High Prevalence of Severe Hepatic Fibrosis in Type 2 Diabetic Outpatients Screened for Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly frequent condition in patients with type 2 diabetes (T2D), but the identification of subjects at higher risk of developing the more severe forms remains elusive in clinical practice. The aim of this study was to evaluate the occurrence and severity of liver fibrosis and its predictive factors in T2D outpatients without a known history of chronic liver disease by using recommended non-invasive methods. METHODS: Consecutive T2D outpatients underwent a set of measurements of clinical and laboratory parameters, FIB-4 score (Fibrosis-4 index), and liver stiffness with controlled attenuation-parameter (CAP) performed by transient elastography (FibroScan) after excluding previous causes of liver disease. RESULTS: Among the 205 T2D outpatients enrolled in the study (median age: 64 years, diabetes duration: 11 years, HbA1c: 7.4%, and BMI: 29.6 kg/m2), 54% had high ALT and/or AST levels, 15.6% had liver stiffness value > 10.1 kPa (severe fibrosis), 55.1% had CAP values > 290 dB/m (severe steatosis), and FIB-4 score was >2 in 11.2% of subjects (>2.67 in 15 subjects). Moreover, 49 (23.9%) T2D patients had clinically meaningful liver harm, with either a FIB-4 score > 2 and/or FibroScan > 10.1 kPa. At regression analysis, BMI, HbA1c, creatinine, and triglycerides values were independent predictors of liver fibrosis. CONCLUSIONS: Liver fibrosis is a frequent finding in T2D outpatients without a known history of liver disease, especially in those with obesity, hypertriglyceridemia, worse glycemic control, and high creatinine levels.

Impact of Sex and Gender on Clinical Management of Patients with Advanced Chronic Liver Disease and Type 2 Diabetes.

Gender differences in the epidemiology, pathophysiological mechanisms and clinical features in chronic liver diseases that may be associated with type 2 diabetes (T2D) have been increasingly reported in recent years. This sexual dimorphism is due to a complex interaction between sex- and gender-related factors, including biological, hormonal, psychological and socio-cultural variables. However, the impact of sex and gender on the management of T2D subjects with liver disease is still unclear. In this regard, sex-related differences deserve careful consideration in pharmacology, aimed at improving drug safety and optimising medical therapy, both in men and women with T2D; moreover, low adherence to and persistence of long-term drug treatment is more common among women. A better understanding of sex- and gender-related differences in this field would provide an opportunity for a tailored diagnostic and therapeutic approach to the management of T2D subjects with chronic liver disease. In this narrative review, we summarized available data on sex- and gender-related differences in chronic liver disease, including metabolic, autoimmune, alcoholic and virus-related forms and their potential evolution towards cirrhosis and/or hepatocarcinoma in T2D subjects, to support their appropriate and personalized clinical management.

Hypergammaglobulinemia before Starting DAA Therapy Is A Strong Predictor of Disease Progression in Cirrhotic Patients Even after HCV Clearance.

The predictive factors of long-term clinical benefits in patients with hepatitis C virus (HCV)­related liver cirrhosis after Direct Antiviral Agents (DAA) treatment are still undefined. The aim of this study was to identify any predictors of liver failure, hepatocellular carcinoma (HCC) and/or death in patients with compensated liver cirrhosis who achieved the sustained virological response (SVR). To this purpose, 324 consecutive cirrhotic patients who started DAA treatment from 1 April 2015 to 31 December 2016 were retrospectively analyzed. All patients were followed up for a median time of 63 months (range 19−77) through clinical/biochemical/instrumental examinations performed at baseline and after stopping the DAA treatment. At the end of the evaluation, 230 (71%) individuals showed stable clinical liver disease over time, 43 (13.3%) developed HCC, and 24 (7.4%) developed hepatic decompensation without HCC. Overall, 49 (15,1%) patients died. Multivariate regression analysis showed that hepatic decompensation was significantly associated with at baseline older age, higher liver stiffness, higher spleen longitudinal size values and hypergammaglobulinemia (p = 0.003, p = 0.005, p = 0.001, p = 0.029, respectively). HCC development was significantly associated with hypergammaglobulinemia (p < 0.001). Death was associated with older age and hypergammaglobulinemia (p < 0.001 and p = 0.007, respectively). Finally, survival analysis confirmed that patients with gamma globulin levels ≥ 1.8 gr/dl had a significantly higher risk of death compared to those with gamma globulin levels < 1.8 gr/dl (p < 0.001). In conclusion, hypergammaglobulinemia before starting DAA therapy represents a strong predictor of hepatic decompensation, HCC and death in cirrhotic patients even after HCV clearance.