Hepatitis: Zheng SS

Zheng SS. · Department of Hepatobiliary-pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicne, Hangzhou 310003, China · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #15779156 No free full text.

This publication has no abstract.

Wu LM, Xu X, Zheng SS. · Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #16286252 links to  free full text

Abstract: BACKGROUND: In recent years, liver transplantation (LT) has been acknowledged as an acceptable option for patients with hepatitis B virus (HBV) related end-stage liver diseases. However, HBV reinfection is an important event affecting the long-term survival of recipients. This paper was to review the risk factors related to HBV reinfection after LT. DATA SOURCES: English literature was reviewed based on MEDLINE focusing on the potential factors related to HBV reinfection after LT. RESULTS: HBV reinfection attributes to the unfavorable prognosis after LT. Many related factors may be responsible for it, including recipent factors (ethnical background, preoperative HBV replication status, extrahepatic HBV existence status), donor factors (compromised donor liver, HLA-A, -B compatibilities), perioperative treatment (use of antiviral agents, drug resistance, virus mutation, immunosuppressants protocol, blood transfusion) and others. CONCLUSIONS: The successful management of HBV reinfection will only be achieved by perfect clarification of its mechanism. The new strategies include new antiviral agents, gene therapy and immune intervention, reliable use of the compromised donor livers, and so on.

Xia WL, Shen Y, Zheng SS. · Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #15730912 links to  free full text

Abstract: BACKGROUND: Hepatitis B related end-stage liver disease is recently acknowledged as one of the main indications for orthotopic liver transplantation (OLT). However, the high recurrence rate of hepatitis B virus infection following transplantation is regarded as a major factor affecting the long-term survival of transplant recipients especially in China. Cyclosporine A (CsA), which is routinely used to prevent the allograft rejection, is reported to have the inhibitory activity on hepatitis B virus (HBV) replication in vitro. In this paper, we review the inhibitory effect and its possible mechanisms of CsA on HBV replication in vitro. DATA RESOURCES: An English-language literature search was conducted using MEDLINE (1990-2004) on cyclosporine A, hepatitis B virus, mitochondria, calcium and other related reports and review articles. RESULTS: Hepatitis B x protein (HBx) is essential to HBV replication. The cytosolic calcium signaling mediated by mitochondria and the Src kinase pathway were involved during HBx activation of HBV replication. CsA inhibits the HBV replication in vitro by its binding to mitochondrial cyclophilin D, then blocking the mitochondria-mediated cytosolic calcium signaling. The derivates of CsA also have the HBV replication inhibitory effect in vitro. CONCLUSIONS: By interacting with mitochondria, preventing the release of intramitochondrial calcium, and then blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in vitro. The derivates of CsA also have this activity.

Meng XQ, Zhang X, Fan J, Zhou L, Hao B, Chen XM, Ma WH, Zheng SS. · Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #19357026 links to  free full text

Abstract: BACKGROUND: The exact roles of human leukocyte antigen (HLA) compatibility, HLA antibodies and underlying diseases in acute rejection of liver transplants are not clear. Moreover, cytomegalovirus (CMV) infection, one of the most common infections after transplantation, is related to HLA genotype and the incidence of acute rejection. METHODS: Since there are controversial reports, we analyzed the impact of HLA matching, HLA antibodies and underlying diseases in 38 liver transplant recipients in China, and assessed the association of CMV infection and HLA compatibility. RESULTS: The frequency of no HLA compatibility was high in patients without antigenemia (P=0.019). All 17 patients with HLA-A matching developed antigenemia (P<0.05). Patients with three HLA locus matches were not found in patients with acute rejection (P<0.05), and no relationship between HLA antibodies and acute rejection was found (P>0.05). In patients with acute rejection, no differences were found in the incidence of acute rejection in transplants for hepatitis B, tumors, or combined hepatitis B and tumors (P>0.05). CONCLUSIONS: There are fewer acute rejections in transplants with more HLA compatibilities. Specific investigations of underlying diseases and HLA typing may be necessary in liver transplantation. The mechanisms of CMV infection and HLA matching should be further studied. HLA before transplantation should be examined for the prevention of acute rejection and CMV infection.

Xu X, Ling Q, He ZL, Gao F, Zheng SS. · Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #18842490 links to  free full text

Abstract: BACKGROUND: Diabetes mellitus (DM) is a frequent and serious complication in patients with liver diseases. We aimed to assess the prevalence and consequences of post-transplant DM (PTDM) in Chinese patients with HBV-related liver diseases and to determine the possible risk factors. METHODS: Altogether 165 patients with HBV infection and undergoing cadaveric related liver transplantation (LT) were enrolled. The clinical data of patients with (PTDM group) and without PTDM (non-PTDM group) were compared. RESULTS: Of the 165 patients, 28 had DM and 12 had impaired fasting glucose (IFG) before LT. Patients with pre-transplant DM or IFG had a survival rate similar to that of the others. Forty patients (24.2%) developed PTDM with a mean time of 36+/-17 days (range 2-300 days) after LT. Of those, 32 developed PTDM within 3 months post-LT and 29 needed insulin treatment. Pre-transplant hepatic encephalopathy and tacrolimus application were found more frequently in the PTDM group than in the non-PTDM group. The plasma tacrolimus levels were notably higher at 1 and 3 months post-LT in the PTDM group than those in the non-PTDM group. Compared to the non-PTDM group, the PTDM group showed remarkably poorer survival and tumor-free survival in patients with hepatocellular carcinoma, and significantly higher incidence of sepsis, fungal infection, chronic kidney diseases and biliary complications after LT. CONCLUSIONS: Pre-transplant DM did not affect the patient survival after LT. Since PTDM is common, it has a negative impact on outcome and may contribute to tumor recurrence. Pre-transplant hepatic encephalopathy, a tacrolimus-based regimen, and high levels of tacrolimus are clearly associated with the occurrence of PTDM.

Zhang F, Wu LM, Zhou L, Chen QX, Xie HY, Feng XW, Zheng SS. · Department of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. · Ann Surg Oncol. · Pubmed #18830757 No free full text.

Abstract: BACKGROUND: Transcriptional regulation of the putative tumor suppressor gene X-linked inhibitor of apoptosis protein-associated factor 1 (XAF1) by promoter methylation has been related to tumor progression in gastric and bladder cancer. The aim of this study was to investigate the methylation status and expression level of XAF1 in human hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) treated with liver transplantation (LT), and to evaluate potential predictive value for tumor recurrence. METHODS: The expression level and methylation status of XAF1 in three liver cancer cell lines (SMMC-7721, HepG2, and Hep3B) and 65 cases of HBV-associated HCC following LT were analyzed by RT-PCR (RT, reverse-transcriptase), immunohistochemistry, and methylation-specific polymerase chain reaction (PCR). RESULTS: XAF1 transcripts were not observed or present at low levels in liver cancer cell lines and were restored by treatment with demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dC). In vivo, methylation status was associated with protein level of XAF1 (P < 0.001) and serum level of alpha-fetoprotein (AFP) (P = 0.009). The expression pattern of XAF1 was associated with portal vein tumor thrombi (PVTT), preoperative AFP level, tumor size, and recurrence. Multivariate analysis revealed that expression level of XAF1 was an independent factor for predicting recurrence-free survival [hazard ratio 0.237, 95% confidence interval (CI) 0.095-0.592, P = 0.002]. However, no significant association was found between methylation status and the risk of tumor recurrence. CONCLUSION: Promoter hypermethylation is a critical, but not the sole, mechanism for gene silencing of XAF1 in HCC. Protein level of XAF1 may serve as a potential biomarker for tumor recurrence after LT.

Luo Y, Zhang AB, Huang H, Zheng SS. · Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. · Chin Med J (Engl). · Pubmed #18710646 links to  free full text

This publication has no abstract.

Jiang ZJ, Liang TB, Feng XN, Wang WL, Shen Y, Zhang M, Wu J, Xu X, Zheng SS. · Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #18693183 links to  free full text

Abstract: BACKGROUND: Hepatic artery thrombosis (HAT) is a frequent complication following liver transplantation, but it is rarely caused by arcuate ligament compression of the celiac artery. This article mainly describes our experience in managing a patient with celiac artery stenosis and HAT after liver transplantation. METHODS: A 44-year-old man with a 15-year history of hepatitis B was admitted to our hospital for hepatocellular carcinoma. Before the operation, he received transarterial chemoembolization once, and pretransplant MR angiography indicated a suspected stenosis at the initiation of the celiac artery, while color Doppler showed normal blood flow in the arterial system. In this case, orthotopic liver transplantation was performed for radical cure of hepatocellular carcinoma. However, B-ultrasonography detected poor blood flow in the intra- and extra-hepatic artery on the first posttransplant day, and during exploratory laparotomy a thrombus was found in the hepatic artery. Thus, re-transplantation was conducted with a bypass between the graft hepatic artery and the recipient abdominal aorta with the donor's splenic artery. RESULTS: The patient made an uneventful recovery and color Doppler showed good blood flow in the artery and portal system. Histology confirmed extensive thrombosis in the left and right hepatic artery of the explanted graft, indicating HAT. CONCLUSIONS: Although HAT caused by celiac trunk compression is rarely reported in liver transplantation, the diagnosis should be considered in patients with pretransplant hepatic artery stenosis on angiography and abnormal blood flow on B-ultrasonography. Once HAT is formed, treatment such as thrombectomy or re-transplantation should be performed as early as possible.

Lu AW, Zheng SS, Wu MP, Shen Y, Yang RW. · Hepatobiliary Pancreatic Surgery Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #18693169 links to  free full text

Abstract: BACKGROUND: Hepatitis B virus (HBV) recurrence may result in hepatic insufficiency or dysfunction of liver grafts. This study was to reevaluate the preventive effect of lamivudine therapy pretransplant on HBV recurrence after liver transplantation with combined lamivudine and hepatitis B immunoglobulin (HBIG) as a prophylactic regimen. METHODS: This is a single-center, retrospective study of 122 liver transplant recipients operated on from January 2002 to September 2006 at our hospital. All subjects showed positive hepatitis B surface antigen (HBsAg) and HBV DNA in blood, without HBV mutation in YMDD at the time of liver transplantation. The protocol with combined lamivudine and HBIG for preventing HBV recurrence was used on the day of operation. The initial immunosuppression therapy was identical. After one year follow-up, the recipients were divided into 2 groups: patients without HBV recurrence (group I) and patients with HBV recurrence (group II). Preoperative lamivudine therapy and postoperative mycophenolate mofetil (MMF) and glucocorticoid therapy were analyzed using the Wilcoxon's test and Stepwise logistic regression method. RESULTS: In the HBV recurrence group, the duration of pre-transplant lamivudine administration was significantly longer than that in the without HBV recurrence group (Z=-4.424, P=0.000). The HBV recurrence rate was significantly higher in patients with preoperative lamivudine therapy than in patients without lamivudine therapy (X2=13.11, P=0.000); the risk of HBV recurrence increased by a 10.909-fold in patients with pre-transplant lamivudine therapy compared with that in patients without lamivudine therapy (OR=10.909; 95% CI for OR: 2.86-41.67). Seven (63.6%) of 11 HBV recurrence recipients had YMDD mutants. The duration of MMF or glucocorticoid was not different between the 2 groups (Z(MMF)=-1.453, P(MMF)=0.146; Z(Pre)=-0.795, P(Pre)=0.427). No significant difference was noted in the HBV recurrent rate in patients with MMF duration < or =6 and >6 months (X2=0.185, P=0.667), as it was in patients with prednisone therapy < or =3 and >3 months (X2=0.067, P=0.793). CONCLUSIONS: With the protocol of combined lamivudine and HBIG for preventing HBV recurrence in liver transplantation recipients, liver transplantation candidates with positive HBV DNA should not be subjected to preoperative administration of lamivudine. A high dose of HBIG during the ahepatic period and in the early stage of post-transplantation can fulfill the treatment target as a long-term lamivudine therapy before liver transplantation. Long-term preoperative lamivudine treatment may result in an earlier HBV mutation in YMDD and increase the HBV recurrence rate and risk in the first year after transplantation.

Sun YL, Yin SY, Xie HY, Zhou L, Xue F, Wu LM, Gao F, Zheng SS. · Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China. · J Gastroenterol Hepatol. · Pubmed #18466286 No free full text.

Abstract: BACKGROUND AND AIM: Recent investigations demonstrate that adult stem cells may be targets for malignant transformation and that the stem-like cells in diseased livers possess the capacity of tumorigenicity in animal models. The aim of this study is to examine expression patterns of stem-cell markers in hepatitis B virus-associated cirrhotic livers and hepatocellular carcinomas (HCC), and to investigate the stem-like cell capacity of tumorigenicity in these tissues. METHODS: Twenty surgically resected HCCs and corresponding adjacent tissues as well as 10 cirrhotic liver tissues were collected and immunohistochemical staining were performed to detect the expression of CD34, Thy-1, CD133, and c-kit. Then the non-cancerous tissues were transplanted into immunodeficient mice and the characteristics of the cells from primary tissue cultures were explored in vitro. RESULTS: Immunohistochemical analysis characterized different expression patterns of stem-cell markers among these tissues. First, CD34 and Thy-1 expression was identified in proliferating bile ductules and it represented hepatic progenitor cells; CD133 and c-kit-positive cells were observed in the parenchyma of these tissues, and some of them were characterized as intermediate hepatocytes morphologically and spatially. Second, in two groups including three mice transplanted with tissues adjacent to HCC-initiated tumors, CD133 and c-kit expression was detected. Finally, our study also indicated that stem-like cells from tissue could express hepatic-lineage markers and possessed great capacities to proliferate, self-renew, and form clones in vitro. CONCLUSION: Our results suggest that the stem-like cells in cirrhotic livers possess the capacity of tumorigenicity and may contain candidates for HCC cancer stem cells.

Xie HY, Wang WL, Yao MY, Yu SF, Feng XN, Jin J, Jiang ZJ, Wu LM, Zheng SS. · Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Multiple Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China. · Arch Med Res. · Pubmed #18375254 No free full text.

Abstract: BACKGROUND: Acute rejection (AR) and hepatitis B virus (HBV) recurrence after liver transplantation (LT) are the two major complications leading to chronic graft dysfunction. Genomic polymorphisms in interleukin (IL)-10, tumor necrosis factor (TNF)alpha and transforming growth factor (TGF)beta1 genes have been found to affect the susceptibility to certain diseases. However, the relationship between cytokine gene polymorphisms and risk of AR as well as HBV recurrence after LT in Han Chinese has not been reported. The objective of the present study was to investigate the association of polymorphisms within these cytokine genes with the risk of AR as well as HBV recurrence. METHODS: One hundred eighty six Chinese LT recipients in which 41 patients developed AR and 29 patients experienced HBV recurrence were enrolled; 151 age- and gender-matched healthy individuals were selected as controls. Single-nucleotide polymorphisms (SNPs) at loci of IL-10 -1082, -819, -592, and TNFalpha -308, -238, as well as TGFbeta1 -988, -800, -509, +869, and +915 were determined by using DNA sequencing and then confirmed by restriction fragment length polymorphism (PCR-RFLP). Analyses of linkage disequilibrium and haplotype frequency were performed using Haploview program. RESULTS: The -819 and -592 polymorphisms in the IL-10 gene were in complete linkage (r(2) = 1). Another linkage was found at -509 and +869 in the TGFbeta1 gene (r(2) = 0.66). A significant difference was observed in the distribution of allelic frequencies at position -819 and -592 in the IL-10 gene between ARs and non-ARs (p = 0.036, OR = 1.134, 95% CI 0.999-1.287 and p = 0.036, OR = 1.134, 95% CI 0.999-1.287, respectively). After adjustment for a Bonferroni correction, there was no significant difference between the polymorphism and AR (p >0.05). Furthermore, the overall genotype distribution between HBV recurrence patients and non-HBV recurrence patients was also not significantly different (p >0.05). CONCLUSIONS: Our study suggests that gene polymorphisms of IL10, TNFalpha, and TGFbeta1 do not have a major independent role in AR and HBV recurrence after LT and may not be risk factors of AR and HBV recurrence after LT in Chinese liver transplant recipients.

Wang WL, Zhang GL, Wu LH, Yao MY, Jin J, Jia CK, Xie HY, Zhou L, Jiang ZJ, Zheng SS. · Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Organ Transplantation, Zhejiang Province, Ministry of Public Health, First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China. · Chin Med J (Engl). · Pubmed #17908480 links to  free full text

Abstract: BACKGROUND: Although the use of hepatitis B immunoglobulin (HBIG) may lead to a significant reduction in recurrent hepatitis B virus (HBV) infection and improve the survival of patients who have undergone liver transplantation (LT) for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients. METHODS: Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing (ABI 3037). Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred. RESULTS: Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 (45.5%) subjects, whereas TG in 31 (40.3%) and GG in 11 (14.3%). In the 559G carrier group (n = 42, 54.5%), the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group (n = 35, 45.5%), the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups (P < 0.05). CONCLUSIONS: A single nucleotide polymorphism (T/G) at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detecting FCGR3A genotypes can be a clinical reference of the HBIG administration.

Xie HY, Xia WL, Zhang CC, Wu LM, Ji HF, Cheng Y, Zheng SS. · Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Multiple Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. · Acta Pharmacol Sin. · Pubmed #17588333 links to  free full text

Abstract: AIM: The effect of cyclosporine A (CsA) on hepatitis B virus (HBV) replication was investigated, and proteomics expression differentiation after CsA treatment was studied in order to provide clues to explore the effect of CsA on HBV replication. METHODS: Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the cytotoxicity of CsA. The HBV replication level in the HBV genomic DNA transfected HepG2.2.15 cell line was determined by an ELISA analysis of hepatitis B surface antigens (HBsAg) and Hepatitis B e antigens (HBeAg) in culture supernatant, while the intracellular HBV DNA replication level was analyzed by slot blot hybridization. Two-dimensional electrophoresis was used to investigate the alteration of protein expression in HepG2.2.15 after CsA treatment in vitro. The differentially-expressed proteins were identified by Matrix-assisted laser desorption/ionization-time of flight mass spectrometry combined with an online database search. RESULTS: CsA was able to inhibit the expression of HBsAg, HBeAg, and HBV DNA replication in vitro in a dose-dependent manner. A proteomics analysis indicated that the expression of 17 proteins changed significantly in the CsA treatment group compared to the control group. Eleven of the 17 proteins were identified, including the overexpression of eukaryotic translation initiation factors (eIF) 3k, otubain 1, 14.3.3 protein, eIF2-1 alpha, eIF5A, and the tyrosine 3/tryptophan 5-mono-oxygenase activation protein in CsA-treated HepG2.2.15 cells. The downregulation of the ferritin light subunit, erythrocyte cytosolic protein of 51 kDa (ECP-51), stathmin 1/oncoprotein, adenine phosphoribosyl-transferase, and the position of a tumor protein, translationally controlled 1, was shifted, suggesting it had undergone posttranslational modifications. CONCLUSION: Our study identified the inhibitory effect of CsA on HBV replication, and found that a group of proteins may be responsible for this inhibitory effect.

Wu FS, Zheng SS, Wu LJ, Ding W, Ma ZM, Wang ZM, Teng LS, Zhao WH. · Department of Surgical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Zhonghua Wai Ke Za Zhi. · Pubmed #16784653 No free full text.

Abstract: OBJECTIVE: To analyze the prognostic value of hepatocyte growth factor (HGF) and c-met for patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Twenty-five patients undergoing partial hepatectomy for HCC were studied. Serum HGF level was determined using ELISA kit before and after operation respectively. c-met protein and mRNA expression in cancerous and paracancerous tissues were detected by immunohistochemical and RT-PCR methods respectively. The correlations of clinical-pathologic parameters with the HGF level in serum and c-met expression in cancerous tissue were analyzed respectively. RESULTS: HCC patients had a significantly higher concentration of serum HGF than normal controls and chronic hepatitis B respectively [(1.03 +/- 0.09) ng/ml vs (0.69 +/- 0.02) ng/ml and (0.74 +/- 0.09) ng/ml]. No significant difference in serum HGF was observed between HCC and cirrhosis patients with Child-Pugh score B/C [(1.03 +/- 0.09) ng/ml vs (1.04 +/- 0.11) ng/ml]. Serum HGF concentrations were positively correlated with tumor size (> 5 cm), node cirrhosis, portal vein tumor thrombi (PVTT) and preoperative alpha-fetoprotein (AFP) level (> or = 400 microg/L). After the resection of tumor, serum HGF concentration had a peak on the third postoperative day (POD), and then declined, but did not return to normal level on the tenth POD. From preoperative day to third POD, HGF concentration had a higher elevation in patients with major resection than with local resection. Moderately or strongly positive expression of c-met protein was observed in 21 cancerous regions (21/25), and only in 5 paracancerous regions. The intensive expression of c-met mRNA was 100% (25/25) detectable in the cancerous tissues, but only 24% (6/25) in the paracancerous tissues. The expression extent of c-met protein was correlated with portal vein tumor thrombi (PVTT). In paracancerous tissues, the expression of c-met protein was more intense in patients with cirrhosis than those without cirrhosis. The patients with recurrence or metastases after operation had a higher level of serum HGF and more intensive expression of c-met than other patients. No significant association was observed between HGF in serum and c-met expression in cancerous tissue. CONCLUSIONS: The over-expression of HGF and its receptor c-met indicate an adverse prognosis for HCC patients. The sustained high level of serum HGF after hepatectomy may be a factor related to early tumor recurrence and metastasis.

Wang WL, Zheng SS, Xu X, Liang TB, Jin J, Shen Y, Zhang M, Wu J. · The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #16686060 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of emergency liver transplantation in treating patients with benign end-stage liver diseases and explore the possible prognostic factors. METHOD: The clinic data of 46 cases of recipients who underwent ELT were retrospectively analyzed. clinicopathological variables (including age, gender, etiology, serum creatinine, PT, INR, albumin, total bilirubin) were compared between the survival group (n = 32) and the dead group (n = 14). And the prognostic values of CTP and MELD score were analyzed. RESULTS: Higher serum creatinine level, MELD score and CTP score were found in the dead group, as compared to those in survival group. The survival rates among CTP or MELD categories showed significant difference. Three-and six months and one year survival rates of total recipients were 73.9% , 71.7% and 69.6% respectively. CONCLUSION: Emergency liver transplantation is an effective treatment to salvage patients in end-stage. Serum creatinine is the important prognostic factor to the posttransplant survival. MELD score system is more sensitive than CTP classification in predicting the prognosis.

Xia WL, Xie HY, Shen Y, Wu LM, Zhang F, Zheng SS. · Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #16620716 No free full text.

Abstract: OBJECTIVE: To investigate the effects of ciclosporin (CsA) and tacrolimus (FK506) on replication of hepatitis B virus (HBV) in vitro. METHODS: HBV genome permanently transfected human liver cancer cells of the line HepG2.2.15 were cultured. CsA and FK506 at different concentrations were added into the culture fluid so as to identify the nontoxic concentrations by MTT method. Then the HepG2.2.15 cells were treated by CsA and FK506 at different nontoxic concentrations respectively for 4 days. ELISA was used to detect the HB surface antigen (HBsAg) and HB e antigen (HBeAg) in the supernatant. The relative replication level of HBV DNA was detected by slot blot analysis. RESULTS: MTT method confirmed that the nontoxic concentrations of CsA and FK506 were 0-40.0 microg/ml and 0-400 ng/ml respectively. After the treatment of CsA at the concentration of 1.3, 2.5, and 5.0 microg/ml, in comparison to the control group, the suppression rates of HBsAg expression in the HepG2.2.15 cells were 16.5% +/- 9.4%, 21.5% +/- 8.9%, and 33.1% +/- 5.3% respectively (all P < 0.05); the suppression rates of HBeAg expression in the HepG2.2.15 cells were 7.8% +/- 2.2%, 11.0% +/- 2.3%, and 20.8% +/- 1.5% respectively (all P < 0.05); and the HBV DNA replication levels were 56 +/- 16, 42 +/- 11, and 40 +/- 10 respectively (P > 0.05, P < 0.05, and P > 0.05). However, FK506 at different nontoxic concentrations showed no significant inhibitory effect on the levels of HBsAg, HBeAg, and HBV DNA. CONCLUSION: CsA dose-dependently inhibits the HBV replication in vitro, and FK506 does not exercise similar effects.

Wu J, Zheng SS. · Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #15138103 links to  free full text

Abstract: BACKGROUND: The past decade has witnessed the rapid development of liver transplantation in China. The 1-year survival of liver transplant patients comes to 80% in many leading medical centers and the number of liver transplantation is increasing. However, liver transplantation in China is facing several challenges including recipient with hepatocellular carcinoma (HCC), recurrence of HCC and hepatitis B, long-term postoperative care, the bridge to liver transplantation, and shortage of liver donor. This review was to understand the status of and problems in liver transplantation in China. DATA RESOURCES: An English-language literature search using MEDLINE (1990-2003) on liver transplantation and other related reports and review articles in Chinese from major transplant centers in China. RESULTS: HCC is one of the main indications for liver transplantation in China but different centers adopted different criteria for selection of patients. Hepatitis B virus reinfection is a vital problem after liver transplantation in HBV-related patients. More and more attention was focused on long-term postoperative care and donor shortage. Artificial liver support system has been applied in patients waiting for a graft in many centers. CONCLUSIONS: HCC remains to be one of the main indications for liver transplantation in China; combined hepatitis B immune globulin and lamivudine is considered effective to prevent hepatitis B virus reinfection. Apart from long-term postoperative care for the improvement of the survival rate, early steroid withdrawal is feasible in liver transplantation. Living donor liver transplantation, split liver transplantation, and marginal donor transplantation can deal with donor shortage to some extent. Artificial liver assist system serves as a bridge to liver transplantation.

Xie SB, Yao JL, Zheng SS, Yao CL, Zheng RQ. · Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #14607739 links to  free full text

Abstract: OBJECTIVE: To study the relationship between the serum levels of hyaluronic acid (HA), procollagen type III (PCIII), collagen type IV (CIV) and the histological degree of hepatic fibrosis evaluated by image analysis, and the clinical significance of serum HA, PCIII, CIV in the diagnosis of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: The concentrations of serum HA, PCIII, CIV in 151 patients with chronic viral hepatitis were measured by radioimmunoassay. Liver biopsies were performed in all the patients. Histological sections of 4 microm thickness were stained with Masson's trichrome for fibrosis assessment. Morphometric quantitative measurements for hepatic fibrosis assessment in the 4 microm sections were performed using a fully automated image analysis system. Serum levels of HA, PCIII, and CIV were analyzed at different stages of liver pathology and compared with the morphometric quantitative measurements of hepatic fibrosis. RESULTS: The serum levels of HA, PCIII, CIV all elevated gradually with the progression of the disease, and all reached the highest in patients with liver cirrhosis. There was a significant difference in the levels of these 3 components between liver cirrhosis group and the other groups (P<0.05). They all increased steadily with the histological stages of hepatic fibrosis, and reached the highest levels in stage IV. The serum levels of HA, PCIII, CIV were all positively correlated with the histological stages of liver sections and the morphometric measurement (P<0.001). The coefficients with stages were 0.694, 0.493, 0.552 (P<0.001), respectively and with surface density of total collagen on liver biopsy sections by image analysis were 0.715, 0.595, 0.573 (P<0.001), respectively. CONCLUSION: The serum levels of HA, PCIII, CIV were in consistent with the degree of hepatic fibrosis, and the determination of these marks is valuable for detecting hepatic fibrosis.

Zheng SS, Wu J, Liang TB, Wang WL, Huang DS, Xu X. · Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #14607701 links to  free full text

Abstract: OBJECTIVES: To prevent and early diagnose hepatitis B virus reinfection and recurrent hepatitis B following liver transplantation, and to discuss the further treatment of recurrent hepatitis B. METHODS: Liver transplantation recipients received lamivudine for prophylaxis of HBV reinfection. Virological and biochemical data, serum HBV DNA, and immunohistological staining for HBsAg and HBcAg in liver biopsy specimens were tested in due time. RESULTS: Five patients with hepatitis B virus reinfection and two patients with hepatitis B recurrence were observed after liver transplantation. One patient with recurrent hepatitis B developed chronic severe hepatitis B despite treatment. One patient improved after a series of treatment. CONCLUSIONS: Hepatitis B virus reinfection or recurrent hepatitis B following liver transplantation occurs mostly 6-12 months after operation. The diagnosis of hepatitis B recurrence should be taken into account when liver biochemical data becomes poor during this period. The treatment for recurrent hepatitis B after liver transplantation includes increased dosage of lamivudine, application of famciclovir, and other liver protection measures.

Zheng SS, Liang TB, Wang WL, Huang DS, Shen Y, Zhang M, Xu X, Mou LJ. · Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #14607672 links to  free full text

Abstract: OBJECTIVE: To sum up the experience in liver transplantation in a period of ten years at a single center. METHODS: We retrospectively reviewed the clinical records of 120 patients receiving liver transplantation from April 1993 to October 2002. The patients' clinical characteristics, surgical techniques, complications and survival were compared in the phases of 1993-1997 (phase I), 1999 (phase II), and 2000-2002 (phase III). RESULTS: Malignant liver diseases were major indications for liver transplantation in phase I (100%) and II (53.3%), but decreased markedly in percentage in phase III (34.0%). When compared with recipients in phase I and II, the survival of recipients with benign liver diseases in phase III was significantly improved with the 3-month, 6-month and 1-year survival rates of 85.7%, 84.5% and 83.1%, respectively. For patients with malignant liver diseases, the 3-month, 6-month and 1-year survival rates were 87.4%, 81.1% and 46.0%, respectively. The reinfection rate of hepatitis B virus was 24% 12 months after transplantation. With technical refinements, the incidence of postransplantation vascular complications has significantly decreased from 29.4% in phase I and II to 4.9% in phase III. Biliary complications remained one of the major obstacles to long-term survival. No veno-venous bypass was applied in phase III, providing a promising outcome. CONCLUSION: Strict selection of potential recipients, technical refinement, appropriate management of vascular and biliary complications, and prophylaxis of recurrences of hepatitis B and malignant liver diseases are important to obtain long-term survival of patients receiving liver transplantation in China.

Wu J, Xie HY, Jiang GP, Xu X, Zheng SS. · Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #14599949 links to  free full text

Abstract: OBJECTIVE: To use 2.2.15 cell line to determine the effects of mycophenolate acid (MPA) on hepatitis B virus (HBV) replication and viral protein synthesis in vitro. METHODS: The 2.2.15 cells were treated with different concentration of MPA (1-50 mug/ml) for 12 days. HBsAg and HBeAg were detected in the supernatant fluid by ELISA and intracellular HBV DNA was analyzed quantitatively by slot blot hybridization. RESULTS: MPA could suppress the expression of HBsAg and HBeAg, and the higher concentration of MPA induced lower expression of HBsAg and HBeAg. The suppression rates of MPA for HBsAg and HBeAg at a concentration of 50 micrograms/ml were 34.2% and 24.1% respectively. The expression of HBV DNA was only 49% as compared with controls when treated with MPA at a concentration of 50 micrograms/ml. CONCLUSIONS: Mycophenolate acid can suppress the expression of HBsAg and HBeAg as well as the replication of HBV DNA in the 2.2.15 cell. The suppressive degree is dose-dependent.

Liang TB, Zheng SS, Wang WL, Huang DS, Shen Y, Zhang M. · Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China. · Zhonghua Wai Ke Za Zhi. · Pubmed #12760747 No free full text.

Abstract: OBJECTIVE: To summarize our clinical experience in liver transplantation while considering the background in this field in China. METHODS: Ninety-five patients who had received liver transplantation from April 1993 to March 2002 were analyzed retrospectively. Three periods were defined objectively as period I (1993 - 1997), II (1999) and III (2000 - 2002). Operative techniques, recipients, original diseases, complications and survival rates were compared among the three periods. RESULTS: Malignant liver lesions were the main cause for liver transplantation in period I and II. The ratio of number of malignant disease to total recipients decreased gradually from period I to III (100%, 53% and 35%, respectively). The 1-year survival rate in patients with benign liver disease was 85% and the total operative mortality was 5% in period III. The incidence of hepatitis B virus reactivation or reinfection was 24% twelve months after liver transplantation. Vascular complication decreased but biliary complications did not and remained a major long-standing problem. No veno-venous bypass technique was used in period III, and its advantages were obvious when comparing with those with veno-venous bypass in period I and II. CONCLUSIONS: Strict selection of recipients, fine operative technique, familiarity with various complications and correct therapeutic methods, prophylaxis of recurrence of hepatitis B and hepatocellular carcinoma are necessary to improve long-term results of liver transplantation in China.

Fang ZP, Lin ZC, Zhu ZL, Zheng SS. · Department of General Surgery, Taizhou Hospital, Zhejiang Province, Linhai 317000, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #12716524 No free full text.

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