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.     

Angioinvasive,cutaneous infection due to Colletotrichum siamense in a stem cell transplant recipient: Report and review of prior cases

Colletotrichum is an important fungal plant pathogen, yet an uncommon cause of human disease. Herein we report a case of invasive, cutaneous infection in a stem cell transplant recipient due to Colletotrichum species, with accompanying review of the literature. The infection was successfully treated with a combination of liposomal amphotericin B and voriconazole. Multilocus phylogenetic analysis revealed that the distinct isolate belongs to Colletotrichum siamense, a member of the Colletotrichum gloeosporioides species complex not previously described as a human pathogen. Colletotrichum infection remains in the differential for skin lesions in the immune compromised host.