Search

Improvements in the hepatocellular carcinoma (HCC) recurrence rate and survival have been frequently reported following virus eradication after hepatitis C virus (HCV)-related HCC cure. However, the efficacy of direct-acting antiviral (DAA) therapy in patients who included those with advanced HCC and decreased hepatic functional reserve is unknown. A comparative examination was retrospectively conducted of 141 patients with hepatitis C who started DAA therapy within 1 year after undergoing curative HCC treatment and showed a sustained viral response (SVR) and 327 patients who underwent curative treatment for HCV-related HCC and did not subsequently receive antiviral therapy. Whether DAA therapy was given was identified as an independent factor related to both HCC recurrence and survival. Both the recurrence and survival rates improved significantly with DAA therapy in Child-Pugh (CP)-A, whereas no difference in the recurrence rate was seen with DAA therapy in CP-B. However, the survival rate was significantly higher in the DAA group in this class. Similarly, dividing the patients by the Milan criteria showed significant improvements in the recurrence rate and survival with DAA therapy in patients within the Milan criteria. Patients with HCC beyond the Milan criteria showed no difference in recurrence rates, but the DAA group tended to have higher survival rates. Thus, DAA after curative therapy for HCC can be expected to improve survival in patients with advanced HCC or decreased hepatic functional reserve. HCV should be aggressively eradicated in all patients eligible for curative treatment of HCC.

We herein report a case of glossopharyngeal neuralgia with repeated syncope caused by the recurrence of esophageal carcinoma. The typical symptoms of glossopharyngeal neuralgia are paroxysmal, stabbing, electric shock-like pain in the pharynx and/or base of the tongue on swallowing and talking. In addition, syncope can also be caused by glossopharyngeal neuralgia. The diagnosis of glossopharyngeal neuralgia is not always easy because of its rarity. In the present case, we suspected that repeated syncope was caused by glossopharyngeal neuralgia due to the recurrence of esophageal carcinoma. Concurrent chemoradiation therapy was effective in reducing the tumor size, which resulted in the complete resolution of the symptoms.

A woman in her 70s was admitted to our hospital because of epigastric pain and anorexia. Laboratory evaluations revealed elevated levels of liver transaminases, biliary enzymes, and amylase. CT and MRCP showed dilatation of the bile and pancreatic ducts and a large juxtapapillary diverticulum filled with contents. There were no gallstones or tumors present. Our differential diagnosis included obstruction of the papilla of Vater, so we performed an urgent ERCP. Endoscopic examination showed the juxtapapillary diverticulum filled with food residue;however, we were unable to locate the papilla of Vater. We rinsed out and removed food residue from the diverticulum using a retrieval balloon catheter used for gallstones. After the endoscopic removal of the food residue, the patient's epigastric pain immediately subsided and her cholangitis and pancreatitis improved gradually.

Aim To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non-hemodialysis (non-HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV). Methods A total of 1113 non-HD patients and 67 HD patients were assessed. To evaluate pretreatment factors contributing to sustained virological response at 12 weeks (SVR12), univariate and multivariate analyses were carried out. To adjust for differences in patient background, propensity score matching was undertaken. Results The overall SVR12 rates were 91.6% in non-HD patients and 95.5% in HD patients. Compared with non-HD patients, HD patients were younger, were more likely to be male, were less likely to have received interferon-based pretreatment, had a lower viral load, and had lower levels of alanine transaminase, hemoglobin, and α-fetoprotein. Multivariate analysis revealed that viral load, α-fetoprotein, L31 substitution negative, and Y93 substitution negative were independent predictive factors for SVR12 in non-HD patients. The proportion of patients with undetectable HCV-RNA during the initial 4 weeks was significantly higher in HD patients than in non-HD patients. The SVR12 rate was clearly higher in HD patients than in non-HD patients, although the difference was not statistically significant. After propensity score matching to adjust for viral load, α-fetoprotein, L31 substitution, and Y93 substitution, these trends disappeared. Conclusions For treatment of HCV genotype 1 infection, daclatasvir plus asunaprevir is useful not only in non-HD patients but also in HD patients. Viral load, α-fetoprotein levels, L31 substitution, and Y93 substitution influence treatment course and outcome.

AIM The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. RESULTS Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naive patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P

Background and aim This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. Methods This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. Results AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. Conclusions There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non-hemodialysis (non-HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV).A total of 1113 non-HD patients and 67 HD patients were assessed. To evaluate pretreatment factors contributing to sustained virological response at 12 weeks (SVR12), univariate and multivariate analyses were carried out. To adjust for differences in patient background, propensity score matching was undertaken.The overall SVR12 rates were 91.6% in non-HD patients and 95.5% in HD patients. Compared with non-HD patients, HD patients were younger, were more likely to be male, were less likely to have received interferon-based pretreatment, had a lower viral load, and had lower levels of alanine transaminase, hemoglobin, and α-fetoprotein. Multivariate analysis revealed that viral load, α-fetoprotein, L31 substitution negative, and Y93 substitution negative were independent predictive factors for SVR12 in non-HD patients. The proportion of patients with undetectable HCV-RNA during the initial 4 weeks was significantly higher in HD patients than in non-HD patients. The SVR12 rate was clearly higher in HD patients than in non-HD patients, although the difference was not statistically significant. After propensity score matching to adjust for viral load, α-fetoprotein, L31 substitution, and Y93 substitution, these trends disappeared.For treatment of HCV genotype 1 infection, daclatasvir plus asunaprevir is useful not only in non-HD patients but also in HD patients. Viral load, α-fetoprotein levels, L31 substitution, and Y93 substitution influence treatment course and outcome.

A 47-year-old Japanese man was first admitted to our hospital for 8 days because of an asthma attack. After discharge he changed his diet. On the 12th day after his discharge, he was re-admitted to our hospital because he exhibited transient loss of consciousness with flapping tremor. His plasma ammonia level was extremely high (245 μg/dL; normal,90 μg/dL), suggesting hepatic encephalopathy. He underwent intravenous administration of branched-chain amino acids (Aminoleban(®)) and oral administration of lactulose and kanamycin sulfate; however, the hyperammonemia did not improve. Analysis of the amino acids and citrin gene led to the diagnosis of adult-onset type II citrullinemia (CTLN2). Following this diagnosis, the carbohydrate content of his diet was mildly restricted. As a result, his plasma ammonia level markedly improved (ammonia, 40-60 μg/dL) and he became symptom-free without any medication. CTLN2 is a metabolic disorder characterized by increased plasma concentrations of citrulline and ammonia, which occurs by the failure of compensatory mechanisms associated with diet. Here, we report a case of a patient for whom a change in eating habits during his hospitalization disturbed his compensatory mechanism resulting in clinical CTLN2, which was reversed with an appropriate diet.

In this paper, two experiments for locally hard facing of cast iron and cast steel will be presented. In the case of locally hard faced spheroidal graphite cast iron with hard alloy briquettes, the inserted layer as formed with penetration of the molten cast iron among tungsten carbide (henceforth, it is described as WC) particles in the hard alloy briquette. The base metal of inserted layer showed a microstructure of gray cast iron due to a hindrance to spheroidalization caused by a reaction the molten cast iron to the elements of W and Co in the hard alloy. The hardness of mother spheroidal graphite cast iron was about Vickers hardness (henceforth, it is described as HV) 200 while the hardness of the inserted layer ranged from HV600 to HV1600. In the case of locally hard faced cast steel, the inserted layer was also formed with similar process to that of the spheroidal graphite cast iron, while intermediate phases with very hard complex carbide were formed at the bonding region between the inserted layer and the base metal. The hardness of mother cast steel was about HV300, while the hardness of the inserted layer ranged from HV800 to HV1400. Especially, the intermediate layer with complex carbide showed the highest hardness of HV1800. Therefore, the inserted methods with hard alloy particles are considered to be a very effective one for locally hard facing of cast iron and cast steel.

In order to improve wear resistance of cast steel, hard alloy powder layer was inserted by molten cast steel at 1843K. The vertical cross-section of the inserted layer was examined on the microstructure and the hardness. The results obtained are as follows. Sound inserted layer of 3mm in thickness was confirmed to be formed without any defects on the surface of cast steel.A reaction layer with some lump shaped particles was formed in the interface between the inserted layer and the mother metal (cast steel). The lump shaped particles were identified to be Fe3W3C phase which had a cubic structure with a lattice constant of 11.1094×10-8cm. The particles were considered to be formed by a reaction between the Co bond phase dissolving WC in hard alloy powder and the molten iron dissolving low concentration of C in molten steel. The hardness of cast steel was about Hv300, while the inserted layer exihibited high hardness of Hv600 to 800.Especially, the reaction layer showed peak hardness of Hv1800, but the layer was not brittle. The toughness of the reaction layer was considered to be due to a mixed structure of tough bainite and retained austenite around the hard Fe3W3C particles. The present method using the inserted hard alloy powder layer is therefore to be very effective one for local hard facing of cast steel.

Intrahepatic lymphoid follicle (ILF) formation is one of the most characteristic and commonly observed histological features in patients with chronic hepatitis C. However, little is known regarding whether follicles in the liver belong to functional lymphoid tissues, where B cells are activated, differentiated, and proliferated, or if the lymphocytes are merely infiltrated after recruitment from the secondary lymphoid organs. To ascertain this possibility, we examined the expression of markers for B-cell activation, differentiation, and proliferation in ILFs in patients with chronic hepatitis C using surgically resected specimens, and compared them with specimens of perihepatic lymph nodes by an immunohistochemical technique. Germinal center (GC) formation in the ILFs was frequently found in HCV-positive cases. The distribution of immunoglobulin M (IgM)-, IgD-, and IgG-positive cells and the expression patterns of Ki-67, CD23, or bcl-2 and bcl-6 gene products in the follicles with GC formation in the liver of patients with chronic hepatitis C were similar to those of lymph nodes, indicating that B cells are activated, proliferated, and differentiated in the ILFs with GC formation in patients with chronic hepatitis C. Oligoclonal expansion of B cells in the livers with ILFs was confirmed by an analysis of immunoglobulin heavy chain (IgH) gene rearrangement determined by polymerase chain reaction (PCR). These data strongly suggest that ILFs with GC formation, which are frequently found in patients with chronic hepatitis C, may functionally be the same as those found in lymph nodes with respect to B-cell expansion and maturation.

Background/Aims: To examine the T-cell repertoire which is involved in the immunopathogenesis of chronic hepatitis, we analyzed the T-cell receptor Vβ gene usage in liver-infiltrating lymphocytes by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical technique. Methods: Complementary DNA was synthesized from RNA which was extracted from 26 liver biopsy specimens and from peripheral blood lymphocytes from eight subjects, and amplified by RT-PCR. Radioactivity of each amplified product using 32 P-labeled primers was measured and the percentage of each Vβ expression was calculated. Results: The mean frequency of Vβ5.1 (11.1%) in liver-infiltrating lymphocytes of chronic hepatitis C was highest among those of all Vβ regions, and was significantly higher than that in both peripheral blood lymphocytes of chronic hepatitis C and liver-infiltrating lymphocytes of chronic hepatitis B. In the immunohistochemical analysis, Vβ5.1-positive cells were mostly observed in portal areas where inflammatory reactions occurred. The sequence of the complementarity determining region (CDR)3 on T-cell receptor expressing Vβ5.1 were examined in six patients with chronic hepatitis C. The sequences were similar to each other and all had one common amino acid (valine) irrespective of different HLA haplotype. Conclusions: These data suggest that Vβ5.1-positive cells are preferentially accumulated in the liver of chronic hepatitis C and are involved in the immunopathogenesis of the disease. Sequence analysis showed that Vβ5.1-positive cells recognize a common conventional antigen and valine recognized at the same position of the CDR3 may be a key residue in determining an antigen/major histocompatibility complex contact point.

5種類のヒト肝癌細胞株培養上清中の各種サイトカインを測定したところ,いずれの細胞株においても他のサイトカインと比べ高濃度のInterleukin (IL)-8が検出された.肝癌細胞培養上清中のIL-8濃度は,IL-1βやTNF-αの添加により増加し,その際にはIL-8mRNA発現の増強を伴っていた.肝癌細胞(PLC/PRF/5)培養上清は組み換え型IL-8と同様に,ヒト内皮細胞株であるHUVECsの増殖を濃度依存性に促進し,その活性は抗IL-8あるいは抗塩基性線維芽細胞増殖因子(bFGF)中和抗体で部分的に抑制された.外科的に切除されたヒト肝癌組織,あるいは非癌部組織中のIL-8mRNAの発現をreverse transcription polymerase chain reac-tion法で調べたところ,調べた肝癌組織すべてにIL-8mRNAの発現を認め,半定量的な比較では同一肝の非腫瘍部と比べ,その発現量は多い傾向を認めた.以上より,ヒト肝癌から産生されるIL-8は,血管新生因子の一つとして働いている可能性が考えられた.

Thirteen of 81 patients with chronic hepatitis and positive hepatitis C virus (HCV) antibody developed hepatocellular carcinoma (HCC) during a follow-up period of 54 +/- 38 months. The histopathological findings in HCC-bearing liver in these patients included six cases of chronic persistent hepatitis [CPH; mean hepatitis activity index (HAI) score: 5.8] and seven cases of chronic aggressive hepatitis (CAH) 2A, or 2B (HAI) score: 13.6). Multiple biopsies of the liver in six cases revealed that five cases, including four with CPH at the time of HCC diagnosis, previously had histopathological findings identical to CAH 2A, and another case constantly had CPH during the 8-year follow-up. These findings suggest that HCV-associated HCC can occur even in patients with HCV antibody positivity and inactive or mild chronic hepatitis. This is of interest in the pathogenetic mechanisms of HCV-associated HCC.

Surface expression and shedding of intercellular adhesion molecule-1 (ICAM-1) in the absence and presence of cytokines were measured in seven human liver cancer cell lines. All cancer cell lines were positive for ICAM-1 on the surface of the cells, and the percentages of positive cells ranged from 60 to 97% as analyzed by flow cytometry. Mean fluorescence was increased in the presence of IL-1β, TNF-α, IFN-α or IFN-γ, and the effect was augmented in a dose-dependent fashion. In the culture medium of all cancer cell lines, a soluble form of ICAM-1 was detected even in the absence of cytokines by enzyme-linked immunosorbent assay, and the concentration was increased by IL-1β, TNF-α, or IFN-γ. In two of seven cancer cell lines, the patterns of modulation by cytokines on the surface expression of ICAM-1 and the shedding of the molecules were clearly distinct, suggesting that the mechanisms for these two phenomena might be different. Soluble ICAM-1 was recently reported to suppress non-MHC-restricted cytotoxicity mediated by natural killer and lymphokine-activated killer cells. Our present data suggest that human liver cancer cells may escape from host immune surveillance by shedding of ICAM-1.

A 26-year-old woman was admitted to our hospital with epigastric pain, a husky voice, high-grade fever, hepatosplenomegaly and enlargement of the kidneys. An upper gastrointestinal endoscopy revealed scattered non-circular erythematous erosions, up to 5mm in diameter, in the gastric body and fornix. A histological examination of the biopsied specimens stained with hematoxylin and eosin showed the presence of intranuclear inclusion bodies in the glandular epithelial cells. Cytomegalovirus (CMV) antigen was found in the inclusion bodies using the enzyme-labeled antibody method. Subsequently, a needle biopsy taken from the kidney revealed a non-Hodgkin's lymphoma. Our review of the literature indicates that CMV-induced gastric lesions are endoscopically characteristic and can be diagnosed from their multiple, erythematous, non-circular depressed lesions.

Background/Aims : Idiosyncratic immune response to drugs causes two types of liver injury, cholestasis or hepatitis. However, the underlying immune mechanisms of drug-induced liver injury are presently unclear. Methods : We examined the cytokine production of peripheral blood mononuclear cells (PBMCs) from 17 patients with drug-induced liver injury and healthy controls during their incubation with and without the drug by flow cytometry. We also analyzed the cytokine production in PBMCs from eight patients after stimulation with the drug-pulsed HepG2 lysates to examine the possibility that the drug or its metabolites conjugated with a putative molecule derived from HepG2 cells might be more immunogenic. Results : Among several cytokines produced by the drug or the drug-pulsed HepG2 lysates, interferon-γ production from CD8 + cells was associated with hepatocellular injury, and tumor necrosis factor-α production from CD14 + cells was with cholestasis. Especially, the latter was apparent when the drug-pulsed HepG2 lysates were used as stimulants, suggesting that a complex consist of the drug, or its metabolite, and a putative molecule derived from HepG2 cells might be more immunogenic than the drug itself. Conclusions : The analysis of intracytoplasmic cytokine in PBMCs after stimulation with the drug or the drug-pulsed HepG2 lysates is useful to analyze the immune mechanism underlying drug-induced liver injury.

We present a case of portal-systemic encephalopathy due to intrahepatic multiple portal-hepatic venous shunts. A 71-year-old woman was admitted to our hospital because of recurrent episodes of disturbed consciousness. She showed no clinical signs of portal hypertension. Liver function was normal, except for an indocyanine green retention rate of 34% at 15 min and blood ammonia level of 282 microg/dL. Portal venography revealed dilatation of the portal vein and multiple portal-hepatic venous shunts, and a liver biopsy specimen revealed almost normal liver. Further clinical examination revealed a huge pelvic tumour. At laparotomy, two dilated veins were seen to arise from the pelvic tumour with blood flow into the mesentery. The tumour was resected successfully and a histological diagnosis of leiomyoma was made. The blood ammonia concentration decreased to the normal range postoperatively. A follow-up portal venogram demonstrated decreased portal vein dilatation and minor portal-hepatic venous shunts, considered to be congenital in origin. It is concluded that hepatic encephalopathy was produced in this patient due to an excess portal blood flow from the huge pelvic leiomyoma via the mesentery, with portosystemic shunting through pre-existent (probably congenital) intrahepatic anastomoses.

We have previously reported that human liver cancer cell lines produce interleukin-8 (IL-8) at high levels. Those tumor cells appeared to express two kinds of IL-8 receptor on their surface. In order to analyze the role of IL-8 on the biological characteristics of those tumor cells, we suppressed IL-8 production from human liver (HuH-7 and HuCC-T1) and pancreatic cancer cell lines (HuP-T4) by treatment with IL-8 antisense oligonucleotides. Suppression of IL-8 production resulted not only in inhibition of cell growth, but also in an increase in the concentrations of some tumor-associated substances such as carbohydrate antigen 19-9 (CA19-9) in the medium. These data indicate that IL-8 produced by human liver and pancreatic tumors may act as an autocrine growth factor and may control the production of some tumor-associated substances. Furthermore, surface expression of sialyl-Lewis(a), which is a ligand for ELAM-1 on human umbilical vein endothelial cells (HUVEC), HuCC-T1 and HuP-T4 cells was decreased and the attachment of these tumor cells to HUVEC was inhibited by treatment with IL-8 antisense oligonucleotide. Since the soluble form of CA19-9 (sialyl-Lewis(a)) was shown to inhibit the tumor cell binding to HUVEC, the decrease in release of CA19-9 into the medium and increase in the expression of sialyl-Lewis(a) on the cell surface may suggest that IL-8 production from the tumor cells enhances metastatic potential by augmenting the binding activity of the tumor cells to HUVEC. These data demonstrate that a cytokine produced by tumor cells may function as an autocrine growth factor and affect tumor cell dissemination.

The autotumor (AuTu)-specific cytolytic T lymphocyte (CTL) line established from the peripheral blood of a patient with oral squamous cell carcinoma ( Cancer Res. 53, 1461, 1993) contained >95% of CD8 + and + T cells. This CTL line was infected with Herpesvirus saimiri to increase its life span in culture. Two transformed T cell sublines were obtained: the monoclonal CD4 + line (TCR Vβ2 + Vα15 + ) and the oligoclonal CD8 + line (TCR Vβ6 + , Vβ7 + and Vβ9 + ) both of which were maintained in culture for >6 months without AuTu restimulation and which did not produce any virus. The virus-transformed and untransformed T cell lines were compared for phenotypic and functional characteristics, including the ability to kill AuTu, induce expression of the major histocompatibility complex (MHC) antigens on AuTu, and respond to AuTu by cytokine production and/or proliferation. The H. saimiri -transformed CD4 + T cells expressed higher levels of surface adhesion molecules and CD45RO than untransformed cells and lysed AuTu by inducing DNA fragmentation as well as necrosis. This lysis was inhibited by antibodies to CD4 but not to class I or II MHC molecules. The CD4 + T cells produced IL2, TNF-α, and GM-CSF and proliferated in response to AuTu. They induced and sustained proliferation of CD8 + T cells in cocultures with AuTu. Supernatants obtained from cocultures of the CD4 + T cells with AuTu also induced proliferation of the CD8 + T cell line. In contrast, the H. saimiri -transformed CD8 + T cells did not kill AuTu or release cytokines in response to AuTu. However, upon pretreatment of AuTu with IFN-γ to increase expression of MHC antigens, these T cells regained the ability to recognize and kill AuTu targets. Coincubation of AuTu with the CD4 + or CD8 + T cells significantly augmented expression of class I and II MHC antigens on AuTu. These data indicate that H. saimiri -transformed tumor-reactive T cell lines provide a useful model of interactions between immune effector cells and AuTu, and that CD4 + T cells play a critical role in the regulation of immune responses to squamous cell carcinoma of the head and neck.

Proliferating tumour cells in 92 patients with hepatocellular carcinoma (HCC) were identified by an immunohistochemical method using a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The rate of PCNA-positive cells in HCC tissues was positively correlated with histological grade and the tumour size and T factor of the tumour. In order to analyse the relationship between prognostic factors and cumulative survival rate after obtaining tumour specimens, 49 patients whose clinical courses could be followed after needle biopsy were selected for evaluation. These patients were treated by medical therapy alone. Analyses of prognostic factors by Cox's proportional hazard model revealed that the patient's prognosis was significantly correlated with PCNA-positive rates as well as the tumour size and mode of therapy. Moreover, the cumulative survival rates were significantly (P < 0.001) higher in patients with rates of PCNA-positive cells

The tumour cells of a human cholangiocarcinoma cell line, HuCC-T1, were found to express mRNA of interleukin-6 (IL-6) and to secrete a large amount of biologically active IL-6 in the culture medium at the concentration of 22.6 ng/mL. Interleukin-6 was demonstrated in the cytoplasm of the cells by immunohistochemical staining. Furthermore, these cells showed the presence of receptors for IL-6 on the surface, and DNA synthesis of the cells was stimulated by the exogenous addition of recombinant human IL-6 into the culture medium. The cell growth was significantly inhibited in the presence of anti-human IL-6 antibody in the culture medium. These findings indicate that IL-6 is one of the autocrine growth factors of this cell line in vitro.

To analyze the T cell repertoire of liver-infiltrating lymphocytes, 35 liver biopsy specimens taken for diagnostic purposes were stained by immunohistochemical technique using monoclonal antibodies (mAb) against CD3, CD8, CD45RO, and CD45RA and seven different variable (V) regions of the T cell receptor (TCR). Major populations of the infiltrating lymphocytes were CD3- and CD45RO- positive cells. The mean percentage (±SD) of Vβ5.1-positive cells was significantly (P < 0.05) higher in chronic hepatitis C (18.2 ± 13.3%, n = 15) than that in either chronic hepatitis B (5.7 ± 6.0%, n = 12) or autoimmune hepatitis (1.3 ± 1.2%, n = 3). In cases with primary biliary cirrhosis, only one case showed a high percentage (66%) of Vβ5.1-positive cells with mean ± SD of 19.3 ± 26.2% (n = 5). The percentages of Vβ5.1-positive cells correlated inversely with the Knodell histological activity index scores in cases with chronic hepatitis C. These data suggest that Vβ5.1-positive T cells may play a regulatory role in the immuno-pathogenesis of chronic hepatitis C.