Identifying advanced MAFLD in a cohort of T2DM and clinical features.

Background: MAFLD is the most common cause of chronic liver disease, affecting 25% of the global population. Patients with T2DM have an increased risk of developing MAFLD. In addition, patients with T2DM have a higher risk of advanced forms of steatohepatitis and fibrosis. Identifying those patients is critical in order to refer them to specialist and appropriate management of their disease. Aims and Objectives: To estimate advanced fibrosis prevalence in a cohort of patients with T2DM and to identify possible predictors. Methods: subjects with T2DM during regular health check-up were enrolled. Demographic and general characteristics were measured, including metabolic parameters and homeostasis model assessment of insulin resistance (HOMA2-IR). Four non-invasive fibrosis scores (NAFLD fibrosis scores, FIB-4, APRI, Hepamet fibrosis score) were measure and compared with transient elastography (TE). Results: 96 patients (21%) presented risk of significant fibrosis (≥F2) measured by TE and 45 patients (10%) presented with risk of advanced fibrosis F3-F4. Liver fibrosis was related to BMI, AC, HOMA2-IR. The results of the non-invasive fibrosis scores have been validated with the results obtained in the TE. It is observed that the index with the greatest area under the curve (AUC) is APRI (AUC=0.729), with a sensitivity of 62.2% and a specificity of 76.1%. However, the test with better positive likelihood ratio (LR+) in our study is NAFLD fibrosis score. Conclusions: Our results show that in a general T2DM follow up, 10% of patients were at risk of advanced fibrosis. We found a positive correlation between liver fibrosis and BMI, AC and HOMA2-IR. Non-invasive fibrosis markers can be useful for screening, showing NAFLD Fibrosis score a better LHR+ compared to TE. Further studies are needed to validate these results and elucidate the best screening approach to identify those patients at risk of advanced MAFLD.

Dysphagia secondary to autoimmune necrotizing anti-HGMCR myopathy.

We present the case of an 87-year-old female who presented with upper dysphagia to solids, weight loss of 5 kg and weakness in the upper limbs of a seven months duration. Gastroscopy showed a hiatal hernia and an esophagogram showed gastroesophageal reflux and contrast aspiration into the trachea. Esophageal manometry was not possible due to intolerance. Analytics showed elevated CPK (3,386 UI/l; 34-145) and positivity to anti-HMGCR antibodies. An electromyogram was performed, with more intense myopathy data in the proximal regions of the upper limbs and signs of myositis. A muscle biopsy was performed (deltoids and biceps) that showed signs of necrotizing myopathy. Treatment with oral steroids and methotrexate was started with a good subsequent evolution.

Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients.

Objectives: Sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are the drug combinations of choice for treating individuals with genotype 3 hepatitis C virus (G3-HCV) infection. The objective of this study was to evaluate the effectiveness and safety of SOF/VEL±RBV compared with GLE/PIB for treating G3-HCV infection under routine clinical practice conditions. Methods: We conducted a prospective observational cohort study of individuals with G3-HCV infection who initiated treatment with SOF/VEL +/-RBV or GLE/PIB between April 2017 and July 2018. Prisoners and children were excluded. The outcome variable of effectiveness was sustained virological response 12 weeks after completing treatment (SVR12). The safety variable was withdrawal secondary to severe adverse events (SAEs). Covariates included sex, age, HIV co-infection, previous liver transplant, cirrhosis, hepatic fibrosis and previous antiviral treatment. Statistical significance was calculated using Fisher's exact test or the Mann-Whitney U-test. Results: A total of 76 patients were included in the analysis, of whom 46 were treated with SOF/VEL±RBV and 30 were treated with GLE/PIB. No baseline differences were observed between treatment groups with respect to age, sex, HIV co-infection, fibrosis stage, cirrhosis and previous antiviral treatment. Of the patients treated with SOF/VEL±RBV and GLE/PIB, 95.7% and 96.7% reached SVR12, respectively (P=0.7). Of patients with and without cirrhosis, 83.3% and 98.4% reached SVR12, respectively (P=0.09). Of the patients with low-grade hepatic fibrosis (F0-2) and advanced fibrosis (F3-4), 100% and 85.7% reached SVR12, respectively (P=0.03). In treatment-naïve and treatment-experienced patients, 95.7% and 100% reached SVR12, respectively (P=0.57), without significant differences independent of the treatment group (P=0.28 for SOF/VEL±RBV; P=0.18 for GLE/PIB). The incidence of AEs was 21.1% (95% CI 11.3% to 30.9%). None of the patients developed an SAE or required antiviral treatment withdrawal. Conclusions: SOF/VEL±RBV or GLE/PIB are safe and effective for treating G3-HCV-infections, with a lower effectiveness in patients with advanced fibrosis F3-4.

Effectiveness and safety of direct-acting antivirals in hepatitis C infected patients with mental disorders: Results in real clinical practice.

The aim of this study is to analyze the effectiveness and safety of direct-acting antivirals (DAAs) in psychiatric patients with chronic hepatitis C (CHC). Secondary objectives included adherence and drug-drug interaction (DDIs) evaluations. Prospective observational comparative study carried out during 3 years. Psychiatric patients were included and mental illness classified by a psychiatric team based on clinical records. Main effectiveness and safety variables were sustained virologic response (SVR) at posttreatment week 12 (SVR12) and rate of on-treatment serious drug-related adverse events (AEs), respectively. A total of 242 psychiatric and 900 nonpsychiatric patients were included. SVR12 by intention-to-treat (ITT) analysis of psychiatric vs nonpsychiatric patients was 92.6% (95% confidence interval [CI], 89.1-96.1) vs 96.2% (95% CI, 94.9-97.5) (P = .02). SVR12 by modified-ITT analysis was 97.8% (95% CI, 95.0-99.3) vs 98.4% (95% CI, 97.5-99.3) (P = .74). 92.2% of psychiatric patients with mental disorders secondary to multiple drug use (MDSDU) and 93.0% of psychiatric patients without MDSDU vs 96.2% of nonpsychiatric patients reached SVR12 (P = .05 and P = .20, respectively). The percentage of adherent patients to DAAs did not show differences between cohorts (P = .08). 30.2% of psychiatric patients and 27.6% of nonpsychiatric patients presented clinically relevant DDIs (P = .47). 1.7% vs 0.8% of psychiatric vs nonpsychiatric patients developed serious AEs (P = .39); no serious psychiatric AEs were present. DAAs have shown a slightly lower effectiveness in psychiatric patients with CHC, as a result of loss of follow up, which justifies the need for integrated and multidisciplinary health care teams. DAAs safety, adherence, and DDIs, however, are similar to that of nonpsychiatric patients.

Altered Underlying Renal Tubular Function in Patients With Chronic Hepatitis B Receiving Nucleos(t)ide Analogs in a Real-World Setting: The MENTE Study.

BACKGROUND: Cases of renal tubular dysfunction have been reported in patients with hepatitis B and in patients with human immunodeficiency virus who are undergoing tenofovir treatment. However, little is known about the impact on tubular function in patients with chronic hepatitis B (CHB) under long-term use of entecavir (ETV) and tenofovir disoproxil fumarate (TDF). We evaluated markers of renal tubular function and bone turnover in patients with CHB treated with ETV or TDF. PATIENTS AND METHODS: A multicenter, cross-sectional study was performed on markers of renal tubular function and bone turnover in hepatitis B virus-monoinfected patients on long-term treatment with Entecavir or Tenofovir (the MENTE study). The analyzed parameters were: retinol-binding protein/creatinine, neutrophil gelatinase-associated lipocalin/creatinine, excretion of phosphates, uric acid excretion, glomerular filtrate, protein/creatinine, albumin/creatinine, serum creatinine, phosphate, CTX, P1NP, vitamin D, and parathormone. RESULTS: A total of 280 patients (ETV: 89, TDF: 69, control: 122) were included in this study. The TDF group was associated with altered levels of retinol-binding protein (RBP)/creatinine (TDF 25% vs. 7% ETV and control; P<0.001). Protein/creatinine, uric acid excretion, P1NP1, and parathormone were higher in the TDF group. The proportion of patients with serum phosphate <2.5 mg/dL was higher in both the ETV and the TDF groups compared with the control. The multivariate analysis showed that the use of TDF was independently associated with a higher risk of altered excretion of RBP/creatinine (4.4; interquartile range: 1.4 to 14; P=0.013). CONCLUSIONS: We found an independent association between TDF use and altered RBP excretion. This finding indicates subclinical tubular damage. Because tubular dysfunction can precede the decline of renal function, close monitoring of RBP levels in patients with CHB on nucleos(t)ide analog treatment must be performed for early detection of TDF-related renal toxicity. In this study, these differences in tubular function were not associated with concomitant changes in markers of bone turnover.

[Follow-up of patients with chronic hepatitis B infection with no indication for treatment. Ultrasound follow-up for carriers of the hepatitis B surface antigen]. / Seguimiento de los pacientes con infección crónica por virus B sin indicación de tratamiento. Seguimiento ecográfico en los portadores del antígeno de superficie del virus de la hepatitis B.

Ultrasonography enables us to easily study HBV liver disease progression. The presence of an irregular border in the liver, a hyperechoic pattern and an increase in the size of the caudate lobe are objective signs of cirrhosis. The slowing of the portal flow measured by Doppler echocardiography has a high specificity and sensitivity for establishing the noninvasive diagnosis of portal hypertension. For HBV carriers with no active replication data and no associated liver disease, the periodicity of ultrasound examinations for the early diagnosis of hepatocarcinoma has not been established. One of the limitations of this technique is the interobserver and intraobserver variability. Staff who are assigned to this technique need sufficient experience and dedication.