Specific metabolic impairments indicate loss of sustained liver improvements in metabolic dysfunction-associated steatotic liver disease treatment

Background:High liver fat content(LFC)induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease(MASLD),while maintaining a significant decline in magnetic resonance imaging-based proton density fat fraction(MRI-PDFF)(≥30%decline relative to baseline)without worsening fibrosis results in improved histological severity and prognosis.However,the factors associated with the loss of sustained responses to treatment remain unclear,and we aim to identify them.Methods:Consecutive treatment-naïve MASLD patients between January 2015 and February 2022,with follow-up until April 2023,were included in this prospective cohort study.LFC quantified by MRI-PDFF and liver stiffness measurements(LSM)determined by two-dimensional shear wave elastography(2D-SWE)were evaluated at weeks 0,24 and 48.MRI-PDFF response was defined as a≥30%relative decline in PDFF values,and LSM response was defined as a≥1 stage decline from baseline.Results:A total of 602 MASLD patients were enrolled.Of the 303 patients with a 24-week MRI-PDFF response and complete follow-up of 48 weeks,the rate of loss of MRI-PDFF response was 29.4%,and multivariable logistic regression analyses showed that 24-week insulin resistance(IR),still regular exercise and caloric restriction after 24 weeks,and the relative decline in LFC were risk factors for loss of MRI-PDFF response.Loss of LSM response at 48 weeks occurred in 15.9%of patients,and multivariable analysis confirmed 24-week serum total bile acid(TBA)levels and the relative decline in TBA from baseline as independent predictors.No significant association was found at 48 weeks between loss of MRI-PDFF response and loss of LSM response.Conclusions:MASLD patients with IR and high TBA levels are at higher risks of subsequent diminished sustained improvements of steatosis and fibrosis,respectively.

Discrepancies between Nonalcoholic and Metabolic-associated Fatty Liver Disease by Multiple Steatosis Assessment

Background and Aims:The redefinition of metabolic-as-sociated fatty liver disease(MAFLD)from nonalcoholic fat-ty liver disease(NAFLD)has caused a revolution in clinical practice,and the characteristics of patients with steatosis but not MAFLD remain unclear.The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steato-sis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD.Methods:A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020.Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat frac-tion(MRI-PDFF),ultrasound,controlled attenuation param-eter(CAP),and fatty liver index(FLI).Fibrosis was assessed by the NAFLD fibrosis score,transient elastography,or shear wave elastography.Results:The study enrolled 14,985 Chi-nese adults.The agreement of MAFLD and NAFLD diagnoses were 83%for FLI,95%for ultrasound,94%for both CAP and MRI-PDFF,and 95%for liver biopsy.The body mass index,blood pressure and lipid levels among non-MAFLD-NAFLD pa-tients were similar metabolic parameters(p>0.05 for all),but not the alanine aminotransferase and the proportion of pa-tients with insulin resistance,which were significantly higher in non-MAFLD-NAFLD with significant fibrosis.Conclusions:The new MAFLD definition ruled out 5-17%of NAFLD cases.NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD.Non-MAFLD-NAFLD patients with significant fibrosis had more se-vere liver injury and increased glycemic dysregulation within the normal range.Attention should be paid to its progression.

Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China:A multicenter prospective observational study

Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.