https://www.journal-of-hepatology.eu/article/S0168-8278(14)00933-7/pdf

NAFLD: A multisystem disease

Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

NAFLD is a spectrum of progressive liver disease that encompasses simple steatosis, NASH, fibrosis and, ultimately, cirrhosis. NAFLD is recognized as the hepatic component of the metabolic syndrome, as these conditions have insulin resistance as a common pathophysiological mechanism. Therefore, NAFLD is strongly associated with type 2 diabetes mellitus and abdominal obesity. As lifestyles have become increasingly sedentary and dietary patterns have changed, the worldwide prevalence of NAFLD has increased dramatically and is projected to be the principal aetiology for liver transplantation within the next decade. Importantly, a growing body of clinical and epidemiological evidence suggests that NAFLD is associated not only with liver-related morbidity and mortality, but also with an increased risk of developing both cardiovascular disease and type 2 diabetes mellitus. This article reviews the evidence that suggests NAFLD is a multisystem disease and the factors that might determine interindividual variation in the development and progression of its major hepatic and extrahepatic manifestations (principally type 2 diabetes mellitus and cardiovascular disease).

Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis.

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome—including Bacteroides , Selenomonas , and Prevotella species—is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium -associated colorectal cancer.

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer

https://www.journal-of-hepatology.eu/article/S0168-8278(16)30199-4/pdf

Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis

Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the natural course of which has not been well documented. This study aimed to perform a prospective cohort study to investigate NAFLD in a Chinese population.



METHODS:  Using our previous epidemiological survey, 3543 patients were followed-up for a median of 4 years (range 3.6–4.8 years). Of these patients, 624 participated in a new survey. Interviews, physical examinations, biochemical tests and abdominal ultrasonography were repeated for these patient.



RESULTS:  The annual incidence of NAFLD was 9.1% (male 7.3% vs female 9.7%, P = 0.047). Among 117 NAFLD patients at baseline, 51 (43.6%) remained unchanged, 26 (22.2%) became worse, and 40 (34.2%) improved. Patients with simultaneous metabolic syndrome (MS) showed accelerated progression (P = 0.026). For the NAFLD patients, both general annual mortality rates and cardiovascular disease deaths (both 0.54%) were significantly higher than those of patients without NAFLD (0.19% and 0.17%, P = 0.005). Age and several variables related to MS were risk factors for NAFLD progression.



CONCLUSIONS:  The incidence of NAFLD in southern China is relatively lower in comparison with that of the developed countries. Patients with NAFLD have a benign prognosis. Variables related to MS are risk factors for NAFLD occurrence and progression.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-2980.2011.00571.x

Natural course of nonalcoholic fatty liver disease in southern China: A prospective cohort study

The aim of this study was to examine the effects of metabolic syndrome (MS) and the number of MS components on the development of non-alcoholic fatty liver disease (NAFLD). A total of 1,343 males and 574 females aged ≥50 years without NAFLD at baseline were included. Information on lifestyle, including alcohol use and personal history, was collected by face-to-face interviews. Biochemical parameters were assayed using fasting blood samples. NAFLD was diagnosed by abdominal ultrasonography. During follow-up at an average of 4.8 years, 223 patients developed NAFLD. Following adjustment for multiple covariates, age was an independent protective predictor [hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.95–0.98], while the independent risk predictors were obesity (HR, 2.81; 95% CI, 2.14–3.69), higher triglycerides (HR, 2.56; 95% CI, 1.95–3.32) and alanine aminotransferase (HR, 1.004; 95% CI, 1.000–1.008). Participants with a diagnosis of MS had a significantly increased risk of developing NAFLD (HR, 3.17; 95% CI, 2.42–4.14). A greater number of MS components was significantly associated with a higher risk of NAFLD (all adjusted P for trend <0.001). Compared with those without any components of MS, participants with only one component of MS had a 3.6-fold higher risk of developing NAFLD (adjusted HR, 3.64; 95% CI, 1.50–8.88). The diagnosis and the number of components of MS were prospectively associated with the risk of developing NAFLD. Even in those with only one component of MS, the risk increased by 2.6-fold compared with that for the individuals without any components, suggesting a beneficial effect of intervention at the very early stage of MS on the prevention of NAFLD.

/pdf/association-between-metabolic-syndrome-and-the-development-4v3mcu3jzr.pdf

Association between metabolic syndrome and the development of non-alcoholic fatty liver disease.

OBJECTIVE Our studies in vitro and in vivo aimed to investigate the influence of DNA methylation of peroxisome proliferator activated receptor-α (PPAR-α) gene in non-alcoholic fatty liver disease (NAFLD) pathogenesis and to observe whether the DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) and the herbal medicine curcumin might reverse the effect both in vivo and in vitro. METHODS Steatotic hepatocyte model of cell lines and NAFLD rat models were established following protocols documented in previous studies. Subsequently, the models received 5-Aza-CdR and curcumin treatment. Morphological, histological and laboratory variables in each group were determined by routine methods, including PPAR-α mRNA expression by polymerase chain reaction (PCR), PPAR-α protein expression by Western blot and DNA methylation by pyrosequencing. RESULTS The steatotic hepatocyte model and NAFLD rat model were completely established. The expressions of PPAR-α mRNA and protein were significantly lower in the steatotic hepatocyte and NAFLD rat model groups than in the controls (P < 0.05). The mean DNA methylation levels of the PPAR-α gene were significantly higher in the two steatotic model groups than in the controls, especially at several CpG sites (P < 0.05). 5-Aza-CdR and curcumin treatment significantly reversed the DNA methylation levels, increased PPAR-α mRNA and protein expression, and improved lipid accumulation in the two steatotic models (P < 0.05). CONCLUSIONS DNA methylation at the PPAR-α gene is involved in the pathogenesis of NAFLD and is possibly reversible by 5-Aza-CdR and curcumin. Curcumin may be a promising candidate for NAFLD therapy.

Fatty liver mediated by peroxisome proliferator-activated receptor-α DNA methylation can be reversed by a methylation inhibitor and curcumin

Nonalcoholic fatty liver disease (NAFLD) is defined as excessive accumulation of fatty acid in the liver, a common disease in the world. The research of single nucleotide polymorphisms (SNPs) provides a new approach for managing NAFLD. SNPs may increase or decrease the functions of the target genes and their encoding proteins. Peroxisome proliferator-activated receptor (PPAR) plays a key role in modulating metabolism of hepatic triglycerides and consequently magnitude of NAFLD. In this study, we investigated the effect of three SNPs in the PPAR-γ gene i.e. rs10865710 (C-681G), rs7649970 (C-689T) and rs1801282 (C34G, also termed Pro12Ala) on susceptibility to NAFLD. The participants were selected from our epidemiological survey. Totally 169 participants were enrolled in NAFLD group, and 699 healthy subjects were included as controls. PCR-RFLP was applied to detect the SNPs. The G allele frequency of rs10865710 in NAFLD group (41.1%) was significantly higher than that (34.8%) in controls (p = 0.03). Differences in other two loci (rs7649970 and rs1801282) were not statistically significant between the two groups (p > 0.05). This result was confirmed by haplotype analysis. The GCC haplotype (a set of 3 adjacent SNPs in linkage disequilibrium, corresponding to the three alleles of above polymorphisms in order) was a risk factor for the susceptibility to NAFLD (p = 0.03). This study has revealed that the G allele of rs10865710 in the PPAR-γ gene is associated with the increased susceptibility to NAFLD. Our findings may provide novel diagnostic biomarkers and therapeutic targets for NAFLD.

Yong Jian Zhou

Papers

Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients

Natural course of nonalcoholic fatty liver disease in southern China: A prospective cohort study

Association between metabolic syndrome and the development of non-alcoholic fatty liver disease.

Fatty liver mediated by peroxisome proliferator-activated receptor-α DNA methylation can be reversed by a methylation inhibitor and curcumin

The C-681G polymorphism of the PPAR-γ gene is associated with susceptibility to non-alcoholic fatty liver disease.