MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort.

BACKGROUND: The rs641738 C > T single-nucleotide polymorphism of MBOAT7 has been associated with hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Latin Americans have high rates of HCC and NAFLD, but no assessment between MBOAT7 and HCC has been performed in this population. AIMS: We provide the first assessment of the impact of MBOAT7 on HCC risk in Latin Americans. METHODS: Patients were prospectively recruited into the ESCALON network, designed to collect samples from Latin American patients with HCC in 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru, and Colombia). A European cohort and the general Hispanic population of gnomAD database were included for comparison. Associations between HCC and MBOAT7 were evaluated using logistic regression. RESULTS: In total, 310 cases of HCC and 493 cases of cirrhosis without HCC were assessed. The MBOAT7 TT genotype was not predictive of HCC in Latin Americans (TT vs CC OR adjusted = 1.15, 95% CI 0.66-2.01, p = 0.610) or Europeans (TT vs CC OR adjusted = 1.20, 95% CI 0.59-2.43, p = 0.621). No significant association was noted on subgroup analysis for NAFLD, viral hepatitis, or alcohol-related liver disease. The TT genotype was increased in the NAFLD-cirrhosis cohort of Latin Americans compared to a non-cirrhotic NAFLD cohort (TT vs CC + CT OR = 2.75, 95% CI 1.10-6.87, p = 0.031). CONCLUSION: The rs631738 C > T allele of MBOAT7 was not associated with increased risk of HCC in Latin Americans or Europeans. An increase in the risk of cirrhosis was noted with the TT genotype in Latin Americans with NAFLD.

Epidemiology and risk factors for histopathologic characteristics of non-alcoholic fatty liver disease in South America.

BACKGROUND: The burden of non-alcoholic fatty liver disease (NAFLD) in South America is among the highest in the world. However, the epidemiology and risk factors for NAFLD are insufficiently described in the region. AIM: To explore the associations between clinical characteristics and histopathological features of NAFLD METHODS: This was a descriptive study of 2722 patients with NAFLD from 8 medical centres across 5 South American countries. We collected clinical, biochemical and histopathological data using a templated chart. Fibrosis was assessed by elastography or fibrosis scores and confirmed with biopsy when available. We examined associations between histopathological features and clinical characteristics with logistic regression models. Models were adjusted for country, age and sex. RESULTS: The median age was 53 years (IQR: 41-62), and 63% were women. Subjects from Brazil had the highest body mass index at 42 kg/m2 . Sixty-seven percent had dyslipidemia, 46% had obesity, 30% had hypertension, 17% had type 2 diabetes mellitus (T2DM) and 34% had metabolic syndrome. Biopsy reports were available for 948 (35%), of which 58% showed fibrosis, 91% steatosis and 65% inflammation; 25% showed significant fibrosis and 27% severe steatosis. Metabolic syndrome, T2DM and hypertension were significantly associated with significant fibrosis (OR = 1.94, p < 0.001; OR = 2.93, p < 0.001 and OR = 1.60, p = 0.003, respectively), severe steatosis (OR = 2.05, p < 0.001; OR = 1.91, p = 0.001 and OR = 2.17, p < 0.001, respectively) and liver inflammation (OR = 1.66, p = 0.007; OR = 2.00, p = 0.002; OR = 1.62, p = 0.001, respectively). CONCLUSIONS: In the largest NAFLD cohort study to date from South America, metabolic syndrome, hypertension and T2DM were independently associated with significant fibrosis, severe steatosis, and inflammation. The prevalence of T2DM was lower than the reported global prevalence.

Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse.

BACKGROUND: Identification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management. STUDY DESIGN: A retrospective analysis of patients diagnosed with EoE from 2011 to 2018 was conducted. Clinical and diagnostic variables including demographics, endoscopic, and esophagram findings were compared between PPI responders and PPI nonresponders. All patients underwent a standard 8-week twice-daily PPI trial, with PPI responsiveness defined as < 15 eos/hpf on repeat EGD. Univariate and multivariable analyses were conducted to identify risk factors for nonresponse, and ROC curves were created to identify cutoff values. RESULTS: A total of 223 EoE patients (135 male, median age 39 (29-51)) were identified, with PPI nonresponse (PPI-NR) in 71% of patients. PPI-NR was seen in all 10 patients with failure of scope passage, with an OR of 9.06 by univariate analysis (P = 0.1485). In a multivariable model, age per 10 years (OR 0.71; P = 0.007), BMI per 1 kg/m2 (OR 0.94; P = 0.03), and peripheral eosinophil count per 100 per mm3 (OR 1.37; P = 0.003) were independent risk factors. Dichotomization to maximize sensitivity and specificity identified age ≤ 36 years old, BMI ≤ 25.2 kg/m2, and peripheral eos > 460 per mm3 as predictive thresholds for PPI-NR. The probability of PPI-NR was 72.4-84.5% with 1 risk factor, 87.9-93.8% with 2 risk factors, and 97.2% with all 3 risk factors. CONCLUSIONS: Young age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.

Depression Outcomes in Smokers and Nonsmokers: Comparison of Collaborative Care Management Versus Usual Care.

Background: Depression is common in the primary care setting and tobacco use is more prevalent among individuals with depression. Recent research has linked smoking to poorer outcomes of depression treatment. We hypothesized that in adult primary care patients with the diagnosis of depression, current smoking would have a negative impact on clinical outcomes, regardless of treatment type (usual primary care [UC] vs collaborative care management [CCM]). Methods: A retrospective chart review study of 5155 adult primary care patients with depression in a primary care practice in southeast Minnesota was completed. Variables obtained included age, gender, marital status, race, smoking status, initial Patient Health Questionnaire-9 (PHQ-9), and 6-month PHQ-9. Clinical remission (CR) was defined as 6-month PHQ-9 <5. Persistent depressive symptoms (PDS) were defined as PHQ-9 ≥10 at 6 months. Treatment in both CCM and UC were compared. Results: Using intention to treat analysis, depressed smokers treated with CCM were 4.60 times as likely (95% CI 3.24-6.52, P < .001) to reach CR and were significantly less likely to have PDS at 6 months (adjusted odds ratio [AOR] 0.19, 95% CI 0.14-0.25, P < .001) compared with smokers in UC. After a 6-month follow-up, depressed smokers treated with CCM were 1.75 times as likely (95% CI 1.18-2.59, P = .006) to reach CR and were significantly less likely to have PDS (AOR 0.45, 95% CI 0.31-0.64, P < .001) compared with smokers in UC. Conclusions: CCM significantly improved depression outcomes for smokers at 6 months compared with UC. However, in the UC group, smoking outcomes were not statistically different at 6 months for either remission or PDS. Also, nonsmokers in CCM had the best clinical outcomes at 6 months in both achieving clinical remission and reduction of PDS when compared with smokers in UC as the reference group.