Serum Creatinine as an Independent Predictor of Moderate to Severe Fibrosis in Chinese American Non-obese Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to the obesity epidemic. However, non-obese MASLD (body mass index [BMI] < 25 kg/m2 for Asians) is not uncommon, especially among Asian American populations. Preliminary research has demonstrated sarcopenia, a muscle-wasting syndrome, to be a major risk factor for non-obese Chinese MASLD. This study examined serum creatinine (SCr), a sarcopenia biomarker, and other prominent MASLD biomarkers for their ability to predict moderate to severe fibrosis (≥7.5 kPa or ≥F2 fibrosis) in the Chinese American MASLD population. METHODS: A total of 296 Chinese American MASLD patients were categorized by BMI and fibrosis severity. As per World Health Organization guidelines for Asians, we identified obese MASLD (BMI ≥ 25 kg/m2) in 191 subjects (64.5%) and non-obese MASLD (BMI < 25 kg/m2) in 105 subjects (35.5%). Multivariate logistic regressions were performed to ascertain which biomarkers served as independent predictors of ≥F2 fibrosis. Wilcoxon signed-rank tests were conducted to compare MASLD cohorts (stratified by gender) and the healthy adult population on SCr distribution. RESULTS: The obese MASLD cohorts had higher rates of ≥F2 fibrosis and type 2 diabetes mellitus compared to their older, non-obese counterparts. For obese MASLD patients, higher age (P < 0.05), increased BMI (P < 0.01), increased AST (P < 0.05), and decreased platelets (P < 0.05) independently predicted ≥F2 fibrosis. For non-obese MASLD patients, lowered SCr (P < 0.05) levels served as the main predictor of ≥F2 fibrosis. Female MASLD patients had markedly lower SCr distributions (P < 0.001) compared to the healthy female population, with 26.8% having SCr levels below the normal range. CONCLUSIONS: In summary, SCr was the predominant predictor of moderate to severe fibrosis in non-obese Chinese American MASLD patients. The high rate of decreased SCr levels in Chinese American MASLD women suggests that this population may be at higher risk for muscle mass loss, which can lead to liver fat accumulation.

Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

BACKGROUND AND OBJECTIVES: Ischemic stroke despite a direct oral anticoagulant (DOAC) is increasingly common and portends a high risk of subsequent ischemic stroke. The efficacy and safety of antithrombotic regimens after the condition are unclear. We aimed to compare the outcomes of patients with ischemic stroke despite DOACs with and without an alternative antithrombotic regimen and determine the risk factors of recurrent ischemic stroke while on anticoagulation. METHODS: In a population-based, propensity score-weighted, retrospective cohort study, we compared the clinical outcomes of DOAC-to-warfarin switch, DOAC-to-DOAC switch (DOACswitch), or addition of antiplatelet agents, with those of unchanged DOAC regimen (DOACsame) among patients with nonvalvular atrial fibrillation (NVAF) who developed the first ischemic stroke despite a DOAC from January 1, 2015, to December 31, 2020, in Hong Kong. The primary outcome was recurrent ischemic stroke. Secondary outcomes were intracranial hemorrhage, acute coronary syndrome, and death. We performed competing risk regression analyses to compare the clinical endpoints and determined the predictors of recurrent ischemic stroke in an unweighted multivariable logistic regression model. RESULTS: During the 6-year study period, among 45,946 patients with AF on a DOAC as stroke prophylaxis, 2,908 patients developed ischemic stroke despite a DOAC. A total of 2,337 patients with NVAF were included in the final analyses. Compared with DOACsame, warfarin (aHR 1.96, 95% CI 1.27-3.02, p = 0.002) and DOACswitch (aHR 1.62, 95% CI 1.25-2.11, p < 0.001) were associated with an increased risk of recurrent ischemic stroke. In the DOACsame group, adjunctive antiplatelet agent was not associated with a reduced risk of recurrent ischemic stroke. Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators, and large artery atherosclerotic disease (LAD) were predictors of recurrent ischemic stroke. DISCUSSION: In patients with NVAF with ischemic stroke despite a DOAC, the increased risk of recurrent ischemic stroke with switching to warfarin called for caution against such practice, while the increased ischemic stroke with DOAC-to-DOAC switch demands further studies. Adjunctive antiplatelet agent did not seem to reduce ischemic stroke relapse. Because diabetes mellitus, the use of CYP/P-gp modulators, and LAD were predictors of recurrent ischemic stroke, further investigations should evaluate whether strict glycemic control, DOAC level monitoring, and routine screening for carotid and intracranial atherosclerosis may reduce ischemic stroke recurrence in these patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF experiencing an ischemic stroke while being treated with a DOAC, continuing treatment with that DOAC is more effective at preventing recurrent ischemic stroke than switching to a different DOAC or to warfarin.

Comparative analysis of metabolic risk factors for progression of non-alcoholic fatty liver disease.

AIM OF THE STUDY: Non-alcoholic fatty liver disease (NAFLD), a globally prevailing chronic liver condition, refers to a spectrum of disease ranging from bland steatosis to steatohepatitis causing fibrosis without significant alcohol intake. Prominent risk factors (RFs) include obesity, type 2 diabetes mellitus, and dyslipidemia. Currently, no established hierarchy exists for the influence of metabolic RFs on NAFLD progression. This retrospective cohort study investigated and ranked the independent and combined effects of three major RFs on NAFLD progression. MATERIAL AND METHODS: 652 NAFLD patients with ≥ 1 RF were categorized by RF combination to examine yearly changes in RF severity with liver stiffness measurement (LSM) over five years. Body mass index (BMI), hemoglo- bin A1c (HbA1c), total cholesterol (TC), and LSM were reviewed. RESULTS: In patients with any single improving RF, decreases in BMI were associated with a yearly LSM change of -1.26 kPa, while decreases in HbA1c and TC were associated with a change of -0.51 kPa and -0.56 kPa, respectively. In patients with any single worsening RF, increases in BMI were correlated with an LSM change of +0.74 kPa and increases in HbA1c and TC were correlated with a change of +0.43 kPa and +0.16 kPa, respectively. Patients with three RFs had the greatest LSM changes for both improving (-3.68 kPa) and worsening (+3.19 kPa) groups. The strongest predictors for LSM change were BMI and HbA1c, with standardized ß coefficients of 0.236 and 0.226 (p < 0.001), while TC had the least influence [0.112 (p < 0.01), F(3,647) = 11.458, p < 0.001, R 2 = 0.155]. CONCLUSIONS: Obesity was the most prominent RF. Treatment of all three RFs over a five-year period presented a high likelihood of fibrosis stage regression for NAFLD patients.

Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B.

AIM: To compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) in Asian and non-Asian chronic hepatitis B (CHB) patients. METHODS: The efficacy and safety of the initial 48 wk of treatment with TDF was compared in a post-hoc analysis of combined data from 217 Asians and 299 non-Asians included in Studies 102 and 103 and a post-approval, open-label trial (Study 123). Patient groups were compared according to baseline hepatitis B e antigen (HBeAg) status and viral load. The main outcome measures included the proportion of patients who achieved a hepatitis B virus (HBV) DNA level < 400 copies/mL at Week 48 of treatment. Secondary measures included: HBV DNA and alanine aminotransaminase (ALT) levels over time; proportion of patients with normal ALT levels; proportion of patients with HBeAg loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion; changes in liver histology. Safety and tolerability were evaluated by the occurrence of adverse events (AEs), serious AEs, laboratory abnormalities, discontinuation of the study drug due to AEs, or death. The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug. RESULTS: At week 48, similar proportions of Asians and non-Asians reached HBV DNA < 400 copies/mL (96% of Asian and 97% of non-Asian patients with HBeAg-negative CHB and 83% of Asian and 79% of non-Asian patients with HBeAg-positive CHB had HBV DNA) and normal ALT (78% of Asian and 81% of non-Asian patients with HBeAg-negative CHB and 71% of Asian and 74% of non-Asian patients with HBeAg-positive CHB had normal ALT). On-treatment HBV DNA decline rates were similar between Asians and non-Asians regardless of baseline HBeAg status and viral load. HBV DNA decline during the first four weeks was 2.9 log10 copies/mL in HBeAg-negative Asians and non-Asians, and in HBeAg-positive non-Asians, and 3.1 log10 copies/mL in HBeAg-positive Asians. HBeAg loss and seroconversion was achieved in 14% of Asians vs 26% and 24%, respectively, in non-Asians. Liver histology improved in 77.2% of Asians and 71.5% of non-Asians. No resistance to TDF developed. No renal safety signals were observed. CONCLUSION: TDF demonstrated similar viral suppression, normalization of ALT, improvements in liver fibrosis, and no detectable resistance in Asian and non-Asian patients regardless of baseline HBeAg status.

Efficacy and safety of tenofovir disoproxil fumarate in Asian-Americans with chronic hepatitis B in community settings.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) disproportionately affects the Asian-American population in the USA. Tenofovir disoproxil fumarate (TDF) has demonstrated potent antiviral activity in clinical trials, but data in Asian-Americans from community studies are lacking. METHODS: Adult Asian-American patients with CHB from private medical and community-based practices were prospectively enrolled and treated with open-label TDF 300 mg once daily in a single-arm study for 48 weeks. After Week 48, patients had the option to transition to commercially available CHB therapy. The primary efficacy endpoint was hepatitis B virus (HBV) DNA <400 copies/mL at Week 48. Secondary endpoints were safety and tolerability, serologic and biochemical responses, liver fibrosis by FibroTest, and the development of drug-resistant mutations. RESULTS: Of the 90 patients enrolled, 53 (58%) were hepatitis B e antigen (HBeAg)-positive at baseline. At Week 48, 74 patients (82% overall; 70% HBeAg-positive and 100% HBeAg-negative) had HBV DNA <400 copies/mL. Six (12%) HBeAg-positive patients achieved HBeAg loss/seroconversion. The percentage of patients with alanine aminotransferase in the normal range increased from 26% at baseline to 66% at Week 48. The percentage of patients with F0 (no or minimal) fibrosis by FibroTest increased from 48% to 51%, and those with F4 (severe) fibrosis decreased from 4% to 1%. No resistance to TDF developed. Treatment was well tolerated. Most adverse events were mild in severity and considered unrelated to study drug. CONCLUSIONS: TDF is effective and well tolerated in Asian-American CHB patients in community clinic-based settings, consistent with larger registration trials. Improvement in liver fibrosis was seen in a proportion of patients. No resistance to TDF developed through 48 weeks of treatment. TRIAL REGISTRATION: Clinicaltrial.gov identifier NCT00736190.