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.

Effect of fish oil supplementation on the concentration of miRNA-122, FGF-21 and liver fibrosis in patients with NAFLD: Study protocol for a randomized, double-blind and placebo-controlled clinical trial.

BACKGROUND & AIMS: To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD. METHODS: A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4 g/day supplementation of fish oil (2100 mg EPA and 924 mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%. CONCLUSION: The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature. REGISTRATION: ReBEC number RBR-8dp876.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Validation and Performance of FibroScan®-AST (FAST) Score on a Brazilian Population with Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIM: FAST score has a good performance for diagnosing the composite of NASH + NAS ≥ 4 + F ≥ 2. However, it has not been evaluated in Latin American individuals with nonalcoholic fatty liver disease (NAFLD). We aimed to analyze the performance of the FAST score in a Brazilian NAFLD population. METHODS: Cross-sectional study was held in ≥ 18 years NAFLD patients diagnosed by ultrasonography and submitted to liver biopsy (LB). Liver stiffness (LSM) and CAP measurements were performed with FibroScan®, using M (BMI < 32 kg/m2) or XL probes. Area under receiver operating characteristic (AUROC) curves were calculated as well as sensitivity (S), specificity (Spe), positive predictive value (VPP) and negative predictive value (NPV) for the previously established FAST score cut-offs. RESULTS: Among 287 patients included (75% female; mean age 55 ± 10 years), NASH + NAS ≥ 4 + F ≥ 2 was reported in 30% of LB. For the FAST cut-off of 0.35, the S and NPV to rule out NASH + NAS ≥ 4 + F ≥ 2 were 78.8% and 87.8%, respectively. Regarding the cut-off of 0.67, the Spe and PPV to rule-in NASH + NAS ≥ 4 + F ≥ 2 were 89.1%, 61.8%, respectively. The AUROC of FAST for all included patients was 0.78 (95% CI 0.72-0.84) and for those with ≥ 32 kg/m2 was 0.81 (95% CI 0.74-0.88). CONCLUSION: FAST score has a good performance in a Brazilian NAFLD population, even in patients with higher BMI when the XL probe is adopted. Therefore, FAST can be used as a noninvasive screening tool mainly for excluding the diagnosis of progressive NASH, reducing the number of unnecessary liver biopsies.

Impact of Long-Term Supplementation with Fish Oil in Individuals with Non-Alcoholic Fatty Liver Disease: A Double Blind Randomized Placebo Controlled Clinical Trial.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.

Can gadoxetic acid-enhanced magnetic resonance imaging be used to avoid liver biopsy in patients with nonalcoholic fatty liver disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. The diagnosis of nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD, is crucial and has prognostic and therapeutic implications. However, currently this diagnosis is based on liver biopsy and has several limitations. AIM: To evaluate the performance of gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) in differentiating isolated steatosis from NASH in patients with NAFLD. METHODS: In this prospective study, 56 patients with NAFLD (18 with isolated steatosis and 38 with NASH) underwent GA-MRI. The contrast enhancement index (CEI) was calculated as the rate of increase of the liver-to-muscle signal intensity ratio from before and 20 min after intravenous GA administration. Between-group differences in mean CEI were examined using Student's t test. The area under the receiver operator characteristic curve and the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging were evaluated. RESULTS: The mean CEI for all subjects was 1.82 ± 0.19. The mean CEI was significantly lower in patients with NASH than in those with isolated steatosis (P = 0.008). Two CEI cut-off points were used: < 1.66 (94% specificity) to characterize NASH and > 2.00 (89% sensitivity) to characterize isolated steatosis. CEI values between 1.66 and 2.00 indicated liver biopsy, and the procedure could be avoided in 40% of patients with NAFLD. CONCLUSION: GA-MRI is an effective noninvasive method that may be useful for the differentiation of NASH from isolated steatosis, and could help to avoid liver biopsy in patients with NAFLD.

Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20-30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

The performance of M and XL probes of FibroScan for the diagnosis of steatosis and fibrosis on a Brazilian nonalcoholic fatty liver disease cohort.

OBJECTIVES: Recently, controlled attenuation parameter (CAP) was incorporated for XL probe. However, its performance through M and XL probes has been scarcely evaluated in nonalcoholic fatty liver disease (NAFLD). The performance of probes regarding transient elastography by Fibroscan is still under debate. AIM: Compare the performance of CAP and transient elastography in NAFLD patients obtained through XL with M probes using histological analysis as gold standard. METHODS: NAFLD patients underwent liver biopsy and FibroScan/CAP with M and XL probes the same day. C-statistic evaluated CAP performance in the identification of moderate/severe (≥33%) and severe (≥66%) steatosis by both probes and transient elastography performance for identification of significant fibrosis (≥F2). RESULTS: Eighty-one patients (74% female; age 54.2 ± 9.9 years; BMI 32.8 ± 5.2/ BMI ≥ 25 92.6%; 96% metabolic syndrome; 60% diabetes mellitus) were included. Mean CAP with M and XL probes was 314 ± 39 and 325 ± 47 dB/m, respectively. The areas under receiver operating characteristic curves (AUROCs) of the M and XL probes for steatosis detection ≥33% were 0.75 (0.64-0.84) and 0.76 (0.65-0.84) (P = 0.95) and for steatosis ≥66% 0.83 (0.73-0.90) and 0.82 (0.71-0.89) (P = 0.73), respectively, with similar performances for both degrees of steatosis. Regarding transient elastography, AUROCs of M and XL probes for ≥F2 were 0.82 (0.71-0.93) and 0.80 (0.69-0.92) (P = 0.66). CONCLUSION: Performance of M and XL probes is similar for the diagnosis of moderate and severe steatosis and significant fibrosis even on a overweight population with NAFLD.

Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. It is often related to metabolic syndrome, presenting an increased risk of advanced liver disease and cardiovascular-related death. In some etiologies of chronic liver disease, thrombocytopenia has been associated not only with advanced stages of fibrosis but also with autoimmune disease. In NAFLD, however, its prevalence and related factors are still unknown. The aim of this study is to evaluate the prevalence of thrombocytopenia in NAFLD patients without cirrhosis and to investigate its related risk factors. PATIENTS AND METHODS: This was a retrospective study carried out in two tertiary hospitals in the South and Southeast regions of Brazil. Patients diagnosed with NAFLD by liver biopsy were included. Those with other causes of liver disease and/or cirrhosis were excluded. For analysis, patients were divided into two groups, with and without thrombocytopenia. Data was analyzed using a significance level of 5%. RESULTS: 441 non-cirrhotic patients with NAFLD (evaluated by liver biopsy) were included in the study. The prevalence of thrombocytopenia was 3.2% (14/441 patients). In the comparative analysis between groups, thrombocytopenia was associated with male sex (p=0.007) and level of hemoglobin (p=0.023). CONCLUSION: Thrombocytopenia is an infrequent event in NAFLD patients without cirrhosis and is related with male sex and higher hemoglobin levels.

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION AND AIM: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.

Efficacy of diacerein in reducing liver steatosis and fibrosis in patients with type 2 diabetes and non-alcoholic fatty liver disease: A randomized, placebo-controlled trial.

The aim was to assess, in a randomized, double-blinded, placebo-controlled trial, the efficacy of diacerein, an anti-inflammatory drug, in improving liver fibrosis and steatosis in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sixty-nine diabetic patients with NAFLD were randomized to 24-month treatment with placebo (35 patients) or diacerein 100 mg/day (34 patients). Liver stiffness and steatosis were assessed by transient elastography (Fibroscan®) at baseline, and 12 and 24 months of follow-up. The primary outcome was the difference in mean liver stiffness and steatosis changes during treatment. Adjusted differences in mean changes on intention-to-treat analyses were estimated by generalized repeated-measures mixed-effects regressions. Diacerein significantly reduced liver stiffness in contrast to placebo by 1.6 kPa (95% CI: -2.6 to -0.5 kPa; p = 0.003), whereas no significant difference in mean changes in liver steatosis was observed. The reduction in liver stiffness was already evident at the 12-month examination, and accentuated at the 24-month examination. Eight patients reduced liver fibrosis stage during treatment, seven of whom were in the diacerein group (p = 0.020). In conclusion, a 2-year treatment with diacerein significantly reduced liver fibrosis in diabetic patients with NAFLD.

The Correlation Between Obesity-Related Diseases and Non-alcoholic Fatty Liver Disease in Women in the Pre-operative Evaluation for Bariatric Surgery Assessed by Transient Hepatic Elastography.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common, severe disease in obese patients. However, NAFLD is usually underestimated by ultrasonography. Liver biopsy is not routinely done in bariatric surgery or during the follow-up. This study therefore examined the correlation between metabolic syndrome and NAFLD in morbidly obese patients based on an assessment using transient hepatic elastography (THE). MATERIAL AND METHODS: This study involved 50 female patients in the pre-operative phase for bariatric surgery. Before surgery, we collected clinical, laboratory, and anthropometric variables. THE measurements were obtained using a FibroScan® device (Echosens, Paris, France), and steatosis was quantified using Controlled Attenuation Parameter software (CAP). Statistical analyses were done using linear correlation and the Kruskal-Wallis test. RESULTS: The mean of THE and CAP values were 7.56 ± 4.78 kPa and 279.94 ± 45.69 dB/m, respectively, and there was a significant linear correlation between the two measurements (r = 0.651; p < 0.001). The numbers of metabolic syndrome parameters did not influence the THE (p = 0.436) or CAP (p = 0.422) values. HbA1c and HOMA-IR showed a strong linear correlation with CAP (r = 0.643, p = 0.013 and r = 0.668, p = 0.009, respectively) and a tendency to some linear correlation with THE (r = 0.500, p = 0.05 and r = 0.500, p = 0.002, respectively). CONCLUSION: Morbidly obese women submitted to FibroScan® presented a high prevalence of severe steatosis and advanced fibrosis in our sample. Insulin resistance parameters were correlated with steatosis, but less with fibrosis.

Non-alcoholic fatty liver disease and diabetes: from physiopathological interplay to diagnosis and treatment.

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2 diabetes are at a particularly high risk for developing the progressive forms of NAFLD, non-alcoholic steatohepatitis and associated advanced liver fibrosis. Moreover, diabetes is an independent risk factor for NAFLD progression, and for hepatocellular carcinoma development and liver-related mortality in prospective studies. Notwithstanding, patients with NAFLD have an elevated prevalence of prediabetes. Recent studies have shown that NAFLD presence predicts the development of type 2 diabetes. Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients. The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods, although histopathological evaluation is still considered the gold standard diagnostic method. An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking. We sought to outline the published data including epidemiology, pathogenesis, diagnosis and treatment of NAFLD in diabetic patients, in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

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.

Factors associated with carotid intima-media thickness and carotid plaques in type 2 diabetic patients.

OBJECTIVE: Factors associated with carotid atherosclerosis are unclear in type 2 diabetic patients. The aim was to investigate the independent correlates of carotid intima-media thickness (IMT) and plaques in these individuals. METHODS: In a cross-sectional study, we measured carotid IMT at three sites (common carotid, bifurcation and internal carotid artery) and the severity of extracranial carotid artery (ECCA) atherosclerosis by plaque score in 441 type 2 diabetic patients. Nontraditional cardiovascular risk factors [ambulatory blood pressures (BPs), aortic stiffness, C-reactive protein and ankle-brachial index) were obtained. Multivariate linear and logistic regressions assessed the independent correlates of carotid IMT and ECCA plaque score. RESULTS: Patients with greater carotid IMT or plaque scores had worse clinical and laboratory profile than those with lower IMT and plaque scores, including higher BPs, aortic stiffness and prevalences of diabetic complications. On multivariate analysis, carotid IMT and plaques were mainly associated with older age, male sex, current-past smoking and ambulatory BPs, but not with clinic BPs. Night-time pulse pressure was the most important modifiable determinant of increased carotid IMT. No microvascular complication was independently associated with carotid atherosclerosis, except retinopathy for plaque score. Additionally, internal carotid IMT and plaque score were associated with ankle-brachial index in the subgroup of patients without macrovascular diseases. CONCLUSION: In type 2 diabetic patients, older age, male sex, smoking status and ambulatory BPs, particularly night-time pulse pressure, were the main independent correlates of ultrasonographic carotid atherosclerosis. This finding reinforces the importance of ambulatory BP monitoring in type 2 diabetes management.

Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM). However, data regarding the prevalence and correlates of its histopathological stages are scarce. The aim was to investigate the prevalence and correlates of the more severe histopathological features of NAFLD, nonalcoholic steatohepatitis (NASH) and advanced fibrosis, in T2DM. METHODS: From 125 patients with ultrasonographic evidence of NAFLD, 98 patients underwent liver biopsies, which were examined by two independent pathologists regarding the presence of NASH and graded according to the NASH Clinical Research Network scoring system. Agreement between pathologists was assessed by weighted κ coefficients and independent correlates of NASH and advanced fibrosis (grade ≥ 2) by multivariate logistic regression. RESULTS: Ninety-two (94%) patients presented histological NAFLD. Interobserver agreement was substantial to excellent for NASH diagnosis (κ=0.82) and steatosis grading (κ=0.76), and moderate for the NAFLD activity score (κ=0.58) and fibrosis grading (κ=0.52). The prevalence of NASH was 78%, and its independent correlates were hypertriglyceridaemia (P=0.034), high alanine aminotranferase level (P=0.044) and low serum high-density lipoprotein-cholesterol (P=0.079). The prevalence of advanced fibrosis ranged from 34% in the best scenario (lowest fibrosis score) to 60% in the worst scenario (highest score). Its independent correlates were a high serum γ-glutamyl transferase (P=0.002), older age (P=0.022) and male gender (P=0.064). No diabetes-related clinical characteristic was associated with NASH or advanced liver fibrosis. CONCLUSIONS: The prevalence of the severe features of NAFLD is high in T2DM patients. Liver biopsy shall be considered in all diabetic patients with ultrasonographic evidence of NAFLD.

Prevalência do anticorpo contra hepatite C (anti VHC) em doadores de sangue no Rio de Janeiro, Brasil: sua relaçäo com ALT e anti HBc / Prevalence of antibodies to hepatitis C (anti HCV) in blood donors in Rio de Janeiro, Brazil: its relation with ALT and anti HBC

Estudamos no período de maio a julho de 1990, 933 doadores de sangue atendidos no Serviço de Hemoterapia. Após entrevista e exames rotineiros, foram realizados testes de triagem: antiHBc total, antiVHC e transminase glutâmico pirúvica (ALT). Os marcadores virais foram determinados por técnica de enzimaimunoensaio. 94% dos doadores eram do sexo masculino com média de idade de 33 anos (19-65). A positividad para o antiVHC foi de 3,1%. Entre os doadores antiVHC+, 13,29(44,8%) apresentaram ALT>40UI/L, 9/29(31%) foram positivos para o antiHBc e 5(17,2%) tinham ambos os marcadores. De 109 doadores com ALT > UI/L 13(11.9%) foram anti VHC+. Enquanto de 153 doadores anti HBC+, a positividade para o anti VHC foi de 5,8%, pouco maior que a do grupo total. Conclusöes: 1) Nossos doadores apresentam elevada prevalência de anti VHC(método de ELISA) quando comparada à de outros países estudados; 2) a determinaçäo de ALT e a pesquisa de anti HBc no soro de doadores foi incapaz de detectar 41,4% de doadores anti VHC+; 3) houve maior prevalência de ALT elevada nos doadores antiVHC+ com relaçäo amostra/cutoff > 4