The association of Human Leukocyte Antigens Complex with Type 1 Diabetes in Omanis

Background: Identifying the human leukocyte antigens (HLA) high risk alleles, genotypes and haplotypes in different populations is beneficial for understanding their roles in type 1 diabetes (T1D) pathogenesis and intervention practices. Objective: The aim of this study was to identify T1D associated HLA gene alleles in the Omani population. Methods: Our case-control study included 73 diabetic seropositive children (mean age 9.08±3.27 years) and 110 healthy controls. HLA–A, -B, -C, -DRB1, and -DQB1 genes were genotyped using sequence specific primer polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, while one class I (B*51) and three class II (DQB1*05, DQB1*06, and DRB1*16) alleles were associated with T1D protection. HLA- DRB1*03 and DQB1*02 alleles showed the strongest risk association among all alleles. Six DRB1 residues (E9, S11, S13, Y30, V70 and K71) were significantly associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and DQB1*02/*03 were significantly associated with T1D susceptibility (P=4.29E-07, OR=63.2 and P=0.02, OR=3.6, respectively). Furthermore, we detected a significant combined action of DRB1*03-DQB1*02 haplotype in T1D risk (P=1.76E-05, OR=15), and DRB1*16-DQB1*05 haplotype in protection (P=3.12E-2, OR=0.48). Conclusion: Known HLA class II gene alleles are associated with T1D in Omani children. Keywords: Type 1 diabetes; human leukocytes antigens; zygosity; alleles; residues; haplotypes, case-control study; Oma

Two-Tier Care Pathways for Liver Fibrosis Associated to Non-Alcoholic Fatty Liver Disease in HIV Mono-Infected Patients

(1) Background: Developing strategies to identify significant liver fibrosis in people with HIV (PWH) is crucial to prevent complications of non-alcoholic fatty liver disease (NAFLD). We aim to investigate if five simple serum biomarkers applied to PWH can optimize a care pathway to identify significant liver fibrosis defined by transient elastography (TE). (2) Methods: A two-tier fibrosis pathway was applied to three prospective cohorts of PWH undergoing TE with CAP. NAFLD was diagnosed as a controlled attenuation parameter ≥ 248 dB/m. Five simple fibrosis biomarkers (FIB-4 < 1.3, BARD score 0–1, NAFLD fibrosis score < −1.455, AST:ALT ratio < 0.8 and APRI < 0.5) were applied as first-tiers to exclude significant liver fibrosis. We determined the decrease in referral for TE that would have occurred based on biomarker assessment and the discordance between low simple fibrosis biomarkers and high TE (≥7.1 kPa), indicating significant liver fibrosis. (3) Results: Of the 1749 consecutive PWH, 15.1% had significant liver fibrosis by TE and 39.1% had NAFLD. The application of the fibrosis biomarkers as first tiers would have resulted in a decrease in TE referrals between 24.9% (BARD score) and 86.3% (APRI). The lowest discordance rate was with NAFLD fibrosis score (8.5%). After adjustments, BMI (odds ratio (OR) 1.12, 95% CI: 1.08–1.17) and triglycerides (OR 1.26, 95% CI: 1.11–1.44) were independent predictors of discordance for APRI < 0.5 and TE ≥ 7.1. The performance of the two-tier pathways was similar in PWH with and without NAFLD. (4) Conclusions: Implementing a two-tier pathway could save a substantial proportion up of TE examinations, reducing costs and helping resource optimization in HIV care. Patients with metabolic risk factors for NAFLD and low fibrosis biomarker may still be considered for TE referral

Two-tier care pathways for liver fibrosis associated to non-alcoholic fatty liver disease in HIV mono-infected patients

(1) Background: Developing strategies to identify significant liver fibrosis in people with HIV (PWH) is crucial to prevent complications of non-alcoholic fatty liver disease (NAFLD). We aim to investigate if five simple serum biomarkers applied to PWH can optimize a care pathway to identify significant liver fibrosis defined by transient elastography (TE). (2) Methods: A two-tier fibrosis pathway was applied to three prospective cohorts of PWH undergoing TE with CAP. NAFLD was diagnosed as a controlled attenuation parameter ≥ 248 dB/m. Five simple fibrosis biomarkers (FIB-4 \u3c 1.3, BARD score 0-1, NAFLD fibrosis score \u3c -1.455, AST:ALT ratio \u3c 0.8 and APRI \u3c 0.5) were applied as first-tiers to exclude significant liver fibrosis. We determined the decrease in referral for TE that would have occurred based on biomarker assessment and the discordance between low simple fibrosis biomarkers and high TE (≥7.1 kPa), indicating significant liver fibrosis. (3) Results: Of the 1749 consecutive PWH, 15.1% had significant liver fibrosis by TE and 39.1% had NAFLD. The application of the fibrosis biomarkers as first tiers would have resulted in a decrease in TE referrals between 24.9% (BARD score) and 86.3% (APRI). The lowest discordance rate was with NAFLD fibrosis score (8.5%). After adjustments, BMI (odds ratio (OR) 1.12, 95% CI: 1.08-1.17) and triglycerides (OR 1.26, 95% CI: 1.11-1.44) were independent predictors of discordance for APRI \u3c 0.5 and TE ≥ 7.1. The performance of the two-tier pathways was similar in PWH with and without NAFLD. (4) Conclusions: Implementing a two-tier pathway could save a substantial proportion up of TE examinations, reducing costs and helping resource optimization in HIV care. Patients with metabolic risk factors for NAFLD and low fibrosis biomarker may still be considered for TE referral

Diagnosis of liver fibrosis in ageing patients with HIV at risk for non-alcoholic fatty liver disease in Italy and Canada: assessment of a two-tier pathway

Background: Since the introduction of effective antiretroviral therapy, liver-related mortality has increased ten-fold in ageing people with HIV. This trend is driven by ageing-related metabolic conditions that cause non-alcoholic fatty liver disease (NAFLD), which affects 35-65% of people with HIV. Clinically significant (stage 2-4) liver fibrosis develops in over 15% of people with HIV who have NAFLD. Strategies are needed to identify people with HIV at risk for significant liver fibrosis and reduce cirrhosis-related complications. Non-invasive tests to diagnose liver fibrosis include ultrasound-based transient elastography and serum biomarkers. Transient elastography is a feasible tool to assess liver fibrosis, but it is not largely accessible in HIV clinics. We aimed to determine whether a two-tier care pathway with assessment of simple serum biomarkers for fibrosis as first tier could reduce the need for the specialist transient elastography test (second tier). Methods: Patients were consecutively identified through a clinical programme for liver disease in people with HIV in Canada and Italy. We applied a two-tier care pathway to three prospective cohorts of people with HIV at risk for NAFLD, defined as those with elevated liver transaminases, body mass index (BMI) of 25 or greater, or diabetes. Patients with alcohol abuse or coinfection with hepatitis B or C viruses were excluded. Five simple serum biomarkers of fibrosis, based on liver transaminases, platelets, and BMI (fibrosis-4 index [FIB-4], BARD [BMI, AST to ALT ratio, diabetes] score, NAFLD fibrosis score, AST to ALT ratio, and AST-to-platelet ratio index [APRI]) were applied as a first-tier assessment to exclude significant liver fibrosis. All patients then received transient elastography. We assessed the decrease in referral for transient elastography that would have occurred based on biomarker assessment and discordance between high transient elastography (≥7·1 kPa), indicating significant liver fibrosis, and low serum fibrosis biomarkers (FIB-4 &lt;1·3, BARD score 0-1, NAFLD fibrosis score less than -1·455, AST to ALT ratio &lt;0·8, and APRI &lt;0·5). We also assessed independent factors associated with that discordance by multivariable logistic regression analysis. Findings: We included 1202 people with HIV at risk for NAFLD (mean age 51·2 years [SD 10·1], 914 [76%] male and 288 [24%] female, mean HIV duration 16·3 years [SE 9·7], mean BMI 26·5 Kg/m2 [SD 4·5]; prevalence of diabetes 49·5%). 222 (18·5%) of these participants had significant liver fibrosis according to transient elastography. Assessment of simple fibrosis biomarkers would have decreased transient elastography referrals between 22·5% (BARD score) and 82·4% (APRI). Discordance rate ranged from 3·9% (NAFLD fibrosis score) to 11·1% (APRI). After adjustment for age, sex, presence of diabetes, level of HDL cholesterol, and CD4 cell count, BMI (odds ratio 1·12, 95% CI 1·07-1·17) and triglyceride level (1·25, 1·08-1·46) were independent predictors of discordance for low APRI and high transient elastography. Interpretation: Use of a two-tier pathway to identify liver fibrosis in ageing people with HIV at risk for NAFLD could reduce transient elastography examinations by a substantial proportion, reducing costs and helping to optimise use of resources in HIV care

Fibroscan-aspartate aminotransferase (FAST) score predicts liver-related outcomes, but not extra-hepatic events, in a multicenter cohort of people with HIV

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is frequent in people with HIV (PWH). The Fibroscan-aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. METHODS: Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from four prospective cohorts. We used FAST>0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extra-hepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. RESULTS: Of the 1472 PWH included, 8% had FAST>0.35. On multivariable logistic regression, higher BMI (adjusted odds ratio [aOR] 1.21, 95% confidence interval [CI] 1.14-1.29), hypertension (aOR 2.24, 95% CI 1.16-4.34), longer time since HIV diagnosis (aOR 1.82, 95% CI 1.20-2.76) and detectable HIV viral load (aOR 2.22, 95% CI 1.02-4.85) were associated with FAST>0.35. 882 patients were followed for a median of 3.8 years (interquartile range 2.5-4.2). Overall, 2.9% and 11.1% developed liver-related and extra-hepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST>0.35 vs. FAST0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio 4.97, 95% CI 1.97-12.51). Conversely, FAST did not predict extra-hepatic events. CONCLUSION: A significant proportion of PWH without viral hepatitis coinfection may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help risk stratification and management in this high-risk population

Fibroscan-aspartate aminotransferase (FAST) score predicts liver-related outcomes, but not extra-hepatic events, in a multicenter cohort of people with HIV

Background: Nonalcoholic fatty liver disease (NAFLD) is frequent in people with HIV (PWH). The Fibroscan-aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. Methods: Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from four prospective cohorts. We used FAST&gt;0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extra-hepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. Results: Of the 1472 PWH included, 8% had FAST&gt;0.35. On multivariable logistic regression, higher BMI (adjusted odds ratio [aOR] 1.21, 95% confidence interval [CI] 1.14-1.29), hypertension (aOR 2.24, 95% CI 1.16-4.34), longer time since HIV diagnosis (aOR 1.82, 95% CI 1.20-2.76) and detectable HIV viral load (aOR 2.22, 95% CI 1.02-4.85) were associated with FAST&gt;0.35. 882 patients were followed for a median of 3.8 years (interquartile range 2.5-4.2). Overall, 2.9% and 11.1% developed liver-related and extra-hepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST&gt;0.35 vs. FAST&lt;0.35 (45.1, 95% CI 26.2-77.7 vs. 5.0, 95% 2.9-8.6 per 1000 person-years). On multivariable Cox regression analysis, FAST&gt;0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio 4.97, 95% CI 1.97-12.51). Conversely, FAST did not predict extra-hepatic events. Conclusion: A significant proportion of PWH without viral hepatitis coinfection may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help risk stratification and management in this high-risk population