Wey-Ran Lin

Distinct Patterns of the Lipid Alterations between Genotype 1 and 2 Chronic Hepatitis C Patients after Viral Clearance

Background The hepatitis C virus (HCV) genotype-specific impacts on the host metabolic alterations remained inconclusive. Methods A prospective study including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) ≥2.5). Paired t-tests were used to compare the pre- and post-treatment variables. Results Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR) but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001) and apolipoprotein A1 (p = 0.012) were only found in G2, whereas increased triglyceride/HDL (p = 0.01) ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019) and apolipoprotein A1 (p = 0.012) but a decrease in HOMA-IR (p = 0.04), C-peptide (p = 0.019) and hemoglobin A1c (p = 0.047) were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002) was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01) but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041) and triglyceride (p = 0.044) levels than G2 patients. Conclusions G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR.

Granulocyte colony-stimulating factor reduces fibrosis in a mouse model of chronic pancreatitis.

Background Chronic pancreatitis (CP) is a necroinflammatory process resulting in extensive pancreatic fibrosis. Granulocyte colony-stimulating factor (G-CSF), a hematopoietic stem cell mobilizer, has been shown to exert an anti-fibrotic effect partly through the enrichment of bone marrow (BM) cells in fibrotic organ. We aimed to test the effect of G-CSF on fibrosis in a mouse model of CP. Methods CP was induced in C57Bl/6J mice by consecutive cerulein injection (50 µg/kg/day, 2 days a week) for 6 weeks. Mice were then treated with G-CSF (200 µg/kg/day, 5 day a week) or normal saline for 1 week, and sacrificed at week 7 or week 9 after first cerulein injection. Pancreatic histology, pancreatic matrix metallopeptidase 9 (MMP-9), MMP-13 and collagen expression were examined. Pancreatic myofibroblasts were isolated and cultured with G-CSF. Collagen, MMP-9 and MMP-13 expression by myofibroblasts was examined. The BM-mismatched mice model was used to examine the change of BM-derived myofibroblasts and non-myofibroblastic BM cells by G-CSF in the pancreas. Results The pancreatic collagen expression were significantly decreased in the G-CSF-treated group sacrificed at week 9. While collagen produced from myofibroblasts was not affected by G-CSF, the increase of MMP13 expression was observed in vitro. There were no effect of G-CSF in the number of myofibroblasts and BM-derived myofibroblasts. However, the number of non-myofibroblastic BM cells and macrophages were significantly increased in the pancreata of cerulein- and G-CSF-treated mice, suggesting a potential anti-fibrotic role of non-myofibroblastic BM cells and macrophages stimulated by G-CSF. Conclusions Our data indicated that G-CSF contributed to the regression of pancreatic fibrosis. The anti-fibrotic effects were possibly through the stimulation of MMP-13 from myofibroblasts, and the enhanced accumulation of non-myofibroblastic BM cells and macrophages in the pancreas.

Development of a fibrosis index including hepatitis B virus basal core promoter A1762T mutation for pretherapeutic evaluation: A fibrosis score including BCP A1762T

Commonly used non‐invasive fibrosis scores usually included serum transaminase levels in the equations, including Aspartate transaminase to Platelet Ratio Index (APRI) and fibrosis‐4 (FIB‐4). Transaminases fluctuated significantly in chronic hepatitis B patients with exacerbations, leading to unsteady score values. As such, here, we aim to develop a transaminase‐free score suitable for pretherapeutic evaluation of fibrosis stages.

Prognostic Stratification of Advanced Gastric Signet Ring Cell Carcinoma by Clinicopathological Factors and GALNT14 Genotype

Background: Gastric signet ring cell carcinoma (SRCC) is a histologic variant characterized by abundant intracytoplasmic mucin. Although it has been recognized that gastric adenocarcinoma harboring this feature has poorer prognosis, prognostic stratification within gastric SRCCs themselves has not been clearly defined. N-acetylgalactosaminyltransferase14 (GALNT14) genotype has been associated to poorer treatment outcome in mucinous type colorectal cancer. Here we incorporated clinicopathological factors and GALNT14 genotype to stratify prognosis of advanced gastric SRCC. Methods: Totally 347 gastric SRCC patients were retrospectively enrolled for GALNT14 genotyping. Clinicopathological factors were included for prognosis stratification. Results: Of the 347 patients, 341 underwent radical-intent gastrectomy and 6 received palliative gastrectomy. Kaplan-Meier analysis for overall survival indicated that Tumor-Node-Metastasis staging could only stratify the patients into three prognosis-distinguishable groups: group-1 (stage IA); group-2 (stage IB/IIA) and group-3 (the remaining Tumor-Node-Metastasis stages combined). Multivariate Cox-proportional hazard models for group-3 patients revealed GALNT14 “TT” genotype (P = 0.0482). Tumor size (P = 0.0009), node status (P <0.0001), metastasis status (P = 0.0096), and perineural invasion (P = 0.037) independently associated with unfavorable OS. Exploratory subgroup analysis showed that GALNT14”TT” genotype was associated with unfavorable OS in SRCCs with more aggressive phenotypes: node status >0 (P = 0.0013), lymphatic invasion (P = 0.021), vascular invasion (P = 0.0076) and perineural invasion (P = 0.0161). Accordingly, a scoring system was established capable of stratifying advanced gastric SRCC patients into three distinguishable prognostic subgroups. Conclusions: Gastric SRCC could be stratified into different prognostic subgroups by combining clinicopathological factors and GALNT14 genotype.

Combinations of single nucleotide polymorphisms WWOX‐rs13338697, GALNT14‐rs9679162 and rs6025211 effectively stratify outcomes of chemotherapy in advanced hepatocellular carcinoma

A genome‐wide association study (GWAS) had identified a single nucleotide polymorphism (SNP), GALNT14‐rs9679162, capable of predicting chemotherapy responses in advanced hepatocellular carcinoma (HCC). Here, we revisited the GWAS database to search for necessary SNPs that could improve our outcome prediction.

Clinical characteristics of cytomegalovirus colitis: a 15-year experience from a tertiary reference center

Background Cytomegalovirus (CMV) colitis is considered rare in immunocompetent patients. Objective The predictors of mortality and the differences between immunocompetent and immunocompromised patients with this disease remain unknown. Thus, the aim of this retrospective cohort study was to clarify these issues. Patients and methods We enrolled all patients who were histologically diagnosed with CMV colitis between April 2002 and December 2016 in the Linkou Chang Gung Memorial Hospital. Patients were divided into two groups: immunocompetent and immunocompromised, and the differences between them were analyzed to develop in-hospital mortality predictors. Results A total of 69 patients (42, immunocompetent; 27, immunocompromised) were enrolled. The most common symptoms were melena in the immunocompetent group and diarrhea in the immunocompromised group. The in-hospital mortality rate showed no statistically significant difference between the two groups (26.2% vs 25.9%, P=0.981). Early diagnosis was the only significant independent predictor of in-hospital mortality (odds ratio [OR] 1.075, 95% CI 1.005–1.149, P=0.035). The cutoff of diagnostic timing was 9 days from admission, derived from the receiver operating characteristic curve using the Youden index. Conclusion CMV colitis in immunocompetent patients is markedly more common and fatal than has generally been acknowledged. Being alert to different ways in which this disease can present itself will enable early diagnosis and significantly reduce mortality.