scholarly journals Role of glycine-N-methyl transferase in human and murine nonalcoholic steatohepatitis

2021 ◽  
Author(s):  
Connor R. Quinn ◽  
Mario C. Rico ◽  
Carmen Merali ◽  
Salim Merali
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Disease Process ◽  
Chronic Liver ◽  
Label Free ◽  
Methyl Transferase ◽  
Alcoholic Fatty Liver ◽  
The Impact

AbstractNon-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, mirroring the obesity epidemic. NAFLD is the number one cause of chronic liver disease worldwide, with 25% of these patients developing nonalcoholic steatohepatitis (NASH). This significantly increases the risk of cirrhosis and decompensated liver failure. Past studies in rodent models have shown that the knockout of glycine-N-methyltransferase (GNMT) is associated with steatosis, fibrosis, and hepatocellular carcinoma. However, the attenuation of GNMT in subjects with NASH and the molecular basis for its impact on the disease process have yet to be elucidated. To address this knowledge gap, we show the reduction of GNMT protein levels in the liver of NASH subjects compared to healthy controls. To gain insight into the impact of decreased GNMT in the disease process, we performed global label-free proteome studies on the livers from a murine Western diet-based model of NASH. We identified the differential expression of essential proteins involved in hallmark NASH pathogenesis, including lipid metabolism, inflammation, and fibrosis. Significantly, the downregulation of GNMT, the prominent regulator of S-adenosylmethionine (AdoMet), was identified as a contributing factor to these networks, increasing fourfold in AdoMet levels. AdoMet is an essential metabolite for transmethylation reactions and a substrate for polyamine synthesis, and its levels can impact polyamine flux and generate oxidative stress. Therefore, we performed targeted proteome and metabolomics studies to show a decrease in GNMT transmethylation, an increase in flux through the polyamine pathway, and increased oxidative stress.Abstract Figure

scholarly journals The impact of endotrophin on the progression of chronic liver disease

2020 ◽  
Vol 52 (10) ◽  
pp. 1766-1776
Author(s):  
Min Kim ◽  
Changhu Lee ◽  
Dae Yun Seo ◽  
Hyojung Lee ◽  
Jay D. Horton ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Liver Cancer ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Hepatic Inflammation ◽  
Fibrotic Liver ◽  
Alcoholic Fatty Liver ◽  
The Impact

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The fibrotic liver is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Type VI collagen alpha3 (Col6a3) is a biomarker of hepatic fibrosis, and its cleaved form, endotrophin (ETP), plays a critical role in adipose tissue dysfunction, insulin resistance, and breast cancer development. Here, we studied the effects of the Col6a3-derived peptide ETP on the progression of chronic liver diseases, such as NASH and liver cancer. We used a doxycycline (Dox)-inducible liver-specific ETP-overexpressing mouse model on a NAFLD-prone (liver-specific SREBP1a transgenic) background. For this, we evaluated the consequences of local ETP expression in the liver and its effect on hepatic inflammation, fibrosis, and insulin resistance. Accumulation of ETP in the liver induced hepatic inflammation and the development of fibrosis with associated insulin resistance. Surprisingly, ETP overexpression also led to the emergence of liver cancer within 10 months in the SREBP1a transgenic background. Our data revealed that ETP can act as a “second hit” during the progression of NAFLD and can play an important role in the development of NASH and hepatocellular carcinoma (HCC). These observations firmly link elevated levels of ETP to chronic liver disease.

scholarly journals Coffee Consumption and the Progression of NAFLD: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2381
Author(s):  
Rebecca Sewter ◽  
Susan Heaney ◽  
Amanda Patterson
Keyword(s):  
Systematic Review ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Coffee Consumption ◽  
Developed Countries ◽  
Chronic Liver ◽  
Cochrane Library ◽  
Coffee Intake ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed countries. Coffee is one of the most consumed beverages in the world and has been shown to be beneficial in limiting progression in chronic liver disease in general. However, research surrounding the impact of coffee consumption on NAFLD progression is limited. This systematic review aimed to investigate the relationship between coffee consumption and the progression of liver disease, specifically for cases of NAFLD. MEDLINE, EMBASE, CINAHL, the Cochrane Library, and Scopus were searched for published studies that evaluated the effects of coffee consumption on the progression of NAFLD. The results are presented in a narrative synthesis with principal summary measures, including odds ratios, p-values, and differences in mean coffee intake in relation to severity of NAFLD. Five studies met the inclusion criteria and were included in this review. There was no trial evidence among NAFLD patients, rather all studies were of a cross-sectional design. Using the Academy of Nutrition and Dietetics Quality Criteria Checklist, four studies received a positive rating, with the remaining study receiving a neutral rating. Overall, four out of the five studies reported a statistically significant relationship between coffee consumption and the severity of fibrosis. Methods around capturing and defining coffee consumption were heterogeneous and therefore an effective dose could not be elucidated. Results suggest that higher coffee consumption is inversely associated with the severity of hepatic fibrosis in individuals with NAFLD. However, further research is required to elucidate the optimum quantity and form/preparation of coffee required to exert this hepatoprotective role.

The impact of diabetes on HCC.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4029-4029
Author(s):  
Suzanne Graef ◽  
Sarah Berhane ◽  
Mabel Joey Teng ◽  
Anna Skowronska ◽  
Philip James Johnson
Keyword(s):  
Multivariate Analysis ◽  
Risk Factor ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Independent Risk Factor ◽  
Chronic Liver ◽  
Diabetic Patients ◽  
Alcoholic Fatty Liver ◽  
Treatment Of Diabetes ◽  
The Impact

4029 Background: The incidence of hepatocellular carcinoma (HCC) in the UK has increased by 40% over the last 20 years, with a corresponding increase in mortality rate. The rising incidence of obesity and type II diabetes are believed to be contributing factors due to the association with non-alcoholic fatty liver and steatohepatitis. We aimed to examine if diabetes was as an independent risk factor for the development of HCC and to assess the impact of diabetes on overall survival (OS). Methods: Data from 724 patients with HCC and a control group comprising 340 patients with chronic liver disease were collected prospectively between 2007 and 2012. The odds ratio (OR) for HCC in diabetic versus non-diabetic patients was calculated. Univariate and multivariate analysis was performed using logistic regression. Cox proportional hazards analysis was used to estimate hazard ratio (HR) for death for HCC patients, with and without diabetes and for the impact of variation in diabetic treatments. Results: The prevalence of diabetes was 39% within the HCC population and 10.3% within the chronic liver disease group. Univariate analysis demonstrated increased risk of HCC associated with age, sex, diabetes, haemochromatosis, cirrhosis, alcohol abuse and Child’s score. In patients with diabetes OR for HCC was 5.74 (CI 3.9-8.3; p<0.001). Age, sex, cirrhosis, Child’s score, diabetes and diabetes treatment with insulin, retained significance as independent risk factors in multivariate analysis. There was no survival difference for HCC patients with and without diabetes. In diabetic patients with HCC, treatment of diabetes with metformin, compared against other diabetic treatment options, was associated with a significantly longer OS (31 versus 24 months, p = 0.016; HR 0.74, p = 0.027). Conclusions: This study has demonstrated that diabetes is an independent risk factor for the development of HCC in a high risk population and that treatment with insulin appears to confer further independent risk. Diabetes has no effect on survival following the development of HCC but treatment of diabetes with metformin is associated with prolonged survival. In considering the optimal treatment for diabetes in chronic liver disease the beneficial effects of metformin on OS, if HCC develops, should be taken into account.

scholarly journals Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

2021 ◽  
Vol 14 ◽  
pp. 175628482110234
Author(s):  
Mario Romero-Cristóbal ◽  
Ana Clemente-Sánchez ◽  
Patricia Piñeiro ◽  
Jamil Cedeño ◽  
Laura Rayón ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
Critically Ill ◽  
Cox Regression ◽  
Chronic Liver ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

Health-related quality of life in chronic liver disease: the impact of type and severity of disease

2001 ◽  
Vol 96 (7) ◽  
pp. 2199-2205 ◽  
Author(s):  
Zobair M Younossi ◽  
Navdeep Boparai ◽  
Lori Lyn Price ◽  
Michelle L Kiwi ◽  
Marilyn McCormick ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Health Related Quality ◽  
Severity Of Disease ◽  
Related Quality ◽  
Health Related ◽  
The Impact

scholarly journals Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maryam Moini ◽  
Fernanda Onofrio ◽  
Bettina E. Hansen ◽  
Oyedele Adeyi ◽  
Korosh Khalili ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Transient Elastography ◽  
Area Under The Curve ◽  
High Specificity ◽  
Serum Markers ◽  
Chronic Liver ◽  
Alcoholic Fatty Liver ◽  
Advanced Liver Fibrosis ◽  
Independent Association

AbstractReliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4.

scholarly journals Impact of Severity of Chronic Liver Disease on Health-Related Economics

2020 ◽  
Vol 20 (6) ◽  
Author(s):  
Fakhar Ali Qazi Arisar ◽  
Muhammad Kamran ◽  
Ramlah Nadeem ◽  
Wasim Jafri
Keyword(s):  
Socioeconomic Status ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Economic Status ◽  
Treatment Compliance ◽  
Chronic Liver ◽  
Medical Expenses ◽  
Severity Of Disease ◽  
The Family ◽  
The Impact

Background: Chronic liver disease (CLD) is one of the leading causes of morbidity and mortality worldwide. It is accountable for a multifaceted disease encumbrance upsetting the psychological, physical, and economic health of not only the patients but also their caregivers. Objectives: The study purposes to cover the economic aspect of CLD to comprehend the financial burden imposed on the patients. Methods: This cross-sectional study was conducted at a tertiary care hospital in Karachi, Pakistan. The CLD patients presenting in gastroenterology clinics were recruited, and their socio-demographic, financial, and disease-related information including Model for End-stage Liver Disease (MELD) score and Child Turcotte Pugh (CTP) scores were collected. Out of 190 CLD patients enrolled, 127 (67.2%) were males. The mean age was 50.09 years. Variables assessed include self-perceived social/economic status, self-perception of disease responsibility for worsening of social/economic situation, the impact of the disease on economic status due to medical expense, the impact of economic status on treatment compliance due to medical expenses, impact of severity of disease on socioeconomic status and treatment compliance, and impact of gender on disease status and treatment compliance. Results: Regardless of the disease duration, CLD significantly impacted a patient’s life, as 81% and 69% of the patients blamed their disease responsible for the worsening of social and economic conditions, respectively. In our study, 85% of patients had consumed all savings during their course of illness, and 67% had to borrow money for medical expenses. Nearly half of the patients had to leave or cut short their medicines, skip the physician's appointment, or defer their children's education. One-third of patients had unpaid medical and utility bills or even skipped their meals. The severity of disease affected the socioeconomic status significantly (89% in CTP class C vs. 40% in CTP class A). Patients with worsening socioeconomic status had significantly higher MELD scores as compared to those with stable socioeconomic status. Conclusions: Chronic liver disease imposes incredible socioeconomic encumbrance on patients and the family unit, and CLD associated expenditures influence the family unit’s everyday working and therapeutic compliance, which is directly linked to the severity of disease expressed in terms of CTP and MELD scores.

Liver Fibrosis is Associated with a Decrease in Gait Speed in Older Men with Chronic Liver Disease: A Retrospective Cross-Sectional Study

2021 ◽  
Author(s):  
Kenichi Fudeyasu ◽  
Takuo Nomura ◽  
Toshihiro Kawae ◽  
Daisuke Iwaki ◽  
Yuki Nakashima ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Chronic Liver Disease ◽  
Motor Function ◽  
Gait Speed ◽  
Older Patients ◽  
Knee Extension ◽  
Chronic Liver ◽  
Cross Sectional ◽  
The Impact

Abstract Background: Although it has already been reported that chronic liver disease (CLD) can induce sarcopenia, the impact of sarcopenia, especially on motor function, in older patients with CLD is still unclear. Therefore, we investigated the effects of liver fibrosis on motor function in these patients.Methods: In all, 117 older patients with CLD aged above 60 years (men, n=70; women, n=47) were included in this study. We examined the presence or absence of sarcopenia and checked motor functions such as muscle strength and walking speed. The results were compared between patients with FIB-4 index of >3.25, indicative of severe-degree liver fibrosis (SLF), and those with an index of <3.25, indicative of low-degree liver fibrosis (LLF). We also analyzed the factors related to the decrease in gait speed.Results: The decrease in gait speed (<1.0 m/s) was significantly higher (P = 0.027) and the knee extension force (KEF) was significantly lower (P = 0.010) in men with SLF than in those with LLF. In this study, liver fibrosis (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.56–0.90) and KEF (OR = 1.09, 95% CI = 1.02–1.16) were identified as factors associated with the decrease in gait speed.Conclusions: Older male patients with CLD have decreased motor function as the disease progresses. We found that the decrease in gait speed is related to liver fibrosis and KEF. It is necessary to focus on the motor function of older patients with CLD, especially the gait speed.

A Silybinphospholipid Complex Prevents Mitochondrial Oxidative Stress in Models of Chronic Liver Disease

2010 ◽  
Vol 49 ◽  
pp. S177
Author(s):  
Francesco Bellanti ◽  
Alessandro Arduini ◽  
Rosanna Tamborra ◽  
Tiziana Rollo ◽  
Maria Blonda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Mitochondrial Oxidative Stress
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