Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes.

BACKGROUND AND AIMS: We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D). METHODS AND RESULTS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH. CONCLUSIONS: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

Surveillance of the progression and assessment of treatment endpoints for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease (NAFLD) characterized by steatosis-associated inflammation and liver injury. Without effective treatment or management, NASH can have life-threatening outcomes. Evaluation and identification of NASH patients at risk for adverse outcomes are therefore important. Key issues in screening NASH patients are the assessment of advanced fibrosis, differentiation of NASH from simple steatosis, and monitoring of dynamic changes during follow-up and treatment. Currently, NASH staging and evaluation of the effectiveness for drugs still rely on pathological diagnosis, despite sample error issues and the subjectivity associated with liver biopsy. Optimizing the pathological assessment of liver biopsy samples and developing noninvasive surrogate methods for accessible, accurate, and safe evaluation are therefore critical. Although noninvasive methods including elastography, serum soluble biomarkers, and combined models have been implemented in the last decade, noninvasive diagnostic measurements are not widely applied in clinical practice. More work remains to be done in establishing cost-effective strategies both for screening for at-risk NASH patients and identifying changes in disease severity. In this review, we summarize the current state of noninvasive methods for detecting steatosis, steatohepatitis, and fibrosis in patients with NASH, and discuss noninvasive assessments for screening at-risk patients with a focus on the characteristics that should be monitored at follow-up.

Effectiveness and Economic Evaluation of Polyene Phosphatidyl Choline in Patients With Liver Diseases Based on Real-World Research.

Aims: Liver disease has high prevalence, number, and disease burden in China, and polyene phosphatidyl choline (PPC) is a widely used liver protective drug. We aim to explore the effectiveness and economy of PPC in patients with liver diseases based on real-world research and compare with other hepatoprotective drugs. Methods: This is a "three-phase" study from three medical centers, including descriptive study of patients using PPC injection, self-control case study of patients using PPC injection, and specific-disease cohort study of patients using PPC injection or control drugs. The major measurements of liver function for effectiveness analysis were the alanine transaminase (ALT) level changes and recovery rate. The main statistical methods were Wilcoxon signed rank test, χ 2 test, and Mann-Whitney U test. Propensity score matching was applied to reduce bias. Cost-effectiveness analysis, cost minimization analysis, and sensitivity analysis were used for economic evaluation. Results: PPC alone or in combination with glutathione and magnesium isoglycyrrhizinate shows less total hospitalization cost (p < 0.05) and smaller cost-effectiveness ratio and was effective in protecting liver function, especially in patients with liver transplantation or postoperation of nontumor liver disease (ALT decreased significantly after PPC treatment; p < 0.05). Glutathione and magnesium isoglycyrrhizinate combined with PPC could enhance the protective function of liver. Conclusion: PPC was an effective and economic liver protective drug in patients with specific liver diseases, and PPC could enhance the liver protective function of glutathione and magnesium isoglycyrrhizinate.

Epidemiology of nonalcoholic fatty liver disease in non-obese populations: Meta-analytic assessment of its prevalence, genetic, metabolic, and histological profiles.

OBJECTIVE: As a subgroup of nonalcoholic fatty liver disease (NAFLD), patients with non-obese NAFLD may also have an increased risk of adverse hepatic and metabolic outcomes. We aimed to estimate the prevalence and incidence of non-obese NAFLD and to describe its clinical characteristics in this systematic review and meta-analysis. METHODS: We performed a systematic search of 1235 citations published up to Mar 2020. Meta-analyses, stratified analyses and meta-regression were all performed. RESULTS: Of the 46 studies included, 28 cross-sectional and longitudinal studies of 155 846 non-obese participants reported a pooled NAFLD prevalence of 14.5% (95% confidence interval [CI] 12.3%-17.1%). A multivariate meta-regression analysis showed the trend that the prevalence varied by their geographical location. Further stratified analyses showed that NAFLD was relatively prevalent among people aged ≥45 years (16.2%; 95% CI 10.8-23.4) and those in South America (25.7%; 95% CI 24.4-27.0). The PNPLA3 rs738409 gene polymorphism was more frequently observed in non-obese NAFLD than in both obese NAFLD and non-obese controls, while the metabolic profiles of non-obese NAFLD were less severe than those of the obese NAFLD group. Patients with non-obese NAFLD had 4.81-fold and 5.43-fold higher risk of diabetes mellitus and metabolic syndrome, respectively, than the non-obese controls. CONCLUSIONS: Non-obese NAFLD is common, particularly in South America and among people aged ≥45 years. Metabolic diseases and PNPLA3 rs738409 gene polymorphism are more frequent in the non-obese NAFLD group than in non-obese controls.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data.

BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.

Controlled attenuation parameter for noninvasive assessment of hepatic steatosis using Fibroscan®: validation in chronic hepatitis B.

BACKGROUND AND AIM: The controlled attenuation parameter (CAP) using transient elastography (TE) was validated in chronic hepatitis C to evaluate hepatic steatosis; however, limited data are available on chronic hepatitis B (CHB). Therefore, we assessed the accuracy and the efficacy of CAP for the detection of steatosis in CHB. METHODS: Consecutive CHB patients underwent liver biopsy and liver stiffness measurements (LSM) with simultaneous CAP determination using the M probe of the TE. The area under the receiver operating characteristics curve (AUROC) was used to evaluate the performance of CAP in diagnosing steatosis compared with biopsy. RESULTS: A total of 340 patients were included: 60 % were male, the median age was 37 years; the body mass index (BMI) was ≥ 28 kg/m(2) for 14 % of the subjects; and the distribution of the steatosis grade was S0 58.2 %, S1 34.2 %, S2 5.0 % and S3 2.6 %. The median (range) of CAP was 218 (100-400) dB/m, and CAP correlated with the BMI (ρ = 3.622) and steatosis grade (ρ = 29.203) according to a multivariate analysis (both P < 0.001). CAP could detect the different grades of steatosis: ≥ S1 with AUROC of 0.81 at a cutoff of 224 dB/m, ≥ S2 with AUROC of 0.90 at a cutoff of 236 dB/m and ≥ S3 with AUROC of 0.97 at a cutoff of 285 dB/m. Furthermore, the LSM and fibrosis and activity grades on biopsy did not influence the CAP performance. CONCLUSIONS: CAP presented excellent diagnostic performance for severe steatosis with high sensitivity and specificity in Chinese patients with CHB.

Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients.

AIM: To evaluate the performance of a novel non-invasive controlled attenuation parameter (CAP) to assess liver steatosis. METHODS: This was a multi-center prospective cohort study. Consecutive patients (aged ≥ 18 years) who had undergone percutaneous liver biopsy and CAP measurement were recruited from three Chinese liver centers. Steatosis was categorized as S0: < 5%; S1: 5%-33%; S2: 34%-66%; or S3: ≥ 67%, according to the nonalcoholic fatty liver disease (NAFLD) activity score. The FibroScan(®) 502 equipped with the M probe (Echosens, Paris, France) was used to capture both CAP and liver stiffness measurement values simultaneously. Receiver operating characteristic curves were plotted, and the areas under the curves were calculated to determine the diagnostic efficacy. The accuracy of the CAP values at the optimal thresholds was defined by maximizing the sum of sensitivity and specificity (maximum Youden index). RESULTS: A total of 152 patients were recruited, including 52 (34.2%) patients with NAFLD and 100 (65.8%) with chronic hepatitis B (CHB) virus infection. After adjustment, the steatosis grade (OR = 37.12; 95%CI: 21.63-52.60, P < 0.001) and body mass index (BMI, OR = 6.20; 95%CI: 2.92-9.48, P < 0.001) were found independently associated with CAP by multivariate linear regression analysis. CAP was not influenced by inflammation, fibrosis or aetiology. The median CAP values and interquartile ranges among patients with S0, S1, S2 and S3 steatosis were 211 (181-240) dB/m, 270 (253-305) dB/m, 330 (302-360) dB/m, and 346 (313-363) dB/m, respectively. The cut-offs for the CAP values in all patients with steatosis ≥ 5%, ≥ 34% and ≥ 67% were 253 dB/m, 285 dB/m and 310 dB/m, respectively. The areas under the curves were 0.92, 0.92 and 0.88 for steatosis ≥ 5%, ≥ 34% and ≥ 67%, respectively. No significant differences were found in the CAP values between the NAFLD group and the CHB group in each steatosis grade. CONCLUSION: CAP appears to be a promising tool for the non-invasive detection and quantification of hepatic steatosis, but is limited by BMI.