL group compared to (0%) in normal controls (P = 0.036).…”

Section: Resultsmentioning

confidence: 95%

“…Non-alcoholic fatty liver disease (NAFLD) is a frequent and growing cause of chronic liver diseases, affecting about 20%-30% of the general population worldwide. Patients with NAFLD and especially those with nonalcoholic steatohepatitis (NASH), are at risk of progression to cirrhosis and its complications, presenting also a high rate of cancer and cardiovascular events compared to subjects without fatty liver [1].…”

Section: Introductionmentioning

confidence: 99%

PNPLA3 and GCKR Gene Polymorphisms influence genetic Susceptibility to NAFLD in Obese Egyptians

Mahmoud

Shousha

Nahass

et al. 2020

Frontiers in Scientific Research and Technology

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Environmental and genetic factors have a crucial role in the development and progression of non-alcoholic fatty liver disease (NAFLD). The aim of the present study is to investigate the association between single nucleotide polymorphism (SNP) rs738409 in PNPLA3 gene and rs1260326 in GCKR gene and the development of NAFLD in obese Egyptian population. Forty obese subjects (20 with NAFLD and 20 without NAFLD) and 20 control subjects were enrolled in this study. All subjects were genotyped for (rs738409) PNPLA3 and (rs1260326) GCKR gene polymorphisms using the TaqMan assay. Results revealed that the homozygous mutant GG genotype of the PNPLA3 was the most frequent among patients with NAFLD (15%) as compared to controls (0%) (p=0.036). Regarding the GCKR rs1260326; the homozygous mutant TT genotype was most frequent among patients with NAFLD (40%) as compared to controls (20%) with trend significance (p=0.083) and as compared to obese non-FL group (10%) (p=0.014). The frequency of the T allele was found to be significantly higher in NAFLD patients (62.5%) compared to obese non-FL group (42.5%) (p=0.037). In conclusion our study confirmed the association between PNPLA3 (rs738409) and GCKR (rs1260326) polymorphisms and susceptibility to NAFLD.

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Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

Cited by 109 publications

References 100 publications

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

PNPLA3 and GCKR Gene Polymorphisms influence genetic Susceptibility to NAFLD in Obese Egyptians

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