scholarly journals NAFLD-Related Hepatocarcinoma: The Malignant Side of Metabolic Syndrome

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2034
Author(s):  
Anna Michelotti ◽  
Marco de Scordilli ◽  
Lorenza Palmero ◽  
Michela Guardascione ◽  
Mario Masala ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Developed Countries ◽  
Molecular Pathways ◽  
Alcoholic Fatty Liver ◽  
Common Cancer ◽  
Alcoholic Fatty Liver Disease ◽  
Related Mortality

Hepatocellular carcinoma (HCC) is the seventh most common cancer worldwide and the second leading cause of cancer-related mortality. HCC typically arises within a cirrhotic liver, but in about 20% of cases occurs in absence of cirrhosis. Among non-cirrhotic risk factors, non-alcoholic fatty liver disease (NAFLD) currently represents the most important emerging cause of HCC in developed countries. It has been estimated that annual incidence of HCC among patients with non-cirrhotic NAFLD is approximately 0.1–1.3 per 1000 patients/year and ranges from 0.5% to 2.6% among patients with non-alcoholic steatohepatitis (NASH) cirrhosis. However, only a few clinical trials enrolling HCC patients actually distinguished NAFLD/NASH-related cases from other non-cirrhotic causes and therefore evidence is still lacking in this subset of patients. This review aims to describe the biology underpinning NAFLD development, to investigate the main molecular pathways involved in its progression to NASH and HCC and to describe how different pathogenetic mechanisms underlying the onset of HCC can have an impact in clinical practice. We hereby also provide an overview of current HCC treatment options, with a particular focus on the available data on NAFLD-related cases in practice-changing clinical trials.

scholarly journals Current and Future Treatments in the Fight against Non-Alcoholic Fatty Liver Disease

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1714 ◽  
Author(s):  
Benoit Smeuninx ◽  
Ebru Boslem ◽  
Mark A. Febbraio
Keyword(s):  
Risk Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Critical Factor ◽  
Developed Countries ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Obesity is recognised as a risk factor for many types of cancers, in particular hepatocellular carcinoma (HCC). A critical factor in the development of HCC from non-alcoholic fatty liver disease (NAFLD) is the presence of non-alcoholic steatohepatitis (NASH). Therapies aimed at NASH to reduce the risk of HCC are sparse and largely unsuccessful. Lifestyle modifications such as diet and regular exercise have poor adherence. Moreover, current pharmacological treatments such as pioglitazone and vitamin E have limited effects on fibrosis, a key risk factor in HCC progression. As NAFLD is becoming more prevalent in developed countries due to rising rates of obesity, a need for directed treatment is imperative. Numerous novel therapies including PPAR agonists, anti-fibrotic therapies and agents targeting inflammation, oxidative stress and the gut-liver axis are currently in development, with the aim of targeting key processes in the progression of NASH and HCC. Here, we critically evaluate literature on the aetiology of NAFLD-related HCC, and explore the potential treatment options for NASH and HCC.

scholarly journals An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 643
Author(s):  
Wei-Qiang Leow ◽  
Pierre Bedossa ◽  
Feng Liu ◽  
Lai Wei ◽  
Kiat-Hon Lim ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Alcoholic Fatty Liver ◽  
Discriminatory Ability ◽  
Alcoholic Steatohepatitis ◽  
Singapore General Hospital ◽  
Peking University ◽  
Stage 1 ◽  
Alcoholic Fatty Liver Disease

Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists. Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People’s Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions. Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases. Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials.

Small Intestinal Bacterial Overgrowth Is Associated with Non- Alcoholic Fatty Liver Disease

2016 ◽  
Vol 25 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Andrea Fialho ◽  
Andre Fialho ◽  
Prashanthi Thota ◽  
Arthur J. McCullough ◽  
Bo Shen
Keyword(s):  
Risk Factors ◽  
Fatty Liver Disease ◽  
Bacterial Overgrowth ◽  
Small Intestinal Bacterial Overgrowth ◽  
Study Group ◽  
Alcoholic Fatty Liver ◽  
Intestinal Bacterial Overgrowth ◽  
Small Intestinal ◽  
Alcoholic Fatty Liver Disease

Background: Changes in gut bacteria play a role in type 2 diabetes mellitus (DM) and hepatic steatosis. There is a lack of studies evaluating the frequency and risk factors for non-alcoholic fatty liver disease (NAFLD) in patients tested for small intestinal bacterial overgrowth (SIBO). Aim: To evaluate the frequency of NAFLD and associated risk factors in patients tested for SIBO. Methods: In this case-control study, 372 eligible patients submitted to glucose hydrogen/methane breath test for SIBO who also had an abdominal imaging study were included. Patients were divided into SIBO-positive and SIBO-negative groups. Clinical, demographic and laboratory variables were evaluated in addition to the presence of NAFLD on abdominal imaging. Results: Of the 372 eligible patients, 141 (37.9%) were tested positive for SIBO (study group) and 231 (62.1%) were negative for it (control group). NAFLD occurred in 45.4% (64/141) of the study group compared to 17.3% (40/231) of the control group (p<0.001). Patients in the study group were found to have higher rates of elevated aspartate aminotransferase (AST) (20.6% vs. 11.3%; p=0.034) and alanine aminotransferase (ALT) levels (56.0% vs. 40.7%; p= 0.039), type 2 diabetes (23.4% vs. 13.9%; p=0.041), hypertension (54.6% vs. 40.3%; p=0.046) and metabolic syndrome (78.0% vs. 60.2%; p=0.020). In the multivariate analysis, SIBO (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.14-3.31; p=0.014), type 2 DM (OR: 3.04; 95%CI: 1.57-5.90; p=0.001) and obesity (OR: 3.58; 95%CI: 1.70-7.54; p=0.001) remained associated with NAFLD.Conclusion: Patients with SIBO have an increased risk for hepatic steatosis and may benefit from aggressive control of the risk factors for NAFLD including metabolic syndrome. Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; CTE: computed tomography enterography; DM: diabetes mellitus; ETOH: ethanol; IL: interleukin; LPS: lipopolysaccharide; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PPI: proton pump inhibitor; SIBO: small intestinal bacterial overgrowth; TLR-4: toll-like receptor 4; TMAO: trimethylamine-N-oxide (TMAO); TNF-α: tumor necrosis factor alpha.

New therapy for fatty liver

2018 ◽  
Vol 1 (2) ◽  
pp. 24-28
Author(s):  
Tanita Suttichaimongkol
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Liver Insulin Resistance ◽  
Alcoholic Fatty Liver Disease ◽  
Related Mortality

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of death from liver cirrhosis, endstage liver disease, and hepatocellular carcinoma. It is also associated with increased cardiovasculardisease and cancer related mortality. While lifestyle modifications are the mainstay of treatment,only a proportion of patients are able to make due to difficult to achieve and maintain, and so moretreatment options are required such as pharmacotherapy. This review presents the drugs used inmanaging NAFLD and their pharmacologic targets. Therapies are currently directed towards improvingthe metabolic status of the liver, insulin resistance, cell oxidative stress, apoptosis, inflammation orfibrosis. Several agents are now in large clinical trials and within the next few years, the availability oftherapeutic options for NAFLD will be approved.     Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis  

scholarly journals Non-alcoholic fatty liver disease in polycystic ovary syndrome women

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Young Bin Won ◽  
Seok Kyo Seo ◽  
Bo Hyon Yun ◽  
SiHyun Cho ◽  
Young Sik Choi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Liver Enzyme ◽  
Fatty Liver Disease ◽  
Polycystic Ovary ◽  
Insulin Level ◽  
University Hospital ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractTo evaluate risk factors leading to non-alcoholic fatty liver disease (NAFLD) occurrence in polycystic ovarian syndrome (PCOS) women. A retrospective cohort study of a total of 586 women diagnosed with PCOS aged 13–35 years at the gynecology department at a university hospital was done to evaluate PCOS phenotype, metabolic syndrome (MetS) diagnosis, body composition, insulin sensitivity, sex hormones, lipid profile, liver function, and transient elastography (TE). In PCOS women with NAFLD compared to those without, MetS diagnosis (Hazard ratio [HR] 5.6, 95% Confidence interval [CI] 2.2–14.4, p < 0.01) and hyperandrogenism (HA) (HR 4.4, 95% CI 1.4–13.4, p = 0.01) were risk factors significantly associated with subsequent NAFLD occurrence, whereas 2-h insulin level in 75 g glucose tolerance test (GTT) (HR 1.2, 95% CI 0.5–2.5, p = 0.70) and body mass index (BMI) > 25 kg/m2 (HR 2.2, 95% CI 0.6–8.0, p = 0.24) was not. Among NAFLD patients who underwent TE, a higher number of MetS components indicated a worse degree of fibrosis and steatosis. MetS diagnosis and HA at PCOS diagnosis were risk factors associated with NAFLD, while 2-h insulin level in 75 g GTT and obesity were not. Although elevated aspartate aminotransferase levels were significant for NAFLD risk, liver enzyme elevations may not be present until late liver damage. Further prospective studies of PCOS women with MetS or HA are warranted to determine whether patients without liver enzyme elevations should undergo preemptive liver examinations.

scholarly journals Implementation of a care bundle improves the management of patients with non-alcoholic fatty liver disease

2021 ◽  
pp. flgastro-2020-101480
Author(s):  
Laura Jane Neilson ◽  
Louise Macdougall ◽  
Phey Shen Lee ◽  
Timothy Hardy ◽  
David Beaton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Risk Factors ◽  
Care Bundle ◽  
Metabolic Risk ◽  
Lifestyle Advice ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is common and is associated with liver-related and cardiovascular-related morbidity. Our aims were: (1) to review the current management of patients with NAFLD attending hospital clinics in North East England (NEE) and assess the variability in care; (2) develop a NAFLD ‘care bundle’ to standardise care; (3) to assess the impact of implementation of the NAFLD care bundle.MethodsA retrospective review was conducted to determine baseline management of patients with NAFLD attending seven hospitals in NEE. A care bundle for the management of NAFLD was developed including important recommendations from international guidelines. Impact of implementation of the bundle was evaluated prospectively in a single centre.ResultsBaseline management was assessed in 147 patients attending gastroenterology, hepatology and a specialist NAFLD clinic. Overall, there was significant variability in the lifestyle advice given and management of metabolic risk factors, with patients attending an NAFLD clinic significantly more likely to achieve >10% body weight loss and have metabolic risk factors addressed. Following introduction of the NAFLD bundle 50 patients were evaluated. Use of the bundle was associated with significantly better documentation and implementation of most aspects of patient management including management of metabolic risk factors, documented lifestyle advice and provision of NAFLD-specific patient advice booklets.ConclusionThe introduction of an outpatient ‘care bundle’ led to significant improvements in the assessment and management of patients with NAFLD in the NEE and could help improve and standardise care if used more widely.

scholarly journals Expert Opinion on the Management of Non-Alcoholic Fatty Liver Disease (NAFLD) in the Middle East with a Focus on the Use of Silymarin

2021 ◽  
Vol 12 (2) ◽  
pp. 155-165
Author(s):  
Ahmed Hashem ◽  
Yogesh Shastri ◽  
Malfi Al Otaibi ◽  
Elwin Buchel ◽  
Hussam Saleh ◽  
...  
Keyword(s):  
Liver Disease ◽  
Middle East ◽  
Fatty Liver Disease ◽  
Expert Panel ◽  
Treatment Options ◽  
Current Treatment ◽  
Alcoholic Fatty Liver ◽  
Liver Disease Progression ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty disease (NAFLD) is amongst the leading causes of chronic liver disease worldwide. The prevalence of NAFLD in the Middle East is 32%, similar to that observed worldwide. The clinicians in this region face several challenges in diagnosing and treating patients with NAFLD. Additionally, there are no national or regional guidelines to address the concerns faced with current treatment options. Silymarin, derived from milk thistle, provides a rational and clinically proven approach to hepatoprotection. This article focuses on addressing regional diagnostic challenges and provides clear guidance and potential solutions for the use of Silymarin in the treatment of NAFLD in the Middle East. Both clinical and preclinical studies have highlighted the efficiency of Silymarin in managing NAFLD by reducing liver disease progression and improving patient symptoms and quality of life, alongside being safe and well tolerated. An expert panel of professionals from the Middle East convened to establish a set of regional-specific diagnostics. A consensus was established to aid general physicians to address the diagnostic challenges in the region. In conclusion, Silymarin can be considered beneficial in treating NAFLD and should be initiated as early as possible and continued as long as necessary.

scholarly journals The albumin-to-alkaline phosphatase ratio as an independent predictor of future non-alcoholic fatty liver disease in a 5-year longitudinal cohort study of a non-obese Chinese population

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Guotai Sheng ◽  
Nan Peng ◽  
Chong Hu ◽  
Ling Zhong ◽  
Mingchun Zhong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Fatty Liver Disease ◽  
Chinese Population ◽  
Independent Predictor ◽  
Multiple Regression Model ◽  
Obese People ◽  
Alcoholic Fatty Liver ◽  
Obese Subjects ◽  
Alcoholic Fatty Liver Disease

Abstract Background The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. Methods The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. Results The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend< 0.0001). Additionally, there were significant interactions between the AAPR and BMI, blood pressure and lipids (P-interaction < 0.05). Stratified analysis showed that the risk of AAPR-related NAFLD decreased in people with normal blood pressure and lipid levels, while the risk of AAPR-related NAFLD increased abnormally in people who were underweight. Conclusions This longitudinal cohort study provides the first evidence that the AAPR is an independent predictor of future NAFLD events in non-obese people. For non-obese people with a low AAPR, especially those with BMI < 18.5 kg/m2, more attention should be given to the management of risk factors for NAFLD to prevent future NAFLD.

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