Is metabolic-dysfunction-associated fatty liver disease or advanced liver fibrosis associated with erythropoietin stimulating agent hypo-responsiveness among patients with end-stage kidney disease on haemodialysis?

AIM: This study aims to determine if metabolic-dysfunction-associated fatty liver disease (MAFLD) or advanced liver fibrosis is associated with erythropoietin stimulating agent (ESA) hypo-responsiveness in hemodialysis patients. METHODS: In a cross-sectional study of 379 hemodialysis patients, FibroTouch transient elastography was performed on all patients. Erythropoeitin resistance index (ERI) was used to measure the responsiveness to ESA. Patients in the highest tertile of ERI were considered as having ESA hypo-responsiveness. RESULTS: The percentage of patients with ESA hypo-responsiveness who had MAFLD was lower than patients without ESA hypo-responsiveness. FIB-4 index was significantly higher in ESA hypo-responsive patients. In multivariate analysis, female gender (aOR = 3.4, 95% CI = 1.9-6.2, p < 0.001), dialysis duration ≥50 months (aOR = 1.8, 95% CI = 1.1-2.9, p < 0.05), elevated waist circumference (aOR = 0.4, 95% CI = 0.2-0.8, p = 0.005), low platelet (aOR = 2.6, 95% CI 1.3-5.1, p < 0.01), elevated total cholesterol (aOR = 0.5, 95% CI 0.3-0.9, p < 0.05) and low serum iron (aOR = 3.8, 95% CI = 2.3-6.5, p < 0.001) were found to be independent factors associated with ESA hypo-responsiveness. Neither MAFLD nor advanced liver fibrosis was independently associated with ESA hypo-responsiveness. However, every 1 kPA increase in LSM increased the chance of ESA-hyporesponsiveness by 13% (aOR = 1.1, 95% CI = 1.0-1.2, p = 0.002) when UAP and LSM were used instead of presence of MAFLD and advanced liver fibrosis, respectively. CONCLUSION: MAFLD and advanced liver fibrosis were not independently associated with ESA hypo-responsiveness. Nevertheless, higher FIB-4 score in ESA hypo-responsive group and significant association between LSM and ESA hypo-responsiveness suggest that liver fibrosis may be a potential clinical marker of ESA hypo-responsiveness.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced liver fibrosis among hemodialysis patients in a multiethnic urban population in Malaysia.

BACKGROUND: Metabolic-dysfunction-associated fatty liver disease (MAFLD) and end stage kidney disease (ESKD) are complications of the metabolic syndrome. Our aim is to study the prevalence of MAFLD and advanced liver fibrosis and the associated factors among hemodialysis patients in a multiracial urban population in Malaysia. METHODS: A cross-sectional study of hemodialysis patients from 10 hemodialysis centers was used. FibroTouch examination was performed on all patients. Fatty liver was diagnosed based on ultrasound attenuation parameter ≥248 dB/m while advanced liver fibrosis was diagnosed based on liver stiffness measurement ≥10 kPa. RESULTS: This study included 447 hemodialysis patients (median age 59 [50-67], male 55%, Chinese 61%, Malay 20%, Indian 18%). Dialysis vintage was 49 (22-93) months. The prevalence of MAFLD was 43.4%. Independent factors associated with MAFLD were elevated waist circumference (aOR = 10.1, 95% CI = 5.3-19.4, p < 0.001), normal platelet count (aOR = 3.1, 95% CI = 1.3-7.3, p < 0.05), low HDL cholesterol (aOR = 2.3, 95% CI = 1.3-4.2, p < 0.01), elevated fasting blood sugar (aOR = 2.3, 95% CI = 1.3-3.8, p < 0.01), elevated hsCRP (aOR = 2.2, 95% CI = 1.2-4.0, p < 0.01), and advanced liver fibrosis (aOR = 3.0, 95% CI = 1.6-5.6, p < 0.001). The prevalence of advanced liver fibrosis was 25.5%. Independent factors associated with advanced liver fibrosis were male gender (aOR = 1.8, 95% CI = 1.0-3.0, p < 0.05), elevated waist circumference (aOR = 2.0, 95% CI = 1.0-4.0, p < 0.05), low platelet count (aOR = 5.4, 95% CI = 2.7-11.0, p < 0.001), elevated GGT (aOR = 5.0, 95% CI = 2.9-8.8, p < 0.001), and MAFLD (aOR = 3.2, 95% CI = 1.7-5.9, p < 0.001). CONCLUSION: A high prevalence of MAFLD and advanced liver fibrosis was observed among hemodialysis patients. Nephrologists should consider a more proactive approach in diagnosing MAFLD and/or advanced liver fibrosis in hemodialysis patients.

Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis with Renal and Lung Involvement.

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a rare and heterogeneous disease. Moreover, optimal treatment is still lacking. We described the case of a 44-year-old lady with underlying Graves' disease who had cough, blood-streaked sputum, and impaired renal function. A strongly positive anti-myeloperoxidase antibody (>200 U/mL) along with pauci-immune glomerulonephritis and pulmonary hemorrhage resulted in the diagnosis of PTU-induced AAV, given that the patient had been on PTU for 3 years. PTU withdrawal, therapeutic plasma exchanges, and oral cyclophosphamide provided favorable clinical and biochemical outcomes. She remained well on azathioprine 50 mg daily as maintenance therapy and clinically euthyroid with carbimazole 2.5 mg daily. The effective treatment for drug-induced ANCA vasculitis remains controversial, but rapid withdrawal of the offending medication should be the mainstay of treatment. In severe drug-induced ANCA vasculitis with pulmonary hemorrhage and/or life-threatening organ involvement such as kidney failure requiring dialysis, therapeutic plasma exchange with immunosuppressants is often required. In this case, we have shown that patient achieved remission after therapeutic plasma exchange with cyclophosphamide in the acute stage of treatment and remained symptom-free with azathioprine in the maintenance phase of treatment for 24 months.

Nonalcoholic Fatty Liver Disease: A Global Perspective.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing over the years and is now as high in Asia as in the Western world, so much so that it should no longer be considered a Western disease. In fact, China is expected to have the largest increase in the number of NAFLD cases in the coming years. The increase in prevalence of NAFLD in Asia lags behind that of the Western world; thus, there will be a lag in more severe liver disease in Asia despite a similar prevalence of the disease. NAFLD is more prevalent among patients with diabetes mellitus, which is also an important risk factor for more severe liver disease. Patients with diabetes mellitus thus represent an important target for screening for NAFLD and more severe liver disease. Although the PNPLA3 gene polymorphism is the most studied in NAFLD, it is increasingly clear that the cumulative effect of multiple genes likely predisposes to NAFLD and more severe liver disease in the different ethnic groups, and polygenic risk scores are emerging. Lean NAFLD has been largely reported in Asia but is increasingly recognized worldwide. Multiple risk factors have been identified for the disease that manifests in metabolically unhealthy normal weight individuals; however, it responds to lifestyle intervention, similar to the disease in obese individuals. Lastly, the newer term "metabolic dysfunction-associated fatty liver disease" provides a more accurate reflection of the disease, giving more focus to clinicians and researchers in tackling this increasingly common and challenging disease.