EHMT2 promotes the pathogenesis of hepatocellular carcinoma by epigenetically silencing APC expression.

BACKGROUND: Hepatocellular carcinoma (HCC), the second leading cause of cancer death worldwide, alone accounts for over half (466,100) of new cancer cases and 422,100 deaths based on the average year incidence rates of 2009 to 2011 in China. Due to unclear and complex underlying mechanisms for HCC development, effective therapy for HCC is still unavailable. The Wnt-ß-catenin pathway is a critical contributor of HCC pathogenesis: 40-70% of HCCs from patients harbor the nuclear accumulation of ß-catenin protein. However, the mechanisms for ß-catenin activation are not fully understood. METHODS: The deletion of EHMT2 in Hep3B and Huh1 cells was achieved by transiently transfecting cells with pX459 plasmids, which carry EHMT2 specific small guide RNA (sgRNA) sequences for Cas9 protein. All experiments were performed in triplicate and repeated more than three times. RESULTS: In the present study, we observed that EHMT2 (but not EHMT1) mRNA and protein levels were significantly elevated in HCC compared with normal controls. Next, the results of Ki67 staining, as well as MTT, soft-agar and xenograft assays, in wild-type and EHMT2-/- Hep3B and Huh1 cancer stem cells collectively revealed that the elevation of EHMT2 expression is required for the tumorigenesis of HCC. Meanwhile, we found that elevated EHMT2 expression contributes to the activation of Wnt-ß-catenin signaling: deletion of EHMT2 in Hep3B or Huh1 cells promoted the cytoplasmic localization of ß-catenin and restrained the expression of Wnt-ß-catenin signaling targets such as Myc, CCND1, MMP-7, etc. We demonstrated that EMHT2 directly mediates the H3K9me2 methylation of the APC promoter to epigenetically silence its expression. More intriguingly, our findings also showed that UNC0642, a specific inhibitor of EHMT2, exhibits anti-tumorigenesis effects in HCC both in vitro and in vivo, which were largely abolished by deletion of EHMT2 or overexpression of APC in Hep3B and Huh1 cells. CONCLUSION: Altogether, our observations emphasize that the EHMT2-APC axis is a critical contributor to Wnt-ß-catenin pathway activation in HCC, and UNC0642 may be a potential candidate for target drug treatment of HCC.

Preliminary single-center experience of Helicobacter pylori eradication among the liver transplant recipients.

OBJECTIVE: To investigate the prevalence of Helicobacter pylori infection among orthotopic liver transplant (LT) recipients and explore the efficacy and safety of H. pylori eradication therapy. METHODS: Liver transplant recipients receiving regular follow-up in our center were assessed by 13C-urea breath test between February 2018 and July 2020. A group of healthy tested patients were selected as control group at a rate of 1:3. All LT recipients with H. pylori were recommended to receive eradication therapy with bismuth-containing quadruple therapy (BQT), which included esomeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + bismuth 220 mg, twice daily for 14 days. RESULTS: The prevalence of H. pylori infection among the LT recipients was 19.6% (30/153), which was significantly lower than the control group (30/153 [19.6%] vs. 200/459 [43.6%], p < 0.001). In LT recipients who received transplantation at <1 year, 1-3 years, and >3 years, the prevalence of H. pylori infection was 10.6% (5/47), 17.5% (10/57), and 30.6% (15/49), respectively, which increased with the time after transplantation (p = 0.04). With BQT, the eradication rate of H. pylori was 91.3% (21/23). During the process of eradication, the blood trough concentration of immunosuppressants increased from 1.7 to 3.6 times, and reducing the dose of the drugs to one-third of what they were before the eradication therapy could avoid excessively elevated concentration of immunosuppressants. Adverse effects occurred in 55.2% (11/23), of the LT recipients and 21.0% (42/200) of the control group (p < 0.01), which was probably caused by the increased blood concentration of immunosuppressants. Normal liver function was observed, while transient abnormal kidney function was occurred in one recipient. CONCLUSION: The prevalence of H. pylori infection was 19.6% among the LT recipients, which increased with the postoperative time. With BQT, H. pylori eradication was safe and effective in LT recipients.

Chronic atrophic gastritis and Helicobacter pylori infection status in liver transplant recipients.

AIM: To investigate the abnormalities of the upper gastrointestinal tract in liver transplant (LT) recipients, especially the prevalence of Helicobacter pylori infection and the incidence of chronic atrophic gastritis (CAG), and to explore the efficacy and safety of H pylori eradication treatment. METHODS: Endoscopic screening was performed prospectively on LT recipients who received regular follow-up in our center. A group of healthy subjects with same age and sex was selected as a control group at a ratio of 1:3 with propensity score matching. All H pylori-positive recipients received Bismuth-containing quadruple therapy (esomeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + bismuth 220 mg, all of the medicines were applied twice daily, for 14 days). RESULT: The prevalence of H pylori infection was significantly lower in LT group than control group [12/102 (11.8%) vs 98/306 (32.0%), P < .001], whereas the prevalence of CAG was similar between the two groups [48/102 (47.1%) vs 138/306 (45.1%), P = .731]. Meanwhile, the incidence of reflux esophagitis [18/102 (17.6%) vs 31/306 (10.1%), P = .043] and bile regurgitation [19/102 (18.6%) vs 30/306 (9.8%), P = .018] were higher in LT group. No correlation between the incidence of upper gastroduodenal abnormalities and postoperative time after liver transplantation was found. The success rate of H pylori eradication therapy was 100% (10/10). The blood concentration of immunosuppressants was 1.7-3.6 times above baseline values during H pylori eradication therapy; however, no severe adverse effects were observed during the proceed with dose adjustments of the immunosuppressants. CONCLUSION: Although the prevalence of H pylori infection was lower in LT recipients than in control subjects, the prevalence of CAG was like that of the general population. H pylori eradication therapy was safe and effective after liver transplantation in our preliminary study.

Somatic Mutation Profiling of Intrahepatic Cholangiocarcinoma: Comparison between Primary and Metastasis Tumor Tissues.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) exhibited increasing incidence and mortality around the world, with a 35% five-year survival rate. In this study, the genetic alteration of primary ICC and metastasis ICC was exhibited to discover novel personalized treatment strategies to improve the clinical prognosis. METHODS: Based on 153 primary and 49 metastasis formalin-fixed paraffin-embedded ICC samples, comprehensive genomic profiling was carried out. RESULTS: In primary tumor samples (PSs) and metastasis tumor samples (MSs), the top alteration genes were TP53 (41.8% vs 36.7%), KRAS (30.7% vs 36.7%), and ARID1A (22.2% vs 14.2%). In the top 20 most frequent alteration genes, BRAF showed lower mutation frequency in MSs as compared to PSs (0 vs 11.1%, P=0.015), while LRP1B exhibited opposed trend (22.4% vs 10.4%, P=0.032). In PSs, patients with MSI-H showed all PDL1 negative, and patients with PDL1 positive exhibited MSS both in PSs and MSs. It was found that the Notch pathway had more alteration genes in MSI-H patients (P=0.027). Furthermore, the patients with mutated immune genes in PSs were more than that in MSs (28.8% vs 8.2%, P=0.003, odd ratio = 0.2). Interestingly, the platinum drug resistance pathway was only enriched by mutated genes of MSs. CONCLUSIONS: In this study, the identification of two meaningful mutated genes, BRAF and LRP1B, highly mutated immune gene harbored by primary ICC patients. Both in PSs and MSs, no patients with MSI-H showed PDL1 positive. The Notch pathway had more alteration genes in patients with MSI-H. And the enrichment of the platinum drug resistance pathway in MSs might offer reference for the novel therapeutic strategy of ICC.

NLRP3 inflammasome is involved in nerve recovery after sciatic nerve injury.

The activation of the inflammasome plays an important role in the central nervous system. However, only a few studies have investigated the effects of inflammasome activation in the peripheral nerve, especially in the sciatic nerve, and the mechanism of this activation remains elusive. Moreover, how interleukin-1 beta (IL-1ß) is produced after sciatic nerve injury is also unknown. In our study, we aimed to investigate whether the nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) inflammasome is activated after sciatic nerve injury and to explore its role in sciatic nerve injury. The results of immunoblotting and immunofluorescence microscopy indicate that the NLRP3 inflammasome was activated after sciatic nerve injury in wild-type (WT) mice, as demonstrated by upregulated inflammasome-related components, e.g., NLRP3, procaspase-1 and ASC. Furthermore, upregulated inflammasome-related components cis-cleavage precursor IL-1ß (proIL-1ß) and precursor interleukin-18 (proIL-18) to IL-1ß and IL-18, contributing to the inflammatory response. Consequently, the inflammatory response after sciatic nerve injury in NLRP3 knockout (NLRP3-KO) mice was less severe than that in WT mice. Moreover, NLRP3-KO mice exhibited an increased sciatic functional index (SFI), which was determined by footprint analysis, suggesting that NLRP3 deficiency is beneficial to sciatic nerve recovery after injury. Therefore, our results indicate that NLRP3 is involved in the recovery from sciatic nerve injury and mediates the production of inflammatory factors, such as IL-1ß, after sciatic nerve injury.

Combination of liver graft sonographic grading and point shear wave elastography to reduce early allograft dysfunction after liver transplantation.

OBJECTIVE: To analyze the performance of a liver graft sonographic grading system and point shear wave elastography (PSWE) in predicting early allograft dysfunction (EAD) after liver transplantation (LT). METHODS: Successive brain-dead donors and liver recipients in our hospital from March 2017 to May 2018 were retrospectively recruited. All donors underwent PSWE examination, abdominal ultrasonography, and sonographic grading (grade 0 to grade 5). Donors with ≥ 10 valid PSWE examinations and a failure rate of < 60% were included. For all recipients, abdominal ultrasonography and blood tests for biologic parameters were performed preoperatively and daily postoperatively to screen for EAD. The recipients and their grafts were classified into EAD and non-EAD groups. Statistical analyses were performed to analyze the correlations among liver stiffness (LS), liver graft sonographic grading, and EAD. RESULTS: Thirty-two donors and 32 corresponding liver recipients were enrolled (15 cases in the EAD group; 17 in the non-EAD group). There were no grade 0, 1, or 2 cases in the two groups. For prediction of EAD in recipients after LT, the AUC for PSWE was 0.929 and the AUC for combination of PSWE and sonographic grading system was 0.935. CONCLUSIONS: Combination of PSWE and sonographic grading system can predict postoperative EAD in LT recipients with high sensitivity. Abnormal results may suggest a need for liver biopsy preoperatively, thus avoiding unnecessary surgical preparation for liver procurement. KEY POINTS: • Combination of PSWE with new sonographic grading system is useful for preoperative evaluation of liver grafts from brain-dead donors. • EAD is as a criterion for evaluating the diagnostic value of PSWE and sonographic grading system. • Combination of PSWE and sonographic grading system can predict postoperative EAD in LT recipients with high sensitivity.

Transient elastography for assessment of fibrosis and steatosis of liver grafts from brain-death donors.

BACKGROUND: An objective and accurate evaluation of liver grafts is required to improve the prognosis of liver transplant recipients and to increase the number of available liver grafts. AIM: To compare outcomes using FibroScan with that of pathology in liver grafts from brain-dead donors (DBD). METHODS: Liver grafts from 52 DBD were examined using ultrasound (US), FibroScan before liver transplantation (LT). Blood tested before LT and a biopsy was performed pre- or intra-operation to determine pathology. The diagnostic accuracy of the FibroScan results was compared with the pathology results, which is the gold standard for evaluating liver grafts. The donors enrolled were grouped by the stage of liver fibrosis (F0-F4) and steatosis (S0-S3), based on Kleiner's scoring system of nonalcoholic fatty liver disease, respectively. RESULTS: The liver stiffness (LS) value in group F1 was significantly increased compared with group F0 (8.74±1.32kPa and 5.93±1.64kPa, respectively, P<0.01). The LS value had a significant positive correlation with the liver graft fibrosis stage (r=0.73, P<0.01). The area under receiver operating characteristic curves (AUROC) for F1 stage fibrosis was 0.93 (P<0.01). Significant differences in the controlled attenuation parameter (CAP) were found among groups S0, S1, and S2 (173.30±38.36dB/m, 230.29±23.27dB/m, 250.00±57.01dB/m, respectively; F=12.41, P<0.01). The CAP was associated with the liver graft steatosis stage (r=0.64, P<0.01). The AUROC for S1 and S2 stage steatosis in liver grafts was 0.89 (P=0.002) and 0.83 (P=0.007), respectively. CONCLUSIONS: Transient elastography quantifies fibrosis and steatosis in liver grafts from 52 DBD with a high diagnostic accuracy and provides further imaging evidence for use in assessing liver grafts.

Cross-regulation by TLR4 and T cell Ig mucin-3 determines severity of liver injury in a CCl4-induced mouse model.

Acute liver injury is a common pathological basis for a variety of acute liver diseases in the clinic, which can eventually lead to liver fibrosis and even liver failure. In this study, we found that T cell Ig and mucin domain protein 3 (Tim-3) and TLR4 receptors play important roles in CCl4-induced acute liver injury. Tim-3 is a negative regulator that is expressed by T cells and macrophages. Using antibodies against Tim-3 (anti-Tim-3 Ab), we studied the Tim-3 signal in an animal model of acute liver injury and found that a large number of inflammatory factors were upregulated. In vitro experimental data shown that anti-Tim-3 Ab treatment increased interferon-É£ production by concanavalin A (ConA)-stimulated spleen T cells, and we found that the expression level of interleukin (IL)-6 was increased in a macrophage/spleen T cell coculture system, while administration of galectin-9 (Gal-9, a Tim-3 ligand) reduced the IL-6 production. This indicates the importance of the Tim-3/Gal-9 signalling pathway in maintaining hepatic homeostasis. The Tim-3 signalling pathway inhibits TLR4-mediated NF-κB activity, and an anti-Tim-3 Ab does not affect the liver injury in TLR4-deficient mice. Regulation between Tim-3 and TLR4 determines the severity of liver damage. The negative regulation of Tim-3 reflects the protective mechanisms of patients with impaired liver function, and these results provide important information about innate and adaptive responses in the regulation of liver damage. This finding is potentially important for the study of early liver injury.

Macrophage transcriptome modification induced by hypoxia and lactate.

The production of lactate under hypoxic conditions or by cancer cells was reported to promote the M2 polarization of tumor-associated macrophages. However, the exact effect of lactate on macrophages, particularly under hypoxic conditions, has remained largely elusive. In the present study, an in-depth bioinformatics analysis of previously published transcriptome data of macrophages was performed. A total of 6, 101 and 764 upregulated genes were identified in the lactate, hypoxia and hypoxia-lactate groups, respectively, whereas 4, 41 and 588 genes were downregulated in the same respective groups. Furthermore, differentially expressed genes (DEGs) of the hypoxia and hypoxia-lactate groups were significantly enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway and the Hedgehog pathway. Upregulation of the mTOR and Hedgehog pathways in the hypoxia-lactate group was identified by gene set enrichment analysis. Furthermore, a set of HIF-1 pathway-associated genes was identified to be positively correlated with hypoxia using weighted gene co-expression network analysis. Lactate was indicated to inhibit the cell cycle in a hypoxia-independent manner. The DEGs of the hypoxia and hypoxia-lactate groups, including C-C motif chemokine receptor type 1 and 5, were enriched in the cytokine-cytokine receptor interaction pathway. In conclusion, under normoxic conditions, lactate exerted a weak effect on macrophages, while the combination of lactate and hypoxia markedly promoted the M2-polarization of macrophages via the HIF-1, Hedgehog and mTOR pathways. Lactate and hypoxia may also contribute to the formation of the spatial structure of tumor niches by inhibiting the proliferation of resident macrophages and by regulating the recruitment of peripheral macrophages.

The Effect of Splenectomy on the Reversal of Cirrhosis: a Prospective Study.

BACKGROUND: Studies have demonstrated that liver fibrosis can be reversed by medication treatments. After splenectomy, cirrhosis patients have short-term changes in several serum markers for cirrhosis and liver stiffness. AIMS: To investigate the effect of splenectomy on the severity of cirrhosis. METHODS: A total of 62 patients with cirrhosis and portal hypertension receiving splenectomy from December 2014 to July 2017 were enrolled. The degree of cirrhosis was preoperatively and postoperatively evaluated by serum markers, including hyaluronan (HA), laminin, amino-terminal propeptide of type III procollagen (PIIINP), type IV collagen (C-IV), liver stiffness (FibroScan), and liver volume. RESULTS: HA levels significantly increased at 1 week and 1 month postoperation (both P < 0.05), whereas the levels of PIIINP and C-IV significantly decreased from 1 month to 12 months postoperation (all P < 0.05). In addition, elastography examination demonstrated that the FibroScan score significantly reduced from 1 month to 24 months postoperation as compared with the baseline level (all P < 0.05). CT scan showed that the liver volume significantly increased at 6 months postoperation (P < 0.05). Furthermore, the alteration trends of these serum markers and the FibroScan score were further confirmed by the multivariate linear regression. CONCLUSIONS: These observations suggested that splenectomy may result in long-term reversal of cirrhosis.

Laparoscopic splenectomy for littoral cell angioma of the spleen: A case report.

RATIONALE: Littoral cell angioma (LCA) is a rare primary vascular neoplasm of the spleen. It can be benign or malignant. Pathology and immunohistochemistry are the gold standards for the diagnosis of LCA. Therefore, splenectomy is recommended for the purpose of diagnosis and treatment, and subsequent follow-up is necessary. There are limited reports about LCA. Here, we present a case of a female patient with LCA undergoing laparoscopic splenectomy in order to provide clinical experience in LCA treatment. PATIENT CONCERNS: A 32-year-old female attended the outpatient Department of Hepatobiliary Surgery for follow-up of hepatic hemangiomas. The patient presented with intermittent abdominal distension, which was slightly under no obvious inducement. DIAGNOSIS: Physical examination found no signs of abdominal tenderness and rebound tenderness, and liver and spleen were impalpable. The contrast-enhanced computed tomography (CT) showed multiple space-occupying lesions in the spleen, mottled low-density lesions, multiple hypoattenuating nodules with no contrast enhancement on the arterious phase. Delayed contrast-enhanced helical CT scan displayed incomplete filling of hypodense splenic lesions. INTERVENTIONS: Given that it was uncertain whether it was a benign or a malignant tumor, a laparoscopic total splenectomy was performed. OUTCOMES: The final pathological diagnosis was LCA. Her postsurgical course was uneventful, and no surgery-related complications were found. No signs of recurrence were observed in the 16 months after the operation. LESSONS: LCA was a rare primary vascular neoplasm of the spleen, and laparoscopic splenectomy for LCA was safe and feasible, and postoperative course was uneventful. However, regular follow-up and long-time monitoring after splenectomy for LCA is recommended because of its potential malignant biological behavior.

A novel HBx genotype serves as a preoperative predictor and fails to activate the JAK1/STATs pathway in hepatocellular carcinoma.

BACKGROUND & AIMS: Genetic variability in the hepatitis B virus X gene (HBx) is frequently observed and is associated with hepatocellular carcinoma (HCC) progression. However, a genotype classification based on the full-length HBx sequence and the impact of genotypes on hepatitis B virus (HBV)-related HCC prognosis remain unclear. We therefore aimed to perform this genotype classification and assess its clinical impact. METHODS: We classified the genotypes of the full-length HBx gene through sequencing and a cluster analysis of HBx DNA from a cohort of patients with HBV-related HCC, which served as the primary cohort (n = 284). Two independent HBV-related HCC cohorts, a validation cohort (n = 171) and a serum cohort (n = 168), were used to verify the results. Protein microarray assay analysis was performed to explore the underlying mechanism. RESULTS: In the primary cohort, the HBx DNA was classified into 3 genotypes: HBx-EHBH1, HBx-EHBH2, and HBx-EHBH3. HBx-EHBH2 (HBx-E2) indicated better recurrence-free survival and overall survival for patients with HCC. HBx-E2 was significantly correlated with the absence of liver cirrhosis, a small tumor size, a solitary tumor, complete encapsulation and Barcelona Clinic Liver Cancer (BCLC) stage A-0 tumors. Additionally, HBx-E2 served as a significant prognostic factor for patients with BCLC stage B HCC after hepatectomy. Mechanistically, HBx-E2 is unable to promote proliferation in HCC cells and normal hepatocytes. It also fails to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3)/STAT5 pathway. CONCLUSION: Our study identifies a novel HBx genotype that is unable to promote the proliferation of HCC cells and suggests a potential marker to preoperatively predict the prognosis of patients with BCLC stage B, HBV-associated, HCC. LAY SUMMARY: We classified a novel genotype of the full-length hepatitis B virus X gene (HBx), HBx-E2. This genotype was identified in tumor and nontumor tissues from patients with hepatitis B virus-related hepatocellular carcinoma. HBx-E2 could preoperatively predict the prognosis of patients with intermediate stage hepatocellular carcinoma, after resection.

Fatigue and its associated factors in liver transplant recipients in Beijing: a cross-sectional study.

OBJECTIVES: Fatigue is a highly prevalent symptom experienced by patients who underwent the liver transplantation. However, the influencing factors of fatigue are poorly understood by healthcare professionals. The aim of this study was to examine the intensity, interference, duration and prevalence of fatigue in liver transplantation recipients and to explore the influencing factors of post-transplantation fatigue. DESIGN: A cross-sectional design was used in this study. METHODS: A convenience sample of liver transplant recipients was recruited at an outpatient transplant clinic of a general hospital in Beijing, China. Self-report survey data were provided by liver transplant recipients using the Fatigue Symptom Inventory (FSI), the Hospital Anxiety and Depression Scale (HADS), the Perceived Social Support Scale (PSSS) and the Athens Insomnia Scale (AIS). Demographic, clinical and psychosocial parameters were evaluated as fatigue influencing factors. RESULTS: Participants (n=285) included 69 women and 216 men. Fatigue was found in 87.0% of liver transplant recipients. Mean scores of fatigue intensity items were 4.47±2.85, 1.93±1.97, 3.15±2.13 and 2.73±2.42 (most fatigue, least fatigue, average fatigue in the week prior to assessment and fatigue at the point of assessment). The mean score of fatigue interference was 2.27±2.09.The number of days fatigued in the week prior to assessment was 2.26±2.02 and the amount of time fatigued each day was 2.75±2.44. Spearman's correlation analysis showed that fatigue intensity was positively associated with anxiety, depression and insomnia (p<0.001 for all), while fatigue interference was positively associated with gender, anxiety, depression and insomnia (p<0.05 for all). In the multiple linear regression analysis, anxiety and insomnia were positively associated with fatigue intensity (p<0.001), and insomnia, depression and anxiety were positively associated with fatigue interference (p<0.001). CONCLUSIONS: Fatigue is common in liver transplant recipients, and it is strongly associated with insomnia, anxiety and depression.

miR-744 is a potential prognostic marker in patients with hepatocellular carcinoma.

Identification of new biomarkers for aggressiveness of hepatocellular carcinoma (HCC) to supplement the current group of prognosis algorithms is a significant clinical need. To clarify expression levels of microRNA-744 (miR-744) in HCC tissues and to explore its clinicopathological significance in HCC patients following liver transplantation (LT), we quantified miR-744 using real-time quantitative reverse transcription polymerase chain reaction in 96 paired cancerous tissues and para-cancerous normal liver tissues. We investigated relationships among miR-744 expression, clinicopathological parameters, and overall survival (OS). Of 96 paired samples, 68 cancer tissues expressed low miR-744 compared with their matched normal liver tissues. Patients with microvascular invasion or multi-tumor nodules showed significantly lower miR-744 expression; miR-744 was further decreased in patients with post-LT HCC recurrence compared with non-recurring patients. Patients with lower miR-744 expression showed significantly poorer recurrence-free survival and OS than individuals with higher miR-744 levels. Multivariate analysis revealed that lower miR-744 was an independent predictor of poor prognosis. Our results associate decreased miR-744 expression with HCC recurrence and prognosis, and also suggest that miR-744 is an independent predictor of survival in HCC patients after LT and may therefore be a potential biomarker for their prognosis.

Pathotyping and clinical manifestations of biliary cast syndrome in patients after an orthotopic liver transplant.

OBJECTIVES: To summarize the pathotyping and clinical manifestations of biliary cast syndrome in patients after an orthotopic liver transplant. MATERIALS AND METHODS: The clinical manifestations, auxiliary examination, therapeutic regimen, and clinical efficacy of 103 biliary cast syndrome patients who underwent an orthotopic liver transplant were retrospectively analyzed. Patients were divided into 6 groups from type 1 to type 6, according to the injury level of the biliary duct epithelium. RESULTS: Many biliary cast syndrome patients showed symptoms including jaundice, dark urine, argillaceous stool, itchy skin, and fever. Serum levels of alanine aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin were increased. In addition, total white cell counts in peripheral blood also were increased. T-tube cholangiography showed filling defects of various amounts. Optical fiber choledochoscope examination revealed that the biliary tract was filled with solid substances, and necrosis of the biliary tract epithelium was observed in some biliary cast syndrome patients. From type 1 to type 6 biliary cast syndrome patients, the probability of clinical symptoms and biliary tract stricture gradually increased, the time needed for supporting gradually prolonged after removal of the biliary cast, and T-tube cholangiography showed that the filling defects gradually expanded. CONCLUSIONS: Clinical manifestations and cholangiography presentations mainly depend on pathotyping.

Pediatric liver transplantation in 31 consecutive children.

BACKGROUND: Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. METHODS: Thirty-one children (< or = 18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. RESULTS: Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively. CONCLUSIONS: The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The early postoperative management is the key to success. Postoperative bile leak was common, but most patients underwent liver transplantation had a better prognosis.

[Monitoring vascular complications following liver transplantation using color Doppler flow imaging].

OBJECTIVE: To assess the value of color Doppler flow imaging (CDFI) in monitoring vascular complications following orthotopic liver transplantation (OLT). METHODS: Seven hundred ninety-two patients who received OLT from April 2002 to December 2006 in the Organ Transplantation Center, General Hospital of Chinese People's Armed Police Forces, Beijing, and underwent CDFI examinations in different periods after OLT were enrolled in this study. Their vascular complications were monitored by CDFI and confirmed by angiography or spiral CT. RESULTS: Of the 792 patients, 54 were diagnosed with vascular complications that occurred 1-360 days after their OLT operations. These complications occurred within 1-30 days, 31-60 days, 61-90 days, 91-180 days, 181-360 days, with the proportions of 46.30%, 22.22%, 14.81%, 9.26% and 7.41% respectively. The proportion of hepatic artery and portal vein complications and outflow occlusions were 61.11%, 35.19% and 3.70% respectively. CONCLUSION: Most vascular complications occurred within six months after the OLT operation. The continuous and careful monitoring by CDFI is beneficial in an early diagnosis of vascular complications after OLT.

[Clinical manifestation and patho-typing of biliary cast syndrome in patients after orthotopic liver transplantation].

OBJECTIVE: To summarize the Patho-typing and the clinical manifestation of biliary cast syndrome (BCS) in patients after orthotopic liver transplantation. METHODS: The clinical manifestation, findings,therapeutic means and efficacy of 103 patients with biliary cast syndrome after orthotopic liver transplantation were retrospectively analyzed. According to the injury level of biliary duct epithelium, patients were divided into different groups. All cases were followed up for twelve months. The place, degree and time after operation would be recorded when non-anastomotic biliary stricture was found. RESULTS: There were 59 BCS cases in the general hospital of armed police force of China. The incidence rate of BCS was 9.1%. Many BCS patients showed symptoms such as jaundice, deep urine color, gray stools, itch of skin and fever. Some were asymptomatic. In laboratory test, the liver functional enzyme in serum were increased, the total white cell count in peripheral blood was increased either. Cholangiography via T tube of biliary tract might show filling defect. According to the change degree of the biliary tract tree, there were four types filling defect concluded from all the presentation in BCS patients. Solid obturation of biliary tract were found by the check with optical fiber choledochoscope in all BCS patients, necrosis of biliary tract epithelium were observed in partial BCS patients. According to the injury level of biliary duct epithelium (gradually aggravated), BCS patients were divided into six groups (type I, type II, type III, type IV, type V and type VI). Fourteen cases were found in type I and 18 in type II. No clinical symptom was found in these two groups, a few indicators in serum (alanine aminotransferase ALT, total bilirubin TBIL, direct bilirubin DBIL) were in normal range, and others (gamma-glutamyl transferase GGT, alkaline phosphatase ALP) were heightened in 5 patients. There was no biliary cast (BC) found anymore in the period of follow-up in two groups. No stricture was found in both group. Twenty-seven cases in type III and 23 cases in type IV, it was found there were about 33.4% patients accompanied with fever and 25.9% accompanied with jaundice in type III. Paralleled,there were about 30.4% and 34.8% patients in type IV. The liver functional enzyme in serum were found increased in both type. After supporting treatment for 3-6 months,there were 5 and 3 patients present as mild non-anastomotic biliary stricture in type III and type IV group. In the group type V, there were 13 patients. The detected liver functional indicators in serum were increased. After supporting treatment for 6-12 months,there were 4 patients present as moderate non-anastomotic biliary stricture in this group. There were 18 patients in type VI group, all indicators of the liver functional enzyme in serum before the treatment were elevated conspicuously. All patients in this group were found serious stricture up to three places that have not been sustained in the period of follow-up. Nine died of MOSF, 1 died of AOSC, 8 had undergone retransplantation. In the retransplantation patients, 4 died of post operation MOSF, 3 recovered to normal, 1 patient was found BCS once more 15 d after the retransplantation and the third-transplantation was performed 7 months after the second transplantation, no BCS was found again. The deaths total rate was 13.6%, death rate of retransplantation was 44.0%, total cure rate was 54.0%, total improvement rate was 71.0% and total stenosis rate was 29.0%. CONCLUSIONS: (1) According to the check with optical fiber choledochoscope, there are 6 types of patho-typing in BCS patients. The clinical manifestation includes jaundice and fever. The filling defect of the biliary tract tree might showed 4 appearances. (2)The patho-typing contributes to the clinical manifestation and the filling defect of the biliary tract tree.