Is duodenal biopsy always necessary for the diagnosis of coeliac disease in adult patients with high anti-tissue transglutaminase (TTG) antibody titres?

Objective: Avoiding duodenal biopsy in adults for coeliac disease (CD) diagnosis is controversial. Some retrospective and prospective studies have shown that CD can be reliably diagnosed in adults with serology rather than duodenal biopsies. This study aimed to check the accuracy of a cut-off value of ≥10 upper limit of normal of anti-tissue transglutaminase antibody (anti-TTG IgA) titres for CD diagnosis in adult patients. Method: We retrospectively analysed adult patients (≥16 years) who underwent gastroscopy from 2013 to 2018 for positive coeliac serology. The relationship between titres and disease was determined by using linear models, whereas sensitivity and specificity were assessed by receiver operator curve. Results: We analysed 144 newly anti-TTG antibody-positive adult patients with a median age of 48.5 years (IQR 32-62); among them, 86 (60%) patients had CD (Marsh III: n=68 and Marsh II and I: n=18) with a higher prevalence in females (n=59 (69%)) and Europeans (n=60 (70%)). Fifty (58%) patients with CD had colonoscopy and five (6%) had imaging; only six patients were diagnosed with additional conditions. An anti-TTG IgA titre cut-off value of 150 U/L was 100% specific for CD in our dataset, with 70% (95% CI: 60% to 88%) sensitivity for this patient group. Conclusion: Coeliac serology using anti-TTG IgA with titres ≥10× normal value is an excellent predictor of CD, irrespective of age, gender and ethnicity. Duodenal biopsy may not be necessary in selected adult patients with CD, especially younger than 50 years of age without additional gastrointestinal red-flag signs and symptoms.

Changing ethnic and clinical trends and factors associated with successful home haemodialysis at Auckland District Health Board.

BACKGROUND: The health and diversity of the population in New Zealand (NZ) is changing under the influence of many socio-economic factors. This may have shifted the landscape of home haemodialysis (HHD). AIMS: To examine the demographic and clinical changes, determinants of HHD training and technique outcome and mortality between 2008 and 2015 at Auckland District Health Board, NZ. METHODS: We compared three incident cohorts of HHD patients between 2008 and 2015. Relevant factors, including demographic and clinical characteristics, training failure, technique failure and mortality were recorded. Factors associated with training and technique failure were examined by multivariate logistic regression. RESULTS: Of 152 patients, 133 completed training, 13 (10%) experienced technique failure and 15 (11%) died. Significant changes in ethnicity (increased: Maori 1.7-fold, Asian 1.7-fold and Pasifika 1.4-fold; decreased: NZ European 2.7-fold, P = 0.001), and major comorbidities, ≥2 major comorbidities (1.8-fold increase, P = 0.03), diabetes (2.1-fold increase, P = 0.013) and heart failure (P = 0.04) were seen. HHD as first renal replacement therapy modality increased 15-fold (P = 0.0001) and training time increased by 4.5 weeks (P = 0.004). Death and technique failure were unchanged over time. Shorter training time, employment and lower C-reactive protein were associated with 'Successful HHD'. 'Unsuccessful HHD' patient characteristics differed by ethnicity. CONCLUSIONS: The HHD population has become more representative of the NZ population, but significantly more comorbid over time. Patient training time has increased, but mortality and technique failure remain stable. 'Successful HHD' is predicted by social and clinical factors, and 'unsuccessful HHD' may have different mechanisms in different patient groups.

Adherence to medication, glycaemic control and hospital attendance in young adults with type 2 diabetes.

Type 2 diabetes is becoming common among people in their 20s and 30s. Glycaemic control is suboptimal in this group and is associated with poor medication adherence. We studied medication adherence over a 24-month period in all diabetes clinic registrants (n = 266) between the ages of 18 and 39 years. We reviewed their glycaemic control using mean HbA1c over the study period and examined hospital records to determine the number of hospital attendances during this time. We found that less than half the group (47%) had good adherence (>90%) and 21% of the group had very poor adherence (<50%). Mean adherence was slightly poorer in women compared to men (73% vs 76%, P = 0.04). There was a marked inverse relationship between adherence and glycaemic control. Mean HbA1c is 70 mmol/mol among those with good adherence and mean HbA1c is 97 mmol/mol among those with very poor adherence (P < 0.05). Fifty-seven per cent of the study group had at least one hospital attendance during this time. Eighty-eight hospital attendances were due to a medical cause. Study of trend showed more medical admissions among those with very poor adherence (P = 0.03). Mean HbA1c was higher in those who required medical admissions (87 mmol/mol vs 75 mmol/mol) when compared to those with no hospital attendance. Our study shows that poor adherence is common and significantly related to glycaemic control as well as unplanned hospital attendances for medical conditions. Despite limitations, our study provides valuable information on medication adherence and its impact on glycaemic control and morbidity among young people with type 2 diabetes.

A Pharmacogenetic Approach to the Treatment of Patients With PPARG Mutations.

Loss-of-function mutations in PPARG cause familial partial lipodystrophy type 3 (FPLD3) and severe metabolic disease in many patients. Missense mutations in PPARG are present in ∼1 in 500 people. Although mutations are often binarily classified as benign or deleterious, prospective functional classification of all missense PPARG variants suggests that their impact is graded. Furthermore, in testing novel mutations with both prototypic endogenous (e.g., prostaglandin J2 [PGJ2]) and synthetic ligands (thiazolidinediones, tyrosine agonists), we observed that synthetic agonists selectively rescue function of some peroxisome proliferator-activated receptor-γ (PPARγ) mutants. We report on patients with FPLD3 who harbor two such PPARγ mutations (R308P and A261E). Both PPARγ mutants exhibit negligible constitutive or PGJ2-induced transcriptional activity but respond readily to synthetic agonists in vitro, with structural modeling providing a basis for such differential ligand-dependent responsiveness. Concordant with this finding, dramatic clinical improvement was seen after pioglitazone treatment of a patient with R308P mutant PPARγ. A patient with A261E mutant PPARγ also responded beneficially to rosiglitazone, although cardiomyopathy precluded prolonged thiazolidinedione use. These observations indicate that detailed structural and functional classification can be used to inform therapeutic decisions in patients with PPARG mutations.

Hepatitis C Virus Eradication with New Interferon-Free Treatment Improves Metabolic Profile in Hepatitis C Virus-Related Liver Transplant Recipients.

Interferon (IFN)-free, direct-acting antiviral (DAA) therapy agents provide a safe and efficacious treatment for liver transplant recipients with recurrent hepatitis C virus (HCV) infection. The aim of this study is to evaluate the impact of HCV eradication on the metabolic factors in liver transplant recipients. We completed a retrospective single-center study on HCV-related liver transplant recipients treated with IFN-free DAAs including both treatment-naive and treatment-experienced patients. IFN-free DAAs impact on the metabolic profile were assessed at baseline and sustained virological response (SVR) between 24 and 48 weeks. In total, 91 liver transplant recipients with recurrent HCV infection received IFN-free DAA treatment, 62 patients had IFN-based treatment failure, and 29 were treatment-naïve, of whom 87 (96%) achieved SVR. Eradication of recurrent HCV infection was associated with reduction in the treatment of diabetes and hypertension by 38% and 22% from the baseline respectively. Hemoglobin A1c (HbA1c) levels declined from mean 35.5 ± 4.3 mmol/mol to 33.3 ±3.6 mmol/mol at 44 weeks posttreatment (P = 0.03). Total cholesterol levels increased from 3.8 ± 0.9 mmol/L to 4.9 ± 0.9 mmol/L at 41 weeks posttreatment (P < 0.0001), reflecting a significant increase in serum low-density lipoprotein (LDL) levels (2.0 ± 0.8 to 2.9 ± 0.8; P < 0.0001). Estimated glomerular filtration rate (eGFR) levels increased from 64.9 ± 20 mL/minute to 69.6 ± 20 mL/minute at 24 weeks posttreatment (P = 0.0004). Glucose, lipid profile, and eGFR changes were independent of weight changes and immunosuppression dosage and trough levels. In conclusion, eradication of recurrent HCV infection by DAA therapy has beneficial impacts on glucose metabolism and renal profile and reverses the hypolipidemic effect of HCV in liver transplant recipients. These extrahepatic effects of DAA therapy need to be validated by larger prospective studies.

Type 2 diabetes in young adults in Central Auckland: demography and complications.

BACKGROUND: Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications. AIMS: To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration. METHODS: In total, 310 young adults with T2D (<40 years) were registered with the Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications. RESULTS: Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand-born Pasifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty-four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4-5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001). CONCLUSIONS: New migrants, New Zealand-born Pasifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications.