Impact of PNPLA3 and TM6SF2 polymorphisms on the prognosis of patients with MASLD and type 2 diabetes mellitus.

BACKGROUND/AIMS: Longitudinal studies assessing the impact of genetic polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are scarce. This study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic and extrahepatic outcomes in T2DM-MASLD individuals. METHODS: Patients' polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and CT + TT; combined comparing no mutant allele, one allele G or T or ≥2 alleles G or T. Hierarchical models were built to assess associations between polymorphisms and outcomes, independently of confounding factors. Multivariate logistic regression was used for cirrhosis and its complications and extrahepatic cancer, and Cox regression for cardiovascular events (CVEs) and all-cause mortality. RESULTS: In total, 407 T2DM-MASLD patients (62.1 ± 10.5 years, 67.6% women) were followed for 11 (6-13) years. Having at least one G or T allele independently increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if two or more risk alleles were present (OR 18.48; 95% CI 6.15-55.58; p < .001). Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 CT + TT, also with an even higher risk when two or more risk alleles were present in the combined evaluation (OR 27.20; 95% CI 5.26-140.62; p < .001). There were no associations with CVEs or mortality outcomes. CONCLUSION: In T2DM, PNPLA3 and TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an increased risk of cirrhosis and its complications.

Serum biomarkers in type 2 diabetic patients with non-alcoholic steatohepatitis and advanced fibrosis.

AIM: Advanced stages of non-alcoholic fatty liver disease (NAFLD) are highly prevalent in type 2 diabetes (T2DM), however, no diabetes-related or biochemical variable seems to be predictive of severity of NAFLD. The aim of this study was to investigate the association of several serum biomarkers with the more severe histopathological stages of NAFLD in T2DM. METHODS: In a cross-sectional design, 84 T2DM patients with biopsy-proven NAFLD had adiponectin, tumor necrosis factor-α, transforming growth factor (TGF)-ß1, interleukin (IL)-6, -8 and -10, and C-reactive protein measured. NAFLD severity was evaluated by two hepatopathologists according to the non-alcoholic steatohepatitis (NASH) Clinical Research Network scoring system. Independent associations of cytokines with NASH and advanced fibrosis were evaluated by multivariate logistic regressions. RESULTS: Sixty-six patients (78.6%) had NASH, and 52 patients (61.9%) had advanced fibrosis considering the highest score between the two pathologists. Patients with NASH or with advanced fibrosis had equal cytokine levels to those without NASH or with absent/light fibrosis, except for a lower serum adiponectin (8.59 vs 12.77 µg/mL; P = 0.015) in patients with NASH and a lower TGF-ß1 (170 vs 180 pg/mL; P = 0.026) in patients with advanced fibrosis. In multivariate analysis, lower adiponectin was independently associated with NASH (odds ratio = 7.7, 95% confidence interval = 1.5-39.9, P = 0.014, for the subgroup with adiponectin below the median value), whereas both lower adiponectin and lower TGF-ß1 levels were associated with advanced fibrosis. CONCLUSION: Low adiponectin and low TGF-ß1 are associated with severest NAFLD stages in T2DM and may be a valuable tool to support liver biopsy indication in this setting.

Prognostic value of nocturnal blood pressure reduction in resistant hypertension.

BACKGROUND: The prognostic value of nocturnal blood pressure (BP) reduction in resistant hypertension (RH) is unknown. The objective of this prospective study was to evaluate its importance as a predictor of cardiovascular morbidity and mortality. METHODS: At baseline, 556 patients with RH underwent clinical and laboratory examinations and 24-hour ambulatory BP monitoring. The primary end points were a composite of fatal or nonfatal cardiovascular events, all-cause mortality, and cardiovascular mortality. Multiple Cox regression was used to assess associations between the nocturnal BP reduction and the subsequent end points. RESULTS: After a mean follow-up of 4.8 years (range, 1-103 months), 109 patients (19.6%) reached the composite end point, with 70 all-cause and 46 cardiovascular deaths. A nondipping pattern was present in 360 patients (65.0%). After adjustment for age, sex, body mass index, diabetes, smoking status, physical inactivity, dyslipidemia, previous cardiovascular disease, number of antihypertensive drugs in use, and office and 24-hour ambulatory BP readings, the nondipping pattern was an independent predictor of the composite end point (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.12-2.71) and of cardiovascular mortality (HR, 2.31; 95% CI, 1.09-4.92). In subgroup analysis, the reduced (HR, 1.71; 95% CI, 1.03-2.83) and reverted (HR, 1.89; 95% CI, 1.04-3.43) dipping patterns were predictive of total cardiovascular events. The effect of the nondipping pattern on cardiovascular prognosis was stronger in younger patients and in those with true RH. CONCLUSIONS: The nocturnal BP variability patterns provide valuable prognostic information for stratification of cardiovascular morbidity and mortality risk in patients with RH, above and beyond other traditional cardiovascular risk factors and mean ambulatory BP levels.

Bioprótese mitral: avaliaçäo clínica, radiológica, eletrocardiográfica e ecocardiográfica / Mitral bioprosthesis: clinical, roentgenographic, electrocardiographic and echocardiographic evaluation

Foram estudados 26 pacientes portadores de doenç a mitral reumática submetidos a troca valvar por bioprótese, quanto à sua evoluçäo clínica, eletrocardiográfi, radiológica e ecocardiográfica. O tempo médio de implante foi de 53,65 meses. Na avaliaçäo clínica observamos melhora funcional em 25 pacientes e evidências de disfunçäo valvar em cinco (19,23%). Na avaliaçäo radiológica houve reduçäo significativa do índice cardiotorácico (p < 0,01) no pós-operat-orio. No estudo eletrocardiográfico observamos média (p < 0,05) do pós-operatório em relaçäo ao pré-operatório. No estudo ecocardiográfico observamos aspectos e medidas normais das biopróteses e confirmamos aspectos anormais nos pacientes com evidencias clínicas de disfunçäo protética, coincidentes com a literatura. A presença de sinais sugestivos de calcificaçäo dos folhetos foi a alteraçäo mais freqüente encontrada em oito (30,8%) dos pacientes estudados. Esse dado, presente tanto nos pacientes com sinais clínicos de disfunç äo protética como naqueles sem evidências de comprometimento da prótese, sugere que essa alteraçäo anteceda as demais alteraçöes estruturais e funcionais da bioprótese e possa ser incluída como critério de degeneraçäo tissular das próteses biológicas