Role of Functional IFNL4, IFNLR1, IFNA,IFNAR2 Polymorphisms in Hepatitis B virus‐related liver disease in Han Chinese population

Recent studies show that variants in some interferon genes together with interferon receptor genes are associated with the outcome of infectious diseases. We examined the association between the risk of hepatitis B virus (HBV)‐related liver disease and the functional polymorphisms within IFNL4, IFNLR1, IFNA1, IFNA2, IFNA5 and IFNAR2 genes (14 loci in all) in a Han Chinese population. A total of 3128 people participated and were divided into 5 groups: healthy controls, natural clearance, chronic hepatitis B(CHB), liver cirrhosis and hepatocellular carcinoma (HCC). Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with HBV infection, and IFNLR1‐rs4649203 was associated with HBV recovery. Moreover, we demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with HCC. Three SNPs in IFNL4 gene may be important susceptible factors for the progression of HBV‐related liver disease by trend chi‐square test. The IFNL4 haplotype conformed by rs12971396_G, rs8113007_T and rs7248668A was more frequent in HCC than CHB and LC group. Three polymorphisms in the 5′ region of the IFNL4 gene are associated with the progression of HBV‐related liver disease. IFNA1‐ rs1831583 and IFNA2‐ rs649053 are associated with the development of HCC. IFNLR1‐ rs4649203, rs7525481 are predictors for HBV infection, and rs4649203 is a predictor of spontaneous clearance. IFNAR2 ‐rs1051393, rs12233338 may be predictive markers of HBV infection in the Chinese population.     

Role of IFN‐λs,IFN‐λs related genes and the DEPDC5 gene in Hepatitis B virus‐related liver disease

Recent studies have associated genetic variation near the interleukin 28B (IL28B/IFN‐λ3) gene with natural clearance of the hepatitis C virus (HCV) infection, and a common variant in the DEP domain containing 5 (DEPDC5) locus on chromosome 22 has been shown to affect susceptibility to hepatocellular carcinoma (HCC) in Japanese individuals with chronic HCV infection. This study was conducted to determine whether polymorphisms near or in interferon‐lambda (IFN‐λs) genes and their receptor genes such as interleukin 28 receptor, alpha (IL28RA) and interleukin 10 receptor, beta (IL10RB) as well as p21_activated kinases 4 (PAK4) and iron/zinc purple acid phosphatase‐like protein (PAPL), which are locate upstream of IFN‐λs, and lastly the DEPDC5 gene are associated with hepatitis B virus‐related liver disease in Han Chinese. The study subjects included 507 normal healthy controls, 350 individuals with natural clearance of HBV and 792 HBV‐infected patients. The patients were categorized into 157 inactive carriers (Case I), 216 active carriers (Case II), 111 cirrhotics (Case III) and 308 HCC patients (Case IV) subgroups. Seven single nucleotide polymorphisms (SNPs) were genotyped using the Matrix‐assisted Laser Desorption/Ionisation mass spectrometric (MALDI‐TOF MS) SNP genotyping assay. Rs423058 upstream of PAPL, rs2834167 in IL10RB and rs1012068 in DEPDC5 were associated with chronic HBV status, HBV natural clearance and the presence of HCC (P = 0.0004–0.024), respectively. PAPL, IL10RB and DEPDC5 polymorphisms have an impact on progression of HBV‐related liver disease. However, IFN‐λs genes as a tool to differentiate between different clinical courses of HBV infection were not useful in the Han Chinese population.     

Measurements of immature platelets with haematology analysers are of limited value to separate immune thrombocytopenia from bone marrow failure

Detection of immature platelets in the circulation may help to dissect thrombocytopenia due to platelet destruction from bone marrow failure (BMF ). We prospectively tested the predictive value of immature platelets, measured as immature platelet fraction (IPF ) on the XE‐5000 (Sysmex, Kobe, Japan) or percentage of reticulated platelets (rPT ) on the CD Sapphire (Abbott Diagnostics, Santa Clara, CA, USA) to separate immune thrombocytopenia (ITP ) from BMF (leukaemia, myelodysplastic syndrome, aplastic anaemia). We analysed 58 samples of patients with BMF , 47 samples of patients with ITP and 97 controls. Median rPT (CD Sapphire) was increased to 9·0% in ITP and to 10·9% in BMF , compared to 1·9% in controls. Median IPF (XE‐5000) was 16·2% in ITP , 10·2% in BMF and 2·5% in controls. We found an inverse correlation between high fractions of immature platelets and low platelet counts in thrombocytopenic samples regardless of the diagnosis. In conclusion, we observed a broad overlap of immature platelets between ITP and BMF , which may be caused by an accelerated release of immature platelets in any thrombocytopenic state and decreased production in many patients with ITP . Despite this, IPF (XE‐5000) had some power to discriminate ITP from BMF , whereas rPT (CD Sapphire) was of no predictive value.     

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 Pāsifika 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 Pāsifika 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.