ALT小于2倍正常上限的HBeAg阴性慢性HBV感染者肝脏病理改变及相关因素分析

目的探讨ALT小于2倍正常值上限(upper limits of normal,ULN)的HBeAg阴性慢性HBV感染者中与肝脏病理学改变相关的临床指标。方法将60例ALT2×ULN的HBeAg阴性慢性HBV感染者按照不同肝脏炎症程度及纤维化程度分组,对比各组患者性别比例、年龄、血清ALT、HBV DNA定量、脾脏厚度、门静脉内径、肝脏瞬时弹性探测仪(FibroScan)测定肝硬度值(liver stiffness measurement,LSM)的变化情况。结果 60例患者肝脏炎症改变在G1~G3级,纤维化程度在S0~S2期,其中≥G2、达S2者分别为49例(81.7%)、19例(31.7%)。60例患者中,随着肝脏炎症及纤维化程度的加重,男性患者比例、年龄、脾脏厚度、门静脉内径、LSM值均明显增加,差异均有统计学意义(P均0.05);血清ALT水平、HBV DNA定量随肝脏炎症程度的加重亦明显增加,差异均有统计学意义(P均0.05),但以上两指标随肝脏纤维化程度的加重无明显变化。结论对于ALT2×ULN的HBeAg阴性慢性HBV感染者,仍然有相当部分患者的肝脏病变在G2或/和S2以上,对于这部分人群,尤其是男性患者,密切随访年龄、血清ALT、HBV DNA、脾脏厚度、门静脉内径、LSM值的变化对于协助了解肝脏病理变化有一定的提示作用。     

Effects of sodium-glucose co-transporter-2 inhibitors on serum alanine aminotransferase levels in people with type 2 diabetes: A multi-institutional cohort study

Clinical trials have indicated that sodium-glucose co-transporter-2 (SGLT2) inhibitors have a favourable effect on serum alanine aminotransferase (ALT) levels in people with type 2 diabetes (T2D), but supporting evidence from real-world studies is lacking. We identified patients with T2D who initiated SGLT2 inhibitors during the period 2016 to 2017 from Chang Gung Research Database, which covers 1.3 million individuals from seven hospitals (6% of the Taiwan population). We classified patients by baseline ALT level and evaluated changes in ALT values from baseline to 1 year after initiation of SGLT2 inhibitors. We identified 11 690 new users of SGLT2 inhibitors with a mean (SD) age of 59.3 (11.8) years. The mean (SD) glycated haemoglobin and ALT levels were 8.9 (1.7)% and 34.7 (28.9) U/L at baseline, respectively. The mean change in ALT levels was −5.0 U/L (95% confidence interval [CI] –6.4, −3.5) 1 year after initiation of SGLT2 inhibitors. In patients with ALT levels ≤1× the upper limit of normal (ULN), the change in ALT levels was 1.6 U/L (95% CI –0.1, 3.4), while in those with ALT levels >1× ULN, the change in ALT levels was −26.5 U/L (95% CI –28.6, −24.3). The higher the baseline ALT level, the greater the decline after SGLT2 inhibitor treatment. Our findings suggest the initiation of SGLT2 inhibitors for T2D management could improve serum ALT levels in clinical practice, particularly in patients with especially high ALT levels.     

Non-Viral Related Liver Enzymes Elevation After Kidney Transplantation

Background:

Liver enzymes elevations (LEE) can be observed after kidney transplantation due to multifactorial causes.

Objectives:

We performed a retrospective study on 1589 kidney transplants, 971 male and 618 female, who were hepatitis B surface antigen (HBsAg) and hepatitis C virus-antibody (HCV Ab) negative, and had no other liver diseases, to detect the prevalence of LEE and its risk factors in these patients between May 2008 and May 2010.

Patients and methods:

Liver enzymes and other biochemical parameters were measured in all recipients. Patients were divided into three groups, according to laboratory test time since transplantation: Group I, less than 3 months, Group II, 4 - 12 months after transplantation, and Group III, more than one year post-transplantation.

Results:

The highest LEE was more frequent in older patients (P < 0.001) and male individuals (P < 0.001). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in patients who received kidneys from deceased donors (10.4% and 23.8%, respectively) as compared to living donor transplants (5.6% and 14.8%, respectively) (P < 0.001). The elevation of ALT was the liver enzyme abnormality after kidney transplantation with the highest prevalence (34.3%). The levels of ALT and AST were significantly elevated within the first 3 months after transplantation, followed by the 4-12 months period (P < 0.001). There was a reverse correlation between liver enzyme levels and renal allograft function in both univariate and linear regression analyses. This correlation increased over time. There was also a significant relation between cyclosporine blood levels and liver enzyme values in the univariate analysis. However, this relationship was attenuated over time. Elevated liver enzymes also correlated with anemia.

Conclusions:

The LEE is a common finding among kidney transplant recipients. Serial monitoring of aminotransferases, particularly ALT, should be performed in all patients after kidney transplantation.     

口腔医院住院患者丙型肝炎病毒感染现状分析

目的：研究口腔医院感染丙型肝炎病毒（hepatitis C virus,HCV）的住院患者在性别、年龄、年份、病种上的分布及感染者的肝功能状况。方法：收集2008-2012年在南京医科大学附属口腔医院进行过丙肝抗体检测的住院病人的数据,按性别、年龄及检测年份的不同分组比较丙肝抗体的阳性率,并观察丙肝抗体阳性病人的病种情况。分析丙肝抗体阳性病人的丙氨酸氨基转移酶（alanine aminotransferase,ALT）和天门冬氨酸氨基转移酶（aspartate aminotransferase,AST）数据,以期了解感染者的肝功能状况。结果：口腔医院住院患者抗-HCV阳性率为0．25％,低于文献中所述的一般人群3．2％的抗．HCV阳性率流行率;住院患者抗-HCV阳性病人的肝功能异常率为53．33％,较乙型肝炎表面抗原（hepatitis B surface antigen,HBsAg）阳性患者17．77％肝功能异常率有显著性提高（X^2=9．11,P〈0．01）。结论：对口腔患者术前和创伤性治疗前的抗。HCV的检测能及早发现HCV感染者;同时口腔医院的医护员工需加强对病人和自身的保护,严格消毒操作器械,防止HCV的医院内传播;HCV感染者需定期进行肝功能检查,防止肝脏的损伤。     

Longitudinal changes of the laboratory data of chronic hepatitis C patients with sustained virological response on long-term follow-up

There is no study that follows up longitudinal changes in laboratory data of patients with C-viral chronic liver disease (C-CLD) who achieved sustained virological esponse (SVR) with interferon treatment in a long-term study. We investigated the laboratory data in a long-term retrospective cohort study of 581 patients with C-CLD who underwent liver biopsy between January 1986 and December 2005. 467 were treated with interferon and 207 of these patients achieved SVR with follow-up periods of 8.36 ± 5.13 years. Alanine aminotransferase (ALT) levels, albumin levels, platelet counts, and the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values were serially examined during the follow-up period. None of the 207 patients with SVR exhibited hepatitis C virus (HCV) RNA positivity more than 6 months after the end of IFN treatment. Platelet counts and albumin levels increased only in those with eradication of HCV. APRI values decreased more in patients with SVR than in those with nonsustained virological responses (non-SVR). Patients who achieved SVR and had fibrosis stage 0-1 and 2-4 at enrolment had platelet counts that longitudinally increased by 2.81 ± 3.95 and 5.49 ± 4.53 × 10(3) /μL during the 10-year follow-up period, respectively. Albumin levels continuously increased during the first 2 years by 0.15 ± 0.31 and 0.33 ± 0.37 in fibrosis stage 0-1 and 2-4, respectively and then plateaued. ALT levels decreased rapidly one year after the start of treatment by 110.3 ± 140.0 and 100.5 ± 123.4 in fibrosis 0-1 and 2-4, respectively. HCV RNA negativity persisted in all patients with SVR, and laboratory data including APRI longitudinally improved during the long-term follow-up period.     

Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa‐2a/ribavirin

Summary. It is unclear whether the current threshold for ‘high’ hepatitis C virus (HCV) RNA level (800 000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono‐infected and 176 HIV–HCV co‐infected patients treated with peginterferon alfa‐2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono‐infected patients, the difference in SVR rates between those with low and high baseline HCV RNA levels was 27% (70%vs 43%) when 400 000 IU/mL was used and 16% (59%vs 43%) when 800 000 IU/mL was used. In HIV–HCV genotype 1 co‐infected patients, the difference was 51% (71%vs 20%) when 400 000 IU/mL was used and 43% (61%vs 18%) when 800 000 IU/mL was used. A lower threshold (200 000 IU/mL) was identified for genotype 1 mono‐infected patients with ‘normal’ alanine aminotransferase (ALT) levels. No threshold could be identified in HCV genotype 2 or 3 patients. A threshold HCV RNA level of 400 000 IU/mL is optimal for differentiating high and low probability of SVR in genotype 1‐infected individuals with elevated ALT.     

Arginase and α‐smooth muscle actin induction after hyperoxic exposure in a mouse model of bronchopulmonary dysplasia

The L‐arginine/NO pathway is an important regulator of pulmonary hypertension, the leading cause of mortality in patients with the chronic lung disease of prematurity, bronchopulmonary dysplasia. L‐arginine can be metabolized by NO synthase (NOS) to form L‐citrulline and NO, a potent vasodilator. Alternatively, L‐arginine can be metabolized by arginase to form urea and L‐ornithine, a precursor to collagen and proline formation important in vascular remodelling. In the current study, we hypothesized that C3H/HeN mice exposed to prolonged hyperoxia would have increased arginase expression and pulmonary vascular wall cell proliferation. C3H/HeN mice were exposed to 14 days of 85% O₂ or room air and lung homogenates analyzed by western blot for protein levels of arginase I, arginase II, endothelial NOS (eNOS), ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and α‐smooth muscle actin (α‐SMA). Hyperoxia did not change arginase I or eNOS protein levels. However, arginase II protein levels were 15‐fold greater after hyperoxia exposure than in lungs exposed to room air. Greater protein levels of ODC and OAT were found in lungs following hyperoxic exposure than in room air animals. α‐SMA protein levels were found to be 7‐fold greater in the hyperoxia exposed lungs than in room air lungs. In the hyperoxia exposed lungs there was evidence of greater pulmonary vascular wall cell proliferation by α‐SMA immunohistochemistry than in room air lungs. Taken together, these data are consistent with a more proliferative vascular phenotype, and may explain the propensity of patients with bronchopulmonary dysplasia to develop pulmonary hypertension.     

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

Amino acid signatures in the developing mouse retina

This study characterizes the developmental patterns of seven key amino acids: glutamate, γ-amino-butyric acid (GABA), glycine, glutamine, aspartate, alanine and taurine in the mouse retina. We analyze amino acids in specific bipolar, amacrine and ganglion cell sub-populations (i.e. GABAergic vs. glycinergic amacrine cells) and anatomically distinct regions of photoreceptors and Müller cells (i.e. cell bodies vs. endfeet) by extracting data from previously described pattern recognition analysis. Pattern recognition statistically classifies all cells in the retina based on their neurochemical profile and surpasses the previous limitations of anatomical and morphological identification of cells in the immature retina. We found that the GABA and glycine cellular content reached adult-like levels in most neurons before glutamate. The metabolic amino acids glutamine, aspartate and alanine also reached maturity in most retinal cells before eye opening. When the overall amino acid profiles were considered for each cell group, ganglion cells and GABAergic amacrine cells matured first, followed by glycinergic amacrine cells and finally bipolar cells. Photoreceptor cell bodies reached adult-like amino acid profiles at P7 whilst Müller cells acquired typical amino acid profiles in their cell bodies at P7 and in their endfeet by P14. We further compared the amino acid profiles of the C57Bl/6J mouse with the transgenic X-inactivation mouse carrying the lacZ gene on the X chromosome and validated this animal model for the study of normal retinal development. This study provides valuable insight into normal retinal neurochemical maturation and metabolism and benchmark amino acid values for comparison with retinal disease, particularly those which occur during development.