Relationship between survivin expression and recurrence, and prognosis in hepatocellular carcinoma

AIM： To study the expression of the inhibitor of apoptosis protein survivin in hepatocellular carcinoma （HCC）, and its correlation with clinicopathological factors, cell proliferation, recurrence and prognosis after hepatectomy. METHODS： Immunohistochemical staining of survivin and Ki-67 was performed by the standard streptavidin- peroxidase technique on paraffin sections of 55 cases of HCC. RESULTS： The positive rate of survivin in HCC was 52.7% （29/55）. Significant correlation was found between survivin expression with portal vein thrombi and intrahepatic matastasistic nodes （P 〈 0.05）. The recurrent rate in survivin-positive HCC was significantly higher than that in survivin-negative HCC after hepatectomy, the 1- and 3-year survival rate in patients with survivin-positive tumors was significantly lower than that in patients with survivin-negative tumors （58.62 and 10.34% vs 76.92 and 30.77%, P 〈 0.05, log-rank test）. The proliferation index （Ki-67） in survivin-positive HCC （33.83% ± 18.90%） was significantly higher than that in survivin-negative HCC （19.60% ± 19.35%） （P 〈 0.05）. CONCLUSION： Survivin may play an important role in progression of HCC by promoting cell proliferation, and may be positively correlated with high risk of disease recurrence and poor prognosis in HCC. Its expression may serve as a prognostic factor for patients with HCC after hepatectomy.     

Hepatectomy for hepatitis B-, hepatitis C-, and dual hepatitis B- and C-related hepatocellular carcinoma in Taiwan

To evaluate the surgical results of patients with hepatitis B‐, hepatitis C‐ and dual hepatitis B‐ and C‐related hepatocellular carcinoma (HCC), we reviewed the clinical records 252 patients (196 men and 56 women) with complete profiles of hepatitis B and hepatitis C infection who had hepatectomies to treat HCC from March, 1992, to August, 1998. The patients were divided into four groups, 30 patients (11.9%) without either hepatitis B surface antigen or anti‐hepatitis C antibody (N‐HCC group), 133 patients (52.8%) with hepatitis B infection only (B‐HCC group), 66 patients (26.2%) with hepatitis C infection only (C‐HCC group), and 23 patients (9.1%) with dual hepatitis B and C infection (BC‐HCC group). Compared with the patients in the other groups, the patients in the C‐HCC group were older and had more severe cirrhotic change of the liver. The surgical complication rates and hospital mortalities in the C‐HCC and BC‐HCC groups were 30.3% and 12.1% and 30.4% and 17.4%, respectively, which were higher than those in the N‐HCC (13.3%, 3.3%) and B‐HCC (15.8%, 3.8%) groups. The mean disease‐free survivals for the N‐HCC, B‐HCC, C‐HCC, and BC‐HCC groups were 31.4, 25.4, 38.9 and 13.8 months, respectively, with the difference between the four groups being significant (P < 0.05). However, the mean overall survival times, 38.3 months for the N‐HCC group, 37.2 months for the B‐HCC group, 52.1 months for the C‐HCC group, and 32.7 months for the BC‐HCC group, were not significantly different (P = 0.146). In conclusion, surgical treatments for HCC related to hepatitis C or dual hepatitis B and C infection were associated with a higher surgical complication rate and hospital mortality. Hepatocellular carcinoma related to dual hepatitis B and C infection recurred earlier after hepatectomy, but the overall survival of the four groups was not significantly different.     

Diabetes mellitus affects long-term survival in hepatitis B virus-related hepatocellular carcinoma patients: A propensity score-matched analysis

Diabetes mellitus (DM) increases the risk of developing hepatocellular carcinoma (HCC), and how DM affects the prognosis of HCC have not been elucidated. The aim of this study was to compare clinicopathological characteristics and survival between hepatitis B virus (HBV)-related HCC patients with and without DM and to determine risk factors for overall survival after hepatectomy.Among 474 patients with HBV-related HCC, 119 patients had DM. Patients were divided into the diabetic group and nondiabetic group. The short-term and long-term outcomes were evaluated by using propensity score matching analysis.After 1:2 propensity score matching, there were 107 patients in diabetic group, 214 patients in nondiabetic group. The proportion of vessels invasion were higher in diabetic group. The overall survival rate in the diabetic group was 44.7% at 3 years, which was lower than that in the nondiabetic group (56.1%, P = .025). The multivariate analysis indicated that fasting blood glucose >7.0, capsular invasion, microvascular invasion and satellite were independent risk factor of poor prognosis in HCC.DM dose affect the recurrence-free survival and overall survival in HBV-related HCC patients after hepatectomy. One of the more significant findings to emerge from this study is that DM induced higher proportion of major vessel invasion in HCC patients implied unfavorable prognosis.     

Age-related comparison of the profiles of patients with hepatocellular carcinoma

BACKGROUND/AIMS: It is not known whether the putative etiologic factors and clinical and pathological features of hepatocellular carcinoma differ between young adults and older patients. Therefore this study aims to evaluate whether the clinicopathological features in young patients with HCC significantly differ from those of elderly patients. METHODOLOGY: A total of 1014 consecutive patients with HCC were divided into two groups based on age. Among them, 73 patients younger than 50 years of age comprised the first group and 941 patients 50 years and older made up the second. Clinical, laboratory, and pathological characteristics were compared between the two age groups. RESULTS: The male: female ratio and the incidence of positive hepatitis B surface antigen were significantly higher in young patients than in elderly patients. Tumor size, pathological grading of the tumor, and the severity of liver disease did not differ between the two groups. Especially in those patients demonstrating positive antibody to hepatitis C virus, alanine aminotransferase was higher in the younger, and platelet count was lower. Younger patients also had a higher ratio of alcohol consumption compared to elderly patients. CONCLUSIONS: There were age-related differences in the clinicopathological characteristics of HCC patients. Concerning hepatocarcinogenesis, male and HBsAg positive patients were at high risk in young. Of the HCV-related HCC patients, heavy drinking may accelerate the progression from chronic hepatitis to cirrhosis and HCC.     

Splenectomy before hepatectomy for patients with hepatocellular carcinoma and hypersplenism: A retrospective study

The spleen plays an important role in tumor progression and the curative effects of splenectomy before hepatectomy for hypersplenism and hepatocellular carcinoma (HCC) are not clear. We investigated whether splenectomy before hepatectomy increases survival rate among patients with HCC and hypersplenism compared with that of patients who underwent synchronous hepatectomy and splenectomy or hepatectomy alone.Between January 2011 and December 2016, 266 patients who underwent hepatectomy as a result of HCC and portal hypertension secondary to hepatitis were retrospectively analyzed. Their perioperative complications and survival outcome were evaluated.Patients underwent synchronous hepatectomy and splenectomy (H-S group) and underwent splenectomy before hepatectomy (H-preS group) exhibited significantly higher disease-free survival (DFS) rates than those of patients underwent hepatectomy alone (H-O group). The DFS rates for patients in the H-S group, H-preS group, and H-O group were 74.6%, 48.4%, 39.8%, and 80.1%, 54.2%, 40.1%, and 60.5%, 30.3%, 13.3%, at 1, 3, and 5 years after surgery, respectively. Tumor size, tumors number, and levels of alpha fetoprotein (AFP) were independent risk factors for DFS. Gender and tumor size were independent prognostic factor for overall survival (OS). The preoperative white blood cell (WBC) and platelet (PLT) counts were significantly higher in the H-preS group than in those of the H-S group and the H-O group. After operation, the WBC and PLT counts in the H-S group and H-preS groups were significantly higher compared to those of the H-O group.No matter splenectomy before hepatectomy or synchronous hepatectomy and splenectomy, hepatectomy with splenectomy may improve DFS rates in patients with HCC and hypersplenism, and splenectomy before hepatectomy alleviates hypersplenism without an increased surgical risk.     

Risk factors for postoperative infectious complications after hepatectomy

Background/purpose

This study aimed to clarify the incidence of surgical site infections (SSIs) after hepatectomy.

Methods

The database records of three hundred and eight patients who underwent elective surgical treatment for hepatolithiasis, hepatocellular carcinoma (HCC), and metastatic carcinoma were retrospectively analyzed to determine the occurrence of postoperative infectious complications. The incidences of SSIs, classified as superficial or deep incisional SSIs and organ or space SSIs, and all other infectious complications within 30?days after hepatectomy were evaluated.

Results

The incidences of SSIs after a hepatectomy for hepatolithiasis (23.8%) were higher than those after a hepatectomy for HCC (11.3%) (p?=?0.034) and after a hepatectomy for metastatic carcinoma (2.7%) (p?<?0.001), and the incidence of SSIs after a hepatectomy for HCC was higher than that after a hepatectomy for metastatic carcinoma (p?=?0.028). However, there was no significant difference in the incidence of remote site infections between the three groups. The incidence of superficial or deep incisional SSIs after a hepatectomy for hepatolithiasis (11.9%) was higher than that after a hepatectomy for metastatic carcinoma (1.4%) (p?<?0.001) and the incidence of superficial or deep incisional SSIs after a hepatectomy for HCC (7.8%) was higher than that after a hepatectomy for metastatic carcinoma (1.4%) (p?=?0.050). There was a significant difference in the incidence of space/organ SSIs between the patients with hepatolithiasis (11.9%) and HCC patients (3.6%) (p?=?0.029), and between the patients with hepatolithiasis and metastatic carcinoma patients (1.4%) (p?<?0.001). The rate of positive bile culture was 36.2% in all patients in this study, and the rates were 83.3, 7.8, and 10.0% for patients with hepatolithiasis, HCC, and metastatic carcinoma, respectively. A significantly higher (p?<?0.001) positive bile culture rate was observed in patients with hepatolithiasis as compared with HCC or metastatic carcinoma patients.

Conclusions

Our study suggests the existence of a relationship between postoperative SSIs and bile infection, thus supporting the proposed relationship between post-hepatectomy infection and such variables as liver function, blood sugar control, and nutritional status.     

Peg‐interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti‐HBV efficacy and long‐term survival among HBV DNA‐positive hepatocellular carcinoma patients after hepatectomy/ablation

Antiviral therapy has been shown to improve the prognosis of hepatitis B virus (HBV) DNA‐positive hepatocellular carcinoma (HCC) after radical treatment, but antiviral treatments require further optimization. This study aimed to evaluate the efficacies of different antiviral strategies with HCC patients after hepatectomy/ablation. This prospective, randomized, controlled and multi‐centre trial enrolled HBV DNA‐positive primary HCC patients after hepatectomy/ablation between January 2007 and January 2009. Patients were divided into four groups: early combination (entecavir plus Peg‐interferon [IFN]α‐2a co‐administration during year 1); late combination (addition of Peg‐IFNα‐2a for 48 weeks after 1 year of entecavir); nucleos(t)ide analogue[NA] monotherapy; and non‐antiviral treatment. Primary endpoints included recurrence‐free survival and overall survival. A total of 447 patients were enrolled. The 2‐year and 8‐year recurrence‐free survival and 8‐year overall survival rates were significantly higher in the early combination group than in the other two antiviral groups (P < .05). After 48‐week treatment, more patients achieved an HBsAg reduction >1500 IU/mL and the mean HBsAg level was significantly lower in the early combination group compared with the late combination and NA monotherapy groups (P < .05). Multivariate analysis showed that early combination therapy and a reduction in HBsAg by >1500 IU/mL after 48 weeks of therapy correlated with reduced mortality and disease recurrence. Early introduction of combination antiviral treatment may represent a more effective therapeutic strategy for patients with HBV DNA‐positive HCC after hepatectomy/ablation. A reduction in HBsAg by >1500 IU/mL after 48‐week treatment is associated with reduced mortality and disease recurrence of HBV DNA‐positive HCC patients after hepatectomy/ablation.     

肝细胞癌高危人群标准的探讨

目的 从肝细胞癌患者中确立高危因素,探讨肝细胞癌高危人群的确立, 并由此推算高危人群普查及其定期自我检验的重要意义。方法 对1725例行肝细胞癌切除术的患者进行回顾性随访,将随访资料完整的1457例进行临床分期及其与肝内无瘤生存的相关分析,根据频数表划分肝细胞发病危人群段。结果 肝细胞癌患者年龄分布呈相对正态分布,取90％可信区间,高危人群年龄段为31－65岁。亚临床期肝细胞癌患者术后无瘤生存状况明显好于临床期者。结论 可将血清抗－HBc阳性或／及HBsAg阳性,尤其是乙型肝炎病史,年龄31－65岁者作为国内肝细胞癌的高危人群。加对此人群普查,增强其定期体检意识,可使大部份肝细胞癌患者得以在亚临床期早发现早治疗,在现有的医疗技术条件下将肝细胞癌的治疗提高到一个新水平。     

Hepatitis C in the elderly: a multicentre cross-sectional study by the Italian Association for the Study of the Liver

BackgroundThe prevalence of hepatitis C virus infection increases with advancing age, but elderly hepatitis C virus patients remain an understudied population.AimTo define the virological, epidemiological and clinical profiles of Italian outpatients aged 65 years and over infected by hepatitis C virus.MethodsWe evaluated 1544 anti-hepatitis C virus positive patients aged ≥65 years referred to 34 Italian outpatient specialty clinics over a two-year period.ResultsThe study population included 1134 (73%) early elderly (65–74 years) and 410 (27%) late elderly patients (≥75 years). Late elderly subjects were less likely to have their virus genotyped, their viral load assessed or a histological evaluation of liver disease. Overall, 30% of patients had advanced liver disease whose prevalence increased with increasing age. In both age groups, about 40% of patients had normal transaminase levels. Excluding patients with past infection, 51% had not received any antiviral treatment and only 25% were treated after the age of 65. Late elderly patients, women and patients with advanced liver diseases had been less frequently treated. The main reason for exclusion from treatment was age followed by the presence of comorbid conditions.ConclusionsElderly hepatitis C virus patients referred to Italian specialty clinics have advanced and underestimated liver disease. Nevertheless, they are progressively understudied in parallel with increasing age.     

Risk factors of intrahepatic recurrence after curative resection of hepatocellular carcinoma

BACKGROUND/AIMS: Although the risk factors for the development of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC) have been widely studied, little attention has been given to the prognostic factors affecting such patients. METHODOLOGY: Intrahepatic recurrence occurred in 105 (56%) of 188 patients who underwent curative hepatic resection of HCC and were discharged from the hospital. Among them, 17 (16%) also had simultaneous extrahepatic recurrence. Independent prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that presence of extrahepatic recurrence, hepatitis B, and non-surgical treatments for recurrence were independent predictors of poor overall survival after initial hepatic resection or after recurrence. Risk factors of extrahepatic recurrence were young age, solitary and large HCC, high hepatitis activity, and large amount of intraoperative blood loss and blood transfusion. CONCLUSIONS: Survival of patients with intrahepatic recurrent HCC after resection should be stratified by the type of recurrence, type of hepatitis, and type of treatment for recurrence.     

Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma

Aim: The aim of this study was to investigate the characteristics of super‐elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Methods: Between March 1992 and December 2008, 278 patients who underwent curative hepatectomy for HCC were investigated. Super‐elderly patients were defined as those aged 80 years or more. Clinicopathological data and outcomes after hepatectomy were compared between super‐elderly and non‐super‐elderly groups. Results: Preoperative parameters, such as biochemical examinations, and liver function tests in the non‐super‐elderly group were comparable with those of the super‐elderly group (n = 11). Exceptionally, albumin level in the super‐elderly group was lower than that in the non‐super‐elderly group (P = 0.03). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. No mortality was observed in the super‐elderly and non‐super‐elderly group. Conclusions: Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection.     

Chronic hepatitis B virus infection in Asian countries

Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.     

Efficacy of preoperative portal vein embolization prior to major hepatectomy for patients with impaired liver function: A retrospective study

Hepatocellular carcinoma (HCC) is often associated with chronic liver disease, such as hepatitis or cirrhosis, and this association may limit the use of surgery as a therapy, and if surgery is pursued, may give rise to postoperative hepatic failure. We evaluated the outcome in patients with HCC given preoperative portal vein embolization (PVE) before they underwent major hepatectomy. After PVE, portal pressure increased significantly. Two weeks after PVE, both the volume of the non-embolized lobe and the 15-min indocyamine green retention rate (ICG R15) were significantly increased. The prognostic score, calculated on the basis of age, ICG R15, and the resection rate, was significantly decreased. The operative mortality rate was significantly lower in patients who underwent PVE before surgery than in patients who did not receive PVE. The cumulative survival rate of the PVE patients, even those with cirrhosis of the liver, was significantly higher. Prior PVE appears to allow more extensive major hepatectomy and to lessen the risk of this invasive surgery. However, patients in whom the portal pressure immediately after PVE was more than 30cm H₂O and/or whose prognostic score exceeded 50 points developed postoperative hepatic failure. These features should be kept in mind when it is decided whether surgery is indicated. Nevertheless, preoperative PVE appears to be a beneficial procedure for patients undergoing major hepatectomy, particularly those with chronic liver disease.     

立体定向放疗治疗老年单发肝细胞肝癌近期疗效分析

目的探讨立体定向放疗治疗老年单发肝细胞肝癌（hepatocellular carcinoma, HCC）的近期疗效及安全性。 方法选取浙江大学医学院附属第一医院收治的22例老年HCC患者（均为单发肝内病灶且肿瘤最大径<5 cm）,均行立体定向放疗,放疗后1、3、6个月行肝脏增强MRI检查评价近期疗效（分为完全缓解、部分缓解、局部稳定、局部进展）和不良反应（主要包括骨髓抑制、肝功能损伤、放射性胃肠炎、放射性肝病等）。 结果与放疗前比较,放疗后1、3、6个月的HCC病灶均显著缩小（t=6.211、4.824、4.209,均P<0.01）。随访期内总有效率相对稳定,放疗后1、3、6个月的近期总有效率（完全缓解率+部分缓解率）分别为81.8%、77.3%、72.7%。治疗及随访期间主要不良反应为骨髓抑制、肝功能损伤、放射性胃肠炎,患者均能耐受。 结论立体定向放疗治疗老年单发HCC效果良好,不良反应可耐受。     

肝癌组织IFITM3蛋白表达水平及其与肝细胞癌患者手术切除术后肝内肿瘤复发的相关性分析*

目的 探讨肝细胞癌（HCC）组织干扰素诱导跨膜蛋白 3（IFITM3）表达水平及其临床意义。方法 在我院接受根治性手术切除治疗的43例HCC患者,术中取癌组织和癌旁肝组织,分别采用Western blot法和免疫组化法检测组织IFITM3蛋白表达情况,比较肝内肿瘤复发与未复发患者癌组织IFITM3表达的差异。结果 经Western blot法检测肝癌组织IFITM3表达水平为（1.2386±0.1901）,显著高于癌旁组织的（0.9496±0.0995,t=8.832,P=0.000）;免疫组化法检测显示肝癌组织IFITM3蛋白阳性率为72.1%（31/43）,明显高于癌旁组织的14.0%（6/43,x²=29.647,P=0.000）;中分化肝癌组织IFITM3蛋白阳性率为90.9%（10/11）,低分化肝癌组织为95.2%（20/21）,均明显高于高分化组的9.1%（1/11）（x²=14.727, P=0.000;x²=23.748,P=0.000）;术后复发组癌组织IFITM3蛋白阳性率为81.0%（17/21）,未复发组为22.7%（5/22）,两者比较差异具有统计学意义（x²=14.578,P=0.000）。结论 HCC组织IFITM3蛋白呈高表达,且肝癌分化越差,IFITM3表达也越强,并可能与术后肿瘤复发有关。     

Surgical outcome in cirrhotic patients with hepatitis C-related hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to clarify the surgical outcome in cirrhotic patients with hepatitis C-related hepatocellular carcinoma (HCC). METHODOLOGY: The surgical outcome of 26 HCVAb-positive cirrhotic patients with hepatitis C antibody (the C-related HCC group) and 18 HCVAb-negative cirrhotic patients with (the non-C-related HCC group) undergoing hepatectomy for HCC were compared. The C-related HCC group was HCVAb[+], HBsAg[-] for hepatitis B surface antigen in 25 patients and HCVAb[+], HBsAg[+] in 1, and the non C-related HCC group was HCVAb[-], HBsAg[+] in 15 and HCVAb[-], HBsAg[-] in 3. RESULTS: Preoperative aspartate and alanine aminotransferase in the C-related HCC group were significantly (P < 0.01) higher than in the non-C-related HCC group. There were no significant differences in the operative method, intraoperative blood loss and weight of resected liver or pathological data between the 2 groups. In the recurrence pattern, the incidence of multicentric occurrence in the C-related HCC group (53.3%) was significantly (P < 0.05) higher than in the non-C-related HCC group (7.7%). The mortality rate in both groups was 0% and no operative death was encountered. The crude survival and disease-free survival rates at 3 years were similar: 80.8% and 57.7% in the C-related HCC group and 77.8% and 55.6% in the non-C-related HCC group, respectively. CONCLUSIONS: Although surgically treated cirrhotic patients with C-related HCC showed worse preoperative hepatitis status and a higher incidence of recurrence due to multicentricity compared with non-C-related HCC, the mortality and prognosis of patients with C-related HCC did not differ from that of non-C-related HCC. The indication of hepatic resection and consideration for the high incidence of postoperative multicentric occurrence in the patients with C-related HCC should therefore be more careful than in patients with non-C-related HCC.     

Lamivudine treatment enabling right hepatectomy for hepatocellular carcinoma in decompensated cirrhosis

A 69-year-old man was admitted to our hospital in October 2003, for further examination of two liver tumors. He was diagnosed with hepatocellular carcinoma (HCC) arising from decompensated hepatitis B virus (HBV)-related cirrhosis. Long-term lamivudine administration improved liver function dramatically despite repeated treatment for HCC. His Child-Pugh score was 9 points at start of lamivudine treatment, improving to 5 points after 1 year. His indocyanine green at 15 min after injection test score was 48% before lamivudine treatment, improving to 22% after 2 years and to 5% after 4 years. Radiofrequency ablation controlled the HCC foci and maintained his liver function. In April 2009, abdominal computed tomography revealed a tumor thrombus in the right portal vein. Since his indocyanine green test results had improved to less than 10%, we performed a right hepatectomy, which was successful. To our knowledge, there have been no documented reports of patients undergoing successful right hepatectomy for HCC arising from decompensated cirrhosis. The findings observed in our patient indicate the importance of nucleoside analogs for treating HBV-related HCC.     

Hepatocellular carcinoma developed in a living donor after left lobe donation: a case for caution

Although it has been recognized that those who are positive for anti‐hepatitis B core antibody (anti‐HBcAb) and negative for hepatitis B surface antigen (HBsAg) with normal liver function could be donors for living donor liver transplantation under appropriate prophylaxis, the negative impact of positive HBcAb on such donors themselves has not been reported. We present a case of a living donor with positive HBcAb, who donated his left lobe for his sister with unresectable giant hepatic hemangioma, and the donor himself developed a de novo hepatocellular carcinoma (HCC) 10 years after donation. He had been lost from the follow‐up program since 1 year after donation. Imaging studies showed a heterogeneously enhanced mass compatible with HCC, which was 9 cm in size with portal invasion into the anterior portal vein of the remnant liver. Re‐laparotomy for hepatectomy with the removal of the tumor thrombus in the anterior portal vein of the remnant liver was carried out, and he is free from recurrence 6 months after surgery on prophylactic sorafenib. At our institute, 58 (9.6%) donors among the 603 living donors were anti‐HBcAb positive and anti‐HBsAg negative, and we started regular HCC surveillance using sonogram every 6 months for these patients.     

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: A nationwide cohort study

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC ), and surveillance with ultrasound (US ) and alpha‐fetoprotein (AFP ) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR ) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona‐Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0‐3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY ), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI 95% 0.4‐1.5] in 2002‐2003 to 2.9/100 PY [2.4‐3.4] in 2012‐2013. One‐year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP  ≥ 20 ng mL^?1 was 17%. Twenty‐three (21%) patients were diagnosed with early‐stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early‐stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.     

乙型肝炎病毒感染者肝组织IL-12表达及其意义

目的探讨乙型肝炎病毒感染者肝组织白细胞介素12（IL-12）表达与临床表现和肝脏病理学变化的关系。方法应用免疫组化法检测9例正常肝脏组织、183例慢性乙型肝炎（CHB）、41例乙型肝炎肝硬化、37例HBV相关肝癌患者肝组织IL-12表达情况,并与临床特点和病理分级等进行相关性分析。结果 CHB患者肝组织IL-12以弱阳性表达为主,阳性和强阳性表达的比例仅为26.8%,而肝硬化和肝癌患者阳性和强阳性表达的比例分别为36.6%和48.6%,均显著高于CHB患者（P＜0.05）;HBeAg阴转且HBV DNA阴转的CHB患者肝内IL-12阳性表达比例为64.3%,显著高于HBeAg阳性伴肝功能异常者（30.0%）和肝功能正常者（20.4%）（P＜0.05）;未发现IL-12表达与肝脏炎症分级或纤维化分期具有相关性。结论 IL-12可能参与HBV感染后的疾病进展与转归。