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      • Validation of the Performance of MRE for the Detection of Advanced Fibrosis due to NASH across Multiple Clinical Trials

        ( Rohit Loomba ),( Naim Alkhouri ),( Mazen Noureddin ),( Jie Zhang ),( Bryan J. Mccolgan ),( C. Stephen Djedjos ),( Robert P. Myers ),( Michael Middleton ),( Zachary Goodman ),( Kris Kowdley ),( Atsus 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

        Aims: Magnetic resonance elastography(MRE) is a quantitative imaging biomarker for the detection of advanced fibrosis due to NASH. Our aim was to validate the performance of MRE for detection of advanced fibrosis using data from multiple clinical trials. Methods: Baseline data were pooled on 296 subjects with NASH from seven randomized, phase 2 and 3 trials including ATLAS and STELLAR-3/-4 trials. All subjects underwent 2D MRE and liver biopsy with staging of fibrosis according to NASH CRN classification. Associations between MRE-stiffness, fibrosis stage, noninvasive tests (NITs) of fibrosis (ELF, FibroTest, FIB-4, NAFLD Fibrosis Score [NFS]), and NASH activity (NAFLD Activity Score ≥5 vs <5) were determined. The discrimination of MRE for advanced fibrosis (F3-F4 vs F0-F2) and cirrhosis (F4 vs F0- F3) was evaluated using areas under receiver operating characteristic (AUROC) curves, and cutoffs from literature-based MRE thresholds (3.64 and 4.67 kPa, respectively) and optimal thresholds(defined by the maximal sum of sensitivity and specificity) were determined. Results: Among 296 subjects, fibrosis stages were F0-1(6%), F2(11%), F3(44%), and F4(40%); median MRE-stiffness was 4.71 kPa(IQR 3.52, 6.35). MRE-stiffness was correlated with fibrosis stage(Spearman ρ=0.60), and other NITs of fibrosis(ρ =0.47-0.52; all P<0.05). The AUROCs(95% CI) of MRE-stiffness for detecting advanced fibrosis and cirrhosis were 0.85(0.80, 0.90) and 0.81(0.76, 0.86), respectively. In general, cutoffs from the literature and optimal cutoffs derived from this dataset had similar performance for classification of fibrosis by 2D MRE. Among subjects with F0-F2 fibrosis on biopsy, those with MRE-stiffness ≥3.64 kPa (potential misclassification) had higher ELF and FibroSure than those with MRE-stiffness <3.64 kPa (both P<0.05). Conversely, among subjects with F3-F4 fibrosis on biopsy, those with MRE-stiffness <3.64 kPa had lower ELF, FibroSure, FIB-4, and NFS compared with those with MRE-stiffness ≥3.64 kPa(all P<0.05). Conclusions: This multi-center, multi-study validation demonstrates the clinical utility of 2D MRE for the detection of advanced fibrosis due to NASH.

      • HBV : Clinical Characteristics of Patients who Developed HCC While Receiving Tenofovir Disoproxil Fumarate (TDF) Up to 288 Weeks of Therapy

        ( W Ray Kim ),( Rohit Loomba ),( Selim Gurel ),( John Flaherty ),( Eduardo B Martins ),( Leland J Yee ),( Phillip Dinh ),( Maria Buti ),( Patrick Marcellin ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

        Background: Patients with chronic hepatitis B Virus (HBV) infection are at increased risk for hepatocellular carcinoma (HCC). Population-based studies have suggested an increased risk of hepatocellular carcinoma (HCC) in patients with higher levels of HBV-DNA. Therefore, it is possible that anti-viral therapy that reduces HBV-DNA levels may reduce the occurrence of HCC. We examined the clinical and demographic characteristics of HCC cases in patients receiving tenofovir disoproxil fumarate (TDF). Methods: We studied the clinical and demographic characteristics of the 641 patients enrolled in pivotal studies GSUS- 174-0102 and GS-US-174-0103. Results: During the first 288 weeks of studies 102/103, there were 13 cases of HCC. Three cases occurred during the first 48 weeks. 9/13 cases were HBeAg-negative and 3 of these were cirrhotic. 4/13 cases were HBeAg-positive at baseline and 3 of these were cirrhotic. 11/13 cases were male. 2/13 patients had regression of histological cirrhosis on repeat liver biopsies. Among the 13 HCC cases, 5 were genotype (gt)-D, 4 gt-C, 1 gt- B, 1 gt-E, 1 gt-F and 1 unable to genotype. Conclusions: In 288 weeks of TDF therapy, there were only 13 cases of HCC. 3 of the HCC cases were reported within the first 48 weeks of therapy. Despite the small number of cases, HCC surveillance needs to be done in patients on long-time oral antivirals.

      • KCI등재

        Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases

        Tamaki Nobuharu,Kurosaki Masayuki,Loomba Rohit,Izumi Namiki 대한진단검사의학회 2021 Annals of Laboratory Medicine Vol.41 No.1

        An accurate evaluation of liver fibrosis is clinically important in chronic liver diseases. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for liver fibrosis. In this review, we discuss the role of M2BPGi in diagnosing liver fibrosis in chronic hepatitis B and C, chronic hepatitis C after sustained virologic response (SVR), and nonalcoholic fatty liver disease (NAFLD). M2BPGi predicts not only liver fibrosis but also the hepatocellular carcinoma (HCC) development and prognosis in patients with chronic hepatitis B and C, chronic hepatitis C after SVR, NAFLD, and other chronic liver diseases. M2BPGi can also be used to evaluate liver function and prognosis in patients with cirrhosis. M2BPGi levels vary depending on the etiology and the presence or absence of treatment. Therefore, the threshold of M2BPGi for diagnosing liver fibrosis and predicting HCC development has to be adjusted according to the background and treatment status.

      • KCI등재

        Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH

        Theresa J. Hydes,Sujan Ravi,Rohit Loomba,Meagan E. Gray 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.4

        Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and affects approximately one third of adults in the United States. The disease is becoming a global epidemic as a result of the rising rates of obesity and metabolic disease. Emerging data suggest weight loss of ≥10% overall body weight is beneficial in resolving steatosis and reversing fibrosis. Prospective trials comparing various diets are limited by lack of sufficient power as well as pre- and post-treatment histopathology, and therefore no specific diet is recommended at this time. In this narrative review we examine the pathophysiology behind specific macronutrient components that can either promote or reverse NAFLD to help inform more specific dietary recommendations. Overall, the data supports reducing saturated fat, refined carbohydrates, and red and processed meats in the diet, and increasing the consumption of plant-based foods. Diets that incorporate these recommendations include plant-based diets such as the Dietary Approaches to Stop Hypertension, Mediterranean, vegetarian, and vegan diets.

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