Hepatitis viral status in patients undergoing liver resection for hepatocellular carcinoma

BACKGROUND: Hepatitis B and C viruses are the main causative agents of hepatocellular carcinoma (HCC). The influence of hepatitis viral status on liver resection for HCC remains undetermined. METHODS: Patients who underwent curative resection for HCC were divided into four groups: group 1, seronegative for hepatitis B surface antigen (HBsAg) and antihepatitis C antibody (HCVAb); group 2, seropositive for HBsAg only; group 3, seropositive for HCVAb only; and group 4, seropositive for HBsAg and HCVAb. The clinicopathological characteristics and surgical results of the four groups were compared. Resection of HCC was determined according to liver functional reserve and tumour extent. RESULTS: There were 40, 131, 70 and 20 patients in groups 1, 2, 3 and 4 respectively. Due to patient selection bias, there were significant differences in some background features, resectional extent and pathological characteristics among the four groups. Postoperative morbidity and mortality, as well as the Union Internacional Contra la Cancrum tumour node metastasis stages, did not differ. Patients in group 1 had a higher disease-free survival rate than those in group 2 (P = 0. 02). The actuarial survival rates of patients in groups 2 and 4 were lower than those of groups 1 and 3. CONCLUSION: With careful patient selection, the hepatitis viral status does not influence the surgical risks of hepatectomy for HCC. After liver resection for HCC, the long-term survival rate of patients seronegative for HBsAg is greater than that of patients seropositive for HBsAg.     

Clinical and Virologic Outcomes of Hepatitis B and C Viral Coinfection After Liver Transplantation: Effect of Viral Hepatitis D

Hepatitis B (HBV) and C viral (HCV) dual-infection-associated liver disease is an uncommon indication for liver transplantation. The clinical and virologic outcomes in such patients have not been well studied. We retrospectively studied 13 patients with hepatitis B surface antigen (HBsAg) and antibody to HCV positivity who underwent orthotopic liver transplantation (OLT) and survived at least 30 days post-OLT Antibody to hepatitis delta virus (HDV) was negative in 8 patients (group I) and positive in 5 patients (group 11). Eleven of the 13 patients received standard hepatitis B immune prophylaxis, and they all remained HBsAg negative. All group I patients were HCV RNA positive after transplantation; in contrast, all group II patients were HCV RNA negative. Serum alanine aminotransferase levels were elevated in 88% (7 of 8) of the patients in group I compared with 20% (1 of 5 patients) in group II. None of the patients had graft loss from chronic rejection or recurrent hepatitis. Three patients had unsuspected hepatocellular carcinoma in the explant. We conclude that among liver transplant recipients with HBV and HCV coinfection, HDV infection is associated with the suppression of HCV replication and mild inflammatory activity after OLT     

Lamivudine After Hepatitis B Immune Globulin Is Effective in Preventing Hepatitis B Recurrence After Liver Transplantation

The prevention of recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) with hepatitis B immunoglobulin (HBIG) is expensive and requires indefinite parenteral administration. Lamivudine is a nucleoside analogue capable of inhibiting HBV replication. The aim of this study is to determine the efficacy of lamivudine in the prevention of recurrent HBV infection after a course of HBIG in patients who were hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBeAg) negative before OLT. Patients at high risk for recurrent HBV infection (HBeAg positive and HBV DNA positive) were excluded. Thirty HBsAg-positive, HBeAg-negative patients underwent OLT from January 1993 to June 1997. All 30 patients were administered HBIG after OLT and, after 2 years, were given the option of continuing with HBIG or switching to lamivudine. Five patients were excluded: 3 patients were lost to follow-up and 2 patients died of technical complications. Three patients terminated HBIG therapy at 8, 24, and 29 months after OLT, and reinfection with HBV occurred in 1 patient. Six patients elected to continue HBIG therapy for life; 1 patient died of melanoma and the remaining 5 patients are HBsAg negative, with an average follow-up of 73 months. Sixteen patients were converted to lamivudine after a course of HBIG, and all 16 patients are HBsAg negative, with an average follow-up of 51 months after OLT. Five patients have been on lamivudine monotherapy for more than 24 months. These results suggest that lamivudine administered after a posttransplantation course of HBIG can effectively prevent the recurrence of HBV infection in patients who are HBsAg positive and HBeAg negative before OLT. (Liver Transpl 2000;6:434-439.)     

Virologic and biochemical changes and prognosis after liver resection for hepatitis B virus-related hepatocellular carcinoma

BACKGROUND/AIMS: During the natural course of hepatitis B virus (HBV) infection, clearance of HB e antigen (HBeAg) and HB surface antigen (HBsAg) occurs with remission of liver disease. We investigated the effects of postoperative changes in virologic and biochemical parameters on the prognosis after liver resection for HBV-related hepatocellular carcinoma (HCC). METHODS: We investigated the relationship between postoperative changes in virologic and biochemical parameters and the incidence of intrahepatic recurrence and the outcome during a 3-year period following surgery in 30 HCC patients with HBsAg. RESULTS: The incidence of intrahepatic recurrence of HCC was significantly higher in patients with acute postoperative exacerbation of hepatitis (p = 0.0084), a sustained high serum concentration of HBV DNA (> or = 5.0 mEq/ml, p = 0.001), and sustained expression of HBsAg after surgery (p = 0.0421). A high serum concentration of HBV DNA was significantly associated with a shorter survival time (p = 0.0447) and the cause of death was recurrence of HCC. CONCLUSION: Patients with acute postoperative exacerbation of hepatitis, sustained HBsAg expression, and sustained high serum concentrations of HBV DNA after surgery may require more intensive postoperative monitoring for HCC recurrence.     

Comparison of Surgical Outcomes for Hepatocellular Carcinoma in Patients With Hepatitis B Versus Hepatitis C: A Western Experience

Background: We reviewed our experience in patients with hepatocellular carcinoma (HCC) and chronic hepatitis to determine if differences exist in preoperative status and postoperative survival between those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.Methods: We reviewed the records of 240 consecutive patients with HCC who underwent hepatic resection or liver transplantation at Mount Sinai Hospital between February 1990 and February 1998. Patients who tested negative for hepatitis B antigen and hepatitis C antibody (74 patients) as well as those who tested positive for both (2 patients) were excluded. Age as well as preoperative platelet count, prothrombin time (PT), albumin, and total bilirubin were measured in all patients. The presence of encephalopathy or ascites also was noted. Explanted livers and resection specimens were examined for size, number, and differentiation of tumors as well as the presence of vascular invasion and cirrhosis in the surrounding parenchyma.Results: One hundred twenty-one patients with HCC tested positive for HCV, and 43 tested positive for HBV. A significantly higher proportion of patients with HCV required transplant for the treatment of their HCC when compared to those with HBV. In the resection group, patients with HCV were significantly older that those with HBV. They also had significantly lower mean preoperative platelet counts and albumin levels and higher mean PT and total bilirubin levels. Resected patients with HCV had significantly less-differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to those with HBV. There was no statistical difference in the multicentricity and size of tumors between the two groups. The 5-year disease-free survival was significantly higher for HBV patients treated with resection when compared to those with HCV (49% vs. 7%, P 5 .0480). Patients with HCC and HCV had significantly longer 5-year disease-free survival with transplant when compared to resection (48% vs. 7%, P 5 .0001).Transplanted patients with HBV and HCC had preoperative status, pathological findings, and survival similar to those of patients with HCV.Conclusions: Based on preoperative liver function and tumor location, a much higher proportion of HCC patients with HBV were candidates for resection. Significant differences in preoperative status, tumor characteristics and disease-free survival exist between HCC patients with chronic HBV and HCV infection who have not yet reached end-stage liver disease. Serious consideration should be given to transplanting resectable HCC with concomitant HCV, especially in cases with small tumors.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Hepatitis B e antigen-associated membranous nephropathy

A case of hepatitis B virus (HBV)-associated membranous nephropathy (MN) is presented in an 18-year-old Korean male, whose renal disease had begun 9 years previously. He was positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and antibody to hepatitis B core antigen (anti-HBc) in the serum. By immunofluorescence, HBeAg staining was noted in glomerular deposits in association with IgG, C3 and Clq, while neither HBsAg nor HBcAg was found in the glomerular deposits. The presence of glomerular HBeAg staining by FITC-monoclonal anti-HBe F(ab')2 fragments has been reported before, but never in non-Japanese patients. The demonstration of HBeAg in both the glomerular deposits and serum in this case supports the causal relationship of HBeAg and HBV-associated MN.     

肝移植术后预防乙型肝炎病毒再感染的策略

目的探讨预防肝移植术后乙型肝炎病毒（HBV）再感染的综合策略.方法对术前存在HBV感染的130例肝移植患者进行前瞻性研究,采用肌肉注射剂型乙型肝炎免疫球蛋白（IMHBIg）联合口服拉米夫定（lamivudine）作为预防术后HBV再感染的治疗方案;术后监测HBV再感染的情况.结果在130例患者中,128例术后HBsAg转为阴性,检测血清HBsAb呈阳性.平均随访12.2个月,8例出现HBV再感染,再感染率为6.3%;术前HBeAg阳性者再感染率为14.3%,阴性者4.0%,两组间差异有统计学意义（P＜0.05）;术后第一天HBsAg阳性者再感染率为21.1%,阴性者3.7%,两组间差异有统计学意义（P＜0.05）.结论拉米夫定联合肌肉注射剂型的人乙型肝炎免疫球蛋白可有效预防肝移植术后HBV再感染;术前血清HBeAg阳性以及术后第一天HBsAg者是术后HBV复发的高危因素.     

Clinical Characteristics and Surgical Outcome in Hepatocellular Carcinoma without Hepatitis B Virus Surface Antigen or Hepatitis C Virus Antibody

Objective We investigated clinical characteristics and surgical outcome of hepatocellular carcinoma in association with hepatitis viral status. Summary Background Data No consensus exists concerning differences in surgical outcome in patients with hepatocellular carcinoma according to viral hepatitis status, especially those negative for hepatitis B virus surface antigen and antibody to hepatitis C virus. Methods Clinicopathologic data were available for 39 hepatectomy patients with hepatocellular carcinoma who were negative for hepatitis B virus surface antigen and hepatitis C virus antibody. Clinical characteristics and surgical outcome were analyzed retrospectively and compared to those patients with positive hepatitis viral markers. Results Patients negative for viral hepatitis markers were more likely to have large, advanced-stages tumors with relatively well-preserved liver function and had a lower incidence of intrahepatic recurrences (P = 0.009). The intrahepatic recurrence rate reached a plateau at approximately 3 years after resection in patients with negative viral markers, while it continued to increase steadily in patients positive for viral hepatitis markers. By multivariable analysis, the absence of viral hepatitis markers predicted a decreased rate of intrahepatic recurrence (relative risk, 0.222; P = 0.001). Conclusions Adequate surgical resection in hepatocellular carcinoma patients negative for viral markers offers a good survival benefit, regardless of the etiology of the hepatocellular carcinoma.     

Changes in serological markers of hepatitis B virus after renal transplantation

An estimated 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Immunosuppression after renal transplantation seems to enhance viral replication and increase the risk of developing cirrhosis and hepatocellular carcinoma. This retrospective study was performed to assess the prevalence among and serological status of HBV infection after renal transplantation at a single university Brazilian center. Thirty six (4.2%) patients among 850 kidney recipients showed positive HBsAg for more than 6 months; 31 were hepatitis B surface antigen (HBsAg) positive at transplantation. Of the 15 hepatitis B e antigen (HbeAg) positive patients, six had spontaneous HBeAg seroconversion and three also had HBsAg clearance. An additional two showed HBeAg clearance with Lamivudine without seroconversion. Among 15 HBeAg-negative patients, three developed HBeAg reversion with no elevation of alanine transferase (ALT) levels and one had HBsAg clearance. Only one patient had acute exacerbation of hepatitis B (ALT > 20 times normal range) but remained HbeAg negative. During follow-up, five patients became HBsAg positive; two reactivations of resolved hepatitis B, two with previous anti-HBS induced by vaccination, and one with no serological marker for HBV. Lamivudine was prescribed for 16 patients, two of whom had HbeAg clearance without seroconversion and five who developed viral resistance to Lamivudine after a mean of 29.2 months. No hepatocellular carcinoma or deaths related to hepatitis B were seen in this group. In summary, prevalence of HBV in kidney transplant patients was 4.2%. Immunosuppression after renal transplantation in HBV infection led to an increased risk of liver complications and changes in HBV serological status.     

核苷类似物单药口服预防肝移植术后乙型病毒性肝炎复发的研究

目的探讨核苷类似物单药口服预防肝移植术后乙型病毒性肝炎(乙肝)复发的有效性和安全性。方法回顾性分析1999年10月至2014年4月在广东佛山市第一人民医院行肝移植的32例乙肝相关性疾病患者的临床资料。根据供体来源分为两个阶段。第一阶段为1999年10月至2007年9月的6例无心跳供体肝移植,供肝的乙型肝炎病毒(HBV)血清标志物均为(-),受体术前血清乙型肝炎表面抗原(HBsAg)、乙型肝炎核心抗体(抗-HBc)均为(+),其中2例合并乙型肝炎e抗原(HBeAg)(+),1例合并乙型肝炎e抗体(抗-HBe)(+),5例受体术前血清HBV脱氧核糖核酸(DNA)1 000 copies/ml,1例HBV DNA1 000 copies/ml。给予拉米夫定(100 mg/d)单药口服预防肝移植术后乙肝复发。第二阶段为2011年11月至2014年4月的26例心脏死亡器官捐献供体肝移植(其中1例为肝肾联合移植);供肝血清HBsAg(+)6例、(-)20例,乙型肝炎表面抗体(抗-HBs)(+)15例,HBeAg(+)2例,抗-HBc(+)14例,抗-HBe(+)5例;11例受体术前血清HBV DNA500 copies/ml,15例HBV DNA500 copies/ml;25例给予恩替卡韦0.5 mg/d、1例给予替比夫定600 mg/d单药口服预防乙肝复发。结果第一阶段肝移植受体中位随访时间为104个月,全部受体术后血清HBsAg和HBV DNA均转阴,至今未见乙肝复发。第二阶段肝移植受体中位随访时间为50周,20例接受HBsAg(-)供肝,其中1例于术后39周出现一过性HBsAg(+),随后又转阴;另1例肝肾联合移植受体在移植术后28周发生乙肝复发,但血清HBV DNA(-);其中15例采用抗-HBc(+)供体肝移植术后均未见乙肝复发。6例采用HBsAg(+)供体的肝移植受体术后HBsAg均未转阴。所有随访受体均存活,术后均未见HBV DNA复制,亦未发现核苷类似物相关不良反应。结论核苷类似物单药口服预防肝移植术后乙肝的复发是有效和安全的。     

Clinical characteristics of hepatitis B core antibody-positive hepatocellular carcinoma

The pathology and prognosis of hepatitis B surface antigen (HBsAg)-positive hepatocellular carcinoma (HCC) and hepatitis C virus antibody (HCVAb)-positive HCC is well documented. However, patients with HBsAg-negative/hepatitis B core antibody (HBcAb)-positive HCC are included with non-B non-C disease and have been characterized independently. A series of 125 patients who had undergone hepatectomy for HCC were divided into three groups and compared. The HBsAg group comprised 25 HBsAg-positive patients, the HCV group comprised 70 HCVAb-positive patients, and the HBcAb group comprised 22 HBcAb-positive/HBsAg-negative patients. Eight patients of negative virus markers were excluded in this study. Tumors were larger in the HBcAb group (6.2 cm) than in the HBsAg (4.4 cm) and HCV (3.7 cm) groups. Disease-free 1-, 3-, and 5-year survival rates were, respectively, 75.0%, 57.1%, and 57.1% in the HBcAb group; 60.9%, 41.8%, and 41.8% in the HBsAg group; and 88.0%, 54.0%, and 37.8% in the HCV group. HBcAb-positive HCC patients had larger tumors, but their prognosis was relatively good. Although HBsAg and HCVAb are used for conventional screening of patients with hepatic disorders, we believe that screening is also necessary in patients with positive HBcAb titers for early detection of HCC.     

Clinicopathologic Features and Outcome After Liver Resection for Hepatocellular Carcinoma in Patients with Concurrent Versus Previous Chronic Hepatitis B

Purpose We compared the clinicopathologic features affecting outcome after surgery for hepatocellular carcinoma (HCC) between patients with concurrent and previous chronic hepatitis B.Methods Group A consisted of 58 patients with concurrent chronic hepatitis B, defined by seropositivity for the hepatitis B surface antigen (HBsAg), and group B consisted of 18 patients whose HCC was detected after disappearance of the HBsAg. We assessed the influence of various characteristics on outcome.Results The mean age and percentage of patients suffering from alcohol abuse or diabetes mellitus were significantly greater in group B than in group A, whereas histologic hepatitis activity, hepatic fibrosis, and alanine aminotransferase activity were significantly lower in group B than in group A. The tumor-free survival rates were similar between the two groups, but the risk factors of recurrence differed. In group A, relative youth, high aspartate aminotransferase activity, low platelet count, multiple tumors, large tumor size, portal invasion, cirrhosis, nonanatomic resection, and positive surgical margin were risk factors. In group B, large tumor size and poor differentiation were risk factors.Conclusion Hepatitis B status, tumor factors, and the type of operation affected cancer recurrence after surgery for HCC in patients with concurrent chronic HBV, as opposed to only tumor factors in patients with previous chronic hepatitis B.     

血清乙型肝炎病毒标志物不同表现模式及肝功能异常对肾移植受者存活率的影响

目的　探讨血清乙型肝炎病毒标志物不同表现模式对肾移植受者长期存活的影响。方法　对 62例血清乙型肝炎病毒标志物阳性者及 1 96例血清乙型肝炎病毒标志物全阴性者肾移植术后的肝功能、人肾均存活的存活率等指标进行随访和回顾性分析。结果　术后早期血清乙型肝炎病毒标志物阳性组与血清乙型肝炎病毒标志物阴性组比较 ,肝功能异常发生率的差异无显著性 (P >0 .0 5) ;术后中远期 ,HBsAg、HBeAg及抗 HBc阳性者的肝功能受损率明显高于血清乙型肝炎病毒标志物阴性组及HBsAg、抗 HBe、抗 HBc阳性者 (P <0 .0 5) ,其人肾均存活的存活率也最低 (P <0 .0 5)。结论　对HBsAg、抗 HBe及抗 HBc阳性者进行肾移植应慎重 ,而HBsAg、HBeAg及抗 HBc阳性者则不适宜接受肾移植     

替比夫定与HBIG联用预防肝移植术后乙型病毒性肝炎复发的疗效

目的 评价替比夫定与乙型肝炎人免疫球蛋白(HBIG)预防肝移植术后乙型病毒性肝炎(乙肝)复发的疗效和安全性.方法 26例乙肝相关终末期肝病患者,其中HBV 脱氧核糖核酸(DNA)阳性者12例,乙型肝炎表面抗原(HBsAg)阳性20例,乙型肝炎e抗原(HBeAg)阳性7例.无YMDD变异阳性病例.患者均联合应用替比夫定和...     

恩替卡韦联合HBsAg纳米乳剂治疗慢性乙型肝炎的疗效研究

目的:观察恩替卡韦联合HBsAg纳米乳剂治疗慢性乙型肝炎(乙肝)的临床疗效.方法:我院2015年9月-2016年4月收治的慢性乙型病毒性肝炎患者60例,随机分为联合治疗组和恩替卡韦治疗组,每组30例.在保肝治疗的基础上,恩替卡韦治疗组单独给予恩替卡韦治疗,联合治疗组给予恩替卡韦联合HBsAg纳米乳剂口服,比较两组HBV DNA转阴率、HBeAg转阴率以及肝功能(丙氨酸转氨酶和总胆红素)的变化.结果:治疗3个月和治疗6个月后,联合治疗组的HBV DNA水平均较恩替卡韦治疗组明显下降(P＜0.05);治疗6个月后,联合治疗组患者的血清病毒转阴率与HBeAg抗原转阴率分别为(90.00％和26.67％)均显著高于恩替卡韦治疗组(46.67％和3.33％),差异均有统计学意义(P＜0.01).治疗后3个月和6个月联合治疗组的丙氨酸转氨酶和总胆红素均明显低于治疗前,也明显低于恩替卡韦治疗组,差异均有统计学意义(P＜0.05).但联合治疗组有1例治疗后肝功能指标恶化.结论:应用恩替卡韦联合HBsAg纳米乳剂治疗慢性乙型肝炎能有效提高血清乙肝病毒转阴率和HBeAg转阴率,改善肝功能,较单用恩替卡韦治疗效果更好;对其安全性还要加强观察.     

A Study Into the Risk of Exacerbation of Chronic Hepatitis B After Liver Resection for Hepatocellular Carcinoma

Liver resection is commonly performed for solitary hepatocellular carcinoma (HCC) in well-compensated cirrhotic and noncirrhotic patients. Data concerning exacerbation of chronic hepatitis B (ECHB) post-liver resection are scant. To determine the incidence, risk factors, and clinical outcomes of ECHB in patients who underwent hepatic resection for HCC. The methods consisted of a retrospective review of consecutive patients with chronic hepatitis B virus (HBV) infection who had undergone liver resection for HCC from January 2002 to December 2004. Seventy-seven patients underwent 82 liver resections; the mean age was 58.0 ± 12.1 years; 87% male; 20% hepatitis B e-antigen positive. Incidence of all causes of postoperative hepatitis was 25.6% (n = 21), and ECHB was 8.5% (n = 7). Both groups had their peak alanine aminotransferases, 231.0 IU/L (74–1,400) and 312 IU/L (147–1,400), respectively, observed at day 84 postresection. Three patients died as a result of ECHB within 4 months postsurgery. One- and 2-year survival rates were poorest for the ECHB group at 42.9 and 21.4%, compared with those with postoperative hepatitis due to other causes at 60.3 and 45.2% and those without postoperative hepatitis at 87.7 and 73.5% (p < 0.001). Liver resection for HCC in patients with chronic HBV infection carries a risk for ECHB, and affected patients have poorer clinical outcomes. There is a need for close monitoring of these patients preoperatively and in the early postoperative period. This paper was presented as a poster in the American Association for the Study of Liver Disease Liver Meeting in San Francisco in November 2005     

IgA nephropathy and hepatitis B virus. IgA nephropathy unrelated to hepatitis B surface antigenemia

The incidence and pathogenetic role of hepatitis B surface antigen (HBsAg) were evaluated in patients with IgA nephropathy. Among 130 consecutive patients with IgA nephropathy, HBs antigenemia was detected in 4 patients (3.1%). Serum antibody to hepatitis B core antigen was positive in these 4 patients indicating that they were persistent carriers of hepatitis B virus. Serum hepatitis B e antigen (HBeAg) was detected in 1 patient, and antibody to HBeAg was positive in the other 3 patients. The incidence of HBs antigenemia was not significantly higher than the 2.0% of the general population. An immunofluorescent study in the renal tissues from the 4 IgA-nephritic patients with HBs antigenemia did not demonstrate HBsAg or HBeAg in the glomeruli. These findings suggest that HBsAg appears to play no role in the pathogenesis of IgA nephropathy.     

Hepatitis serology predicts tumor and liver-disease characteristics but not prognosis after resection of hepatocellular carcinoma

The impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on survival rates after resection of hepatocellular carcinoma (HCC) is controversial. The objective of this study was to determine whether serologic evidence of HBV or HCV infection ("hepatitis serology") can predict underlying liver disease, tumor factors, and survival rates in patients with HCC. Using a multicenter international database, we identified 446 patients with complete HBV and HCV serology. One hundred twenty-six patients were negative for HBV and HCV, 163 patients had HBV infection only, 79 patients had HCV infection only, and 78 patients had coinfection with HBV and HCV. Patients with hepatitis were more likely to have tumors smaller than 5 cm and bilateral HCC involvement. Hepatitis status (negative vs. HBV vs. HCV vs. coinfection with HBV and HCV) did not predict tumor grade or the presence of multiple tumor nodules. Patients with HCV or coinfection with HBV and HCV exhibited a lower incidence of vascular invasion, but worse fibrosis than patients with negative serology or HBV. The median survival rate was 47.9 months. The presence of hepatitis did not significantly affect the survival rate, but hepatic fibrosis and vascular invasion predicted a decreased survival rate. The prognosis after resection of HCC is influenced by tumor factors and liver disease, but not by HBV or HCV infection. The treatment for HCC should be dictated by the extent of underlying liver disease rather than by hepatitis serology. Presented at the Forty-Fifth Annual Meeting of the Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (oral presentation).     

Recurrence-free long-term survival after liver transplantation for hepatitis B using interferon-alpha pretransplant and hepatitis B immune globulin posttransplant.

OBJECTIVE: The authors determined whether pretransplant reduction of hepatitis B virus (HBV) load using alpha-interferon-2b (IFN) and passive immunoprophylaxis using hepatitis B immunoglobulin (HBIg) posttransplantation can prevent HBV recurrence in patients undergoing liver transplantation (LT) for HBV cirrhosis. SUMMARY BACKGROUND DATA: Liver transplantation in patients with HBV cirrhosis is associated with a high rate of recurrence and reduced survival. In patients with evidence of replicating virus (HBV-DNA or hepatitis B e antigen [HBeAg]-positive serum or both), recurrence is nearly universal. Passive immunoprophylaxis with HBIg alone is not effective in preventing HBV recurrence posttransplant, especially in patients with evidence of active viral replication pretransplant. Higher doses of HBIg posttransplant has reduced recurrence rates to 30% to 50%. Lamivudine, a nucleoside analogue that has shown early promise, also is associated with significant HBV recurrence. The authors report a reliable method of preventing viral recurrence in patients even with evidence for active HBV replication pretransplant. METHODS: Pretransplant patients with evidence of replicating HBV were given IFN starting at 1 million IU 3 times per week subcutaneously. This dose was increased to 2 and then 3 million IU 3 times per week when patient's side effects permitted and was maintained until the patient underwent a LT. All patients were tested every 4 weeks for hepatitis B surface antigen (HBsAg), HBeAg, and HBV-DNA. When patients became negative for HBeAg and HBV-DNA, they were listed for LT. Patients that were only HBsAg positive were listed immediately and received a LT without prior IFN treatment. Post-LT, all patients began receiving HBIg 2000 IU (10 mL) daily from days 1 to 20 and then weekly for the first 2 years. After 2 years, all patients received 2000 IU (10 mL) monthly. Additional HBIg immunoprophylaxis was given during intense immunosuppression for rejection. Posttransplant serum was tested for HBsAg, HBeAg, and HBV-DNA in all patients 1 week, 1 month, and every 3 months thereafter. Liver biopsies were done at least yearly and when liver enzymes were abnormal and were always tested for HBsAg and HBcAg by immunoperoxidase. RESULTS: Thirteen patients with decompensated HBV cirrhosis were transplanted. Pretransplant, eight patients had evidence of active viral replication at the initial assessment (HBeAg or HBV-DNA-positive serum or both). All eight were successfully treated with IFN (median duration, 24 weeks; range, 8-53) and converted to a negative status before transplantation. Side effects from IFN were minimal and well tolerated, except in one patient who required 6 million IU to convert to a nonreplicating status. The five patients that were only HBsAg positive were not treated with IFN pretransplant. After surgery, HBIg given as described achieved consistently serum levels greater than 1000 IU/L. Twelve of the 13 patients are alive with normal liver function and without serologic evidence of HBV recurrence at a median follow-up of 32 months (range, 9-56 months). None have evidence of HBV recurrence as measured by serum HBsAg/HBeAg/HBV-DNA at recent follow-up. The sera of the seven longest survivors has tested negative for HBV-DNA using the polymerase chain reaction method. In addition, a liver biopsy was obtained in six of these patients, the results of which also tested negative for HBV-DNA using polymerase chain reaction. Liver biopsy specimens have been negative for the presence of HBsAg and HBcAg by immunoperoxidase staining in all 12 patients. CONCLUSION: A reduction of viral load pretransplant with IFN and posttransplant HBIg prevents recurrence of hepatitis B and permits LT for HBV cirrhosis, even in patients with evidence of replicating virus. The IFN pretransplant was well tolerated, and the small frequent dosing of HBIg posttransplant did not cause side effects while achieving serum levels > 1000 IU/L.