Genetic variants associated with steatohepatitis and liver fibrosis in HIV-infected patients with NAFLD.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver damage in people living with HIV (PLWHIV). Several studies have investigated candidate genes for susceptibility to NAFLD and to steatohepatitis. PNPLA3, TM6SF2, and MBOAT7-TMC4 have been reported to be associated with elevated ALT levels and the histologic parameters of nonalcoholic steatohepatitis and severity of fibrosis. Our objective was to analyze the relationship between PNPLA3, TM6SF2, and MBOAT7-TMC4 and steatosis, steatohepatitis, and liver fibrosis in PLWHIV with NAFLD. Method: A cohort of PLWHIV with persistently elevated aminotransferase levels and suspected NAFLD who underwent liver biopsy and determination of genetic variants was assessed at two large centers in Spain. All participants included in the current study were genotyped for rs738409 (PNPLA3), rs58542926 (TM6SF2), and rs641738 (MBOAT7-TMC4). Results: The study population comprised PLWHIV who were on stable antiretroviral therapy [7.7% women; median age, 49.3 years (44-53.4)]. The median CD4 count was 829 (650-980), 60% had metabolic syndrome, and 18.5% were diabetic. The median BMI was 28.9 (25.5-30.8). Patients with liver steatosis (any grade) vs. nonsteatosis tended to harbor the PNPLA3 G allele variant [57.6% vs. 16.7% (p = 0.09)], but not TM6SF2 or MBOAT7-TMC4 variants. However, those with steatohepatitis vs. nonsteatohepatitis significantly more frequently had the PNPLA3 G allele variant [69.4% vs. 39.1% (p < 0.05)] and the MBOAT7-TMC4 A allele variant [75% vs. 42% (p < 0.05)]. In our cohort, the TM6SF2 gene variant was not associated with steatosis or steatohepatitis. The PNPLA3 G allele variant was associated with steatohepatitis [OR 4.9 (1.3-18); p 0.02] and liver fibrosis [OR 4.3 (1.1-17.4); p 0.04], and the MBOAT7-TMC4 A allele variant was associated with steatohepatitis [OR 6.6 (1.6-27.6); p 0.01]. Conclusion: The PNPLA3 G allele variant and MBOAT7-TMC4 A allele variant were associated with steatohepatitis and liver fibrosis in PLWHIV with persistently elevated aminotransferases and NAFLD. We recommend routine genotyping for PNPLA3 and MBOAT7-TMC4 in PLWHIV with NAFLD to identify those at higher risk of progression.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods: This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results: Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75-1); CAP, 0.94 (0.88-1); FLI, 0.81 (0.58-1); HSI, 0.74 (0.62-0.87); and TyG, 0.75 (0.49-1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82-1), 0.96 (0.90-1), 0.97 (0.93-1), and 0.85 (0.68-1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97-1, P < .001) and 0.92 (0.77-1, P < .001). Conclusions: Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

Position statement for the management of comorbidities in psoriasis.

BACKGROUND: The association between psoriasis and some diseases has become relevant in recent years. Providing appropriate management of psoriasis from an early stage requires prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat psoriasis potentially related to the onset of comorbidities. OBJECTIVE: To provide the dermatologist with an accurate and friendly tool for systematizing the diagnosis of psoriasis-associated comorbidities, which generally escapes the scope of the dermatology setting, and to facilitate decision-making about the referral and treatment of patients with comorbidities. METHODS: These position statement recommendations were developed by a working group composed of ten experts (four dermatologists, one cardiologist, one rheumatologist, one gastroenterologist, one nephrologist, one endocrinologist and one psychiatrist) and two health services researchers. The expert group selected the psoriasis comorbidities considered according to their relevance in the dermatology setting. The recommendations on diagnostic criteria are based on the current clinical practice guidelines for each of the comorbidities. The information regarding the repercussion of psoriasis medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: Recommendations were developed to detect and refer the following psoriasis comorbidities: psoriatic arthritis, cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), non-alcoholic fatty liver disease, inflammatory bowel disease, kidney disease and psychological disorders (anxiety and depression). In addition, alcohol consumption and tobacco consumption were included. The tables and figures are precise, easy-to-use tools to systematize the diagnosis of comorbidities in patients with psoriasis and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these position statement recommendations will facilitate the dermatologist practice, and benefit psoriasis patients' health and quality of life.

Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients.

BACKGROUND: Some studies have reported a high prevalence of bronchiectasis in patients with uncontrolled asthma, but the factors associated with this condition are unknown. The objective of this study was to determine the prevalence of bronchiectasis in uncontrolled moderate-to-severe asthma and to identify risk factors and their correlation with bronchiectasis in these patients. METHODS: This is a prospective study of data from consecutive patients with uncontrolled moderate-to-severe asthma. Diagnosis of bronchiectasis was based on high-resolution computed tomography. A prognostic score was developed using a logistic regression model, which was used to determine the factors associated with bronchiectasis. RESULTS: A total of 398 patients (60% with severe asthma) were included. The prevalence of bronchiectasis was 28.4%. The presence of bronchiectasis was associated with a higher frequency of chronic expectoration (OR, 2.95; 95% CI, 1.49-5.84; p = 0.002), greater severity of asthma (OR, 2.43; 95% CI, 1.29-4.57; p = 0.006), at least one previous episode of pneumonia (OR, 2.42; 95% CI, 1.03-5.69; p = 0.044), and lower levels of FeNO (OR, 0.98; 95% CI, 0.97-0.99; p = 0.016). The NOPES score was developed on the basis of these variables (FeNO[cut off point 20.5 ppb], Pneumonia, Expectoration and asthma Severity), and it ranges from 0 to 4 points, where 0 means "no risk" and 4 corresponds to "high risk". The NOPES score yielded an AUC-ROC of 70% for the diagnosis of bronchiectasis, with a specificity of 95%. CONCLUSIONS: Almost a third of the patients with uncontrolled moderate-to-severe asthma had bronchiectasis. Bronchiectasis was related to the severity of asthma, the presence of chronic expectoration, a previous history of pneumonia, and lower levels of FeNO. The NOPES score is an easy-to-use scoring system with a high prognostic value for bronchiectasis in patients with uncontrolled moderate-to-severe asthma.

Persistently altered liver test results in hepatitis C patients after sustained virological response with direct-acting antivirals.

Guidelines recommend evaluating persistent alteration of liver tests in HCV-infected patients after sustained virological response (SVR) and its influence on liver disease progression. We studied the prevalence, etiology, associated factors and evolutionary implications of persistent alteration of liver tests in HCV patients after direct-acting antivirals (DAA)-induced SVR. This was a prospective study of HCV-infected patients and SVR after DAA. Those with another previously diagnosed liver disease were excluded. Persistent alteration of liver tests was defined as any increase in ALT, AST or GGT at SVR12 and SVR24. Causes were determined according to standard clinical practice, including liver biopsy and follow-up transient elastography. A total of 1112 patients were included (70.8% males, median age 53 years, 38.8% cirrhosis, 34.9% interferon-experienced, 56.8% HIV-coinfected). Persistent alteration of liver tests was detected in 130/1112 patients (11.7% [95%CI: 9.7-13.6]). Its frequency differed between HCV-monoinfected (45/480: 9.4% [95%CI: 6.7-12.1]) and HIV-coinfected (85/632: 13.5% [95%CI: 10.7-16.2]) (P = .046). In multivariable analysis, cirrhosis (OR 2.12; 95%CI: 1.28-3.53; P = .004) and baseline transient elastography values (OR 1.03; 95%CI: 1.01-1.04; P = .000) were associated with persistent alteration of liver tests. The main etiologies were clinical diagnosis suggestive of nonalcoholic fatty liver disease in 47 (36.2%), alcohol in 30 (23.1%) and drug consumption in 19 (14.6%). Baseline and follow-up transient elastography was performed in 594 patients and showed a significantly different decrease in patients who did or did not have a persistent alteration of liver tests (-21.1% vs -30%, respectively; P = .003), independently of sex, HIV status or baseline TE value. In conclusion, persistent alteration of liver tests is not infrequent after SVR. It is associated with cirrhosis and baseline transient elastography, and the main cause is fatty liver. According to transient elastography changes, persistent alteration of liver tests seems to affect the course of liver disease.

Clinical, Diagnostic, and Therapeutic Implications in Psoriasis Associated With Cardiovascular Disease. / Implicaciones clínicas, diagnósticas y terapéuticas de la psoriasis y enfermedad cardiovascular.

In recent years the concept of psoriasis as a systemic disease has gained acceptance due to its association with numerous comorbid conditions, particularly atherosclerosis and cardiovascular disease. Several studies have shown that patients with psoriasis, especially younger patients and those with more severe forms of psoriasis or with psoriatic arthritis, have a higher prevalence of risk factors and metabolic syndrome, as well as an increased risk of major cardiovascular events such as myocardial infarction, cerebrovascular disease, and peripheral arterial disease. Furthermore, it remains unclear which of the current treatments might be more effective in reducing cardiovascular risk in these patients. It is therefore important for dermatologists to be aware of this increased risk, to be able to detect modifiable risk factors early and, when appropriate, refer patients to other specialists for the prevention of major cardiovascular events.

[Ultrasound-guided biopsy of the pancreas: a multicenter study]. / Punción pancreática ecodirigida: estudio multicéntrico.

OBJECTIVE: Members of "Asociación de Ecografía Digestiva" decided to carry out a multicenter retrospective study on fine-needle aspiration biopsy for pancreatic space-occupying lesions under ultrasonographic guidance and via the percutaneous route in order to assess this technique s performance versus endoscopic ultrasound-guided biopsy. SUBJECTS: 10 hospitals for a total of 222 patients with suspiciously malignant, 8-120-mm pancreatic lesions were included in the study. RESULTS: The analysis of results shows a sensitivity of 89%, a specificity of 98%, a positive predictive value of 99%, and a negative predictive value of 74%, for an overall diagnostic accuracy of 91%. No major complications occurred. CONCLUSION: Percutaneous fine-needle aspiration for pancreatic lesions is highly cost-effective and has few and mild complications.

Lithogenic risk factors for renal stones in patients with Crohn's disease.

OBJECTIVES: Calcium oxalate kidney stones are more common in patients with Crohn's disease (CD). The aims of this study were to verify the prevalence of the main risk factors for calcium oxalate nephrolithiasis in patients with CD and to evaluate the degree of urinary relative supersaturation for calcium oxalate (CaOx), dihydrogen uric acid (DHUA) and monohydrogen calcium phosphate (MHCaP). SUBJECTS AND STUDY PROTOCOL: 42 patients with CD (22 male and 20 female, aged 15-72 years) and 18 controls (8 male and 10 female, aged 26-65) were studied. Nine patients were evaluated during an active episode and 33 in a quiescent phase. All patients had normal glomerular filtration rate. All subjects collected a 24-hr urine sample and fasting venous blood was drawn. Good compliance of urine collection was assessed by the Cockcroft and Gault formula. In urine pH and oxalate (Ox), calcium (Ca), phosphate (P), uric acid (UA), citrate (Cit), magnesium (Mg), sulphate (Sulph), sodium, potassium and chloride concentrations were measured and their excretions calculated. Urinary RS index was obtained using the software EQUIL93. RESULTS: A decreased urinary volume (61.9%) was the most frequent finding. A decreased excretion of Cit, Mg and Sulph (38.1%, 31.0% and 31.0%, respectively) and increased excretion of P, Ox, UA and Ca (33.3%, 23.8%, 16.7% and 14.3%, respectively) were found. Thirty four patients (81.0%) showed at least 2 lithogenic risk factors and only 2 patients showed none. Urine of patients had a higher urinary CaOx and DHUA relative super saturation. Patients studied in an active episode showed a higher urinary CaOx and MHCaP RS than those studied in the quiescent period. CONCLUSIONS: The majority of patients with CD have a multifactorial high risk for calcium oxalate and a single patient usually has several metabolic disturbances which are more evident in an active episode.

Hydrogastric sonography in the preoperative staging of gastric cancer.

PURPOSE: Depth of wall invasion is the main prognostic factor in gastric cancer. We studied the utility of hydrogastric sonography in the evaluation of transmural infiltration by gastric cancer. METHODS: Thirty-seven patients with gastric adenocarcinoma were examined before surgery with a 5-MHz probe after the ingestion of 100-400 ml of water (mean, 330 ml). Sonographic results were compared with pathologic classifications obtained after surgery. RESULTS: Of the 37 tumors, 15 were found at surgery to be in the antrum, 10 were in the gastric body, 5 were proximal, and 7 were diffuse. After surgery, tumors were classified as follows: 2 (5%) T1, 4 (11%) T2, 15 (41%) T3, and 16 (43%) T4. Hydrogastric sonography correctly classified 30 (81%) of the 37 tumors. Sonography was correct for 2 (100%) of the 2 T1 tumors, 2 (50%) of the 4 T2 tumors, 13 (87%) of the 15 T3 tumors, and 13 (81%) of the 16 T4 tumors. Five sonographic errors were due to understaging and 4 to overstaging. With regard to tumor site, sonographic results were correct for 4 (57%) of the 7 diffuse tumors, 3 (60%) of the 5 proximal tumors, 9 (90%) of the 10 gastric body tumors, and 14 (93%) of the 15 antral tumors. CONCLUSIONS: Hydrogastric sonography is useful for preoperative evaluation of transmural infiltration by gastric cancers, particularly tumors in the antrum or gastric body.

[Usefulness of abdominal echography in the diagnosis of active Crohn's disease]. / Utilidad de la ecografía abdominal en el diagnóstico de la enfermedad de Crohn en actividad.

OBJECTIVE: The aim of this study was to evaluate the relevance of the ultrasonography in assessing activity in a series of patients with Crohn's disease. PATIENTS AND METHODS: A series of 24 patients with active (Crohn's disease activity index > 150) ileal or ileocolonic Crohn disease underwent abdominal ultrasonography. RESULTS: There was a significant correlation between bowel wall thickening and the Crohn's disease activity index: the higher the bowel wall thickening was the higher were the values of Crohn's disease activity index. Two or more ultrasound studies were performed in 10 patients with bowel wall > 4 mm during treatment, and a progressive normalization of bowel wall size was observed with new thickening when recurrence occurred. CONCLUSIONS: A bowel wall thickening (> or = 4 mm) was found in patients with active Crohn's disease. A patient with bowel wall thickness > 6 mm should make us suspect the presence of stenosis. Abdominal ultrasonography is an accurate method in the first assessment of Crohn's disease because its high correlation with the Crohn's disease activity index.