Prognostic value of glypican-3 in patients with HBV-associated hepatocellular carcinoma after liver transplantation

BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy.However,its prognostic value in patients with HBV-associated HCC after liver transplantation（LT）is not clear.The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT.METHODS： A cohort of 104 HCC patients with HBV-associ- ated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohis- tochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS： GPC-3 was expressed in samples from 74 （71.2%） of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size （P=0.004）, encapsulation （P=0.018）, pathological stage （P--0.027）, portal vein invasion （P=0.043）, tumor differentiation （P=0.002） and the Milan criteria （P=0.016）. The 5-year survival rate and dis- ease-free survival rate of patients with GPC-3-positive were lower than those （38.2% vs 75.4%, P〈0.001; 30.8% vs 69.7%, P=0.001） of patients with GPC-3-negative. Multivariate Coxregression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate （P=0.031） and disease-free survival rate （P=0.047）, together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein.CONCLUSION： GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.

High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.

Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation

AIM to determine whether diabetes mellitus(DM) affects prognosis/recurrence after liver transplantation(Lt) for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent Lt with antiviral prophylaxis. Patient data were obtained from the China Liver transplant Registry(https://www.cltr.org/). to compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent Lt found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after Lt between the two groups were significant(P = 0.041), but recurrence-free survival rates were not(P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years(P = 0.002), the presence of vascular invasion(P = 0.096), tumors ≤ 3 cm(P = 0.047), two to three tumor nodules(P = 0.007), Child-Pugh grade B(P = 0.018), and preLt alanine aminotransferase levels between 40 and 80 IU/L(P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/m L(P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM(P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after Lt. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor Lt outcomes. Prevention strategies for HCC patients with DM are recommended.

Evolution of liver transplantation in the metabolic dysfunctionassociated steatotic liver disease era: Tracking impact through time

Liver transplantation(LT)for metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing globally due to rising rates of obesity and metabolic syndrome,posing significant challenges.MASLD patients typically present with advanced age,higher body mass index(BMI),and metabolic com-orbidities such as diabetes,hypertension,and dyslipidemia.Comprehensive pre-transplant evaluations are crucial for assessing surgical risks and preparing patients for transplantation.MASLD patients with higher BMI may experience longer operative times,potentially affecting intraoperative outcomes.In the months following LT,MASLD recipients face persistent challenges,including a higher incidence of metabolic syndrome and cardiovascular events compared to non-MASLD recipients.However,survival rates at 1-,3-,and 5-years post-LT do not markedly differ from other etiologies,indicating comparable surgical outcomes.Optimizing outcomes in MASLD patients undergoing LT demands a multidisciplinary approach from pre-transplant assessment to post-transplant care.Strategies must address metabolic comorbidities,manage cardiovascular health,and monitor steatosis recurrence,which can be exacerbated by obesity and diabetes.This approach aims to mitigate long-term graft complications and mortality risks,ultimately enhancing transplant success and patient well-being.Continued research is essential to refine these approaches and meet the evolving challenges posed by MASLD as a leading indication for LT worldwide.

Combined Hangzhou criteria with neutrophillymphocyte ratio is superior to other criteria in selecting liver transplantation candidates with HBV-related hepatocellular carcinoma

BACKGROUND： The elevation of neutrophil-lymphocyte ratio （NLR） has adverse effects on the prognosis of patients with hepatocellular carcinoma （HCC） who have received liver transplantation （LT）. The Hangzhou criteria are set for selecting HCC patients for LT. The present study aimed to establish a set of new criteria combining the NLR and Hangzhou crite- ria for selecting HCC patients for LT.

Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma

We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma （HCC） complicating hepatitis B virus （HBV） cirrhosis. In 2001 （12 years after liver transplantation）, he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCC metastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater than that of those who do not receive immunosuppressive therapy.

Neutrophil-lymphocyte ratio predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation

AIM:To determine whether an elevated neutrophillymphocyte ratio(NLR)is negatively associated with tumor recurrence in patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)after liver transplantation(LT),and to determine the optimal predictive NLR cut-off value.METHODS:The data of HCC patients who had undergone LT came from the China Liver Transplant Registry database.We collected data from 326 liver cancer patients who had undergone LT at our medical center.We divided the patients into groups based on their NLRs(3,4 or 5).We then compared the clinicopathological data and long-time survival between these groups.Meanwhile,we used receiver operating characteristic analysis to determine the optimal NLR cut-off.RESULTS:Of 280 HCC patients included in this study,263 were HBV positive.Patients with an NLR<3 and patients with an NLR≥3 but<4 showed no significant differences in overall survival(OS)(P=0.212)or disease-free survival(DFS)(P=0.601).Patients with an NLR≥4 but<5 and patients with an NLR≥5also showed no significant differences in OS(P=0.208)or DFS(P=0.618).The 1-,3-and 5-year OS rates of patients with an NLR<4 vs an NLR≥4 were 87.8%,63.8%and 61.5%vs 73.9%,36.7%and 30.3%,respectively(P<0.001).The 1-,3-and 5-year DFS rates of patients with an NLR<4 vs NLR≥4 were 83.9%,62.9%and 60.7%vs 64.9%,30.1%and 30.1%,respectively(P<0.001).Univariate and multivariate analyses demonstrated that three factors,including NLR≥4(P=0.002),were significant predictors of tumor recurrence in HCC patients after LT.CONCLUSION:A preoperative elevated NLR significantly increased the risk for tumor recurrence in HCC patients after LT.

Living donor liver transplantation does not increase tumor recurrence of hepatocellular carcinoma compared to deceased donor transplantation

AIM: to compare the recurrence-free survival (RFS) and overall survival (OS) of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT). METHODS: We retrospectively collected clinical data from 408 liver cancer patients from February 1999 to September 2012. We used the chi-squared test or Fisher's exact test to analyze the characteristics of LDLT and DDLT. Kaplan-Meier analysis was used to compare the RFS and OS in HCC. RESULTS: Three hundred sixty HBV-positive patients (276 DDLT and 84 LDLT) were included in this study. The mean follow-up time was 27.1 mo (range 1.1-130.8 mo). One hundred eighty-five (51.2%) patients died during follow-up. The 1-, 3-, and 5-year RFS rates for LDLT were 85.2%, 55.7%, and 52.9%, respectively; for DDLT, the RFS rates were 73.2%, 49.1%, and 45.3% (P = 0.115). The OS rates were similar between the LDLT and DDLT recipients, with 1-, 3-, and 5-year survival rates of 81.8%, 49.5%, and 43.0% vs 69.5%, 43.0%, and 38.3%, respectively (P = 0.30). The outcomes of HCC according to the Milan criteria after LDLT and DDLT were not significantly different (for LDLT: 1-, 3-, and 5-year RFS: 94.7%, 78.7%, and 78.7% vs 89.2%, 77.5%, and 74.5%, P = 0.50; for DDLT: 86.1%, 68.8%, and 68.8% vs 80.5%, 62.2%, and 59.8% P = 0.53). CONCLUSION: The outcomes of LDLT for HCC are not worse compared to the outcomes of DDLT. LDLT does not increase tumor recurrence of HCC compared to DDLT. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome

Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of &#x0201c;hepatitis B virus AND liver transplantation&#x0201d;. We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.

Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors

Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.

Liver transplantation for hepatitis B virus: Decreasing indication and changing trends

AIM: To evaluate the indication and outcome of hepatitis B virus(HBV)-related liver transplantation(LT) in the era of newer antiviral agents.METHODS: We collected data on all patients who underwent transplantation at King Faisal Specialist Hospital and Research Center.These data included demographic,perioperative and long-term postoperative follow-up data including viral serological markers,HBV DNA,and repeated liver imaging.Between January 1990 and January 2012,133 patients(106 males and 27 females) underwent LT for HBV-related cirrhosis at our center.All patients were followed up frequently during the first year following transplantation,according to our standard protocol; follow-up visits occurred every 3-6 mo thereafter.Breakthrough infection was definedas re-emergence of HBV-DNA or hepatitis B surface antigen(HBs Ag) while on treatment.Five patients transplanted prior to 1992 did not receive immediate posttransplant anti-HBV prophylaxis; all other patients were treated with HBIG and at least one nucleos(t)ide analog.RESULTS: One hundred and thirty-three patients underwent LT for HBV and were followed for a median of 82 mo(range: 1-274).The rates of post-LT survival and HBV recurrence during the follow-up period were 89% and 11%,respectively.The following factors were associated with disease recurrence: younger age(44.3 ± 16.2 years vs 51.4 ± 9.9 years,P = 0.02),positive pretransplant hepatitis B e antigen(HBe Ag)(60% vs 14%,P < 0.0001),detectable pretransplant HBV DNA(60% vs 27%,P = 0.03),positive posttransplant HBs Ag(80% vs 4%,P < 0.0001) and positive posttransplant HBe Ag(27% vs 1%,P < 0.0001).Forty-four(33%) patients had hepatocellular carcinoma(HCC).In the first(pre-2007) group,HBV was the second leading indication for LT after hepatitis C virus infection.A total of 64 transplants were performed,including 46(72%) for decompensated HBV cirrhosis,12(19%) for decompensated cirrhosis complicated by HCC and 6(10%) for compensated cirrhosis complicated by HCC.In the second group,nonalcoholic steatohepatitis surpassed HBV as the second leading indication for LT.A total of 69 HBV related transplants were performed,including 43(62%) for decompensated HBV cirrhosis,7(10%) for decompensated cirrhosis complicated by HCC and 19(27.5%) for compensated cirrhosis complicated by HCC.There was a significant(P = 0.007) increase in the number of transplants for compensated cirrhosis complicated by HCC.CONCLUSION: The use of potent anti-HBV agents has led to a changing trend in the indications for LT.HBV is currently the third leading indication for LT in this hyperendemic area.

Comparison of hepatitis B prophylactic outcomes in living donor liver transplantation recipients who meet the Milan or UCSF criteria

BACKGROUND:The tumor burden before liver transplantation indicates that hepatitis B virus(HBV) may hide in the extrahepatic and micrometastatic sites which serve as a source of HBV replication.Currently,many liver transplant centers,especially in Western countries,use the Milan or UCSF criteria to select patients with hepatocellular carcinoma for liver transplantation.This study was undertaken to compare the HBV prophylactic outcomes in two groups of living donor liver transplantation(LDLT) recipients.Patients in group A met the Milan criteria and those in group B exceeded the Milan criteria but were within the UCSF criteria.METHODS:A database of adult-to-adult right-lobe LDLT performed at our institution for HBV-related hepatocellular carcinoma within the Milan or UCSF criteria between June 2002 and May 2012 was used to compare the HBV prophylactic outcomes between patients within the Milan criteria(group A,41 patients) and those exceeding the Milan criteria but within the UCSF criteria(group B,19 patients).RESULTS:The 1-,3-,and 5-year survival rates were similar between groups A and B(87.8%,85.1% and 74.0% vs 73.3%,61.1% and 61.1%,respectively,P=0.067).HBV recurred in 1 patient in 3.1 months after LDLT in group A and in 2 patients in group B(1 in 11.9 months and 1 in 24.1 months after LDLT).The 1-,3-,and 5-year HBV recurrence rates were 2.6%,2.6% and 2.6% in group A,and 7.3%,17.9% and 17.9% in group B,respectively(P=0.118).CONCLUSION:LDLT recipients who exceed the Milan criteria but remain within the UCSF criteria may have post-transplant HBV prophylactic outcomes similar to those who meet the Milan criteria.

Hepatitis D virus and liver transplantation: Indications and outcomes

Hepatitis D virus(HDV)is a dependent virus that relies on hepatitis B virus for its replication and transmission.Chronic hepatitis D is a severe form of viral hepatitis that can result in end stage liver disease.Currently,pegylated interferon alpha is the only approved therapy for chronic HDV infection and is associated with significant side effects.Liver transplantation(LT)is the only treatment option for patients with end-stage liver disease,hepatocellular carcinoma,or fulminant hepatitis due to coinfection with HDV.As LT for HDV and hepatitis B virus coinfection is uncommon in the United States,most data on the long-term impact of LT on HDV are from international centers.In this review,we discuss the indications and results of LT with treatment options in HDV patients.

Value of radiofrequency ablation in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignant disease that substantially affects public health worldwide.It is especially prevalent in east Asia and sub-Saharan Africa,where the main etiology is the endemic status of chronic hepatitis B.Effective treatments with curative intent for early HCC include liver transplantation,liver resection(LR),and radiofrequency ablation(RFA).RFA has become the most widely used local thermal ablation method in recent years because of its technical ease,safety,satisfactory local tumor control,and minimally invasive nature.This technique has also emerged as an important treatment strategy for HCC in recent years.RFA,liver transplantation,and hepatectomy can be complementary to one another in the treatment of HCC,and the outcome benefits have been demonstrated by numerous clinical studies.As a pretransplantation bridge therapy,RFA extends the average waiting time without increasing the risk of dropout or death.In contrast to LR,RFA causes almost no intraabdominal adhesion,thus producing favorable conditions for subsequent liver transplantation.Many studieshave demonstrated mutual interactions between RFA and hepatectomy,effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches.However,treated tumor tissue remains within the body after RFA,and residual tumors or satellite nodules can limit the effectiveness of this treatment.Therefore,future research should focus on this issue.

Liver transplantation in China: problems and their solutions

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 transplanta- tion is increasing. However, liver transplantation in China is facing several challenges including recipient with hepato- cellular carcinoma (HCC), recurrence of HCC and hepati- tis 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 trans- plantation 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 dif- ferent criteria for selection of patients. Hepatitis B virus re- infection is a vital problem after liver transplantation in HBV-related patients. More and more attention was fo- cused 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 indi- cations for liver transplantation in China; combined hepati- tis B immune globulin and lamivudine is considered effec- tive 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 liv- er transplantation, and marginal donor transplantation can deal with donor shortage to some extent. Artificial liver as- sist system serves as a bridge to liver transplantation.

Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements

Primary liver cancers carry significant morbidity and mortality.Hepatocellular carcinoma(HCC)develops within the hepatic parenchyma and is the most common malignancy originating from the liver.Although 80%of HCCs develop within background cirrhosis,20%may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC(NCHCC).NCHCC is often diagnosed late due to lack of surveillance.In addition,the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on noncirrhotic patients.Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC.NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection,signifying the role of Hepatitis B infection in NCHCC.Given the effectiveness of current antiviral therapies,surgical techniques and locoregional treatment options,nowadays such patients have more options and potential for cure.However,these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes.Better understanding of the NCHCC risk factors,tumorigenesis,diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients.In this review,we aim to discuss NCHCC epidemiology,risk factors,and pathogenesis,and elaborate on NCHCC diagnosis and treatment strategies.

乙型肝炎病毒感染相关肝病患者血清T淋巴细胞免疫球蛋白黏蛋白分子-3、高尔基体蛋白73变化及其临床意义的研究

目的:探讨乙型肝炎病毒(HBV)感染相关肝病患者血清T淋巴细胞免疫球蛋白黏蛋白分子-3(TIM-3)、高尔基体蛋白73(GP73)变化及其临床意义。方法:选取2020年9月至2022年10月于河南省郑州市第三人民医院诊治的100例HBV感染相关肝病患者为研究对象,其中47例慢性乙型肝炎(CHB)、35例肝硬化(LC)、18例肝细胞癌(HCC),分别纳入CHB组、LC组、HCC组,另选取本院同期体检的30例健康者纳入对照组。根据病情严重程度不同,CHB组又分为轻度CHB组(16例)、中度CHB组(19例)和重度CHB组(12例),LC组又分为代偿期LC组(15例)和失代偿期LC组(20例),HCC组又分为甲胎蛋白(AFP)阴性HCC组(8例)和AFP阳性HCC组(10例)。比较CHB组、LC组、HCC组和对照组TIM-3、GP73、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白和总胆红素(TBil)水平;比较CHB亚组、LC亚组和HCC亚组患者TIM-3、GP73水平;分析HBV感染相关肝病患者TIM-3和GP73与ALT、AST、白蛋白及TBil的相关性。结果:四组TIM-3、GP73、ALT、AST、白蛋白和TBil水平比较,差异有统计学意义(P<0.001);CHB组、LC组和HCC组TIM-3、GP73、ALT、AST及TBil水平均高于对照组,白蛋白水平均低于对照组(P<0.05);LC组和HCC组TIM-3、GP73、ALT、AST及TBil水平均高于CHB组,白蛋白水平均低于CHB组(P<0.05);HCC组TIM-3、GP73、ALT、AST及TBil水平均高于LC组,白蛋白水平低于LC组(P<0.05)。轻度CHB组、中度CHB组、重度CHB组TIM-3和GP73水平比较,差异有统计学意义(P<0.001);中度CHB组、重度CHB组TIM-3和GP73水平均高于轻度CHB组(P<0.05);重度CHB组TIM-3和GP73水平均高于中度CHB组(P<0.05)。失代偿期LC组TIM-3、GP73水平均高于代偿期LC组(P<0.05)。AFP阳性HCC组TIM-3、GP73水平均高于AFP阴性HCC组(P<0.05)。CHB组、LC组、HCC组患者TIM-3、GP73与ALT、AST、TBil呈正相关,与白蛋白呈负相关(P<0.05)。结论:HBV感染相关肝病患者血清TIM-3、GP73水平明显升高,CHB、LC、HCC不同疾病发展阶段其表达水平升高程度显著,且与病情发展及肝功能损伤密切相关。

Liver transplantation: Yesterday, today and tomorrow

With the advances in technical skills, management of postoperative complications and improvements in immunosuppressive drugs, liver transplantation is the standard treatment for many patients with chronic liver disease. Today, shortage of donor organs seems to be the major limiting factor for the application of liver transplantation. This review focuses on five issues that are challenging to clinical practice of liver transplantation and relevant to gastroenterologists. These include living donor liver transplantation, recurrent viral hepatitis, non-heart-beating donors, hepatocellular carcinoma, and ABO incompatible liver transplantation. Living donor and non-heart beating donor transplantations were initiated as a solution to increase the donor organ pool and it is expected that there will be an increase in the number of these donors. Recurrent hepatitis C and hepatocellular carcinoma following liver transplantation are among major problems and ongoing research in these diseases may lead to better outcomes in these recipients.

Management of occult hepatitis B virus infection:An update for the clinician

Occult hepatitis B virus(HBV) infection(OBI) is defined by the presence of HBV DNA in the liver tissue of individuals who test negative for hepatitis B surface antigen(HBsAg).Patients who have recovered from acute hepatitis B can carry HBV genomes for a long time and show histological patterns of mild necro-inflammation,even fibrosis,years after the resolution of acute hepatitis,without showing any clinical or biochemical evidence of liver disease.At least in conditions of immunocompetence,OBI is inoffensive itself,but when other relevant causes of liver damage are present it might make the course of the liver disease worse.The risk of HBV transmission through transfusion is related to blood donations negative for HBsAg that have been collected during the pre-seroconversion period or during chronic OBI.Use of HBV nucleic acid amplification testing and multivalent anti-HBs antibodies in the HBsAg assays is recommended for detection of true and false OBI,respectively.It is not known if prior hepatitis B immunization with an optimal anti-HBs response in cases of HBV transmission through organ transplantation can effectively modulate or abort the infection.Use of anti-viral agents as prophylaxis in patients with serological evidence of past HBV infection prevents reactivation of OBI after transplantation in most cases.Reactivation of OBI has been observed in other conditions that cause immunosuppression,in which antiviral therapy could be delayed until the HBV DNA or HBsAg becomes detectable.OBI might contribute to the progression of liver fibrosis and hepatocellular carcinoma development in patients with chronic liver disease.

Prevention and treatment of hepatitis B relapse after liver transplantation

OBJECTIVES: To investigate the effect of orthotopic liver transplantation (OLT) on hepatitis B(HB)-related diseases and the efficiency of prevention and treatment with lamivudine on recurrence of hepatitis B posttransplant in China. METHODS: Orthotopic liver transplantation (OLT) under veno-venous bypass was performed in 10, of whom 9 males had hepatitis B and 1 female had hepatocellular cancer (HCC) without HB pretransplant. Eight of the 9 males had fulminant hepatitis B (FHB) and they all had preoperative serious jaundice, ascites and coagulopathy. Six had encephalopathy; 1 was associated with acute renal failure, and 1 with gastrointestinal hemorrhage. Seven of the 10 patients had lamivudine to prevent reinfection with hepatitis B. RESULTS: Of the 8 patients who have survived for 2-12 months, 7 have survived for 6-12 months. Two died, one of recurrent FHB and the other from multi-organ failure (MOF). Seven preoprative HB patients of the 8 survivors have excellent liver function through 1 has positive HBsAg 6 months after OLT. One of the 8 survivors, the female with HCC pretransplant, suffered hepatitis B 6 months after OLT and her hepatic function has been gradually improving with lamivudine therapy. CONCLUSIONS: OLT is an effective therapy for certain cases of FHB and HCC and lamivudine may prevent recurrence of hepatitis B after OLT.