Association of Diabetic Retinopathy with Midlife Hepatic Steatosis Diagnosed by Elastography and Hepatic Steatosis Index in Type 2 Diabetes in an Indian Population.

Aims: People with type 2 diabetes mellitus are at increased risk of developing hepatic steatosis. We determined the prevalence of hepatic steatosis in middle-aged patients with and without diabetic retinopathy (DR) in an Indian population. We feel this information is critical, with trends of increasing chronic liver disease-related mortality at younger ages. Method: Institution-based analytical cross-sectional study with 114 middle-aged type 2 diabetes patients; 57 in each group with <15 years of duration of DM and without excessive drinking. Hepatic steatosis was determined by the hepatic steatosis index (HSI), hepatic ultrasonography (USG), and elastography. Result: The HSI in DR (37.9 ± 3.9) was more (P = 0.012) than in without diabetic retinopathy (NODR) (36.3 ± 3.3). There was no difference between two groups in liver span (P = 0.829) or in the prevalence of fatty liver (P = 0.562) as determined by conventional USG. Elastography value (kPa) was more (P = 0.001) in DR (6.51 ± 1.85) than in NODR (5.14 ± 1.60). On elastography, 50.9% in DR had a likelihood ratio (Metavir score for a stiffness value) for stage 2 Metavir score. In DR, 11.8% of those missed by USG had a likelihood ratio for ≥ stage 2 Metavir score on elastography. The presence of DR was independently correlated with kPa value (P < 0.001). Conclusion: A significantly higher prevalence of hepatic steatosis was observed in DR in this population. DR can be a useful biomarker for early hepatic screening in midlife, particularly with hepatic elastography, so that timely diagnosis of hepatic steatosis can be made.

ALT poorly predicts Nonalcoholic Fatty Liver Disease (NAFLD) and liver fibrosis as determined by vibration-controlled transient elastography in adult National Health and Nutrition Examination Survey 2017-2018.

BACKGROUND: Non-alcoholic fatty liver disease is a growing problem in the United States, contributing to a range of liver disease as well as cardiovascular disease. ALT is the most widely used liver chemistry for NAFLD evaluation. We hypothesized that the normal range many laboratories use was too high, missing many patients with clinically important steatosis and/or fibrosis. METHODS: This study utilized 2017-2018 NHANES data including 9254 participants. We compared four different upper limits of normal for ALT with specific measurements of steatosis and liver stiffness as determined by liver elastography with FibroScan®. Liver stiffness was further characterized as showing any fibrosis or advanced fibrosis. After exclusions, our final pool was 4184 for liver stiffness measurement and 4183 for steatosis grade as measured by Controlled Attenuation Parameter (CAP). Using these variables, we performed logistic regression between ALT and CAP, and ALT and fibrosis/advanced fibrosis, and did a Receiver Operating Characteristic curve. RESULTS: Based on three of the most widely used cut off values for ALT, we found that ALT does not reliably rule out NAFLD in over 50% of cases. It also missed 45.9-64.2% of patients with liver fibrosis. CONCLUSIONS: Our study revealed that ALT is an inaccurate marker for NAFLD as measured by FibroScan® with CAP greater than or equal to 300 dB/m. Accuracy improved specific risk factors were considered. These data also showed that ALT was a poor marker for liver fibrosis. We conclude that there is no single ALT level that accurately predicts hepatic steatosis or fibrosis.

Association between food insecurity and metabolic dysfunction-associated steatotic liver disease/significant fibrosis measured by fibroscan.

PURPOSE: Studies evaluating food insecurity and metabolic dysfunction-associated steatotic liver disease (MASLD) and significant hepatic fibrosis are currently scarce. We evaluated the characteristics of food insecure individuals and whether food insecurity was associated with MASLD and significant hepatic fibrosis in the US population. METHODS: In this cross-sectional study from the National Health and Nutrition Examination Survey 2017-2018, 3441 participants with complete data were enrolled. We defined MASLD and significant hepatic fibrosis (≥ F2) by transient elastography in the absence of other causes of liver disease. The detailed questionnaire assessed and categorized food security as high, marginal, low, and very low food security. RESULTS: Food-insecure subjects were more likely to be female, younger, more impoverished, non-Hispanic blacks, Hispanics, and less likely to be educated, married, and physically active. Food insecurity increased the odds of the prevalence of MASLD by 42% (odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.12-1.78) after adjustment for demographic, lifestyle, and metabolic risk factors. The addition of diabetes and obesity did not change this association (OR: 1.36, 95% CI: 1.03-1.78). The multivariable model showed an independent relationship between food insecurity and significant hepatic fibrosis (OR: 1.40, 95% CI: 1.04-1.88) after adjustment for demographic, lifestyle, and metabolic risk factors, although the association was attenuated and changed insignificantly after adjustment for diabetes and obesity. CONCLUSIONS: Food insecurity was associated with higher odds for MASLD. While there is a relationship between food insecurity and significant hepatic fibrosis, this relationship changed insignificantly after adjustment of diabetes and obesity.

Fibrotic Burden in Patients With Hepatitis B Virus-Related Cirrhosis Is Independently Associated With Poorer Kidney Outcomes.

BACKGROUND: We investigated whether higher fibrotic burden was independently associated with poorer kidney outcomes in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: A total of 1691 patients with radiologically diagnosed HBV-related cirrhosis but without baseline chronic kidney disease (CKD) who underwent transient elastography (TE) between March 2012 and August 2018 were selected. The study outcome was the composite of development of incident CKD, defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 or proteinuria (≥1+ on dipstick test) on 2 consecutive measurements during follow-up, 50% decline in eGFR or onset of end-stage kidney disease (initiation of chronic dialysis), or all-cause mortality. RESULTS: The mean age was 53.4 years and 1030 (60.9%) patients were male. During 8379 person-years of follow-up (median 5.2 years), 60 (3.5%) patients experienced study outcomes. When stratified according to TE-defined fibrotic burden, multivariable Cox models revealed that risk of poorer kidney outcomes was 2.77-fold (95% confidence interval, 1.16-6.63; P < .001) higher in patients with liver stiffness range indicating cirrhosis (≥11.7 kPa), compared to those without significant liver fibrosis (<7.9 kPa). These associations remained significant even after adjusting for vigorous confounders. CONCLUSIONS: Higher fibrotic burden assessed using TE was independently associated with poorer kidney outcomes in patients with HBV-related cirrhosis.

Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV-negative controls: A cross-sectional study nested within the POPPY cohort.

BACKGROUND: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. METHODS: Older (>50 years) and younger (<50 years) people with HIV and older HIV-negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi-squared/Fisher's exact/Kruskal-Wallis tests. RESULTS: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV-negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2 ). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14-0.52) than controls, but male sex (OR 2.45; 95% CI 1.20-4.50) and high waist-to-hip ratio (OR 3.04; 95% CI 1.74-5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV-related variables. CONCLUSIONS: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV-related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care.

Preoperative ultrasound elastography for postoperative pancreatic fistula prediction after pancreatoduodenectomy: A prospective study.

BACKGROUND: Postoperative pancreatic fistulas are the most frequent major complications after pancreatoduodenectomy. The soft pancreatic texture is a critical, independent risk factor for postoperative pancreatic fistulas after pancreatoduodenectomy. The current gold standard for postoperative pancreatic fistula risk evaluation consists of the surgeon's intraoperative palpation of the pancreatic texture and, thus, lacks objectivity. In this prospective study, we used ultrasound-based shear-wave elastography, image data analysis, and a fistula risk score calculator to correlate the stiffness of pancreatic tissue with the occurrence of clinically relevant postoperative pancreatic fistulas. METHODS: We included 100 patients with pancreatic pathologies (71% pancreatic ductal adenocarcinoma) and 100 healthy individuals who were preoperatively assessed via real-time tissue ultrasound-based shear-wave elastography on a Philips EPIQ 7 ultrasound device and had pancreatic parenchyma histologically evaluated with manually stained images. RESULTS: We found a significant difference in the mean elasticity between the soft (1.22 m/s) and the hard pancreas group (2.10 m/s; P < .0001). The mean elasticity significantly correlated with the pancreatic fibrosis rate and the appearance of a postoperative pancreatic fistula after pancreatoduodenectomy. Low elasticity (≤1.2 m/s, mean) correlated with soft and high elasticity (>2.0 m/s, mean) with hard pancreatic parenchyma, as assessed by pathologic evaluation. Multivariate analysis revealed a mean elasticity of <1.3 m/s as a significant cut-off predictor for clinically relevant postoperative pancreatic fistulas (P = .003; Youden-Index = 0.6945). CONCLUSION: Preoperative ultrasound-based shear-wave elastography is a feasible and objective clinical diagnostic modality in evaluating pancreatic tissue stiffness. A mean pancreatic elasticity of <1.3 m/s was a significant independent risk predictor of clinically relevant postoperative pancreatic fistulas after pancreatoduodenectomy.

Nonviral Liver Disease Burden in People Living With HIV and Elevated Transaminases: A Cross-Sectional Study.

INTRODUCTION: Because of improved life expectancy in people living with HIV (PLWH), liver disease is increasingly being recognized. We assessed nonviral chronic liver disease burden in PLWH. METHODS: The HIV non-virAL liver disease study (2014-2021) prospectively recruited PLWH with elevated serum alanine aminotransferase levels and negative hepatitis serology. Clinically significant hepatic fibrosis (CSHF) was defined as liver stiffness measurement of >7.1 kPa and hazardous alcohol use as Alcohol Use Disorders Identification Test score ≥ 8. Primary outcome was prevalence/predictors of CSHF. RESULTS: Total recruited were n = 274, 92% male, median age 52 (45-59) years, and 96% having undetectable HIV viral load. Overall, n = 97 (35%) had hazardous alcohol use, n = 72 (26%) had metabolic syndrome, and 17%-27% had exposure to hepatotoxic antiretrovirals. Prevalence of CSHF was 20% (n = 54), prevalence of cirrhosis (liver stiffness measurement > 12.5 kPa) being 7% (19/274). Risk factors for CSHF were hazardous alcohol use in 44% (n = 24), metabolic syndrome in 46% (n = 25), and hepatotoxic antiretrovirals in 56% (n = 30), most having more than one risk factor. Independent predictors of CSHF were serum high-density lipoprotein (odds ratio [OR] 0.220; 95% confidence interval [CI]: 0.061 to 0.790, P = 0.020) (inverse relationship); serum aspartate aminotransferase (OR 1.033, 95% CI: 1.001 to 1.067, P = 0.045), and didanosine use (OR 2.878, 95% CI: 1.228 to 6.774, P = 0.015). Moderate-severe hepatic steatosis was identified in 52% (n = 142). FIB-4 and aspartate aminotransferase-to-platelet ratio index performed poorly in predicting CSHF (positive predictive value 27.3% and 30.6%, respectively) and advanced fibrosis (≥F3) (positive predictive value 17.6% and 5.9%, respectively). CONCLUSION: In this study, 20% of PLWH had CSHF associated with high prevalence of hazardous alcohol use/metabolic syndrome/potentially hepatotoxic antiretrovirals. These potentially modifiable risk factors need addressing.

Assessment of liver fibrosis in patients with rheumatoid arthritis treated with methotrexate: Utility of fibroscan and biochemical markers in routine clinical practice.

OBJECTIVES: To study the prevalence of liver fibrosis (LF) measured by FibroScan and APRI index in patients with rheumatoid arthritis (AR) undergoing treatment with methotrexate (MTX). METHODS: We included 59 patients with RA on MTX. Medical records, FibroScan measures and serological markers of liver damage were compared on the basis of cumulative methotrexate dose. RESULTS: Mean treatment duration was 82.4±65.1 months and mean cumulative dose was 5214.5±4031.9mg. Five patients met LF criteria by fibroscan, while only one patient had a suggestive APRI score. No statistically significant differences were found in terms of LF measured by both APRI and fibroScan between patients with cumulative doses above and below 4000mg. There was also no relationship between LF and treatment duration. CONCLUSIONS: The occurrence of LF in patients with RA on MTX is a multifactorial process that does not seem directly related to its cumulative dose. FibroScan may be a useful technique in clinical practice to screen for this complication.

Transient Elastography as the First-Line Assessment of Liver Fibrosis and Its Correlation with Serum Markers.

Background and objectives: Recently, rapid progress has been made in the development of noninvasive methods for liver fibrosis assessment. The study aimed to assess the correlation between LSM and serum fibrosis markers to identify patients with advanced liver fibrosis in daily clinical practice. Methods: Between 2017 and 2019, 89 patients with chronic liver disease of various etiology, 58 males and 31 females, were enrolled in the study and underwent ultrasound examination, vibration-controlled transient elastography (VCTE), AST to Platelet Ratio Index (APRI score), Fibrosis-4 (FIB-4) score, and enhanced liver fibrosis (ELF) test. Results: The diagnoses were as follows: NAFLD (30.3%), HCV (24.3%), HBV (13.1%), ALD (10.1%), other (7.8%). Their median age was 49 (21-79), and their median BMI was 27.5 (18.4-39.5). The median liver stiffness measurement (LSM) was 6.7 kPa (2.9-54.2 kPa), the median of the ELF test was 9.0 (7.3-12.6), and the median APRI was 0.40 (0.13-3.13). Advanced fibrosis assessed by LSM was present in 18/89 (20.2%) patients. The LSM values correlated with the ELF test results (r2 = 0.31, p < 0.0001), with the APRI score (r2 = 0.23, p < 0.0001), the age of the patients (r2 = 0.14, p < 0.001), and with the FIB-4 values (r2 = 0.58, p < 0.0001). The ELF test values correlated with the APRI score (r2 = 0.14, p = 0.001), the age (r2 = 0.38, p < 0.0001), and the FIB-4 (r2 = 0.34, p < 0.0001). By determining the confidence intervals of the linear model, we proved that patients younger than 38.1 years have a 95% probability of absence of advanced liver fibrosis when assessed by VCTE. Conclusions: We identified APRI and FIB-4 as simple tools for screening liver disease in primary care in an unselected population of patients. The results also showed that individuals younger than 38.1 years had a negligible risk of advanced liver fibrosis.

Fibroscan-Aspartate Aminotransferase Score Predicts Liver-Related Outcomes, but Not Extrahepatic Events, in a Multicenter Cohort of People With Human Immunodeficiency Virus.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is frequent in people with human immunodeficiency virus (PWH). The Fibroscan-aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. METHODS: Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from 4 prospective cohorts. We used FAST >0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extrahepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. RESULTS: Of the 1472 PWH included, 8% had FAST >0.35. Higher body mass index (adjusted odds ratio [aOR], 1.21 [95% confidence interval {CI}, 1.14-1.29]), hypertension (aOR, 2.24 [95% CI, 1.16-4.34]), longer time since HIV diagnosis (aOR, 1.82 [95% CI, 1.20-2.76]), and detectable HIV RNA (aOR, 2.22 [95% CI, 1.02-4.85]) were associated with FAST >0.35. A total of 882 patients were followed for a median of 3.8 years (interquartile range, 2.5-4.2 years). Overall, 2.9% and 11.1% developed liver-related and extrahepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST >0.35 versus FAST ≤0.35 (45.1 [95% CI, 26.2-77.7] vs 5.0 [95% CI, 2.9-8.6] per 1000 person-years). FAST >0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio, 4.97 [95% CI, 1.97-12.51]). Conversely, FAST did not predict extrahepatic events. CONCLUSIONS: A significant proportion of PWH may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help management of this high-risk population.

Initial outcomes of a dedicated multidisciplinary non-alcoholic fatty liver disease clinic: a retrospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major healthcare burden. Real-world outcomes in dedicated tertiary care settings in Australia remain unknown. AIM: To evaluate the initial outcomes of patients referred to a dedicated multidisciplinary tertiary care NAFLD clinic. METHODS: Retrospective review of all adult patients with NAFLD who attended a dedicated tertiary care NAFLD clinic between January 2018 and February 2020 and who had two clinic visits and FibroScans at least 12 months apart. Demographic and health-related clinical and laboratory data were extracted from electronic medical records. Key outcome measures were serum liver chemistries, liver stiffness measurement (LSM) and weight control at 12 months. RESULTS: A total of 137 patients with NAFLD were included. Median (interquartile range (IQR)) follow-up time was 392 days (343-497 days). One hundred and eleven patients (81%) achieved weight control (i.e. weight loss or stability). Markers of liver disease activity were significantly improved, including median (IQR) serum alanine aminotransferase (48 (33-76) vs 41 (26-60) U/L, P = 0.009) and aspartate aminotransferase (35 (26-54) vs 32 (25-53) U/L, P = 0.020). Median (IQR) LSM across the whole cohort was significantly improved (8.4 (5.3-11.8) vs 7.0 (4.9-10.1) kPa, P = 0.001). No significant reduction was observed in mean body weight or the frequency of metabolic risk factors. CONCLUSIONS: This study highlights a new model of care for patients with NAFLD and demonstrates promising initial outcomes in relation to significant reductions in markers of liver disease severity. Although most patients achieved weight control, further refinements are needed to achieve significant weight reduction including more frequent and structured dietetic and/or pharmacotherapeutic interventions.

The Past, Present, and Future of Noninvasive Test in Chronic Liver Diseases.

Chronic liver disease is a major global health threat and is the 11th leading cause of death globally. A liver biopsy is frequently required in assessing the degree of steatosis and fibrosis, information that is important in diagnosis, management, and prognostication. However, liver biopsies have limitations and carry a considerable risk, leading to the development of various modalities of noninvasive testing tools. These tools have been developed in recent years and have improved markedly in diagnostic accuracy. Moving forward, they may change the practice of hepatology.

Spleen stiffness: a predictive factor of dismal prognosis in liver cirrhosis.

Portal hypertension (PH) is a major complication of liver cirrhosis, as it predisposes to the development of serious clinical manifestations such as ascites, hepatic encephalopathy and variceal bleeding, aggravating the prognosis of patients. Hepatic vein pressure gradient (HVPG) is considered the reference method for the estimation of the presence and severity of PH, but this procedure is available only in specialized centers. Alternatively, many non-invasive methods have been proposed in order to substitute HVPG. Among them, liver stiffness measurement (LSM) has been widely used, as it has been shown to correlate well with HVPG, though this relationship seems to weaken in values of HVPG higher than 12 mmHg, the threshold of serious complications development. Several studies supported the use of spleen stiffness measurement (SSM) instead of LSM, anticipating to a more adequate assessment of this advanced stage of PH. The aim of this paper is to critically appraise and summarize the literature about the role of SSM as a predictive tool of liver decompensation and prognosis, highlighting the strengths and the potential limitations of the studies published so far. EXPERT'S OPINION: The utility of SSM in ruling out high risk for bleeding varices in cirrhotic patients has been demonstrated, driving the Baveno VII consensus to encompass SSM in its last recommendations, though its use in patients with non-viral cirrhosis remains to be validated. We believe that in the near future, SSM alone or combined with other tests, will being used not only for sparing upper endoscopies, but also for predicting decompensation and prognosis in advanced compensated cirrhotic patients, regardless of liver disease's etiology. Herein, we present the data that support this consideration, pointing out these issues that should further be investigated in order to elucidate and intensify the value of SSM in the management of patients with liver cirrhosis.

Noninvasive imaging biomarkers for liver fibrosis in nonalcoholic fatty liver disease: current and future.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the "gold standard" method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.

Screening strategy for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately 25% of the general population worldwide, and is forecasted to increase global health burden in the 21st century. With the advancement of non-invasive tests for assessing and monitoring of steatosis and fibrosis, NAFLD screening is now feasible, and is increasingly highlighted in international guidelines related to hepatology, endocrinology, and pediatrics. Identifying high-risk populations (e.g., diabetes mellitus, obesity, metabolic syndrome) based on risk factors and metabolic characteristics for non-invasive screening is crucial and may aid in designing screening strategies to be more precise and effective. Many screening modalities are currently available, from serum-based methods to ultrasonography, transient elastography, and magnetic resonance imaging, although the diagnostic performance, cost, and accessibility of different methods may impact the actual implementation. A two-step assessment with serum-based fibrosis-4 index followed by imaging test vibration-controlled transient elastography can be an option to stratify the risk of liverrelated complications in NAFLD. There is a need for fibrosis surveillance, as well as investigating the cost-effectiveness of different screening algorithms and engaging primary care for first-stage triage screening.

Identification of high-risk subjects in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease worldwide, and its burden is expected to increase due to the growing epidemic of obesity and diabetes. The key challenge among NAFLD patients is to identify those with advanced fibrosis (F3F4), who are at high risk of developing complications and will benefit from specialized management and treatment with new pharmacotherapies when they are approved. Liver biopsy appears unrealistic and unsuitable in practice, given the large number of high-risk patients and its well-known limitations. Non-invasive sequential algorithms using fibrosis-4 index as first-line test, followed by vibration-controlled transient elastography or patented blood test, are the best strategy for case finding of high-risk subjects. In fact, they are now recommended by several international guidelines, and should be used and disseminated to increase awareness among physicians beyond liver clinics where most NAFLD patients are seen.

Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients.

BACKGROUND/AIMS: The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. METHODS: cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of "treating definite CSPH" strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. RESULTS: One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0-7.4). "Probable CSPH" is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that "treating definite CSPH" strategy is superior to "treating all varices" or "treating probable CSPH" strategy to prevent decompensation using NSBB. CONCLUSION: Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients.

Comparative accuracy of endosonographic shear wave elastography and transcutaneous liver stiffness measurement: a pilot study.

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE) is a validated test for assessing liver fibrosis but may be unreliable in select patients, including those with morbid obesity. The limitations of VCTE may be overcome by EUS-guided shear wave elastography (EUS-SWE). METHODS: This single-center, prospective, nonrandomized tandem study compared the diagnostic accuracy of EUS-SWE and VCTE in consecutive patients undergoing liver biopsy sampling because of unreliable noninvasive testing. EUS-SWE of the left and right lobes were separately performed and then compared with VCTE. Liver elasticity cutoffs for different stages of fibrosis were estimated in 3 ways: optimized sensitivity and specificity using the Youden index; and with sensitivity and specificity fixed at 90% each, Diagnostic accuracy for fibrosis was compared with liver histology using the area under the receiver-operating characteristic curve (AUROC). The primary outcome was the diagnostic accuracy of EUS-SWE for advanced fibrosis. Secondary outcomes were diagnostic accuracy of VCTE, EUS-SWE for left and right hepatic lobes for significant/advanced fibrosis, and cirrhosis. RESULTS: Forty-two patients (39 men, aged 54.5 ± 12.1 years) underwent EUS-SWE, VCTE, and liver biopsy sampling. The cross-validated AUROCs for advanced fibrosis were as follows: VCTE, .87 (95% confidence interval [CI], .76-.97); EUS-SWE left lobe, .8 (95% CI, .64-.96); and EUS-SWE right lobe, .78 (95% CI, .62-.95). The corresponding AUROCs for cirrhosis were as follows: VCTE, .9 (95% CI, .83-.97); EUS-SWE left lobe, .96 (95% CI, .9-1); and EUS-SWE right lobe, .9 (95% CI, .8-1). VCTE was unreliable in 8 patients who successfully underwent EUS-SWE. There was no statistically significant difference in the AUROCs for EUS-SWE and VCTE. CONCLUSIONS: EUS-SWE correlates well with liver histology and is a safe and reliable diagnostic test for assessing liver fibrosis with accuracy comparable with VCTE. (Clinical trial registration number: NCT04533932.).

Risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease.

BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk of advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective study included probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 first-degree relative. A total of 396 first-degree relatives - 220 in a derivation cohort and 176 in a validation cohort - were enrolled in the study, and liver fibrosis was evaluated using magnetic resonance elastography and other noninvasive imaging modalities. The primary outcome was prevalence of advanced fibrosis in first-degree relatives.RESULTSPrevalence of advanced fibrosis in first-degree relatives of probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD was 15.6%, 5.9%, and 1.3%, respectively (P = 0.002), in the derivation cohort, and 14.0%, 2.6%, and 1.3%, respectively (P = 0.004), in the validation cohort. In multivariable-adjusted logistic regression models, age of ≥50 years (adjusted OR [aOR]: 2.63, 95% CI 1.0-6.7), male sex (aOR: 3.79, 95% CI 1.6-9.2), diabetes mellitus (aOR: 3.37, 95% CI 1.3-9), and a first-degree relative with NAFLD with advanced fibrosis (aOR: 11.8, 95% CI 2.5-57) were significant predictors of presence of advanced fibrosis (all P < 0.05).CONCLUSIONFirst-degree relatives of probands with NAFLD with advanced fibrosis have significantly increased risk of advanced fibrosis. Routine screening should be done in the first-degree relatives of patients with advanced fibrosis.FUNDINGSupported by NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515, K23DK119460), NHLBI (P01HL147835), and NIAAA (U01AA029019); Academy of Finland grant 309263; the Novo Nordisk, EVO, and Sigrid Jusélius Foundations; and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA.

The association between non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis with blood selenium level based on the NHANES 2017-2018.

BACKGROUND & OBJECTIVE: Selenium was one of the essential trace elements that played a pivotal role in human health. Although previous studies have investigated the relationship between selenium and non-alcoholic fatty liver disease (NAFLD) and fibrosis, these findings were still inconclusive. Our study was aimed to explore the association between blood selenium level and NAFLD and advanced liver fibrosis diagnosed by vibration controlled transient elastography (VCTE) in US adults. METHODS: All data were extracted from National Health and Nutrition Examination Survey database (2017-2018). Participants were divided into four groups according to quartile of blood selenium level. Liver stiffness and controlled attenuation parameter (CAP) were measured by VCTE. Multiple logistic regression models and subgroup analyses were conducted to determine the association between blood selenium level and NAFLD and advanced liver fibrosis diagnosed by a variety of methods. RESULTS: A total of 3336 participants were enrolled in main analysis. In multiple logistic regression models, the higher blood selenium level (>205.32, ≤453.62 µg/L) had a significant positive association with NAFLD (ß = 1.31). Moreover, high blood selenium level had significantly inversely association to advanced liver fibrosis (ß = 0.61). In subgroup analysis, the main inversely correlation between blood selenium and advanced liver fibrosis was found in males with high blood selenium level. Despite dietary selenium intake being adjusted or in different subgroups, the associations between blood selenium level and NAFLD/advanced liver fibrosis remained significant. CONCLUSIONS: This study showed that blood selenium level were positively association with NAFLD among US population. Participants with lower blood selenium level showed a higher percentage of advanced liver fibrosis. Blood selenium is more likely to cause NAFLD and liver fibrosis due to imbalances in selenium homeostasis rather than dietary selenium intake.Key messagesHigh blood selenium level was association with NAFLD diagnosed by vibration controlled transient elastography.Participants with lower blood selenium level had high percentage of advanced liver fibrosis.NAFLD and liver fibrosis are caused by an imbalance of selenium homeostasis, not by dietary selenium intake.