慢性乙型肝炎、乙肝肝硬化、乙肝肝癌患者Th1/Th2型细胞因子水平变化研究

目的分析慢性乙型肝炎(CHB)、乙肝肝硬化(LC)、乙肝肝癌(HCC)患者血清中Th1/Th2型细胞因子水平变化,为慢性乙型肝炎至肝癌的发生发展过程中的免疫变化研究提供线索,并为患者的临床治疗研究提供免疫学指标。方法选取2010年2月-2011年11月于首都医科大学附属北京佑安医院就诊的40例CHB患者、40例LC患者、53例HCC患者,用Luminex技术检测血清中Th1类细胞因子[白细胞介素(interleukin,IL)-12、干扰素(interferon,IFN)-γ和肿瘤坏死因子(tumor necrosis factor,TNF)-α]水平及Th2类细胞因子(IL-4、IL-6和IL-10)水平,并将25例健康志愿者作为正常对照组进行比较。结果除TNF-α外,CHB组、LC组和HCC组Th1类IL-12、IFN-γ和Th2类IL-4、IL-6、IL-10细胞因子水平均低于正常对照组;CHB组中大部分Th1类和Th2类细胞因子都高于LC组和HCC组;HCC组中TNF-α细胞因子水平要高于CHB组、LC组。结论 CHB、LC和HCC患者体内Th1/Th2细胞因子分泌水平受到抑制,Th1/Th2平衡发生漂移,对HBV病毒的清除作用受到抑制。TNF-α在肝癌发生过程中发挥着重要作用。     

Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis

In a prospective randomised controlled study, 90 patients with chronic active hepatitis C and compensated cirrhosis were assigned symptomatic treatment or interferon alfa (IFN-alpha). We report data on decompensation, detection of hepatocellular carcinoma, and mortality rates. IFN-alpha gave a sustained response in only a small proportion of patients, but worsening of compensated cirrhosis was prevented and development of hepatocellular carcinoma was inhibited, increasing the survival rate. The risk ratio of IFN-alpha versus symptomatic treatment decreased by 0.250 for progression to Child-Pugh grade B, 0.256 for detection of hepatocellular carcinoma, and 0.135 for a fatal outcome.     

Serum concentration of E-selectin in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma

Objectives: High levels of soluble E-selectin have been reported in acute and chronic inflammatory disorders. Moreover, in some types of tumor elevated values have been found while in other types reduced levels have been reported. Our aims were to determine whether soluble E-selectin levels might be useful in monitoring the progression of chronic liver disease, including hepatocellular carcinoma. Methods: Circulating soluble E-selectin was measured by an enzyme-linked immunosorbent assay in the sera of 18 patients with chronic hepatitis, 44 with liver cirrhosis, and 38 with hepatocellular-carcinoma-associated liver cirrhosis. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Results: Serum levels of soluble E-selectin were higher in the chronic hepatitis and liver cirrhosis patients than in the hepatocellular carcinoma patients and healthy controls. Levels in the hepatocellular carcinoma patients and controls were not significantly different. In the liver cirrhosis group, divided according to the Child-Pugh classification, soluble E-selectin decreased with disease severity. Similarly, in patients with liver cirrhosis who developed hepatocellular carcinoma, soluble E-selectin decreased as the disease progressed. Immunohistochemical localization showed strong membrane staining on endothelial cells in areas rich in inflammatory cells in severe chronic hepatitis. In some hepatocellular carcinoma tissues a marked E-selectin staining was observed on endothelial cells of tumor-associated small vessels. Conclusions: The results obtained suggest that high serum levels of soluble E-selectin are associated with chronic hepatitis and liver cirrhosis, and that levels decrease in liver cirrhosis patients as the disease progresses. Patients with hepatocellular carcinoma have different types of soluble E-selectin behaviour the significance of which requires further investigation. Received: 27 July 1999 / Accepted: 24 December 1999     

Helicobacter infection in patients with HCV-related chronic hepatitis,cirrhosis, and hepatocellular carcinoma

Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). HCC represents one of the most common human cancers. Incidence rates for this tumor vary widely on a worldwide, suggesting that environmental factors such as infectious microorganisms, carcinogens, or nutrition play a role in its pathogenesis. Several Helicobacter spp. colonize the liver of animals and induce hepatitis. The aim of this study was to determine whether Helicobacter infection was associated with HCV-related liver diseases in humans. Liver tissue samples, including biopsy and surgically excised tissues, were collected from patients positive for hepatitis C viruses (HCV) RNA in the serum. Genomic DNA was extracted from sections of formalin-fixed paraffin-embedded tissues by using the QIAamp Tissue Kit and subjected to polymerase chain reaction (PCR) analysis using two sets of Helicobacter-specific 16S ribosomal RNA primers. To identify positive samples for H. pylori, a set of primers specific for a conserved region in the H. pylori vacA gene were also used. The patients' H. pylori status was determined by ELISA. Forty-one patients (mean age 54.9, range 19–78 years; 24 men) were studied. Thirty patients had chronic viral hepatitis (CH) without (N = 18) or with (N = 12) cirrhosis (CIR), and 11 patients had HCC. Anti-H. pylori IgG was detected in 54%. The expected 422- and 210-bp fragments of Helicobacter 16S rRNA were amplified from 27% of liver samples, including 17% of CH-CIR and 55% of HCC (P = 0.004). The vacA sequence was amplified in 10 of 41(24%) samples (27% of those with HCC).: These data confirm the presence of H. pylori DNA sequences in human liver and suggest an association of Helicobacter spp. with HCV-related chronic liver diseases. Further studies are needed to ascertain whether Helicobacter spp. infection plays a role in the development of HCC.     

Gut microbiota dysbiosis in patients with hepatitis B virus–induced chronic liver disease covering chronic hepatitis,liver cirrhosis and hepatocellular carcinoma

The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus–induced chronic liver disease (HBVCLD) is limited. In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus–induced chronic liver disease patients and healthy individuals. Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals. The 16S rDNA gene amplification products were sequenced. Bioinformatic analysis including alpha diversity and PICRUSt was performed. A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera were detected. The beta‐diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially. The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls. Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism‐related genes and lipid metabolism–related genes in HBVCLD than in healthy individuals. Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes. Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.     

Angiopoietin-2 serum levels are elevated in patients with liver cirrhosis and hepatocellular carcinoma

OBJECTIVES: Liver cirrhosis is characterized by remodeling leading to nodules that are difficult to discern from hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) serum levels are used for the screening for HCC, with limited success. We evaluated angiopoietin-2 as a serum marker in patients with cirrhosis and with HCC. METHODS: In a retrospective study, we measured angiopoietin-2 serum levels in 131 patients with HCC, 180 patients with cirrhosis, and 40 healthy controls. We also determined AFP serum levels in patients with HCC and compared the test characteristics of both serum markers. The expression patterns of angiopoietin-2 were determined by in situ hybridization in healthy and cirrhotic livers as well as in HCC. RESULTS: Angiopoietin-2 serum levels were elevated in patients with liver cirrhosis (P < 0.0001) compared with healthy controls. Levels were further elevated in patients with HCC compared with healthy controls (P < 0.0001) and cirrhotic patients (P < 0.0001). The combination with AFP measurements led to improved discrimination between HCC and cirrhosis. Angiopoietin-2 message was present in tumor cells of HCCs but was absent from hepatocytes of cirrhotic and healthy livers. In cirrhosis, message was detected within the strands of fibrous tissue. CONCLUSIONS: Serum angiopoietin-2 levels are elevated in patients with cirrhosis, implicating a possible role of the angiopoietin-Tie-2 system for neoangiogenesis in cirrhosis. Serum levels are further elevated in patients with HCC, suggesting the potential use of angiopoietin-2 as a marker for the detection of cirrhosis and HCC.     

Perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis with hepatocellular carcinoma

Liver cirrhosis is reportedly one of the conditions preceding peripheral-type intrahepatic cholangiocarcinoma but not hilar/perihilar cholangiocarcinoma. Herein, we report a case of perihilar cholangiocarcinoma arising in a hepatitis C virus-related cirrhotic liver. The patient was a 69-year-old man. He was diagnosed with hepatitis C virus-related chronic hepatitis at the age of 56 years, and 9 years later, multiple hepatocellular carcinomas were detected by imaging modalities. Despite treatments, including chemotherapy, he died of hepatic failure at the age of 69 years. At autopsy, in addition to multiple nodules of hepatocellular carcinoma, we found a white mucinous and fibrous tumor spreading from the hepatic hilum to the periphery along the left lateral segmental bile ducts in the advanced cirrhotic liver. This tumor was histologically a cholangiocarcinoma that involved mainly the peribiliary glands and showed variable cystic dilation, suggesting that it might have been derived from these peribiliary glands. Immunohistochemically, the cholangiocarcinoma cells were positive for cytokeratin 7 and mucin core protein 1, and negative for cytokeratin 20 and mucin core protein 2. Hilar/perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis has rarely been reported. This case warrants further studies to clarify the possible involvement of hepatitis C virus in tumorigenesis of hilar/perihilar cholangiocarcinoma.     

Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis

OBJECTIVE: Thrombocytopenia is a common manifestation of cirrhosis. The aim of this study was to examine the relationship between serum thrombopoietin concentrations, circulating platelet levels, and the stage of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: The study included 48 patients with chronic viral hepatitis (14 with stage 1 fibrosis; five with stage 2 fibrosis; three with stage 3 fibrosis; 26 with cirrhosis) and 30 healthy volunteers. Serum thrombopoietin levels were measured using an enzyme-linked immunosorbent assay. Spleen size, platelet counts, and prothrombin time were measured. RESULTS: Thrombopoietin levels of patients with fibrosis stage 1 (2.50 +/- 1.60 fmol/ml) or stage 2 (1.89 +/- 0.65) were significantly higher than those in patients with cirrhosis (1.21 +/- 0.55) or healthy volunteers (1.26 +/- 0.74). Mean platelet counts of patients with cirrhosis (8.0 +/- 4.6 x 10(4)/microl) were significantly lower than those with fibrosis stage 1 (18.6 +/- 3.9) or stage 2 (16.0 +/- 5.8), or healthy volunteers (24.5 +/- 7.3). Patients with cirrhosis had larger spleens (30.9 +/- 18.4 cm2) than those with fibrosis stage 1 (18.2 +/- 6.4). Platelet counts showed a significant inverse relationship to spleen size (p = -0.51, p < 0.0005) and a significant positive relationship with thrombopoietin levels (p = 0.34, p < 0.02). Thrombopoietin levels were significantly correlated to prothrombin time (p = 0.45, p < 0.005). CONCLUSIONS: Serum thrombopoietin levels are elevated in patients with an early stage of chronic viral hepatitis. As the disease progresses from mild fibrosis to cirrhosis, decreased production of thrombopoietin may contribute to the further development of thrombocytopenia in cirrhosis.     

慢性丙型肝炎、肝硬化、肝癌患者血清IL-17、IL-6和维生素D水平变化及其临床意义

目的探讨慢性丙型肝炎、丙肝肝硬化、丙肝相关肝癌患者血清IL-17、IL-6和维生素D[25-OH-D和1,25(OH)2D]水平的变化及其临床意义。方法酶联免疫法(ELISA)测定54例慢性丙型肝炎、47例丙肝肝硬化和32例丙肝相关肝癌患者的血清IL-17、IL-6和维生素D水平,并检测患者HCV-RNA滴度、AFP水平,并与50名健康对照者比较。结果与对照组相比,各组患者的血清IL-17、IL-6、HCV-RNA滴度和AFP水平显著增加,而维生素D水平显著降低;三组患者相比,血清IL-17、IL-6、HCV-RNA滴度和AFP水平随着病情的发展逐渐升高(肝癌组肝硬化组慢性丙型肝炎组),而维生素D水平随着病情的发展逐渐降低(肝癌组肝硬化组慢性丙型肝炎组);IL-17与HCV-RNA滴度、AFP和IL-6呈明显正相关,而与维生素D呈明显负相关,IL-6也与HCVRNA滴度、AFP呈明显正相关,而与维生素D呈明显负相关。结论血清IL-17、IL-6和维生素D可能与HCV活跃程度有关,并在HCV感染后引起肝脏损伤、肝硬化、肝癌的发生发展过程中起重要作用。同时,IL-17、IL-6和维生素D的检测可能作为肝脏损伤程度新的标志物及AFP等经典标志物在肝癌诊断中的补充。     

Role of ethnicity in risk for hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis.

BACKGROUND AND AIMS: In the United States, hepatocellular carcinoma (HCC) is more common among Asians and African Americans than Caucasians, with chronic hepatitis C virus (HCV) infection accounting for up to half of the patients. Our study examined ethnicity as a potential risk factor for HCC among patients with chronic hepatitis C. METHODS: We conducted a case-control study of 464 patients with chronic hepatitis C and cirrhosis (207 cancer patients and 257 controls) using medical records and pathology records at 4 medical centers. We estimated odds ratios with 95% confidence intervals by using conditional logistic regression on case-control sets, matched within study centers and study period on sex and age groups (< or =45, 46-55, 56-65, >65 yr). To control for potential confounding caused by severity of cirrhosis and residual confounding caused by age, we also included Child-Turcotte-Pugh (CTP) scores and age (continuous variable) in all regression analyses. RESULTS: Compared with Caucasians, the cancer risk was increased significantly among Asians (adjusted odds ratio, 4.3; 95% confidence interval, 2.1-9.0 for men, and 4.6; 1.2-18.5 for women) and somewhat increased among African-American men (adjusted odds ratio, 2.4; 95% confidence interval, 0.9-6.3). CONCLUSIONS: This study suggests that, among patients with chronic hepatitis C and cirrhosis, liver cancer risk is increased 4-fold in Asians and may be doubled in African-American men, compared with Caucasians. These results need confirmation in larger studies from racially diverse populations, but, if confirmed, these results point to high-risk populations that should be targeted for screening and preventive efforts.     

Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma

Background and Aim: Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis. Detection of HCC at an early stage is critical for a favorable clinical outcome. The study aim was to: (i) compare the levels of des‐γ‐carboxyprothrombin (DCP), α‐fetoprotein (AFP) and AFP‐L3 in HCC patients and in chronic viral hepatitis patients without HCC; (ii) define the level of each tumor marker with the best sensitivity and specificity for HCC diagnosis; and (iii) to correlate the levels of these markers with respect to size and tumor burden. Methods: Two hundred and forty patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were studied. These included 144 with HCC, 47 with chronic hepatitis (fibrosis stage I–III on liver biopsy) and 49 with cirrhosis. Results: Levels of DCP, AFP and AFP L‐3 were significantly higher in patients with HCC than in those without HCC (P ≤ 0.0001). Receiver–operating curves (ROC) indicated that the cut‐off value with the best sensitivity and specificity for each test was ≥84 mAU/mL for DCP, ≥25 ng/mL for AFP and ≥10% for AFP‐L3. The sensitivity, specificity and positive predictive value (PPV) for DCP was 87%, 85% and 86.8%, for AFP 69%, 87% and 69.8%, and for AFP‐L3 56%, 90% and 56.1%, respectively. DCP levels were below the ROC cut‐off in all patients without HCC. In patients with single lesions, there was a direct correlation of DCP to tumor size. High levels of AFP correlated with diffuse type of HCC. All three markers were significantly elevated in the presence of metastatic HCC. No advantage was observed by combining two or three markers for HCC diagnosis. Conclusion: DCP had the highest sensitivity and PPV for HCC diagnosis, had a direct correlation with tumor size, and was not elevated in any patients without HCC. DCP should be used as the main serum test for HCC detection.     

HBsAg及HBV DNA定量水平在慢性乙型肝炎、肝硬化和肝癌患者中的变化

目的 了解HBsAg定量水平在慢性乙型肝炎、乙型肝炎肝硬化、HBsAg阳性的原发性肝癌患者中的变化及其在3组患者中与HBV DNA的相关性. 方法 采集47例慢性乙型肝炎患者(乙型肝炎组),72例乙型肝炎肝硬化患者(肝硬化组)及54例肝癌患者(肝癌组)的血清标本,用雅培化学发光法进行HBsAg定量测定,荧光PCR定量法检测HBV DNA量水平.多组分析采用Kruskal-Wallis检验,两组间比较采用Mann-WhitneyU检验,相关性分析采用Spearman检验.结果 HBsAg定量值在乙型肝炎、肝硬化、肝癌组患者中的中位数分别为2361.10、1001.64、594.35IU/ml,3组间呈逐渐下降趋势,x2= 24.394,P＜0.05,差异有统计学意义;乙型肝炎组与肝硬化组比较,Z= -3.754,P＜0.05,差异有统计学意义;乙型肝炎组与肝癌组比较,Z=-4.630,P＜0.05,差异有统计学意义;而肝硬化组与肝癌组比较,差异无统计学意义.HBeAg阳性患者,HBsAg定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为3259.83、1077.30、789.72 IU/ml,3组间呈下降趋势,x2= 15.643,P＜0.01,差异有统计学意义.对于HBeAg阴性患者,HBsAg定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为1669.00、1001.64、582.05 IU/ml,3组间呈下降趋势,x2 =6.423,P＜0.05,差异有统计学意义.HBV DNA定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为5.3579、 4.2207、1.0000 log10拷贝/ml,4分位数间距分别为(4.3579 ～6.8745)、(0.0000 ～ 5.7393)、(0.0000 ～ 4.6651)log10拷贝/ml,3组HBV DNA定量值比较,x2=31.412,P＜0.05,差异有统计学意义; HBsAg与HBV DNA在乙型肝炎组(r= 0.297,P＜0.05)、肝硬化组(r= 0.346,P＜0.05)、肝癌组(r=0.452,P＜0.05)均呈正相关.结论 HBsAg定量值在慢性乙型肝炎、肝硬化、肝癌患者中逐渐降低,且与HBV DNA水平正相关.     

Multivariate analysis of risk factors for hepatocellular carcinoma in patients with hepatitis C virus-related liver cirrhosis

To elucidate the risk factors for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related liver cirrhosis (LC), we examined 204 cirrhotic patients negative for hepatitis B surface antigen and positive for HCV antibodies. The independent influence of various clinical characteristics in these patients was analyzed by multiple logistic regression, and the risk factors for HCC were identified. Multiple logistic regression analysis identified and ranked the following four risk factors: male sex (P<0.001), habitual heavy drinking (P<0.005), hepatitis B virus antibody positivity (anti-HBs and/or anti-HBc,P<0.05), and age greater than 60 years (P<0.05). The odds ratio of HCC was 4.20 (95% confidence interval; CI, 1.80–9.78) in male patients, 3.27 (95% CI, 1.46–7.30) in habitual heavy drinkers, 2.01 (95% CI, 1.01–3.99) in patients positive for hepatitis B virus antibodies, and 2.06 (95% CI, 1.00–4.23) in patients older than 60 years. The cumulative occurrence rates of HCC after blood transfusion were significantly higher in habitual heavy drinkers (4.8%, 49.4%, and 74.7% at 10, 20, and 30 years, respectively) than in non-drinkers (0%, 21.0%, and 23.3% at 10, 20, and 30 years, respectively,P<0.0003). The mean interval for progression to LC after blood transfusion was significantly shorter in the habitual heavy drinkers than in the non-drinkers (22.4±4.4 years vs 28.4±3.9 years;P<0.0003). This multivariate analysis revealed that habitual heavy drinking and hepatitis B virus antibody positivity are significant risk factors for HCC in HCV-related liver cirrhosis. This work was presented in preliminary form at the annual meeting of the American Association for Study of Liver Diseases, New Orleans, May 16, 1994 and published as an abstract inGastroenterology 14: A875, 1994.     

Aflatoxin levels in chronic hepatitis B patients with cirrhosis or hepatocellular carcinoma in Balıkesir,Turkey

Aflatoxins, the secondary metabolites produced by species of naturally occurring Aspergilli, are commonly found in food such as cereals, dried fruits and juice, wine, beer and spices. They are hepatotoxic and are well known human carcinogens based on evidence from human studies. Aflatoxins are an environmental risk factor for the development of hepatocellular carcinoma (HCC). Chronic hepatitis B‐infected patients are at increased risk of cirrhosis, hepatic failure and liver cancer. This study was designed to determine the serum aflatoxin B₁ (AFB₁), aflatoxin B₂ (AFB₂), aflatoxin G₁ (AFG₁) and aflatoxin G₂ (AFG₂) concentrations using high‐pressure liquid chromatography (HPLC) in hepatitis B‐infected patients with or without cirrhosis and liver cancer, alongside healthy controls in Bal?kesir, Turkey. The mean AFB₁ and total AF levels in patients without liver cancer and cirrhosis were significantly higher than healthy controls. The mean AFB₁ and total AF levels in patients with chronic hepatitis B and HCC were significantly higher than infected patients with or without cirrhosis. These results suggest that patients with chronic hepatitis B who are exposed to AFs are at increased risk for developing HCC, which might be prevented by reducing consumption of contaminated foods.     

Chemoprevention of hepatocellular carcinoma in patients with hepatitis C virus related cirrhosis

Interferon(IFN) therapy has been reported to decrease the risk of hepatocellular carcinoma(HCC) and improve survival by preventing liver-related deaths in patients with chronic hepatitis C virus(HCV) infection, while the role of IFN therapy on the natural history of hepatitis C related cirrhosis is still under debate. The ideal goal of therapy is to prevent the progression into end-stage disease. The use of IFN in patients with HCV compensated cirrhosis reduces the negative clinical evolution independently of the type of laboratoristic and virological response. In our experience, IFN therapy in HCV compensated cirrhosis is barely useful in prevention of HCC, as cirrhosis itself represents a risk of cancer.Some authors noted that IFN treatment reduces the risk of HCC independently of the virological response. It would probably be interesting to evaluate the efficacy of weekly low-dose pegylated(PEG)-IFN therapy in patients with HCV cirrhosis and to assess potential benefits of long-term PEG-IFN plus Ribavirin treatment.     

Serum leptin levels in patients with liver cirrhosis and chronic viral hepatitis

BACKGROUND: The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels. METHODS: Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness. RESULTS: Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes. CONCLUSIONS: These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.     

DNA measurements in chronic hepatitis, cirrhosis and hepatocellular carcinoma

It has been documented that chronic hepatitis may progress to cirrhosis and then develop hepatocellular carcinoma (HCC). To test whether abnormal cellular DNA increases along this line of development, liver tissues from 48 patients with chronic hepatitis, 17 with cirrhosis, and 8 with HCC were investigated for cellular DNA content with a scanning microdensitometer. Seven of 8 HCCs and 2 cirrhotic livers adjacent to HCC had abnormally increased cellular DNA content. Only 4 livers from patients with chronic liver diseases other than HCC had abnormal cellular DNA content. The cellular DNA content in livers not accompanying HCC was not related to the patient's age, histological diagnosis, and hepatitis inflammatory activity. The results confirmed the increase of cellular DNA content in HCC, but did not provide evidence of a progressively increasing DNA content from chronic hepatitis to liver cirrhosis. However, cirrhotic livers with abnormal hepatocytic DNA content deserve careful follow-up for the early detection of HCC.     

Co-occurrence of hepatocellular carcinoma and lymphoma in patients with hepatitis C virus cirrhosis

The association of hepatitis C virus (HCV) with neoplasia is not completely understood. Hepatitis C virus is hepatolymphotrophic. It is considered an inducing factor of hepatocellular carcinoma (HCC) and is associated with various types of lymphomas. We describe a patient with HCV cirrhosis who developed gastric lymphoma and HCC, and we review the current data and theories about the oncogenesis of HCV.     

Resolution of liver cirrhosis and prevention of hepatocellular carcinoma by interferon therapy against chronic hepatitis C

Hepatocellular carcinoma (HCC) is one of the most important medical problems facing the Asian-Pacific region, where the prevalence of chronic hepatitis B and C is so high. Every year, we have approximately 500 admissions to our department due to this malignancy. It is of utmost importance that we have efficient screening, diagnosis and treatment. Over the past several years, there has been steady improvement in elucidating the super-high risk group for HCC, and in the management of these patients. I discuss how effectively we can screen patients by using three tests, conventional AFP, AFP-L3 (lectin fraction) and DCP (des-gamma-carboxy-prothrombin). With these tests we can detect HCC as small as 10 mm. In addition, imaging technology including CT-angiography can effectively pick up small cancer nodules. However, they are not always readily available in all Asian countries. Thus, diagnostic procedures and treatment methods can be modified in each country depending on the situation. One such treatment modality is the percutaneous therapy. The recent introduction of radiofrequency ablation (RFA) has dramatically changed our daily clinical practice. The time needed to treat cancer nodules of 2 to 3 cm in size has been reduced from 1 month or longer with ethanol injection to less than a week with RFA. However, the most important issue is to prevent infection and progression from chronic hepatitis to HCC. The recent introduction of improved antiviral therapy makes us feel optimistically that we might eventually have a comprehensive strategy for HCC in the region where it is most needed.