Prognostic scores in primary biliary cholangitis patients with advanced disease.

BACKGROUND: Due to the chronic progressive disease characteristics of primary biliary cholangitis (PBC), patients with advanced PBC should not be ignored. Most prognostic score studies have focused on early stage PBC. AIM: To compare the prognostic value of various risk scores in advanced PBC to help PBC patients obtain more monitoring and assessment. METHODS: This study considered patients diagnosed with PBC during hospitalization between 2015 and 2021. The clinical stage was primarily middle and late, and patients usually took ursodeoxycholic acid (UDCA) after diagnosis. The discriminatory performance of the scores was assessed with concordance statistics at baseline and after 1 year of UDCA treatment. Telephone follow-up was conducted to analyze the course and disease-associated outcomes. The follow-up deadline was December 31, 2021. We compared the risk score indexes between those patients who reached a composite end point of death or liver transplantation (LT) and those who remained alive at the deadline. The combined performance of prognostic scores in estimating the risk of death or LT after 1 year of UDCA treatment was assessed using Cox regression analyses. Predictive accuracy was evaluated by comparing predicted and actual survival through Kaplan-Meier analyses. RESULTS: We included 397 patients who were first diagnosed with PBC during hospitalization and received UDCA treatment; most disease stages were advanced. After an average of 6.4 ± 1.4 years of follow-up, 82 patients had died, and 4 patients had undergone LT. After receiving UDCA treatment for 1 year, the score with the best discrimination performance was the Mayo, with a concordance statistic of 0.740 (95% confidence interval: 0.690-0.791). The albumin-bilirubin, GLOBE, and Mayo scores tended to overestimate transplant-free survival. Comparing 7 years of calibration results showed that the Mayo score was the best model. CONCLUSION: The Mayo, GLOBE, UK-PBC, and ALBI scores demonstrated comparable discriminating performance for advanced stage PBC. The Mayo score showed optimal discriminatory performance and excellent predictive accuracy.

Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice.

Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.

The Clostridium Metabolite P-Cresol Sulfate Relieves Inflammation of Primary Biliary Cholangitis by Regulating Kupffer Cells.

OBJECTIVE: To study the effect and mechanism of the Clostridium metabolite p-Cresol sulfate (PCS) in primary biliary cholangitis (PBC). METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to detect differences in tyrosine, phenylalanine, tryptophan, PCS, and p-Cresyl glucuronide (PCG) between the serum of PBC patients and healthy controls. In vivo experiments, mice were divided into the normal control, PBC group, and PBC tyrosine group. GC-MS was used to detect PCS and PCG. Serum and liver inflammatory factors were compared between groups along with the polarization of liver Kupffer cells. Additionally, PCS was cultured with normal bile duct epithelial cells and Kupffer cells, respectively. PCS-stimulated Kupffer cells were co-cultured with lipopolysaccharide-injured bile duct epithelial cells to detect changes in inflammatory factors. RESULTS: Levels of tyrosine and phenylalanine were increased, but PCS level was reduced in PBC patients, with PCG showing a lower concentration distribution in both groups. PCS in PBC mice was also lower than those in normal control mice. After oral administration of tyrosine feed to PBC mice, PCS increased, liver inflammatory factors were decreased, and anti-inflammatory factors were increased. Furthermore, Kupffer cells in the liver polarized form M1 transitioned to M2. PCS can damage normal bile duct epithelial cells and suppress the immune response of Kupffer cells. But PCS protects bile duct epithelial cells damaged by LPS through Kupffer cells. CONCLUSIONS: PCS produced by Clostridium-metabolized tyrosine reduced PBC inflammation, suggesting that intervention by food, or supplementation with PCS might represent an effective clinical strategy for treating PBC.

Health-related quality of life questionnaires used in primary biliary cholangitis: a systematic review.

OBJECTIVE: The purpose of this systematic review was to assess the suitability of health-related quality of life (HRQOL) questionnaires in patients with primary biliary cholangitis. METHODS: Relevant studies were compiled from a search of five electronic databases. The properties under investigation included the validity of the translated questionnaires, floor and ceiling effects, internal consistency and test-retest reliability. RESULTS: Forty-four studies were included, from which fifteen HRQOL questionnaires were identified. The most frequently used instruments were the PBC-40 (n = 22), the SF-36 (n = 19), the PBC-27 (n = 4), the CLDQ (n = 3) and the NIDDK-QA (n = 2). The remaining instruments were used only once. Twenty-six studies used a translated HRQOL questionnaire, but only six reported or referenced validating the translated questionnaire. CONCLUSIONS: PBC-specific HRQOL questionnaires generally have good psychometric properties. However, many studies have directly applied HRQOL tools without verifying their validity and reliability in PBC patients. There was no clear indication that one HRQOL tool was superior to another, although the PBC-40 is the most well-studied. Thus, more robust psychometric studies are needed to investigate the measurement properties of HRQOL questionnaires.

Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans.

Purpose: Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the in vivo antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling Candida albicans in the invertebrate Galleria mellonella. Methods: Galleria mellonella larvae were injected with different doses of ZnO-NPs to determine their in vivo toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in G. mellonella followed by C. albicans infection. Then the direct in vitro antifungal effect of ZnO-NPs against C. albicans was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity. Results: Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of C. albicans-infected larvae and decreased the fungal dissemination and burden in the C. albicans-infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae. Conclusion: Prophylactic treatment with lower concentrations of ZnO-NPs protects G. mellonella from C. albicans infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.

Bone marrow mesenchymal stem cells differentiate into intestinal epithelioid cells through the ERK1/2 pathway.

BACKGROUND/AIMS: Previous studies have found that the injection of rat bone marrow mesenchymal stem cells (rBMSCs) in a mouse model of acute hepatic failure significantly relieves intestinal damage and endotoxemia. However, the mechanism of this process remains unknown. This study demonstrated the differentiation of rBMSCs into enterocyte-like cells and possible molecular mechanisms for this with the aim of finding a new treatment for intestinal epithelial injury and endotoxemia during liver failure. MATERIALS AND METHODS: rBMSCs were isolated from rat femurs and tibias. Differentiation was induced by co-culturing rBMSCs with rat intestinal epithelial cells (mIEC-6) using Transwell plates; after three, seven, and ten days of induction, expression of specific differentiation molecules were quantified. To inhibit the activity of the Mitogen-activated protein kinase 1/2 (ERK1/2) signaling pathway, an inhibitor of Mitogen-activated protein kinase kinase 1/2 (MEK1/2) was added to the co-culture medium, and western blot analysis was performed after 36 or 72 h to evaluate the expression of ERK1/2 signaling pathway markers (p-MEK1/2 and p-ERK1/2). RESULTS: The rBMSCs differentiated into enterocyte-like cells when co-cultured with mIEC-6 cells. Inhibition of ERK1/2 signaling abrogated the activity of MEK1/2, but MEK increased after 72 h, and the epithelioid differentiation of rBMSCs was consistent with the change in MEK expression. CONCLUSION: rBMSCs differentiate into intestinal epithelium after co-culture with mIEC-6 by regulation of the ERK1/2 signaling pathway. Further research is needed to elucidate the network of mechanisms.

Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model.

BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our findings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.

The Protective Roles of PPARα Activation in Triptolide-Induced Liver Injury.

Triptolide (TP), one of the main active ingredients in Tripterygium wilfordii Hook F, is clinically used to treat immune diseases but is known to cause liver injury. The aim of this study was to investigate the biomarkers for TP-induced hepatotoxicity in mice and to determine potential mechanisms of its liver injury. LC/MS-based metabolomics was used to determine the metabolites that were changed in TP-induced liver injury. The accumulation of long-chain acylcarnitines in serum indicated that TP exposure disrupted endogenous peroxisome proliferator-activated receptor α (PPARα) signaling. Triptolide-induced liver injury could be alleviated by treatment of mice with the PPARα agonist fenofibrate, whereas the PPARα antagonist GW6471 increased hepatotoxicity. Furthermore, fenofibrate did not protect Ppara-/- mice from TP-induced liver injury, suggesting an essential role for the PPARα in the protective effect of fenofibrate. Elevated long-chain acylcarnitines may protect TP-induced liver injury through activation of the NOTCH-NRF2 pathway as revealed in primary mouse hepatocytes and in vivo. In agreement with these observations in mice, the increase in long-chain acylcarnitines was observed in the serum of patients with cholestatic liver injury compared with healthy volunteers. These data demonstrated the role of PPARα and long-chain acylcarnitines in TP-induced hepatotoxicity, and suggested that modulation of PPARα may protect against drug-induced liver injury.

Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling.

Celastrol, derived from the roots of the Tripterygium Wilfordi, shows a striking effect on obesity. In the present study, the role of celastrol in cholestasis was investigated using metabolomics and transcriptomics. Celastrol treatment significantly alleviated cholestatic liver injury in mice induced by α-naphthyl isothiocyanate (ANIT) and thioacetamide (TAA). Celastrol was found to activate sirtuin 1 (SIRT1), increase farnesoid X receptor (FXR) signaling and inhibit nuclear factor-kappa B and P53 signaling. The protective role of celastrol in cholestatic liver injury was diminished in mice on co-administration of SIRT1 inhibitors. Further, the effects of celastrol on cholestatic liver injury were dramatically decreased in Fxr-null mice, suggesting that the SIRT1-FXR signaling pathway mediates the protective effects of celastrol. These observations demonstrated a novel role for celastrol in protecting against cholestatic liver injury through modulation of the SIRT1 and FXR.

Correlations between VEGF-A expression and prognosis in patients with gastric adenocarcinoma.

Angiogenesis induced by vascular endothelial growth factor A (VEGF-A) plays a critical role in tumor growth and metastasis. The study aimed to evaluate the expression of VEGF-A in gastric adenocarcinoma and investigate its correlations with tumor clinicopathological features and prognostic significance. VEGF-A expression was detected by immunohistochemistry on a tissue microarray containing 90 pairs of human gastric adenocarcinoma and paracancerous tissues. Levels of VEGF-A in gastric adenocarcinoma were significantly higher than those in paracancerous tissues (P=0.018). Furthermore, the result was coincident with that of human gastric adenocarcinoma xenografts in nude-mice (P<0.01). In addition, the VEGF-A expression was positive correlation with TNM stage (P=0.047), tumor size (P=0.028), positive lymph nodes (P=0.002) and lymphovascular invasion (P=0.001). Finally, Kaplan-Meier survival analysis showed that VEGF-A up-regulation indicated a poor prognosis for overall survival (P=0.039). In conclusions, VEGF-A may be used as a biomarker for evaluating both the biological behavior of tumor and the prognosis in patients with gastric adenocarcinoma.

Umbilical cord-derived mesenchymal stem cells inhibit growth and promote apoptosis of HepG2 cells.

Hepatocellular carcinoma is the fifth most common type of cancer worldwide and remains difficult to treat. The aim of this study was to investigate the effects of mesenchymal stem cells (MSCs) derived from the umbilical cord (UC­MSCs) on HepG2 hepatocellular carcinoma cells. UC­MSCs were co­cultured with HepG2 cells and biomarkers of UC­MSCs were analyzed by flow cytometry. mRNA and protein expression of genes were determined by reverse transcription­polymerase chain reaction and flow cytometry, respectively. Passage three and seven UC­MSCs expressed CD29, CD44, CD90 and CD105, whereas CD34 and CD45 were absent on these cells. Co­culture with UC­MSCs inhibited proliferation and promoted apoptosis of HepG2 cells in a time­dependent manner. The initial seeding density of UC­MSCs also influenced the proliferation and apoptosis of HepG2 cells, with an increased number of UC­MSCs causing enhanced proliferation inhibition and cell apoptosis. Co­culture with UC­MSCs downregulated mRNA and protein expression of α­fetoprotein (AFP), Bcl­2 and Survivin in HepG2 cells. Thus, UC­MSCs may inhibit growth and promote apoptosis of HepG2 cells through downregulation of AFP, Bcl­2 and Survivin. US-MSCs may be used as a novel therapy for treating hepatocellular carcinoma in the future.

Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats.

Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis.

Urine and serum metabolomic profiling reveals that bile acids and carnitine may be potential biomarkers of primary biliary cirrhosis.

In order to provide non-invasive, reliable and sensitive laboratory parameters for the diagnosis of primary biliary cirrhosis (PBC), metabolic technology of ultraperformance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to compare small molecule metabolites in blood and urine from patients with PBC and healthy controls. We then screened for bio-markers in the blood and urine of the patients with PBC. Data were processed by Bruker ProfileAnalysis metabonomic software and imported to SIMCA-P software, which utilized principal component analysis (PCA) to create models of patients with PBC and healthy controls. In total, 18 urinary markers were found and the levels of 11 of these urinary markers were elevated in the patients with PBC, whereas the levels of the remaining 7 markers were lower in the PBC group compared to the control group. We also identified 20 blood-based biomarkers in the patients with PBC and the levels of 9 of these markers were higher in the PBC group, whereas the levels of the remaining 11 markers were lower in the patients with PBC compared to the controls. Among these biomarkers, the levels of bile acids increased with the progression of PBC, while the levels of carnitines, such as propionyl carnitine and butyryl carnitine, decreased with the progression of PBC. In conclusion, the findings of the present study suggest that the circulating levels of bile acids and carnitine are differentially altered in patients with PBC.

[Clinical features of patients with primary biliary cirrhosis and anti-SP100 autoantibody positivity].

OBJECTIVE: To evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy. METHODS: The clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test. RESULTS: There was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05). CONCLUSION: SP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Kinetics of phytohemaglutinin-induced IFN-gamma and TNF-alpha expression in peripheral blood mononuclear cells from patients with chronic hepatitis B after liver transplantation.

AIM: To study the association between host immunity and hepatitis B virus (HBV) recurrence after liver transplantation. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation (OLT) before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-gamma and TNF-alpha in culture supernatants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR. RESULTS: The levels of INF-gamma and TNF-alpha in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns (INF-gamma 155.52+/-72.32 ng/L vs 14.76+/-9.88 ng/L vs 13.22+/-10.35 ng/L, F = 6.946, P = 0.027 < 0.05; TNF-alpha 80.839+/-46.75 ng/L vs 18.59+/-17.29 ng/L vs 9.758+/-7.96 ng/L, F = 22.61, P = 0.0001 < 0.05). The levels of INF-gamma and TNF-alpha were higher in groups with phytohemagglutinin (PHA) than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-gamma and TNF-alpha could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated (HBV detected rate: 51.4%, 13.3%, 50% respectively; HBV DNA: 3.55+/-0.674 log10 copies/mL vs 3.00+/-0.329 log10 copies/mL vs 4.608+/-1.344 log10 copies/mL, F = 7.582, P = 0.002 < 0.05). HBV DNA in serum was 4.48+/-1.463 log10 copies/mL before surgery and <10(3) copies/mL after OLT except for one with 5.72 x 10(6) copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-gamma and TNF-alpha were lower in patients with a high HBV load than in those with a low HBV load (HBV DNA detected/undetected in PBMCs: IFN-gamma 138.08+/-72.44 ng/L vs 164.24+/-72.07 ng/L, t = 1.065, P = 0.297 > 0.05, TNF-alpha 80.75+/-47.30 ng/L vs 74.10+/-49.70 ng/L, t = 0.407, P = 0.686 > 0.05; HBV DNA positive/negative: IFN-gamma 136.77+/-70.04 ng/L vs 175.27+/-71.50 ng/L, t = 1.702, P = 0.097 > 0.05; TNF-alpha 75.37+/-43.02 ng/L vs 81.53+/-52.46 ng/L, t = 0.402, P = 0.690 > 0.05). CONCLUSION: The yielding of INF-gamma and TNF-alpha from PBMCs is inhibited significantly by immunosuppressive agents following OLT with HBV load increased, indicating that the impaired immunity of host is associated with HBV recurrence after OLT.

[Early dynamic changes of liver function and its prognostic implications after hepatic transplantation].

OBJECTIVE: To detect the rule of hepatocyte-function change with 1 week following liver transplantation and to select useful parameter to forecast prognosis, we investigated the function of hepatocytes dynamically of patients within 1 week following surgery. METHODS: A retrospective study was undertaken. Data was collected form 149 patients in our hospital from December 1994 to August 2003. AST, ALT, total bilirubin (TB), direct bilirubin (DB), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were examined in the day before operation, 1, 3 and 7 d following surgery. RESULTS: Single peak of all values occurred with 1 week in patients who lived more than 1 month following surgery. The level of FIB, PT and APTT, AST and ALT descended to normal level in 1, 3 and 7 d after liver transplantation respectively. However, double peaks of bilirubin and altered peak of APTT and PT were observed in patients lived less than 1 month after surgery. Furthermore, descents of these values were delayed. Compared with the reversion of patients received classic liver transplantation, that of patients who received piggy back-on liver transplantation showed a slow recovery trend in earlier period after surgery. However, at 7 d following surgery, both can went near to normal level. The level of AST 7 d, DB 1 d and 3 d, PT 1 d following surgery and TB were related closely to the prognosis of patients who underwent liver transplantation. CONCLUSIONS: The levels of ALT, AST, TB, DB, PT, APTT and FIB become normal on the whole within 1 week after liver transplantation. During this period, Single peak of all values occur. Alteration of the hump indicated the occurrence of complications. The shape of hepatic function hump and the level of AST, DB and PT and TB postoperation were useful value to forecast prognosis.

[Evaluation of the changes of HBV serum markers and HBV DNA and the effects of perioperative factors after liver transplantation].

OBJECTIVE: To study the changes of HBV markers and HBV DNA and the perioperative factors influencing them after orthotopic liver transplantation (OLT). METHODS: A retrospective study was undertaken. Data was collected from 97 patients in the First Affiliated Hospital of Sun Yat-sen University from March 1999 to October 2003. Patients were investigated on the 7-14, 14-30, 30-90, 90-180, 180-360 and 360- days after OLT. All the patients who received OLT were serum HBV positive before their operations. RESULTS: Kinetic expressions of HBV serum marker and HBV DNA were established. A few patient's HBeAg was negative (8%) before their operation. Within 7 day following surgery, no patient was HBeAg positive. However, the rate of HBeAg positive increased on the 90-180 day following surgery. The postoperation time of taking lamivudine was different between patients with HBeAg seroconversion and of those without (U = 88.5). Peaks occurred within 14 d of HBsAg negative and 14-30 d of anti-HBs positive after operation. Then they decreased and minimized at 90-180 day after liver transplantation. Patients who suffered more bleeding during the operation were more likely to be anti-HBs positive (3800ml vs. 3000ml, U = 8193.0) and HBsAg negative in serum within 2 week (5200ml vs. 4200ml, U = 1648.5) after OLT. While patient's who received more blood transfusion (1000ml vs. 1600ml, U = 9796.0) during operation were not likely to be anti-HBs positive in serum after surgery. Furthermore, the time of infusing HBIg did not affect the state of anti-HBs (U = 1252.5). At the same time, there were no correlations between the change of HBsAg in serum and in the method of operation (chi2 = 0.042). During this process, presentation of anti-HBc changed a little. CONCLUSION: The advantages brought on by operative factors become blunt 7-14 d following OLT. More attention should be taken to avoid reinfection of HBV 90-180 day after OLT. Tyrosine-methionine-aspartic acid-aspartic acid (YMDD) mutation of HBV is more likely to occur when taking lamivudine longer. Then, HBV DNA should be monitored and a liver biopsy should be scheduled regularly after OLT.