Serum microRNAs as predictors for liver fibrosis staging in hepatitis C virus‐associated chronic liver disease patients

Accurate staging of liver fibrosis is important for clinical decision making and personalized management. Liver fibrosis is influenced by patients’ genomics, including IFNL3 genotype and microRNA expression. However, incorporating microRNAs into fibrosis prediction algorithms has not been investigated. We examined the potential of eight selected serum microRNAs; miR‐122, miR‐126, miR‐129, miR‐199a, miR‐155, miR‐203a, miR‐221, and miR‐223 as non‐invasive biomarkers to stage liver fibrosis in HCV‐associated chronic liver disease (HCV‐CLD). 145 Egyptian HCV‐CLD patients were divided according to Metavir fibrosis scores. MicroRNAs and IFNL3 rs12979860 genotype were assayed by RT‐qPCR and allelic discrimination techniques, respectively. Serum miR‐122 was downregulated, whereas miR‐203a and miR‐223 were upregulated in significant fibrosis (≥F2) compared with no/mild fibrosis (F0‐F1). Serum miR‐126, miR‐129, miR‐203a, and miR‐223 were upregulated in severe fibrosis (≥F3) and cirrhosis (F4) compared with F0‐F2 and F0‐F3, respectively. miR‐221 was upregulated in ≥F3, but unchanged in F4. miR‐155, miR‐199a, and IFNL3 rs12979860 genotype were not significantly different in all comparisons. Differentially expressed serum microRNAs discriminated ≥F2, ≥F3, and F4 by receiver‐operating‐characteristic analysis. Multivariate logistic analysis revealed a model combining miR‐129, miR‐223, AST, and platelet count with high diagnostic accuracy for ≥F3 (AUC=0.91). The model also discriminated F4 (AUC=0.96) and ≥F2 (AUC=0.783), and was superior to APRI and FIB‐4 in discriminating ≥F3 and F4, but not ≥F2. In conclusion, combining serum microRNAs with baseline predictors could serve as a new non‐invasive algorithm for staging HCV‐associated liver fibrosis. Additional studies are required to confirm this model and test its significance in liver fibrosis of other etiologies.     

More improvement than progression of liver fibrosis following antiretroviral therapy in a longitudinal cohort of HIV‐infected patients with or without HBV and HCV co‐infections

We examined the effect of combination antiretroviral therapy (cART) on liver fibrosis among HIV‐infected patients with or without hepatitis B (HBV) or C virus (HCV) co‐infection. This was a retrospective cohort study of HIV‐infected patients receiving cART during 2004‐2016. Liver fibrosis was assessed using Fibrosis‐4 (FIB‐4) score with three classifications: Class 1, <1.45; Class 2, 1.45‐3.25; Class 3, >3.25. Of 3900 participants, 68.6% were HIV mono‐infected, 5.3% were HIV/HBV co‐infected, 23.8% were HIV/HCV co‐infected and 2.3% were HIV/HBV/HCV co‐infected. Participants received follow‐up treatment (median was 3.3 years). Improvement to a lower class was observed in Class 2 (52.6%) and Class 3 (74.2%), respectively. Progression to a higher class was observed in 12.8% and 5.0% in Class 1 and Class 2, respectively, and with a median time of 5.7 months. For improvement to lower classes, older age, male, Dai ethnicity, injection drug use, HCV co‐infection and tenofovir for treatment were negative predictors, but in Class 3 of FIB‐4 and time‐updated increases in CD4 count from baseline were positive predictors. For progression to higher classes, older age, male, Jingpo ethnicity and HCV co‐infection were positive predictors, while baseline CD4 count and in Class 2 of FIB‐4 were negative predictors. Improvement to lower class linked with decreased mortality risk among patients in Class 3. Early cART initiation for HIV‐infected patients with and without hepatitis co‐infections may mitigate or slow down some of liver fibrosis, but special attention should be given to those who are older, male, co‐infected with HCV.     

Fatal Burkholderia gladioli infection misidentified as Empedobacter brevis in a lung transplant recipient with cystic fibrosis

Data describing the risk of lung transplantation (LT), clinical features, and outcomes of patients with cystic fibrosis (CF) infected with Burkholderia gladioli are limited. Herein, we report a case of disseminated B. gladioli infection characterized by bacteremia, necrotizing pneumonia, lung abscess, and empyema in a lung transplant recipient with CF, highlight the importance of accurate microbiological identification, and review published outcomes of LT in CF patients infected with B. gladioli, which include cases of pneumonia, tracheobronchitis, bacteremia, and abscesses, and demonstrate an all‐cause 1‐year mortality of approximately 23%, often after combined medical and surgical treatment.     

Idiopathic pulmonary fibrosis: an Australian perspective

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a dismal median survival of 3 years. Patients typically develop progressive dyspnoea and increasing exercise limitation. With a rising incidence and prevalence, an unpredictable disease course and limited treatment options, it is rapidly becoming an important public health concern. To date, lung transplantation has been the sole viable hope for treatment for those who qualify. However, the landscape of idiopathic pulmonary fibrosis management is changing, with the recent emergence of novel pharmacotherapy shown to have a favourable influence on the natural history of this disease.     

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.