High-Risk NAFLD among Patients with Irritable Bowel Syndrome: Frequency and Effect on Disease Severity

Background Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disease that can change a patient's quality of life and impair their daily activities. Non-alcoholic fatty liver disease (NAFLD), on the other hand, has become a widespread condition as the global obesity rates rises. The prevalence of NAFLD has reached up to 25% of the adolescent population. The etiology of both diseases is still not clearly understood. The mechanism linking the two seemingly similar diseases could be immune system activation and tissue inflammation; thus, the goal of our study was to see if there was a common link between them and to examine NAFLD prevalence and severity in IBS patients. Our study included 150 patients who have symptoms of IBS with different degrees of severity. IBS was diagnosed according to modified ROME IV criteria. Patients were examined to see if they had NAFLD based on abdominal ultrasonography and NAFLD fibrosis score calculation. Results Our current study showed that regarding evaluating the association of IBS with NAFLD, there was a highly statistically significant association between both diseases. Furthermore, there was a high statistical significant association between higher grades of NAFLD and lipid profile parameters. Conclusion Patients with IBS had a higher frequency of NAFLD. In addition, a significant association was noted between IBS severity and increased NAFLD grades.

Plasma sgp130 is an independent predictor of non-alcoholic fatty liver disease severity

Background: Nonalcoholic steatohepatitis (NASH) is a metabolic disease associated with liver failure and cancer. Accurate monitoring of advancing NASH is challenging. There are few reliable, non-invasive biomarkers of early NASH. Since liver inflammation is a main driver of fibrosis, we investigated relationships between circulating components of the interleukin-6 signaling pathway (IL-6, sIL-6R and sgp130) and liver pathology in subjects with NAFLD and NASH. Methods: Predictive performance of plasma IL-6, sIL-6R and sgp130 were investigated in two independent cohorts: 1) patients with biopsy-confirmed NASH (n=49), where magnetic resonance spectroscopy (MRS), imaging (MRI) and elastography (MRE) assessed liver fat, volume and stiffness; and 2) patients with morbid obesity (n=245) undergoing bariatric surgery where Bedossa algorithm and steatosis, activity, and fibrosis scores assessed NASH severity. Correlations were evaluated between circulating IL-6, sIL-6R and sgp130 and anthropomorphic characteristics, plasma markers of metabolic disease or liver pathology, adjusting for covariates of liver disease such as age, sex, BMI and diabetes. Results: In patients with NASH, plasma IL-6 and sgp130 strongly correlated with liver stiffness, which for sgp130, was independent of age, sex, BMI, and chronic disease (diabetes, hyperlipidemia, hypertension or history of HCC). Plasma sgp130 was the strongest predictor of liver stiffness compared to commonly used biomarkers and predictive algorithms. Plasma sIL-6R correlated with liver volume independent of age, sex, and BMI. In stepwise forward regression analysis, plasma sgp130 followed by NAFLD fibrosis score and plasma globulin, predicted up to 74% of liver stiffness with/without adjustment for sex. In morbidly obese subjects, circulating IL-6 correlated with hepatocellular ballooning and sgp130 correlated with advanced liver fibrosis. Conclusions: Circulating sgp130 could represent a robust biomarker of active NASH and may be used alone or in combination with other biomarkers as a non-invasive measure of liver disease severity.

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study

Background The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown. Methods A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs. Results 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels. Conclusions This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.

Non-Invasive Assessment Of Liver Fibrosis In Patients With Non-Alcoholic Fatty Liver Disease In A Tertiary Care Hospital

Aims :To compare the NAFLD fibrosis score and FIBROSIS 4 score to fibroscan, and affirm whether the scores shall be used as a screening tool for liver fibrosis, in place of fibroscan. Methodology: It was a cross-sectional study. Patients with fatty liver on ultrasonological examination with 200 sample size. After obtaining the informed consent the following details were collected socio-demographic details, history, co-morbidities, anthropometric measurements, Laboratory investigations. Results: the ROC curve analysis of fibroscan reveals the area under curve of 0.499 and based on the cut off value of 4.50Kpas the sensitivity and specificity was found to be 85.7% and 83.5% respectively. The ROC curve analysis of fibrosis-4 reveals the area under curve of 0.495 and based on the cut off value of 0.80 the sensitivity and specificity was found to be 91.9% and 92.1% respectively. Analysis of NAFLD fibrosis score reveals the area under curve of 0.476 and based on the cut off value of -1.53 the sensitivity and specificity was found to be 93.1% and 93.9% respectively. Conclusion: Henceforth the study suggests that NAFLD fibrosis score shall be used as a non -invasive bedside assessment of liver fibrosis in high risk population and hence guiding their follow up for prevention of morbidity in resource limited settings.

Impact of statin treatment on non-invasive tests based predictions of fibrosis in a referral pathway for NAFLD

ObjectiveIn non-alcoholic fatty liver disease (NAFLD), fibrosis determines the risk of liver complications. Non-invasive tests (NITs) such as FIB-4, NAFLD Fibrosis Score (NFS) and Hepamet, have been proposed as a tool to triage NAFLD patients in primary care (PC). These NITs include AST±ALT in their calculations. Many patients with NAFLD take statins, which can affect AST/ALT, but it is unknown if statin affects NITs fibrosis prediction.MethodsWe included 856 patients referred through a standardised pathway from PC with a final diagnosis of NAFLD. 832 had reliable vibration controlled transient elastography (VCTE) measurements. We assessed the effects of statins on the association between NITs and VCTE at different fibrosis thresholds.Results129 out of 832 patients were taking a statin and 138 additional patients had indication for a statin. For any given FIB-4 value, patients on a statin had higher probabilities of high VCTE than patients not on a statin. Adjusting for body mass index, diabetes and age almost completely abrogated these differences, suggesting that these were related to patient’s profile rather to a specific effect of statins. Negative predictive values (NPVs) of FIB-4 <1.3 for VCTE >8, 10, 12 and 16 were, respectively, 89, 94, 96% and 100% in patients on a statin and 92, 95, 98% and 99% in patients not on a statin. Statins had similar impact on Hepamet predictions but did not modify NFS predictions.ConclusionIn patients with NAFLD referred from PC, those on statins had higher chances of a high VCTE for a given FIB-4 value, but this had a negligible impact on the NPV of the commonly used FIB-4 threshold (<1.3).

Effect of Nutrition Education in NAFLD Patients Undergoing Simultaneous Hyperlipidemia Pharmacotherapy: A Randomized Controlled Trial

Background: Patients with non-alcoholic fatty liver disease (NAFLD) have a high prevalence of combined hyperlipidemia. The importance of nutritional education is well-known in NAFLD, but the impact of medical nutrition therapy (MNT) is unclear in patients with NAFLD with hyperlipidemia. The purpose of this study is to investigate the effect of MNT on the improvement of steatohepatitis in patients with NAFLD taking antihyperlipidemic medications. Methods: Nondiabetic patients with dyslipidemia were prospectively randomized (1:1) either to the MNT group or the control group with standard advice for 48 weeks with simultaneous statin/ezetimibe combination pharmacotherapy at three tertiary centers in Korea. Results: Sixty-six patients were enrolled. Among them, 18 patients dropped out and, overall, 48 patients (MNT group 27, control group 21) were prospectively analyzed in the study. The serum ALT level at 48 weeks between the two groups was not significantly different (66.6 ± 37.7 IU/L vs. 57.4 ± 36.7 IU/L, p = 0.40). Serum liver enzymes, controlled attenuation parameter and fibrosis-4 index were significantly improved within the MNT group after 48 weeks compared to baseline. There was no significant difference between the two groups other than the NAFLD fibrosis score (p = 0.017). Conclusions: Although there were no significant differences between the two groups in terms of steatosis, metabolic and fibrosis surrogate indicators after 48 weeks, MNT groups showed significant improvement within patient analysis over time. Future studies with a larger number of subjects and a longer study period regarding the effect of MNT are warranted.

Liver fibrosis indices are related to diabetic peripheral neuropathy in individuals with type 2 diabetes

The association between nonalcoholic fatty liver (NAFL) or liver fibrosis and diabetic peripheral neuropathy (DPN) has not been well studied. We aimed to investigate the association of NAFL or liver fibrosis indices and DPN in individuals with type 2 diabetes. In this observational study, we included 264 individuals with type 2 diabetes, and calculated non-alcoholic fatty liver disease (NAFLD) liver fat score, NAFLD fibrosis score, and Fibrosis-4 (FIB-4) index to evaluate the status of NAFLD or liver fibrosis. DPN was diagnosed when the Michigan Neuropathy Screening Instrument—Physical Examination score was ≥ 2.5. The NAFLD fibrosis score and FIB-4 index were significantly higher in individuals with DPN than in those without DPN. Logistic analyses showed that the NAFLD fibrosis score and FIB-4 index were associated with DPN after adjustment for covariates (adjusted odds ratio 1.474 and 1.961, respectively). In the subgroup analysis, this association was only significant in the group with a high NAFLD liver fat score (> − 0.640). Serum levels of fetuin-A, a hepatokine, were decreased in individuals with abnormal vibration perception or 10-g monofilament tests compared with their counterparts. The present study suggests that liver fibrosis might be associated with DPN in individuals with type 2 diabetes.

Association of PNPLA3 I148M with liver disease biomarkers in Latinos

Introduction. Liver disease accounts for approximately 2 million deaths per year worldwide. The majority of liver diseases are due to complications of cirrhosis, viral hepatitis, and hepatocellular carcinoma. Increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may indicate liver disease. Moreover, there are additional noninvasive liver fibrosis indices that help to estimate liver damage, including AST to ALT ratio, AST to platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and nonalcoholic fatty liver disease (NAFLD) fibrosis score. The aims of the present study were to (1) perform an association analysis of the patatin-like phospholipase domain containing 3 (PNPLA3) I148M (rs738409) variant with ALT, AST, and various liver fibrosis indices, and (2) determine whether there are gender related-differences in these associations. Methods. We obtained demographic, anthropometric, and metabolic phenotypes from Latino adult participants (n = 503, 64% female, 36.4 ± 0.5 years) from the Arizona Insulin Resistance (AIR) registry. SNP genotyping of I148M was performed using the TaqMan allelic discrimination assay. We used linear regression for the association analyses of the genotypes with ALT, AST, and the various liver fibrosis indices. We included genotype, age, body mass index (BMI), and alcohol status in the linear regression model. Results. The variant I148M was in Hardy-Weinberg equilibrium, with genotype distribution: non-risk CC = 118, heterozygous CG = 246, and risk GG = 139. The G allele was significantly associated with increased ALT and AST levels (p = 7.8 x 10-7 and p = 9.7 x 10-6, respectively). Moreover, we showed that the G allele was significantly associated with higher APRI (p = 3.7 x 10-7) and FIB-4 score (p = 4.1 x 10-3). When we analyzed the data by gender, we observed similar significant trends for ALT, AST, and APRI (all, p < 0.01). In females, the G allele was significantly associated with increased FIB-4 score (p = 6.9 x 10-3), which was not observed in the males (p > 0.05). There was no association of the I148M variant with AST/ALT ratio nor NAFLD risk score, whether analyzed in all adults or by gender. Discussion/Conclusion. Our findings provide additional evidence of an association of PNPLA3 I148M with several liver disease biomarkers in male and female Latinos residing in the Southwest of the United States.

Does the FT3-to-FT4 ratio easily predict the progression of NAFLD and NASH cirrhosis?

Background Factors causing progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH) and liver cirrhosis remain relatively unknown. We aimed to evaluate the power and effectiveness of the free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio to predict non-alcoholic fatty liver disease (NAFLD)/liver fibrosis and NASH cirrhosis severity. Methods Patients (n = 436) with NASH-associated liver cirrhosis (n = 68), patients with liver biopsy-proven NAFLD (n = 226), or healthy participants (n = 142) were enrolled between January 2010 and January 2020. The aspartate aminotransferase-to-thrombocyte ratio (APRI), NAFLD fibrosis score, albumin–bilirubin score (ALBI), aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio, FT3-to-FT4 ratio, and Fibrosis-4 (FIB-4) were calculated and evaluated. Results All parameters were significantly higher in NASH cirrhosis than in the healthy group. Body mass index, ALT, fasting insulin, homeostatic model assessment for insulin resistance, and triglyceride levels were significantly higher in liver biopsy-proven NAFLD than in the healthy group. The APRI, NAFLD fibrosis score, ALBI, AST-to-ALT ratio, FT3-to-FT4 ratio, and FIB-4 were significantly higher in the NASH cirrhosis group than in the healthy group. In patients with biopsy-proven NAFLD, the FT3-to-FT4 ratio was significantly lower than in the healthy group. Conclusion The FT3-to-FT4 ratio is an effective and useful indicator to predict NAFLD/liver fibrosis and NASH cirrhosis severity.

Diagnostic accuracy and limitations of non-invasive tests in patients with metabolic-associated fatty liver disease

Resumen La incidencia de la enfermedad del hígado graso asociada al metabolismo (MAFLD) ha aumentado en los últimos años debido al estilo de vida actual. La biopsia de hígado sigue siendo la herramienta estándar de oro para detectar y estadificar MAFLD. Por otro lado, se están desarrollando múltiples biomarcadores y pruebas no invasivas para superar las limitaciones de la biopsia hepática, incluidos el costo y la invasividad. Las pruebas no invasivas se centran principalmente en la esteatosis y, en particular, en la fibrosis hepática y se pueden clasificar en pruebas patentadas y no patentadas. Si bien hepatic steatosis index y fatty liver index son las pruebas más comunes utilizadas para la detección de esteatosis, Hepamet Fibrosis Score, NAFLD fibrosis score, FIB-4, OWLiver®, y ELF® son las más utilizadas para la fibrosis hepática. Sin embargo, las pruebas no invasivas también tienen limitaciones que conviene resaltar ya que sus resultados podrían verse afectados por la presencia de diabetes, obesidad o por edades extremas que podrían dar lugar a falsos positivos o negativos. Para maximizar la precisión de los tests no invasivos, se han propuesto diferentes combinaciones integradas en algoritmos escalonados. Esta revisión tiene como objetivo destacar las fortalezas y limitaciones de dichos tests para detectar y estadificar MAFLD.