Long-term consequences of stopping HBIG and/or nucleotide analogues in liver transplant recipients administered hepatitis B vaccination to prevent HBV reinfection.

BACKGROUND: The long-term administration of nucleotide analogues (NAs) and hepatitis B immune globulin (HBIG) comprises standard prophylaxis for patients with hepatitis B virus (HBV)-related liver diseases to prevent HBV reinfection after liver transplantation (LT). However, prolonging the prophylaxis strategy involves safety issues, such as the development of escape mutations and/or emerging resistant strains, and is also associated with high costs; further, it remains unclear how long prophylactic treatment should be continued. METHOD: Liver transplantation recipients responding to hepatitis B vaccination due to HBV-related liver diseases were retrospectively analysed after stopping HBIG and/or NAs, administered to prevent HBV reinfection, after long-term follow-up. The safety and effectiveness of the strategy were then evaluated for these responders. RESULT: Seventy-eight responders were enrolled. All responders discontinued HBIG, among which 36 stopped both HBIG and NAs. During follow-up, four recipients experienced HBV reinfection, which was associated with HBV escape mutations, after the withdrawal of both HBIG and NAs. No death or graft loss occurred in recipients during the follow-up period. CONCLUSION: A careful withdrawal of HBIG and/or NAs is feasible and safe for responders to hepatitis B vaccination receiving transplants for HBV-related liver diseases.

Liver transplantation in acute-on-chronic liver failure patients with high model for end-stage liver disease (MELD) scores: a single center experience of 100 consecutive cases.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. However, there are little published data on risk factors and outcomes of LT for ACLF. METHODS: The objective of this study was to analyze preoperative, intraoperative, postoperative, and overall survival data on 100 consecutive cases with ACLF in order to try to determine for which patients LT are futile. RESULTS: One hundred consecutive patients with pathology-confirmed ACLF who underwent LT from June 2004 to September 2012 were enrolled. The preoperative data showed that all patients were in a serious condition with a median high model for end-stage liver disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed by a Sequential Organ Failure Assessment (SOFA) score of ≥9. The patients had either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3-, and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%, respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%, 72.1%, and 70.6%, respectively. However, the area under receiver operating characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552, 0.547, and 0.547, respectively. CONCLUSIONS: Both deceased and living donor LT are effective therapeutic options for patients with ACLF and the short- and long-term survival rates are encouraging. It is important to conduct more prospective and multi-center studies to define preoperatively which patients would benefit from LT.

[The therapeutic mechanisms of sirolimus treatment for ischemic-type biliary lesions after liver transplantation].

OBJECTIVE: To investigate the pathogenesis of ischemic-type biliary lesions (ITBLs) in post-liver transplant patients and the possible therapeutic mechanisms of sirolimus. METHODS: The clinic data of 32 post-liver transplant patients with ITBLs from May 2004 to December 2010 was analyzed. There were including 25 male and 7 female patients with a median age of 46 years (ranging from 19 to 61 years). Patients were divided into those who received sirolimus (sirolimus group) and those who did not (control group). The expression of IL-2, FoxP3, and IL-10 in the portal area, liver function indexes, and bile duct injury score were assessed pre-ITBL, when ITBLs were identified, and after 6 months of sirolimus treatment. RESULTS: Compared with pre-ITBL optical density (OD) values, there was a significantly increase in IL-2 OD(0.138 ± 0.050 in control group and 0.141 ± 0.052 in sirolimus group), but not FoxP3 and IL-10 OD in both groups at the time ITBLs were diagnosed. After 6 months of treatment, the IL-2, FoxP3, and IL-10 OD values in the control group were not different from those when ITBLs were diagnosed. There was a significant reduction in post-therapy IL-2 OD(0.107 ± 0.043, t = 2.087, P = 0.044), and a significant elevation in FoxP3(0.213 ± 0.039) and IL-10 OD(0.187 ± 0.048) in sirolimus group as compared with those when ITBLs were diagnosed(t = -3.822 and -4.350, both P < 0.01). There was a significant increase in serum levels of ALT, AST, total bilirubin, γ-glutamyl transpeptidase and ALP at the time ITBLs were diagnosed compared with pre-ITBL levels in both groups. After 6 months of treatment, the above indexes had not changed in the control group, but significantly improved in the sirolimus group, and the bile duct injury score in the sirolimus group had significantly decreased(4.4 ± 2.4, Z = -2.568, P = 0.010). The 1-year and 3-year graft survival rates in the control group were 6/13 and 5/13, respectively, and 17/19 and 13/19, respectively, in the sirolimus group (χ(2) = 7.166, P = 0.007; χ(2) = 5.398, P = 0.020, respectively). CONCLUSIONS: Sirolimus can downregulate IL-2 expression and upregulate FoxP3 and IL-10 expression, thereby stimulating FoxP3+ Treg cells, suppressing immunopathological damage, and promoting epithelial repair in bile ducts.

Tripartite motif protein 11 (TRIM11), an oncogene for human lung cancer via the DUSP6-mediated ERK1/2 signaling pathway.

Evidence suggests that Tripartite Motif Containing 11 (TRIM11) has pro-tumor activity in human non-small cell lung cancer (NSCLC). However, the roles and underlying mechanisms of TRIM11 in NSCLC have not yet been fully elucidated. In this work, human lung cancer cell lines (A549, H446, and H1975) were transfected with siRNA or lentiviruses to knockdown or overexpress TRIM11 and dual-specificity phosphatase 6 (DUSP6). The cell tumor response was assessed by determining the rate of proliferation, apoptosis, the uptake of 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose (2-NBDG), and the secretion of lactic acid (LD). Dominant-negative (dn)-MEK1 was used to block the ERK1/2 pathway. The mechanism was investigated by assessing the protein levels of pyruvate kinase isozymes M2 (PKM2) and DUSP6, as well as the activation of ERK1/2 pathway. Our data confirmed the anti-cancer effect of siTRIM11 in human lung cancer by demonstrating inhibition of cancer cell proliferation, induction of apoptosis, prevention of 2-NBDG uptake, suppression of LD production, and prevention of lung cancer cell (A549) tumorigenicity in nude mice. The underlying mechanism involved the up-regulation of DUSP6 and the inhibition of ERK1/2 activity. Overexpression of TRIM11 induced tumorigenesis of NSCLC in vitro, and the activation of ERK1/2 was significantly reversed by DUSP6 overexpression or additional dn-MEK1 treatment. Interestingly, we confirmed TRIM11 as a deubiquitinase that regulated DUSP6 accumulation, indicating that lung cancer progression is regulated via the DUSP6-ERK1/2 pathway. In conclusion, TRIM11 is an oncogene in NSCLC, likely through the DUSP6-mediated ERK1/2 signaling pathway.

A proposed modification for the Barcelona Clinic Liver Cancer staging system: Adding bile duct tumor thrombus status in patients with hepatocellular carcinoma.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system is widely applied to stage hepatocellular carcinoma (HCC). However, it may be inaccurate when applied to East Asian HCC patients. In this study, a large Chinese HCC cohort was analyzed to evaluate possible modifications for the BCLC staging system. METHODS: Between January 1995 and December 2009, 622 HCC patients who underwent hepatectomy were enrolled. Prognostic risk factors were analyzed using univariate and multivariate analyses. The ability of the modified system to predict survival was evaluated by determining the area under the receiver operating characteristic curve. RESULTS: Patients without bile duct tumor thrombus (BDTT; 1-, 3- and 5-year overall survival, 80%, 60% and 48%, respectively) showed a substantial survival advantage over those with BDTT (1-, 3- and 5-year overall survival, 77%, 42% and 23%, respectively; χ2 = 6.280, P = 0.012). In BCLC stage 0-A patients, significant differences were identified between the BDTT group and the non-BDTT group, while no such differences were found in BCLC stage B patients. Based on this finding, BCLC stage 0-A BDTT patients were recategorized into stage B. The modified BCLC classification featured better performance in the prediction of overall survival than the original system (modified BCLC χ2 = 53.596, P < 0.001; original BCLC χ2 = 46.335, P < 0.001). The ability to predict mortality was also slightly higher using the modified BCLC system. CONCLUSIONS: Modification of the BCLC system to include BDTT status might further enhance its prognostic ability.

Splenectomy with Portoazygous Disconnection for Correction of Systemic Hemodynamic Disorders in Hepatic Cirrhosis Patients with Portal Hypertension: A Prospective Single-Center Cohort Study.

Objective: To investigate the effect of splenectomy for correction of systemic hemodynamic disorders in hepatic cirrhosis patients with portal hypertension. Methods: Hepatic cirrhosis patients with portal hypertension were enrolled from April 2015 to July 2018. Systemic hemodynamic parameters (heart rate, mean arterial pressure (MAP), cardiac output, and total peripheral vascular resistance (TPR)) were prospectively measured at baseline and 1 week, 1, 3, and 6 months, and 1, 2, and 3 years postoperatively. Paired analysis was conducted. Results: Sixty-nine patients were eligible, and 55 (79.7%) cases had a history of upper gastrointestinal bleeding. Child-Pugh classification was grade A in 41 (59.4%) cases, grade B in 26 (37.7%) cases, and grade C in 2 (2.9%) cases. The heart rate was significantly higher at 1 week postoperatively versus the baseline (P < 0.001). Meanwhile, the heart rate was significantly lower from 3 months to 2 years postoperatively versus the baseline (P < 0.05). The MAP was significantly higher at 6 months to 2 years postoperatively versus the baseline (P < 0.05). At 1 month postoperatively and 6 months to 2 years, the cardiac output was significantly lower versus the baseline (P < 0.05). At 1 month postoperatively and 6 months to 2 years, the TPR was significantly higher versus the baseline (P < 0.05). Conclusion: Splenectomy corrects systemic hemodynamic disorder in hepatic cirrhosis patients with portal hypertension, and the effect is rapid and durable.

[Mycophenolate mofetil-based calcineurin inhibitor reduced immunosuppressive protocol for the improvement of renal dysfunction after liver transplantation].

OBJECTIVE: Renal dysfunction caused by calcineurin inhibitor (CNI) after liver transplantation is a major complication among the long-term surviving recipients. Several studies have demonstrated that the adverse events could be prevented or avoided by mycophenolate mofetil (MMF)-based CNI reduced immunosuppressive protocol. In this retrospective study, we analyzed the middle-term effect of this regimen upon improving the CNI-associated renal dysfunction. METHODS: 124 OLT recipients' data within the recent three years were reviewed in this study. RESULTS: Renal dysfunction developed in 14 cases and its incidence was 11.29%. Five cases of them were from cyclosporine A (CsA) group and 9 from tacrolimus (TAC) group. The postoperative time ranged from 3-39 months with a mean follow-up duration of 19.26 +/- 9.30 months. The interval between renal impairment and surgery was 12.92 +/- 9.04 (1-31) months. CNI were reduced stepwise by about 55% in TAC group (TAC 2.60 +/- 1.14 mg/d vs 1.10 +/- 0.22 mg/d; t = 3.000, P = 0.040) and about 70% in CsA group (CsA 370 +/- 179 mg/d vs 105 +/- 27; t = 3.359, P = 0.028). Serum creatinine had decreased from 139 +/- 46 micromol/L to 122 +/- 46 micromol/L (t = 3.152, P = 0.004), 114 +/- 53 micromol/L (t = 4.180, P = 0.001) and 93 +/- 18 micromol/L (t = 4.721, P = 0.000) after administrating a mean MMF dose of 1.05 +/-0.15 g/d (0.5-1.5 g/d) for 1, 2 and 3 months respectively. And the creatinine clearance rate increased from 51.83 +/- 21.28 ml/min to 63 +/- 22 ml/min (t = -3.439, P = 0.004), 69 +/- 25 ml/min (t = -4.207, P = 0.001) and 79 +/- 25 m/min (t = -6.149, P = 0.000) during the corresponding period. Improvement was maintained within a follow-up period of 6.00 +/- 3.37 (3-14) months without major immunological or non-immunological side effects, except for 1 recipient from another institution who died of CNI-associated renal failure within 1 month after burst. 71.43% (10/14) of recipients achieved the normalization of serum creatinine and 21.43% (3/14) experienced a significant reduction in their serum creatinine levels. Conclusions MMF-based CNI reduced immunosuppressive protocol can improve substantially CNI-associated renal dysfunction after liver transplantation. And the long-term surviving recipients have excellent profiles of safety and tolerance.

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.

[Enhancing active immunity against hepatitis B virus by HBV vaccine immunization in patients with HBV-related end-stage liver diseases treated with liver transplantation].

OBJECTIVES: To study the active immunity response of liver transplant patients for HBV-related diseases after hepatitis B virus (HBV) vaccine immunization and to investigate the factors that influence the effectiveness of the vaccination in order to find measures to increase its success. METHODS: Thirteen patients who had liver transplants because of HBV-related end-stage liver diseases received hepatitis B virus immunoglobulin and lamivudine for an average of 38 months (range 27-77 months). They received double intramuscular doses (40 microg) of a recombinant vaccine at months 0, 1, 2 and 6. The anti-HBs titers were tested regularly at months 1, 2, 3, 6 and 7. RESULTS: Seven of the 13 patients (53.8%) developed higher serum titers of anti-HBs compared with their titers prior to the vaccinations, 2 patients of the 13 (15.4%) developed an increase by 100 U/L and in 4 patients (30.8%) their base levels were doubled. Those responding patients were followed-up for another 8 months after the fourth vaccination, and only 1 patient among them had a decrease of the anti-HBs titers below the level prior to the vaccination. CONCLUSION: Hepatitis B vaccine immunization can be used to enhance the active immunity against HBV in patients who had liver transplants for HBV-related diseases.

[Emergency right lobe adult-to-adult live-donor liver transplantation for the treatment of acute liver failure following severe hepatitis].

OBJECTIVE: To research the clinical feasibility of emergency right lobe adult-to-adult live-donor liver transplantation in treating acute liver failure following severe hepatitis. METHODS: Consecutive ten severe hepatitis patients (4 acute-on-chronic severe hepatitis and 6 acute severe hepatitis; 9 caused by HBV and 1 with drug-induced acute liver failure) underwent emergency right lobe adult-to-adult live-donor liver transplantation in our hospital from April 2007 to December 2007. The +/- s of model for end-stage liver disease score was 33.22 +/- 6.55. The outcomes of these recipients were prospectively analyzed. RESULTS: Among them, 8 ABO blood group were identical and 2 compatible. One was Rh sub-group negative. Except 2 recipients died (1 acute renal failure caused by veno cava thrombosis, 1 liver graft lose caused by hepatic artery thrombosis), the rest of recipients (80%) and all donors were safe. The mean graft-to-recipient weight ratio was (1.19 +/- 0.14)%, and graft volume to recipient estimated standard liver volume ratio was (65.13 +/- 8.75)%. Right lobe grafts with middle hepatic vein (MHV) 3 cases, without MHV 4 cases, without MHV but followed by V and VIII hepatic vein outflow reconstruction 3 cases. Encouraging outcome was achieved in this group of recipient: elevated serum creatinine, serum endotoxin, decreased serum prothrombin activity (PTA) and total bilirubin returned to normal about on postoperative day (POD) 3, POD 7, POD 14 and POD 28, respectively. CONCLUSIONS: Outcomes of emergency right lobe adult-to-adult live-donor liver transplantation for acute hepatic failure following severe hepatitis are fairly encouraging and acceptable. emergency right lobe adult-to-adult live-donor liver transplantation is an effective and life-saving modality for acute liver failure following severe hepatitis.

A study on risk factors and diagnostic efficiency of posthepatectomy liver failure in the nonobstructive jaundice.

Liver failure remains as the most common complication and cause of death after hepatectomy, and continues to be a challenge for doctors.t test and χ test were used for single factor analysis of data-related variables, then results were introduced into the model to undergo the multiple factors logistic regression analysis. Pearson correlation analysis was performed for related postoperative indexes, and a diagnostic evaluation was performed using the receiver operating characteristic (ROC) of postoperative indexes.Differences in age, body mass index (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time, cumulative portal vein occlusion time, intraoperative blood volume, residual liver volume (RLV)/entire live rvolume, ascites volume at postoperative day (POD)3, supplemental albumin amount at POD3, hospitalization time after operation, and the prothrombin activity (PTA) were statistically significant. Furthermore, there were significant differences in total bilirubin and the supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin amounts, ascites volume at POD3, and their combined diagnosis were performed, which had diagnostic value for postoperative liver failure (area under the curve (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903).Preoperative total bilirubin level and the supplemental albumin amount at POD3 were independent risk factors. PTA can be used as the index of postoperative liver failure, and the combined diagnosis of the indexes can improve the early prediction of postoperative liver failure.

Usefulness of three-dimensional visualization technology in minimally invasive treatment for infected necrotizing pancreatitis.

AIM: To explore the value of three-dimensional (3D) visualization technology in the minimally invasive treatment for infected necrotizing pancreatitis (INP). METHODS: Clinical data of 18 patients with INP, who were admitted to the PLA General Hospital in 2017, were retrospectively analyzed. Two-dimensional images of computed tomography were converted into 3D images based on 3D visualization technology. The size, number, shape and position of lesions and their relationship with major abdominal vasculature were well displayed. Also, percutaneous catheter drainage (PCD) number and puncture paths were designed through virtual surgery (percutaneous nephroscopic necrosectomy) based on the principle of maximum removal of infected necrosis conveniently. RESULTS: Abdominal 3D visualization images of all the patients were well reconstructed, and the optimal PCD puncture paths were well designed. Infected necrosis was conveniently removed in abundance using a nephroscope during the following surgery, and the median operation time was 102 (102 ± 20.7) min. Only 1 patient underwent endoscopic necrosectomy because of residual necrosis. CONCLUSION: The 3D visualization technology could optimize the PCD puncture paths, improving the drainage effect in patients with INP. Moreover, it significantly increased the efficiency of necrosectomy through the rigid nephroscope. As a result, it decreased operation times and improved the prognosis.

Perioperative management of primary liver cancer.

AIM: To minimize the complications and mortality and improve the survival in primary liver cancer (PLC) patients undergoing hepatic resection. METHODS: We conducted a retrospective analysis of 2143 PLC patients treated from January 1990 to January 2004. The patients were divided into two groups using January 1997 as a cut-off. Small tumor size (< 5 cm), preoperative redox tolerance index (RTI), vascular control method, and postoperative arterial ketone body ratio (AKBR) were used as indicators of surgical outcome. RESULTS: Small tumors had less complications and lower mortality and higher overall survival rate. Use of RTI for selecting patients and types of hepatectomy, reduced complications (21.1% vs 11.0%) and mortality (1.6% vs 0.3%). The half liver vascular occlusion protocol (n = 523) versus the Pringle method (n = 476) showed that the former significantly reduced the postoperative complications (25.8% vs 11.9%) and mortality (2.3% vs 0.6%) respectively, and cut mean hospital stay was 3.5 d. Postoperative AKBR was a reliable indicator of the energy status in survivors. CONCLUSION: RTI is of value in predicting hepatic functional reserve, half liver occlusion could protect the residual liver function, and AKBR measurement is a simple and accurate means of assessing the state of postoperative metabolism. Optimal perioperative management is an important factor for minimizing complications and mortality in patients undergoing hepatic resection.

Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1.

BACKGROUND: The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. METHODS: The 4.5-kb mdr1 cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCI-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. RESULTS: The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdr1 cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were (59.7 +/- 7.9)% and (12.28 +/- 2.09)%, respectively, compared with (16.9 +/- 3.2)% and (3.07 +/- 1.06)% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. CONCLUSION: The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis of MDR research.

[Effects of two different dosages of octreotide on portal pressure and hepatic hemodynamics in cirrhotic portal hypertensive patients after portal-azygous devascularization and splenectomy].

OBJECTIVE: Increased portal inflow and intrahepatic resistance may play a part of the role in pathogenesis of portal hypertension in cirrhotic patients. Some vasoactive substances may play an important role in the regulation of hepatic hemodynamics. The aim of this study is to investigate the effects of two different dosages of octreotide on portal pressure and hepatic hemodynamics. METHODS: 26 cirrhotic patients who underwent portal-azygous devascularization and splenectomy were investigated in a randomized and double-blind study. Patients were assigned to receive treatment either with a bolus of octreotide 100 microg, followed by infusion of 50 microg/h for 72 h (Group A, n = 12) or with a bolus of octreotide 100 microg, followed by infusion of 25 microg/h for 72 h (Group B, n = 14). The portal pressure was dynamically measured via a catheter placed in portal vein. The indexes of hepatic hemodynamics, including maximal and mean velocity of portal vein flow (PFV(max), PFV(mean)), maximal and minimal velocity of hepatic artery flow (HAV(max), HAV(min)) were measured using colour sonography at baseline, 72 h after infusion octreotide and 7 days after cessation of the infusion. RESULTS: The portal pressure declined 15.4% on average either in group A or group B after surgery. Portal pressure was significantly decreased after infusion of octreotide in both group A and B as compared with that at baseline. The mean decrease of portal pressure was 20.6%. The portal pressure showed a sustained decrease in group A, but it returned to baseline in group B after stopping of octreotide infusion. The portal pressure in group A and B was statistically different 24 h after stopping octreotide infusion (24.8 +/- 6.5 vs 29.4 +/- 5.8), 48 h (25.3 +/- 6.7 vs 29.9 +/- 7.0), P < 0.05. However, no differences of portal pressure between group A and B before surgery (41.0 +/- 6.6 vs 38.5 +/- 4.7), baseline (32.8 +/- 4.9 vs 33.6 +/- 6.5) and during octreotide infusion were observed. PFV(max) and PFV(mean) were significantly decreased as compared with baseline either before surgery or octreotide infusion. However, HAV(max) and HAV(min) were significantly increased as compared with baseline and before surgery. No relationship between portal pressure and sonography indexes was observed. CONCLUSIONS: Both dosages of octreotide infusion 50 microg/h and 25 microg/h can significantly reduce portal pressure, although with 25 microg/h of octreotide is reflects it seen returned to baseline. The dosage 50 microg/h of octreotide infusion may be more rational for prevention rebleeding of varices in cirrhotic portal hypertensive patients.

[An analysis of long term prophylaxis of virus recurrence with antiviral treatment in HBV infected liver transplant recipient patients].

OBJECTIVE: No optimal prophylactic protocol of hepatitis B immunoglobulin (HBIG) combined with nucleos(t)ide analogue for HBV recurrence has been established yet. By investigating the alterations of HBV markers in HBV related liver disease patients, recipients of a liver transplant, under lamivudine or/and HBIG prophylaxis, we aim to explore the possible HBV recurrence mechanism involved and to find a new option in the prophylaxis of HBV recurrence and to tailor individualized therapy. METHODS: Serial liver biopsy specimens and sera were obtained intraoperationally and at definite time points during follow-up. ELISA and chemiluminescent microparticle immunoassay, HBV DNA fluorescent quantification, immunohistochemistry staining and HBV DNA in situ hybridization were performed. Alterations of HBV markers in specimens of 96 liver transplant recipients were investigated retrospectively. RESULTS: All 17 cases had HBV recurrence (median 37 months) which occurred in the follow-up period after liver transplantation. The overall actual HBV recurrence rate at 2 years was 22% with a significant difference between that of the active and inactive groups (P<0.05); 82.4% HBV recurrence took place within the first 3 years after the operation, and the recurrence ratio of first 3 years to 3 years later after transplantation was 4.7 (P<0.01). The HBV DNA positive patients accounted for 78.6% of the total number of recurrences within the first 3 years. HBcAb and HBeAb positive rates went down with time, but their positivity remained. CONCLUSION: HBV recurrence happens after liver transplantation. In inactive HBV replicative patients with strictly combined prophylaxis and availability of other medications and using 3 years after liver transplantation as a point of time, we think that tapering down the dosage of HBIG and tailoring individualized treatment methods based on virological and immunological situations of each recipient are worth trying.

[Liver transplantation for chronic hepatitis B patients with lamivudine monotherapy or lamivudine combined with individualized low-dose hepatitis B immunoglobulin treatment].

OBJECTIVE: The aim of this study was designed to evaluate the outcomes of liver transplant recipients with chronic hepatitis B (CHB) receiving either lamivudine monotherapy or lamivudine combined with individualized low-dose hepatitis B immunoglobulin (HBIG) therapy. METHODS: A total of 111 liver transplant recipients with CHB were divided not randomly into two groups according to the availability of HBIG before liver transplantation (LT). Thirty-two patients received lamivudine monotherapy (100 mg/d) and 79 patients received lamivudine (100 mg/d) combined with individualized low-dose HBIG (intramuscular administration) to maintain the titer of antibody to hepatitis B virus (HBV) surface antigen (anti-HBs) not less than 100 U/L. The patients were followed-up for a median time of 32 months (1 to 88 months). RESULTS: In the lamivudine monotherapy group, 5 patients hepatitis B relapsed (3/5 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 7.1%, 14.3% and 17.9% and survival rates of 87.5%, 84.4% and 74.6%. In the lamivudine and HBIG combination therapy group, 2 patients hepatitis B relapsed (2/2 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 0, 1.8% and 5.7% (P < 0.01) and survival rates of 83.5%, 80.9% and 77.6% (P > 0.05). CONCLUSIONS: Compared with lamivudine monotherapy, lamivudine combined with individualized low-dose HBIG can further reduce the recurrence risk of hepatitis B in liver transplant recipients. This combined therapy could be used as a rational strategy for prophylaxis of hepatitis B recurrence in such patients.

[Hepatitis B virus surface antigen presenting function of peripheral blood dendritic cells from liver transplant receipients].

OBJECTIVE: To test the hepatitis B virus (HBV) antigen presenting capacity of peripheral blood dendritic cells (DCs) from liver transplant recipients who were in the condition of postoperative HBV clinical clearance. METHODS: Blood samples were obtained from 18 postoperative liver transplant recipients and 6 healthy adults. The peripheral blood mononuclear cells (PBMC) were isolated and cultured in vitro. The DCs were induced by recombainant human interleckin-4 (rhIL-4) and recombainant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and collected on day 7 of the culture. The DCs were then incubated with hepatitis B virus surface antigen (HBsAg) for 3 hours, and cocultured with allogeneic PBMC for 5 days. The 3HTdR was added with 1microci per well 18 hours before the end of the culture. The cpm values were identified for all of the cells. RESULTS: Under the same culture condition, the proliferation of the cells from the liver transplant recipients was poorer than those from the healthy adults (cpm value 4310.8 +/- 1820.3 vs 19002.5 +/- 13357.8, P < 0.001). The capacity of antigen presenting of DCs from the liver transplant recipients was significantly weaker than those from the healthy adults (cpm value 4974.9 +/- 2414.7 vs 39258.4 +/- 5554.9, P < 0.001). CONCLUSION: Antigen presenting capacity of DCs from liver transplant recipients, who are in the condition of postoperative HBV clinical clearance, is weakened. It might be the reason of the deficient immune response to HBV and hepatitis B vaccine of patients with liver transplant. The antigen presenting function is associated with the preoperative HBV replication, length after operation, prophylaxis of HBV re-infection/HB recurrence, and postoperative PBMV HBV DNA.