Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry.

BACKGROUND: It is unclear whether mild to moderate iron overload in liver diseases other than hereditary haemochromatosis (HH) contributes to hepatocellular carcinoma. This study examined the association between hepatic iron grade and hepatocellular carcinoma in patients with end-stage liver disease of diverse aetiologies. METHODS: The prevalence of hepatic iron overload and hepatocellular carcinoma was examined in 5224 patients undergoing liver transplantation. Explant pathology reports were reviewed for the underlying pathological diagnosis, presence of hepatocellular carcinoma and degree of iron staining. The distribution of categorical variables was studied using chi(2) tests. RESULTS: Both iron overload and hepatocellular carcinoma were the least common with biliary cirrhosis (1.8 and 2.8% respectively). Hepatocellular carcinoma was the most common in patients with hepatitis B (16.7%), followed by those with hepatitis C (15.1%) and HH (14.9%). In the overall cohort, any iron overload was significantly associated with hepatocellular carcinoma (P=0.001), even after adjustment for the underlying aetiology of liver disease. The association between hepatic iron content and hepatocellular carcinoma was the strongest in patients with biliary cirrhosis (P<0.001) and hepatitis C (P<0.001). CONCLUSIONS: Iron overload is associated with hepatocellular carcinoma in patients with end-stage liver disease, suggesting a possible carcinogenic or cocarcinogenic role for iron in chronic liver disease.     

Sarcomatous hepatocellular carcinoma without previous anticancer therapy

Sarcomatous hepatocellular carcinoma is a rare neoplasm of the liver. A 79-year-old man with a liver tumor was admitted to our hospital. Enhanced computed tomography and magnetic resonance imaging revealed a cystlike lesion, whereas abdominal ultrasonography revealed a solid tumor. The patient underwent medial segmentectomy of the liver for the presumptive diagnosis of atypical hepatocellular carcinoma. Microscopically, the tumor was diagnosed as hepatocellular carcinoma with sarcomatous change. Although anticancer therapy is presumed to be a cause of sarcomatous change in hepatocellular carcinoma, some cases in which patients had not previously undergone anticancer therapy have been reported. Here we report a case of sarcomatous hepatocellular carcinoma without previous anticancer therapy and present a review of the literature.     

Pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma

Background

Pyogenic liver abscess and hepatocellular carcinoma are common in Taiwan. We investigated the frequency of, risk factors for, and prognosis of pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma over a 12-year period in Taiwan.

Methods

We extracted 32,454 patients with pyogenic liver abscess from a nationwide health registry in Taiwan during the period 1997-2008. The frequency of and risk factors for pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma were determined. The prognosis of these patients was compared with patients with hepatocellular carcinoma but without liver abscess.

Results

A total of 698 (2.15%) patients presented with liver abscess as the initial manifestation of underlying hepatocellular carcinoma during the 12-year period. Liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, and age ≥65 years were independent risk factors for liver abscess as the initial manifestation of underlying hepatocellular carcinoma. Furthermore, these patients had a lower 2-year survival rate than patients with hepatocellular carcinoma but without liver abscess (30% vs 37%; P = .004).

Conclusions

The prognosis of patients who presented with pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma was poor. Physicians should not ignore the possibility of underlying hepatocellular carcinoma in patients with risk factors for the disease in regions with a high prevalence of both pyogenic liver abscess and hepatocellular carcinoma.     

Early diagnosis of hepatocellular carcinoma using a sensitive assay for serum des-gamma-carboxy prothrombin: a prospective study

BACKGROUND/AIMS: Measurement of des-gamma-carboxy prothrombin by conventional methods is of limited use for the early detection of hepatocellular carcinoma for its low sensitivity. The aim of the present study was to investigate the usefulness of measuring des-gamma-carboxy prothrombin by a highly sensitive assay for the early diagnosis of hepatocellular carcinoma in patients with chronic liver disease and for the detection of recurrence after treatment of hepatocellular carcinoma. METHODOLOGY: Des-gamma-carboxy prothrombin levels by a sensitive assay and alpha-fetoprotein levels were sequentially measured in 188 patients with type B or C chronic liver disease and in 63 patients with hepatocellular carcinoma. RESULTS: The positive rate of des-gamma-carboxy prothrombin was 62% in all of hepatocellular carcinoma patients. Hepatocellular carcinoma was detected in 14 of 188 chronic liver disease patients during their follow-up period, the positive rate of des-gamma-carboxy prothrombin and of alpha-fetoprotein being 57% and 71% in these 14 patients, respectively. Des-gamma-carboxy prothrombin level normalized in 67% of 39 patients after the treatment of hepatocellular carcinoma. Of the 19 patients with tumor recurrence, 84% showed re-elevation of des-gamma-carboxy prothrombin level. CONCLUSIONS: Measurement of des-gamma-carboxy prothrombin by this highly sensitive assay combined with alpha-fetoprotein is useful for detecting hepatocellular carcinoma in chronic liver disease patients and for monitoring recurrence after treatment of hepatocellular carcinoma.     

Detection of telomerase activity in hepatocellular carcinoma by fluorescence-based TRAP method

Telomeres are important for the function and stability of eukaryotic chromosomes. Telomeric DNA is shortened every time liver cells divide. Normal human liver cells have a limited proliferative capacity, but immortalized cells prevent the shortening of the end of chromosomes by the expression of telomerase, the enzyme that elongates telomeric DNA. Although many genetic alterations have been reported in hepatocellular carcinoma, whether all hepatocellular carcinoma are immortalized cells is not known. Therefore, the telomerase activity was analyzed in 38 frozen samples from human hepatocellular carcinoma by fluorescence-based TRAP Method. Telomerase activity was detected in 34 (89.47%) of 38 hepatocellular carcinoma tissues regardless of tumor size, but telomerase activity was detected in only 12 (31.58%) of 38 nontumor liver tissues from patients with hepatocellular carcinoma. Diagnosis of hepatocellular carcinoma is sometimes difficult when the hepatomas are small and are of the differentiated type. Our results showed that the expression of telomerase may be of great value in diagnosing hepatocellular carcinoma.     

Bilateral adrenal metastases from hepatocellular carcinoma after liver transplantation

Therapeutic management of hepatocellular carcinoma is a controversial issue. Orthotopic liver transplantation is an alternative for the treatment of hepatocellular carcinoma in a selected group of patients, but recurrence is possible. A 51-year-old patient with liver transplantation due to hepatocellular carcinoma presented bilateral adrenal metastases in a successive manner. A left adrenal gland metastasis was diagnosed five months after liver transplantation, and a left adrenalectomy was carried out. Eight months later, a right adrenal gland metastasis was diagnosed, and a right adrenalectomy was performed. Pathological examination confirmed the diagnosis of a well-differentiated hepatocellular carcinoma. At present, there is no evidence of recurrence 35 months after the second adrenalectomy. Bilateral adrenal gland metastases from hepatocellular carcinoma after liver transplantation have not been previously reported in English literature. Surgical resection of metastases may be indicated in similar patients with successful treatment of the primary tumor, absence of additional metastasic disease, and good performance status.     

非酒精性脂肪性肝病与肝细胞癌发生

肝细胞癌的发病率在全球逐年升高。绝大多数肝细胞癌与肝炎病毒感染有关,然而非酒精性脂肪性肝病也是引起肝细胞癌的重要原因之一。近年来,随着饮食习惯及生活方式的改变,非酒精性脂肪性肝病发病率持续升高,其与肝细胞癌发生的关系也得到了更多的关注。本文主要从非酒精性脂肪性肝病相关肝细胞癌的发病进程、危险因素及发病机制等方面做一介绍。     

HBV感染抗病毒治疗中发生肝细胞癌24例临床分析

目的探讨HBV感染抗病毒治疗过程中发生肝细胞癌(HCC)的原因和诊断方法。方法回顾性分析24例HBV感染(肝炎后肝硬化者18例、CHB者6例)抗病毒治疗过程中发生HCC的病例,分析其发生原因及诊断方法。结果 HBV感染抗病毒过程中发生HCC常见。患肝病时间、男性、抗病毒治疗效果不佳(或发生病原学突破)、吸烟、饮酒、糖尿病是抗病毒治疗过程中发生HCC常见原因。肝硬化发展至肝癌常无症状,慢性肝炎发展至肝癌常有肝区不适、生物化学检测结果异常、HBV载量变化。AFP、彩色多普勒超声、CT联合检查基本可以完成HCC的临床诊断,必要时辅以肝脏病理学检查。结论 HBV感染抗病毒过程中发生HCC常见,提高认识有利于早期发现HCC。     

Liver stiffness measurement using transient elastography and hepatocellular carcinoma

Liver fibrosis has been gaining noticeable attention because it may lead to end-stage liver cirrhosis and ultimately to hepatocellular carcinoma. Thus, a precise estimation of the degree of liver fibrosis is crucial for predicting prognosis and deciding management of patients with chronic liver diseases. Many non-invasive approaches for the evaluation of liver fibrosis have been developed. Among these procedures, transient elastography has recently drawn great attention. Transient elastography has been reported to be well correlated with the degree of liver fibrosis by many investigators and various institutions. Since the degree of liver fibrosis is considered as a strong predictor of risk for hepatocellular carcinoma development, several trials have been performed to verify the usefulness of measurement of liver stiffness to predict the emergence of hepatocellular carcinoma. From these studies, transient elastography seems to be a promising procedure to predict the risk of hepatocellular carcinoma; however, further cohorts with long-term monitoring of liver stiffness are needed to confirm the usefulness of this method.     

双探针原位杂交法检测慢性肝病和肝细胞癌患者肝组织TTV DNA的感染状况

目的 探讨慢性肝病和肝细胞癌患者肝组织TIV DNA的感染状况。方法采用PCR扩增法分别合成G1a、G2b两种亚型的双链TTV DNA探针。应用两型探针对45例肝组织标本进行TTV DNA原位杂交检测，巢氏PCR法检测血清TTV DNA。结果31例血清TTTV DNA阳性患者的肝组织TTV DNA均为阳性(100％)。14例血清TTV DNA阴性的患者肝组织中TTV DNA阳性者7例(50%)。慢性肝病患者的肝组织中TTV DNA散在分布在汇管区周围的肝细胞核内，肝癌患者TTV DNA则集中分布在肝癌细胞核内及癌组织周围的肝细胞核内。结论慢性肝病与肝癌患者肝组织中TTV DNA的感染状态存在一定差异。     

Specificity of androgen receptors of hepatocellular carcinoma and liver in humans

The specificity of androgen receptor in hepatocellular carcinoma and the liver was investigated using auto-radiographic techniques. Partial hepatectomy was carried out on 11 patients with hepatocellular carcinoma and associated parenchymal disease of the liver. Androgen receptors were assayed biochemically for hepatocellular carcinoma and the surrounding liver in all cases. Estrogen receptor was also measured in five patients. In eight patients, fresh resected specimens as thick as 3 mm were first incubated for 15 minutes in a medium containing estradiol and hydrocortisone, and then radio-labeled testosterones were added to the medium. After another 60 minutes incubation, macro-autoradiographic studies were carried out. With the same medium and chemicals, and using the same principle, micro-autoradiographic studies were performed using fresh hepatocellular carcinoma and liver cell suspensions in six cases. The radio-labeled testosterones were incorporated into hepatocellular carcinoma and the liver to a parallel extent with the androgen receptor titers biochemically assayed. The current results seem to indicate that androgen receptors present in hepatocellular carcinoma and the liver of humans specifically bind androgens. Further studies are needed to elucidate the role of AR in hepatocarcinogenesis in humans.     

Liver transplantation in a patient treated by sorafenib for hepatocellular carcinoma

Sorafenib is a multikinase inhibitor currently used in the palliative treatment of advanced hepatocellular carcinoma. In patients with small hepatocellular carcinoma, sorafenib could be suggested as neoadjuvant therapy to control tumor growth during waiting time for liver transplantation. However, up to now, safety of liver transplantation in patients undergoing sorafenib treatment is not known. Herein, we report a case of successful liver transplantation in a patient treated by sorafenib for hepatocellular carcinoma. In this patient, liver transplantation was performed safely and histological examination of explanted liver evidenced complete necrosis of the largest tumor nodule.     

Plasma fucosyltransferase activity in patients with hepatocellular carcinoma, with special reference to correlation with fucosylated species of alpha-fetoprotein

BACKGROUND/AIMS: Our previous results showed that the percentage of fucosylated species of alpha-fetoprotein (AFP) in total AFP, fucosylation index, was a very useful diagnostic tool to distinguish AFP due to hepatocellular carcinoma from AFP due to non-neoplastic liver diseases. On the other hand, alpha1-6 fucosyl-transferase (alphaFT) catalyzes the addition of fucose from GDP-fucose through an alpha1-6 linkage to the reducing end of N-acetylglucosamine residue of N-linked oligosaccharides of glycoproteins. However, the biological and clinical significance of alphaFT in patients with hepatocellular carcinoma is not fully understood. In the present study, we measured alphaFT activity to elucidate the enzymatic background of fucosylated species of AFP in hepatocellular carcinoma. METHODS: Plasma samples from 84 cases of hepatocellular carcinoma, 40 of liver cirrhosis, 40 of chronic hepatitis and 30 of normal controls, and 26 paired samples of hepatocellular carcinoma and surrounding noncancerous tissues were enrolled in the present study. AlphaFT activity was measured by high performance liquid chromatography with a synthesized fluorescence-labeled glycopeptide with an asialoagalactobiantennary sugar chain as a substrate in the presence of GDP-fucose. RESULTS: Plasma alphaFT activities (mean+/-SD, pmol/ml/h) in patients with hepatocellular carcinoma, liver cirrhosis, chronic hepatitis and normal controls were 435+/-271, 490+/-290, 590+/-209 and 380+/-133, respectively. AlphaFT levels in hepatocellular carcinoma and chronic liver diseases were increased compared with that in normal controls. A statistically significant positive correlation was observed between plasma alphaFT activity and fucosylation index of AFP (r=0.34, p= 0.0032) in 60 patients with hepatocellular carcinoma, in which increments of serum AFP were observed. When the tentative cutoff value of fucosylation index was set at 18%, which corresponded to the cutoff value to discriminate between hepatocellular carcinoma and non-neoplastic liver diseases in our previous study, the plasma alphaFT activity in hepatocellular carcinoma patients whose fucosylation index was more than 18% (n=32, 523+/-324 pmol/ml/h) was higher than that in hepatocellular carcinoma patients whose fucosylation index was equal to or less than 18% (n=28, 383+/-229) (p=0.055). An increment of the plasma levels of alphaFT occurred in accordance with an advancement of hepatocellular carcinoma stages. Tissue aFT activity in hepatocellular carcinoma (175+/-178 pmol/mg/h) was higher than those in surrounding noncancerous liver (144+/-134) and in normal liver (79+/-19). The mean alphaFT activities in well-, moderately- and poorly-differentiated hepatocellular carcinoma were 38+/-0.7, 177+/-182 and 219+/-189, respectively, and they tended to increase with dedifferentiation in hepatocellular carcinoma tissues. CONCLUSIONS: The present study indicates that alphaFT is responsible for the formation of the fucosylated species of AFP in hepatocellular carcinoma and suggests that the measurement of alphaFT provides a possible aid in the evaluation of the degree of advancement in patients with hepatocellular carcinoma.     

Hepatocellular carcinoma in a hepatitis C patient with sustained viral response and no fibrosis

Hepatitis C poses a substantial global health burden. Three to five percent of individuals with liver cirrhosis secondary to hepatitis C will develop hepatocellular carcinoma. The development of hepatocellular carcinoma is closely associated with cirrhosis in hepatitis C infection, whereas in hepatitis B virus infection, hepatocellular carcinoma may occur in the absence of cirrhosis. Although uncommon, hepatocellular carcinoma has been reported in hepatitis C patients without cirrhosis and, in very rare cases, in the absence of active viral replication. We report the case of a 51-year-old patient with hepatitis C who developed hepatocellular carcinoma in the absence of fibrosis and after having achieved sustained virological response with combination peginterferon and ribavirin therapy seven years prior. The patient successfully underwent surgical resection, and histopathological examination of the resected tissue demonstrated a poorly-differentiated hepatocellular carcinoma in an otherwise unremarkable liver. The patient continues to do well and has no evidence of tumor recurrence 18 months post-operatively. This case raises question regarding the carcino-genesis of hepatocellular carcinoma as a sequela of chronic hepatitis C in noncirrhotic liver and moreover after achieving sustained virological response.     

Percutaneous microwave coagulation therapy for superficial hepatocellular carcinoma on the surface of the liver

BACKGROUND/AIMS: This study was performed to evaluate the efficacy and safety of percutaneous microwave coagulation therapy for superficial hepatocellular carcinoma located on the surface of the liver. METHODOLOGY: Among 58 cirrhosis patients with 71 hepatocellular carcinomas measuring < or = 20 mm in greatest dimension, 18 patients had a solitary superficial lesion located on the liver surface (superficial hepatocellular carcinoma group) and the other 40 patients had 53 lesions that were not in contact with the liver surface (non-superficial hepatocellular carcinoma group). All patients were treated by percutaneous microwave coagulation therapy alone and the response was assessed by using contrast-enhanced CT. The survival, tumor recurrence, and adverse effects were compared between the superficial and non-superficial hepatocellular carcinoma groups. RESULTS: The 4-year survival rates of the superficial hepatocellular carcinoma group (64.2%) and the non-superficial hepatocellular carcinoma group (58.9%) were not significantly different, and neither were the 4-year local recurrence rates (27.1% vs. 29.8%). Although there was a significantly higher incidence of severe pain during microwave irradiation in the superficial hepatocellular carcinoma group (23/47) when compared with the non-superficial hepatocellular carcinoma group (25/148), there were no differences between them in the incidence of fever or the changes in liver function after treatment. There were no serious adverse effects, such as hemorrhage or tumor cell seeding, in either group. CONCLUSIONS: Percutaneous microwave coagulation therapy can be performed safely, even in patients with superficial hepatocellular carcinoma and cirrhosis, so this method is effective for treating hepatic neoplasms regardless of the tumor location.     

Health-related quality of life of chronic liver disease patients with and without hepatocellular carcinoma

BACKGROUND AND AIM: Impaired health-related quality of life has been reported in patients with cirrhosis and chronic hepatitis. However, only limited data are available concerning the influence of hepatocellular carcinoma. METHODS: Health-related quality of life was assessed in 97 patients with hepatocellular carcinoma who had been treated successfully with percutaneous ablation therapy, and 97 patients with chronic liver disease without hepatocellular carcinoma matched for age and sex, using the Japanese version of Short-Form 36. Raw scores were transformed using norm-based scoring. The relations with objective variables including status of hepatocellular carcinoma and laboratory data were analyzed. RESULTS: Health-related quality of life was lower in both groups than in the general population. Patients with hepatocellular carcinoma and patients in the control group showed similar scores. By multivariate analysis, liver function, especially serum albumin, strongly predicted health-related quality of life, but status of hepatocellular carcinoma did not. CONCLUSIONS: Impaired health-related quality of life was not associated with the presence of hepatocellular carcinoma but dependent on the level of liver function, indicating the importance of preserving liver function in following up patients. Serum albumin level was a useful objective variable to assess health-related quality of life of patients with chronic liver disease.     

肝癌组织中ICAM-1的表达和意义

目的研究细胞间黏附分子-1(1CAM-1)在原发性肝癌中的临床意义.方法以免疫组化方法结合全自动图像分析观察40例肝细胞癌组织及其癌旁组织和28例肝硬化组织中ICAM-1的表达.结果40例肝细胞癌组织ICAM-1表达阳性率为80.0%(32/40)、癌旁组织为57.5%(23/40)、肝硬化为53.6%(15/28),阳性率与组织学分类相关.肝癌组织中ICAM-1含量明显高于癌旁及肝硬化组织(P＜0.05),转移组肝癌中ICAM-1的含量明显高于非转移组(P＜0.05),而癌旁及肝硬化组织中表达差异无显著性(P＞0.05).结论肝癌组织中高度表达ICAM-1,ICAM-1有可能作为判断肝硬化及肝癌发展程度及预后的指标之一.     

Spontaneous total necrosis of hepatocellular carcinoma: report of a case

We report on a 50-year-old man with a liver mass that, when surgically resected, was found to be a hepatocellular carcinoma that had undergone spontaneous complete necrosis without previous treatment. Histologically, no viable tumor cells were observed. The postoperative course was uneventful, and the patient is alive without evidence of recurrence about 5 years after surgery. Spontaneous total necrosis of hepatocellular carcinoma without previous treatment is rare. In particular, spontaneous total necrosis of a hepatocellular carcinoma that has been proven by histologic examination of a surgically resected liver specimen is extremely rare; only three cases of spontaneous complete necrosis of hepatocellular carcinoma have been reported previously. In this report, we present our unusual case and discuss possible causes of spontaneous total necrosis or regression of hepatocellular carcinoma.     

Specificities of serum alpha-fetoprotein in HBsAg+ and HBsAg- patients in the diagnosis of hepatocellular carcinoma.

Serum alpha-fetoprotein level is often elevated in patients with chronic liver disease and patients with hepatocellular carcinoma. One of the most difficult problems frequently encountered in practice is differentiating hepatocellular carcinoma from chronic liver disease. This study investigated the specificity and predictive value positive of serum alpha-fetoprotein at various levels in the diagnosis of hepatocellular carcinoma, using 54 patients with histologically proven hepatocellular carcinoma and 200 patients with chronic liver disease (40 patients with chronic active hepatitis and 160 patients with cirrhosis) as nontumor controls. Among 254 patients, 170 (66.9%) were HBsAg+. A wide range of overlap (from 0 to 6,400 ng/ml) in the distribution of serum alpha-fetoprotein levels between hepatocellular carcinoma and chronic liver disease patients was observed mainly among HBsAg+ patients. In contrast, the overlapping range of serum alpha-fetoprotein levels between HBsAg- patients with hepatocellular carcinoma and chronic liver disease was remarkably narrow (from 0 to 200 ng/ml). Therefore the specificity and predictive value positive of alpha-fetoprotein at a given level were significantly lower in HBsAg+ than in HBsAg- patients, especially when alpha-fetoprotein was between 25 and 200 ng/ml. The specificities of alpha-fetoprotein at 200 ng/ml and 400 ng/ml in HBsAg+ patients were 79.8% and 91.5%, respectively, whereas these specificities were both 100% in HBsAg- patients. The predictive values positive at 200 ng/ml and 400 ng/ml in HBsAg+ patients were 53.6% and 72.5%, respectively, in contrast to 100% at both levels in HBsAg- patients. The serum alpha-fetoprotein level, which showed a predictive value positive of 95% in HBsAg+ hepatocellular carcinoma patients, was 3,200 ng/ml, whereas that in HBsAg- hepatocellular carcinoma patients, was 200 ng/ml. We conclude that serum HBsAg status should be considered when serum alpha-fetoprotein is measured as an independent test to diagnose hepatocellular carcinoma, and suggest that regular serum alpha-fetoprotein determination may be more useful in HBsAg- patients with chronic liver disease for the early diagnosis of hepatocellular carcinoma than in HBsAg+ patients.     

Helicobacter pylori and hepatocellular carcinoma: Correlated or uncorrelated?

Helicobacter pylori can be detected in liver tissue resected from patients with hepatocellular carcinoma. Conflicting reports regarding the relationship between H. pylori and hepatocellular carcinoma mean it is uncertain whether H. pylori acts as a troublemaker, co-risk factor or innocent bystander to the development of hepatocellular carcinoma. Clinical studies in patients without known causes of hepatocellular carcinoma are important to discover whether H. pylori is involved in the carcinogenesis of hepatocellular carcinoma. High quality prospective studies in patients with hepatocellular carcinoma, hepatitis C virus infection and no cirrhosis are needed to determine whether H. pylori is a co-risk factor for hepatocellular carcinoma.