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 or C virus serology as a prognostic factor in patients with hepatocellular carcinoma

It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is a prognostic factor for hepatocellular carcinoma. We performed this study to determine if chronic HBV or HCV infection had any impact on postresection survival or affected patterns of failure. The records of 77 patients undergoing surgical resection for hepatocellular carcinoma between January 1990 and December 1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients (23%) had HBV infection, and 15 patients (20%) had negative serology. There were no differences in age, sex, or tumor size among the groups, and all patients had margin-negative resections. There was a significantly higher incidence of satellitosis and vascular invasion in patients with HCV infection (32 % and 41 %, respectively; P <0.05 vs. other groups). With a median follow-up of 30 months, a significantly decreased local disease-free survival (LDFS) was seen in HBV-positive (5-year LDFS 26%) or HCV-positive (S-year LDFS 38%) patients compared to those with negative serology (S-year LDFS 79%; P <0.05). There was also a trend toward a decreased overall survival in patients with positive hepatitis serology compared to patients with negative serology (37% vs. 79%; P = 0.12). Uuivariate analysis revealed that only satellitosis was related to local recurrence and overall survival. Patients with positive serology for hepatitis B or C undergoing resection for hepatocellular carcinoma have a trend toward worse overall prognosis and a significantly decreased LDFS when compared to patients with negative serology. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract (Ross Research Conference), San Diego, Calif., May 21–24, 2000.     

Longer survival of liver transplant recipients with hepatitis virus coinfections

Hepatitis virus coinfections [HBV plus HCV coinfection (HBV/HCV) or HBV plus HDV coinfection (HBV/HDV)] may progress more rapidly to cirrhosis than hepatitis B or C monoinfections in immunocompetent patients. Only limited information is available on the outcome of coinfected patients after liver transplantation. We studied survival rates of 204 patients with viral hepatitis transplanted at our center between 1972 and 1997. HBV/HDV and HBV/HCV coinfections were present in 23 and nine individuals, respectively, while 97 patients had monoinfection by HCV and 75 had HBV monoinfection. Survival of coinfected patients was significantly longer than that of monoinfected patients (14.4 +/- 0.9 vs. 8.5 +/- 0.6 yr; p = 0.0003). The same was true for graft survival (p = 0.0002). In Cox's regression, viral coinfection (p = 0.0001), absence of hepatocellular carcinoma (HCC) (p = 0.00001) and no retransplantation (p = 0.02) were independently associated with patient survival. After exclusion of patients with HCC (n = 62), survival of coinfected patients was still significantly longer than that of monoinfected individuals (p = 0.002). The improved outcome was similar for both HBV/HDV and HBV/HCV coinfections. In contrast to immunocompetent patients, individuals with multiple hepatitis virus infections had an improved outcome after liver transplantation. Thus, viral coinfections may be associated with ameliorated courses of diseases under certain conditions.     

Lack of impact of hepatitis C virus coinfection in end-stage renal disease patients with hepatitis B virus infection

INTRODUCTION: Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection results in more severe forms of liver disease in nonuremic patients; however, the impact of HCV coinfection is not clearly known in end-stage renal disease (ESRD) patients with HBV infection. We sought to determine the impact of HCV coinfection in HBV-infected ESRD patients. PATIENTS AND METHODS: The HBsAg-positive ESRD patients evaluated between March 1999 and May 2003 were divided into two groups: group B, HBV infection alone, and group BC, HBV-HCV coinfection (anti-HCV-positive). Both groups were compared regarding epidemiological, laboratory, and histological findings. A liver biopsy was obtained in cases with evidence of viral replication and/or elevated alanine aminotransferase. RESULTS: One hundred patients (73% men) with mean age of 42 +/- 11 years (55 patients in group B and 45 in group BC) were studied. Comparison between groups showed a difference in time on hemodialysis and duration of infection, which were higher in group BC (P < .001 and P = .001, respectively) and in history of blood transfusion, which was also more frequent in group BC (P = .04). Liver biopsies, obtained from 15 patients in group B and 28 patients in group BC, showed no difference in frequency of septal fibrosis (60% in group B vs 48% in group BC, P = .46) or interface hepatitis (73% vs 71%, P = .99). CONCLUSIONS: HBV-HCV coinfection was related to a longer time on hemodialysis, longer duration of infection, and history of blood transfusion. Contrary to nonuremic patients, HCV coinfection was not associated with more severe forms of liver disease in ESRD patients.     

Impact of Viral Hepatitis on Outcomes after Liver Resection for Hepatocellular Carcinoma: Results from a North American Center

Background

Hepatitis B (HBV) and hepatitis C (HCV) are well-recognized risk factors for hepatocellular carcinoma (HCC). The characteristics and clinical outcomes of HCC arising from these conditions may differ. This study was conducted to compare the outcomes of HCC associated with HBV and HCV after liver resection.

Methods

Of 386 liver resections for HCC performed between July 1992 and April 2011, 181 patients had HBV and 74 patients had HCV. Patients with HBV/HCV coinfections (n = 20), non-HBV/HCV etiology (n = 94), and postoperative death within 3 months (n = 17) were excluded. Patient, tumor characteristics, and perioperative and oncologic outcomes were compared between patients with HBV and HCV.

Results

The patients with HBV had better overall survival (OS) than patients with HCV (68 vs. 59 months, p = 0.03); however, there was no difference in recurrence-free survival (RFS) between the groups (44 vs. 45 months, p = 0.1). The factors predictive of OS based on multivariate analyses included: vascular invasion [p < 0.01, hazard ratio (HR) = 3.4], Child-Pugh Score (p < 0.01, HR = 4.8), and underlying liver disease (HCV vs HBV) (p = 0.01, HR = 1.9). Vascular invasion and tumor number (p < 0.01, HR = 2.3 and p < 0.01, HR = 2.1) were independent predictors of RFS.

Conclusions

OS but not RFS after liver resection for HCC is better in patients with HBV than HCV. This survival advantage for HBV patients may be due to differences in tumor biology and outcomes after disease recurrence.     

Survival outcomes in liver transplantation for hepatocellular carcinoma, comparing impact of hepatitis C versus other etiology of cirrhosis.

The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide as the most common primary hepatic malignancy. In the US approximately one half of all HCC is related to Hepatitis C virus (HCV) infection. The relationship between the primary disease and HCC recurrence after liver transplantation is unknown. We hypothesized that the primary hepatic disease underlying the development of cirrhosis and HCC would be associated with the risk of recurrent HCC after transplantation. A retrospective review was conducted of all primary liver transplants performed at the University of Rochester Medical Center from May 1995 through June 2004. The pathology reports from the native livers of 727 recipients were examined for the presence of HCC. There were 71 liver transplant recipients with histopathological evidence of HCC. These patients were divided in two groups on the basis of HCV status. Group 1 consisted of 37 patients that were both HCV and HCC positive, and Group 2 consisted of 34 patients that were HCC positive but HCV negative. Patient characteristics were analyzed, as well as number of tumors, tumor size, presence of vascular invasion, lobe involvement, recipient demographics, donor factors, pretransplantation HCC therapy, rejection episodes, and documented HCC recurrence and treatment. There were no statistically significant differences between the 2 groups, with the exception of recipient age and the presence of hepatitis B coinfection. The tumor characteristics of both groups were similar in numbers of tumors, Milan criteria status, vascular invasion, incidental HCC differentiation, and largest tumor size. The HCV positive population had a far lower patient survival rate with patient survival in Group 1 at 1, 3, and 5 years being 81.1%, 57.4%, and 49.3% respectively, compared with 94.1%, 82.8%, and 76.4% in Group 2 (p = 0.049). Tumor-free survival in Group 1 at 1, 3, and 5 years was 70.3%, 43%, and 36.8% respectively, vs. 88.1%, 73%, and 60.8% in Group 2. In a subgroup analysis, tumor-free survival was further examined by stratifying the patients on the basis of Milan criteria. Group 1 patients outside of Milan criteria had a statistically lower tumor-free survival. By contrast, there was no statistical difference in tumor-free survival in Group 2 patients stratified according to Milan criteria. Cox regression analysis identified HCV and vascular invasion as significant independent predictors of tumor-free survival. Our results suggest that Milan selection criteria may be too limiting and lose their predictive power when applied to patients without HCV infection.     

Hepatitis C Virus Infection is a Risk Factor for Tumor Recurrence after Resection of Small Hepatocellular Carcinomas

Hepatocellular carcinoma (HCC) is closely associated with chronic hepatitis B or C virus (HBV, HCV) infection. Tumor recurrence frequently occurs after surgical resection and may adversely affect the outcome. This study aimed to investigate the effect of viral hepatitis in association with HCC recurrence after resection. A total of 248 patients [HBV in 165, HCV in 44, dual HBV+HCV in 15, and non-B non-C (NBNC) in 24] who underwent curative resection for HCC were included. The cumulative recurrence rate was compared according to the etiology of the underlying hepatitis and was stratified by tumor size and other clinicopathologic parameters. Altogether, 116 patients (47%) had a tumor recurrence within 17 ± 11 months after resection. No significant difference in recurrence was noted among the four groups of patients (HBV, HCV, HBV+HCV, NBNC) (p = 0.248). Persistent hepatitis was more common in the HCV group (p < 0.001) after resection. Among the 157 patients with a small (= 5 cm) tumor, the recurrence rate was significantly higher in the HCV group than in the HBV, HBV+HCV, and NBNC groups (p = 0.036). Cox multivariate analysis showed that HCV infection [relative risk (RR) 4.4, 95% confidence interval (CI) 1.3–14.8, p = 0.018] and vascular invasion (RR 3.2, 95% CI 1.2–8.9, p = 0.044) were independent predictors of tumor recurrence. Stratified analysis in other parameters did not show significant differences in terms of tumor recurrence among the four virologic groups (p > 0.1 for all parameters). In conclusion, patients with small HCCs and concurrent HCV infection are at a high risk of tumor recurrence after resection.     

Surgical Results in Patients with Hepatitis B-related Hepatocellular Carcinoma and Positive Hepatitis B Early Antigen

Hepatitis B virus (HBV) infection is the major risk factor in the pathogenesis of hepatocellular carcinoma (HCC). Patients who are positive for hepatitis B early antigen (HBeAg) have active liver disease. The present study aimed to evaluate the possible role of HBeAg in patients with resectable HCC. A series of 249 HCC patients with complete preoperative hepatitis marker who had undergone potentially curative resection were enrolled. Patients with hepatitis C virus infection were excluded. Of these patients, 27 were positive for hepatitis B surface antigen (HBsAg) and HBeAg (group I), 171 were positive for HBsAg and negative for HBeAg (group II), and 51 were negative for hepatitis B markers (group III). The clinicopathologic features and postoperative survivals were compared among the three groups. The prevalence of HBeAg was 10.8%. Group I patients were significantly younger and had worse liver function, smaller tumors, and a higher incidence of liver cirrhosis and chronic active hepatitis than those in groups II and III. No increase in tumor invasiveness was noted in group I patients. The operative morbidity, mortality, and postresection survival were comparable among the three groups. Our findings indicated that HBeAg positivity is not a negative factor for resection in HCC patients and has no significant influence on postresection survival.     

Liver Transplantation for Hepatitis B and C Virus-Related Cirrhosis: Mid-Term Results

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal; cirrhosis develops in up to 30% of cases. Currently there is interest in the midterm outcomes of HCV patients with concomitant hepatitis B virus (HBV) infection among OLT recipients. We therefore retrospectively analyzed our database of patients who underwent OLT for HCV-HBV-related cirrhosis. Between April 1992 and December 2008, 350 patients underwent OLT, including 20 (5.7%) transplanted for HBV-HCV cirrhosis. We assessed patient and graft survivals at 1 and 5 years, as well as the progression of fibrosis. Protocol liver biopsies were available yearly after OLT. The survival curves were analyzed by the Kaplan-Meier approach and chronic hepatitis evaluated according to the Ishak scoring system. At a median follow-up of 68.4 ± 53 months, the 1- and 5-year patient and graft survival rates were 80% and 70%, respectively. The 5-year fibrosis progression rate was 0.17 ± 0.08 units of fibrosis. The only patient who developed histologic cirrhosis within 10 years of follow-up showed a lamivudine-resistant HBV recurrence. Patients transplanted for HBV-HCV coinfection showed a lower fibrosis progression rate compared with HCV monoinfected subjects.     

Indication of liver transplantation for hepatocellular carcinoma in Japan

Approximately 20,000 patients die of hepatocellular carcinoma (HCC) annually in Japan and most of them are hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers. Recently, small HCC, less than 3 cm in diameter, have frequently been found by ultrasonography in the follow-up of patients with chronic liver diseases. Such cases are mainly treated by either surgical resection or percutaneous ethanol injection therapy (PEIT) with a satisfactory 5 year survival rate of 50%. In addition, the survival rate of advanced cases has gradually improved thanks to transcatheter arterial chemo-embolization combined with PEIT, radiation, hyperthermia, or immune therapy. On the other hand, our autopsy study has indicated a high frequency of extrahepatic metastasis in advanced cases. From these results, liver transplantation for HCC does not seem to be the treatment of first choice, at present, in Japan. In the future, the means to control the underlying infection of HBV or HCV as well as making an accurate imaging diagnosis for the detection of extrahepatic metastasis will become inevitably more important for successful liver transplantation in HCC.This report is the gist of a paper read at the 91st Annual Meeting of the Japanese Surgical Society, Kyoto, Japan, 1991     

Hepatocellular Carcinoma in a Patient with Primary Biliary Cirrhosis and Seronegativity for Markers of Hepatitis B Virus and Hepatitis C Virus: Report of a Case

We report a case of hepatocellular carcinoma (HCC) arising in a patient with primary biliary cirrhosis (PBC) in whom both hepatitis B virus (HBV) and hepatitis C virus (HCV) serological tests were negative. A 72-year-old woman was found to have HCC 10 years after a diagnosis of PBC. All serological tests for HBV and HCV were negative. Preoperative liver biopsy findings suggested moderately differentiated HCC. Dynamic computed tomography (CT) showed hypervascular tumors in segments IV and VII. At laparotomy, a 30-mm tumor was palpated in segment VII and a wedge resection was performed. The second tumor, which measured 10 mm in diameter, was detected in segment IV by abdominal ultrasound, and microwave coagulation therapy was done. HCC arising in hepatitis virus marker-negative PBC is rare and past reports do not clarify whether HBV or HCV infections are associated with HCC. Received: January 7, 2002 / Accepted: September 3, 2002 Reprint requests to: H. Sunagawa     

肝细胞肝癌与乙、丙及庚型肝炎病毒感染相关的组织学证据

目的探讨肝细胞肝癌（HCC）与乙、丙及庚型肝炎病毒（HBV，HCV，HGV）感染的相关性。方法采用免疫组化方法检测HCC患者癌及癌旁肝组织中HBV，HCV及HGV表达状况。结果65例HCC患者中，共计52例（80．0％）检出以上三种肝炎病毒抗原，其中乙型肝炎表面抗原（HBsAg），HCVNSS和HGVNSS抗原阳性者分别为47（72．3％），30（46．2％）和10（15．4％）例。52例病毒标志阳性者中，HBV，HCV和HGV三重感染者5例，HBV／HCV，HBV／HGV或HCV／HGV二重感染者各25例，单纯HBV和HCV阳性者各18例和4例，无单纯HGV阳性者。各病毒主要在癌旁组织中表达，但HBV和HCV在癌组织中也较活跃。此外，间或可在肿瘤与正常组织移行处检出HBV或HCV表达，但未见HGV抗原阳性。混合感染、单独感染及病毒标志阴性的HCC比较，肿瘤分化程度无明显区别。结论我国HCC患者肝炎病毒混合感染普遍存在；除HBV和HCV外，HGV感染也可能与肝癌发生有一定关系。     

Significance of HBV DNA in the Hepatic Parenchyma from Patients with Non-B, Non-C Hepatocellular Carcinoma

Introduction The etiologic and prognostic factors for non-B, non-C hepatocellular carcinoma (HCC), which is defined by its seronegativity for both hepatitis B surface antigen and hepatitis C virus (HCV) antibody, remain unclear. Methods Nonneoplastic liver tissue from 46 patients with non-B, non-C HCC were examined for hepatitis B virus (HBV) DNA and HCV RNA using in situ hybridization. Recurrence-free survival rates were compared between patients showing high or low HBV DNA expression. Other potential prognostic factors were examined as well. Results HBV DNA was detected in nonneoplastic liver specimens from 35 patents (76.1%), whereas HCV RNA was not detected in any case. In patents with high HBV DNA group expression, recurrence-free survival rates at 1 and 5 years after onset were 68.8% and 13.8%, respectively; those with low expression had higher rates of 89.2% and 59.2%, respectively. Multivariate analysis identified high tumor stage (P = 0.042) and high HBV DNA expression (p = 0.014) as independent negative prognostic factors. Conclusions In many patients with non-B, non-C HCC, HBV DNA in the liver appears to be involved in the carcinogenesis, with intense HBV DNA expression predicting poor outcome for patients with these cancers.     

Hepatocellular carcinoma in renal transplant patients

INTRODUCTION: Chronic liver diseases, especially those related to hepatitis B (HBV) and C viruses (HCV), are a common problem in renal transplant patients. Hepatocellular carcinoma (HCC) is a complication of chronic liver diseases, incidence in the renal transplant cohort is higher than in the general population (1.4% to 4% vs 0.005% to 0.015%). METHODS: We retrospectively evaluated the incidence of HCC, its clinical presentation, the treatments, and the relation to chronic viral hepatitis among the population transplanted at our center between January 1980 and December 1998 and followed to August 2003. RESULTS: During the study period, six recipients among 534 renal transplants displayed HCC (incidence 1.12% of the entire population and 2.29% of patients with chronic viral hepatitis). Among the cohort five were men, and all had chronic viral hepatitis: three HBV, one HCV, and 2, a coinfection. HCC was diagnosed 124.1 (range 45 to 244) months after transplantation. All patients presented with abnormal liver function tests and tumors larger than 5 cm. Four had more than three tumors and three had an alpha-fetoprotein level higher than 400 IU/mL. Three patients received no treatment (survivals 1, 1, and 4 months); two patients, chemoembolization (survival 6 and 12 months); and one, surgical ethanol injections (survival 4 months). The overall survival was 4.5 months. CONCLUSION: HCC in renal transplant recipients is a common complication among patients with chronic viral hepatitis. The outcome was poor because HCC was detected at an advanced stage. Screening strategies for early diagnosis must be prospectively evaluated.     

乙肝相关性肝癌和丙肝相关性肝癌的临床病理特征及意义

【摘要】〓目的〓探讨乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。方法〓收集2003年12月~2010年10月在南方医科大学附属南方医院行手术治疗C-HCC标本18例和2011年3月~2012年12月行手术治疗的B-HCC标本34例,以及这些肝癌患者的临床病理资料。分析乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。结果〓乙肝相关性肝癌平均年龄(46.9±10.5)显著低于丙肝相关性肝癌组(59.0±9.9),平均住院天数(17.9±6.8)显著低于丙肝相关性肝癌组(34.9±16.5),平均术后住院天数(11.5±4.3)显著低于丙肝相关性肝癌组(19.4±11.9),肝功能分级中A级肝功明显较丙肝相关性肝癌组多,最大肿瘤直径明显大于丙肝相关性肝癌组,差异均有统计学意义(P<0.05)。B-HCC组患者中位无瘤生存时间为13个月,1年、2年无瘤生存率分别为56.3%和32.0%;C-HCC组患者中位无瘤生存时间为16.5个月,1年、2年无瘤生存率分别为75%和75%。Cox模型分析提示肝炎类型是肝细胞癌术后复发的独立影响因素。乙肝相关肝细胞癌术后复发的风险是丙肝相关性肝癌的2.35倍(P=0.108)。结论〓乙肝病毒与丙肝病毒相关肝细胞癌的临床病理特征及预后有显著差异。乙肝相关性肝癌术后恢复较丙肝相关性肝癌快,而丙肝相关肝细胞癌术后复发风险低于乙肝相关肝细胞癌。     

Underlying liver disease, not tumor factors, predicts long-term survival after resection of hepatocellular carcinoma

HYPOTHESIS: A subset of patients can be identified who will survive without recurrence beyond 5 years after hepatic resection for hepatocellular carcinoma (HCC). DESIGN: A retrospective review of a multi-institutional database of 591 patients who had undergone hepatic resection for HCC and on-site reviews of clinical records and pathology slides. SETTING: All patients had been treated in academic referral centers within university-based hospitals. PATIENTS: We identified 145 patients who had survived for 5 years or longer after hepatic resection for HCC. MAIN OUTCOME MEASURES: Clinical and pathologic factors, as well as scoring of hepatitis and fibrosis in the surrounding liver parenchyma, were assessed for possible association with survival beyond 5 years and cause of death among the 145 five-year survivors. RESULTS: Median additional survival duration longer than 5 years was 4.1 years. Women had significantly longer median additional survival durations than did men (81 months vs 38 months, respectively, after the 5-year mark) (P =.008). Surgical margins, type of resection, an elevated preoperative alpha-fetoprotein level, and the presence of multiple tumors or microscopic vascular invasion had no bearing on survival longer than 5 years. However, patients who survived for 5 years who also had normal underlying liver or minimal fibrosis (score, 0-2) at surgery had significantly longer additional survival than did patients with moderate fibrosis (score, 3-4) or severe fibrosis/cirrhosis (score, 5-6) (P<.001). CONCLUSIONS: Death caused by HCC is rare beyond 5 years after resection of HCC in the absence of fibrosis or cirrhosis. The data suggest that chronic liver disease acts as a field of cancerization contributing to new HCC. These patients may benefit from therapies directed at the underlying liver disease.     

Difference in tumor invasiveness in cirrhotic patients with hepatocellular carcinoma fulfilling the Milan criteria treated by resection and transplantation: impact on long-term survival

SUMMARY BACKGROUND DATA: Some previous studies demonstrated better survival after transplantation for small hepatocellular carcinoma (HCC) compared with resection, but the influence of differences in tumor invasiveness between transplanted and resected patients has not been studied. This study compared the tumor characteristics of patients with HCC within the Milan criteria treated by resection or transplantation, and elucidated their impact on long-term survival. PATIENTS AND METHODS: Tumor characteristics and long-term survival of 204 cirrhotic patients with resection and 43 cirrhotic patients with transplantation for HCC within the Milan criteria were compared. A multivariate analysis was performed to determine the prognostic factors of survival in all patients with resection or transplantation. RESULTS: Tumors in the transplanted group were associated with lower incidence of high-grade tumors, microscopic venous invasion, and microsatellite nodules. The overall 5-year survival was better in the transplantation group than the resection group (81% vs. 68%, P = 0.017). However, there were no significant differences in survival between the two groups when stratified according to presence or absence of venous invasion. Multivariate analysis showed that hepatitis C virus serology, tumor size, tumor number, and microscopic venous invasion, but not resection or transplantation, were of prognostic significance. CONCLUSIONS: There were significant differences in tumor invasiveness in HCC treated by transplantation and resection as a result of selection bias, even in patients with the tumors fulfilling the Milan criteria. When the different tumor invasiveness was taken into account, there was no significant difference in the long-term survival after resection or transplantation.     

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     

Liver Retransplantation in Patients With HIV‐1 Infection: An International Multicenter Cohort Study

Liver retransplantation is performed in HIV‐infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV‐infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV‐infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.     

Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis

BACKGROUND: Detailed follow-up of patients with chronic hepatitis has resulted in increased diagnosis of hepatocellular carcinoma (HCC) in patients without cirrhosis. Despite numerous studies on hepatic resection, the prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. METHODS: Among 349 patients with HCC treated in the past 13 years, cirrhosis was absent in 126 patients (36 per cent). Curative hepatic resection was carried out in 100 (79 per cent) of these patients. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. RESULTS: Postoperative morbidity and mortality rates were 22 and 3 per cent respectively. The 5- and 10-year disease-free and overall survival rates were 31 and 50 per cent, and 22 and 47 per cent respectively. Blood loss, surgical resection margin, intrahepatic metastasis, portal vein invasion and extent of hepatic resection were independently associated with overall survival. However, the only risk factors for intrahepatic recurrence were portal vein invasion and hepatitis C virus (HCV) infection. The former was related to early recurrence while the latter was related to later recurrence. The 5-year disease-free survival rate was 58 per cent in patients with hepatitis B virus infection while it was 6 per cent in patients with HCV infection (P < 0.001). CONCLUSION: In the treatment of HCC without cirrhosis, major hepatectomy is advocated to prevent early recurrence. Liver transplantation may be required for patients with HCV infection.