Relationship between quantitative electroencephalogram and interferon-α-induced depression in chronic hepatitis C patients.

BACKGROUND: Quantitative electroencephalogram (qEEG) changes in chronic hepatitis C patients treated with interferon-α (IFN-α) have previously been reported. However, whether IFN-α-induced depression is related to changes in qEEG during IFN-α treatment remains unclear. METHOD: Fifty chronic hepatitis C patients were enrolled and IFN-α was administered intramuscularly at 9 × 10(6) IU daily for the first 4 weeks and then 3 times a week for the next 20 weeks. Serial EEGs obtained before and at 4 weeks after treatment were assessed. The absolute power for each frequency band was determined using qEEG techniques. Differences in the rate of change in absolute power for each of 6 frequency bands (δ, θ1, θ2, α1, α2 and ß) were assessed between patients with and without major depression using the Mann-Whitney U test. When significant differences in the rate of change in absolute power for each frequency band were observed, differences in the rate of change were also assessed between patients with and without psychological complications using the Mann-Whitney U test. RESULTS: Major depression due to psychological complications during IFN-α treatment was reported in 10 out of 50 patients. In the θ1 band, the difference in the rate of change was demonstrated to be significant (p = 0.0036). Moreover, at the central, frontal, parietal, and temporal locations, the rates of change were also significantly different. CONCLUSION: In IFN-α-treated chronic hepatitis C patients who were diagnosed with major depression, qEEG changes were more obvious and widely distributed.

Relationships between quantitative electroencephalographic alterations and the severity of hepatitis C based on liver biopsy in interferon-alpha treated patients.

OBJECTIVE: We have observed alterations of quantitative (q)-EEG findings occurring in interferon (IFN)-alpha treated chronic hepatitis C (CH-C) patients, and found patient's age to be one factor influencing such EEG alterations. In the present study we evaluated the correlation between q-EEG alterations during IFN-alpha treatment and the severity of hepatitis based on liver biopsies. METHODS: A total of 102 CH-C patients underwent blind, prospective and serial q-EEG examinations. The IFN-alpha was administered under the same therapeutic regimen to all patients. Serial EEGs were obtained before, at 2 and 4 weeks, and at 2-3 days after the conclusion of treatment. The absolute powers of each frequency band in different periods were determined by q-EEG. Staging (of fibrosis) and grading (of inflammatory cell infiltration) were scaled according to Desmet's classification. We evaluated the relationship between q-EEG and scales of staging or grading. RESULTS: Age distributions did not differ significantly among stages or grades. As the stage or grade increased, the alterations of EEG during IFN-alpha treatment became more pronounced, and significant (repeated-measures analysis of variances; both, p<0.0001). CONCLUSION: Alterations of the EEG occurring during IFN-alpha treatment became pronounced with more severe pathological findings for CH-C. Alterations in the EEGs during IFN-alpha treatment should be carefully monitored in CH-C patients with severe pathological findings.

Detection of hepatitis E virus RNA and genotype in Bangladesh.

BACKGROUND/AIMS: Hepatitis E virus (HEV) in Bangladesh has not been adequately documented. We report HEV RNA and genotype detection in Bangladesh. METHODS: In total, 82 samples were used; 36 sporadic acute hepatitis (AH), 12 fulminant hepatitis (FH), 14 chronic liver disease (CLD) and 20 from an apparently healthy population (HP) positive for both immunoglobulin (Ig) M and IgG specific anti-HEV antibodies (anti-HEV). The male/female ratio was 61/21, ages 12-67 (mean 30.4) years. RNA was extracted, transcribed to cDNA and amplified in nt 6345-6490 (ORF2) of HEV. Nucleic and amino acid sequences were determined. Homology comparison between Bangladesh clones and other representative HEV clones and phylogenetic tree analyses were done. Relations between HEV RNA-positivity and clinical factors were analyzed. RESULTS: HEV RNA was positive in 9/36 (25.0%) of AH cases, 4/12 (33.3%) FH, 3/14 (21.4%) CLD and 0/20 (0%) HP samples; total 16/82 (19.5%). Four factors correlated significantly with HEV RNA-positivity (Mann-Whitney U test); alanine aminotransferase (ALT) (P = 0.0229), aspartate aminotransferase (AST) (P = 0.0448), and titers of IgG (P = 0.0208) and IgM (P = 0.0095) specific anti-HEV. The 16 HEV clones were divided mainly into two groups, A and B, including six different cDNA sub-groups. CONCLUSION: HEV RNA was found in sporadic AH and FH and sub-clinical CLD cases, but not in HP. HEV RNA-positivity was significantly related to values of ALT and AST and titers of IgG and IgM specific anti-HEV, with IgM specific anti-HEV showing the most significant relationship. All clones were genotype I, which is prevalent in South Asia.

[A case of phlegmonous gastritis which resolved with medical treatment].

A 70-year-old man visited our outpatient clinic with chief complaints of severe upper abdominal pain and fever. Blood tests revealed a markedly enhanced inflammatory reaction. He was hospitalized and diagnosed with phlegmonous gastritis based on findings of esophagogastroduodenoscopy and multidrug-resistant streptococcus detected by gastric juice culture. The clinical symptoms promptly resolved after starting concomitant treatment with vancomycin hydrochloride and levofloxacin. Administration of vancomycin hydrochloride for phlegmonous gastritis was not found in our literature search and the present case is thus considered to provide a valuable example of such use.

Deformability of human red blood cells exposed to a uniform shear stress as measured by a cyclically reversing shear flow generator.

Red blood cells (RBCs) suspended in a dextran solution were at first loaded with a uniform shear stress of 21, 43 and 64 Pa for the duration of 0, 10, 20, 30, 45 and 60 min, respectively, followed with measurement of the dynamic deformation in terms of stretching and recovery, using a cyclically reversing sinusoidal shear flow with the peak stress of 128 Pa at 2 Hz. The L/W value, where L and W were the major and minor axis length of the RBC images, was derived to compare the effects of the uniform shear stress level and the exposure time. The exposure to the uniform shear stress of 21 Pa for the duration of as long as 60 min caused statistically insignificant L/W change in comparison to the control RBCs with L/W of 4.6 +/- 0.1. The exposure to 43 and 64 Pa for longer than 45 and 20 min, respectively, induced statistically significant change in the maximal L/W when compared to that of 21 Pa (p < 0.05). The composition of the maximal L/W values varied depending on the stress level and exposure time; with 21 Pa, the majority of cells exhibited the maximal L/W larger than 4.0 and few cells less than 2.0, whereas with the increase in the stress level to 43 and 64 Pa, cells having less than 2.0 exceeded 50%. Cyclic reversing shear flow is a useful means to measure dynamic deformation capability of RBCs which may be sub-hemolytically sheared without lysis.

Pseudolymphoma of the liver: Sonographic findings and review of the literature.

We report a case of hepatic pseudolymphoma in a 67-year-old woman that was detected during an abdominal sonography screening. The lesion was further evaluated using CT, MRI, angiography, and contrast-enhanced sonography. The imaging features of this tumor are discussed herein. The diagnosis of pseudolymphoma was achieved via sonographically guided biopsy. The lesion regressed completely within 1 year.

Factors influencing treatment efficacy of 24-week combination therapy with interferon alpha-2b plus ribavirin for chronic hepatitis C.

The efficacy of a combination therapy of interferon (IFN) alpha-2b plus ribavirin (RBV) in chronic hepatitis C, and the factors contributing to efficacy, were investigated. One hundred eighty-six cases were enrolled in this study and treated with a combination of IFN alpha-2b plus RBV. IFN alpha-2b was administered at 6-10 mega-units daily for 2-4 weeks and three times per week for 20-22 weeks, in combination with oral intake of RBV at 600 or 800 mg for 24 weeks. Rates of sustained virological response (SVR) were 34.9% in serogroup 1 (SG1) and 82.5% in SG2. SVR rates in cases with both drugs discontinued, reduced, and unchanged were 4.2%, 40%, and 42.7% in SG1 and 42.9%, 76.9%, and 91.9%, in SG2. In terms of the total RBV dose per kilogram body weight, SVR rates were 14.3% and 46.2% with <1600 mg, 36.2% and 91.7% with 1600-2000 mg, and 62.1% and 95% with > or =2000 mg in SG1 and SG2, respectively. Total doses of RBV per body weight and negative HCV RNA at 8 weeks were the significant factors contributing to SVR in SG1 cases. These results indicate that it was critical to tailor the doses of RBV and IFN to the individual. To improve the rate of SVR, it is necessary to make efforts, where possible, not to discontinue drug use or reduce the drug dose.

A case of eosinophilic cholangitis: imaging findings of contrast-enhanced ultrasonography, cholangioscopy, and intraductal ultrasonography.

A 38-year-old woman was referred to our institution due to epigastralgia. She presented with obstructive jaundice and eosinophilia. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing from the distal common bile duct to the bifurcation of the hepatic ducts. An endoscopic plastic biliary stent was inserted; the specimen obtained from the common bile duct wall revealed dense infiltration by eosinophils. Treatment was started with prednisolone 60 mg daily. The patient's biliary stenosis and eosinophilia gradually improved. Eosinophilic infiltration in the lungs or stomach is relatively common, but it is rare in the common bile duct. Most of the reported cases of eosinophilic cholangitis presented with eosinophilia; our patient's eosinophil count was over 1000/mm(3). Since our patient had allergies to pollen and house dust, a relationship between the allergies and the eosinophilic cholangitis was suspected, but no cause was identified.

Helicobacter pylori eradication reduces platelet count in patients without idiopathic thrombocytopenic purpura.

Discrepant outcomes of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura have been reported. Here patients with dyspepsia and no other complications underwent gastroendoscopic examination and evaluation for Helicobacter pylori infection. Helicobacter pylori-infected patients with gastritis and gastric ulcer received eradication therapy: lansoprazole (60 mg/day), clarithromycin (400 mg/day), and amoxicillin (1500 mg/day) for 1 week. Lansoprazole 30 mg/day was administrated additional 7 weeks. Peripheral platelets were counted before treatment, 8 weeks after initiation of therapy, and at follow-up periods. Platelet counts in patients with both gastritis and gastric ulcer were evaluated with reference to the presence of Helicobacter pylori infection. Eighty-seven patients with gastritis and 35 of those with gastric ulcer underwent successful eradication therapy. Peripheral platelet counts in patients with gastritis decreased from 235+/-55 to 228+/-58 (10(3)/microL) (p=0.0337), and those with gastric ulcer decreased from 248+/-60 to 232+/-48 (10(3)/microL) (p=0.020) 8 weeks after initiation of therapy. Non-eradicated patients did not show such a tendency. Helicobacter pylori eradication reduced peripheral platelet counts in patients with gastritis and gastric ulcer. Amelioration of thrombocytopenia by eradicating Helicobacter pylori appears to involve mechanisms specific to idiopathic thrombocytopenic purpura.

Usefulness of rectally administering [1-(13)C]-butyrate for breath test in patients with active and quiescent ulcerative colitis.

OBJECTIVE: Impaired butyrate metabolism plays a part in ulcerative colitis (UC). To assess the usefulness of measuring butyrate metabolism as an indication of inflammatory activity, we investigated the rate of butyrate metabolism by breath test after administering [1-(13)C]-butyrate rectally to patients with UC. MATERIAL AND METHODS: Thirty-eight UC patients (22 active, 16 quiescent) and 15 healthy controls were given [1-(13)C]-butyrate enemas. The (13)CO2 production rate was measured by breath test using an infrared spectrometric analyzer. RESULTS: The quantity of expired (13)CO2 was significantly lower in the active than in the quiescent UC and control groups. Cumulative (13)CO2 production at 240 min showed significant negative correlations with the clinical activity index (r=-0.65, p<0.0001), endoscopic activity index (r=-0.63, p=0.0001) and histology (r=-0.71, p<0.0001) in the active UC group. The (13)CO2 production rate was significantly increased in the quiescent stage as compared with the active stage in six UC patients, in whom clinical remission was achieved, in accordance with improvements in the clinical activity index, the endoscopic activity index, histology and fecal butyrate concentrations. Significant inverse correlations between the cumulative (13)CO2 production rate and these three parameters were seen in these six UC patients assessed in both the active and quiescent stages. CONCLUSIONS: Measurement of expired (13)CO2 after rectally administering [1-(13)C]-butyrate in active and quiescent UC appears to be a promising and reliable method for evaluating disease activity and metabolic changes associated with amelioration of inflammation.

Persistent infection of hepatitis E virus transmitted by blood transfusion in a patient with T-cell lymphoma.

AIM: With advent of reverse-transcription (RT)/polymerase chain reaction (PCR) for detection of the hepatitis E viral genome, we carried out retrospective examinations. METHODS: Serum samples collected from 68 patients diagnosed as viral hepatitis with unknown etiology were tested for viral markers of hepatitis virus. RESULTS: Two of them were found positive for hepatitis E viral RNA. While the clinical course of one patient (patient 1) was typical as acute hepatitis E, another patient (patient 2) was persistently infected with HEV. Patient 2 was infected with the virus via blood transfusion during chemotherapy against T-cell lymphoma. The entire viral genome from the donor was identical with that from the serum of patient 2 obtained on day 170 after the transfusion of the implicated red blood cell (RBC) product, confirming the transmission of HEV by transfusion. The patient remained negative for anti-HEV antibodies for the follow-up period of six months, probably due to immune suppression by lymphoma and chemotherapy. CONCLUSION: We report here an unusual case of long-term HEV infection in a patient with T-cell lymphoma. Persistent infection with HEV was probably due to the absence of anti-HEV antibodies, which was caused by lymphoma and chemotherapy.

BCAA-enriched snack improves nutritional state of cirrhosis.

OBJECTIVE: A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis. METHODS: In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study. RESULTS: Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group. CONCLUSION: Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.

Green Tea Polyphenols Reduce Gastric Epithelial Cell Proliferation and Apoptosis Stimulated by Helicobacter pylori Infection.

Recently the finding of gastric cancer in Helicobacter pylori (H. pylori)-infected mouse models was reported. Studies of humans and animal models have shown that H. pylori infection stimulates gastric epithelial cell proliferation and apoptosis. Polyphenols contained in green tea and related compounds were reported to have a variety anti-tumor effects and bactericidal properties. We studied the effect of green tea polyphenols on gastric cell proliferation and apoptosis in an H. pylori-infected mouse model. This model was prepared by inoculating Balb/c mice with 10(8) cfu of H. pylori (NCTC 11637 strain) by gavage. Beginning 18 weeks after inoculation, 0.5% polyphenols were given in drinking water every day for 2 weeks. Mice were sacrificed 1 h after bromodeoxyuridine (BrdU) was given i.p. for preparation of paraffin-embedded specimens. Cell proliferation and apoptosis were examined by the avidin-biotin complex method using anti-BrdU antibody and the TUNEL method, respectively. H. pylori infection resulted in increased BrdU-labeled cells in both the antrum and the bodies. Administration of polyphenols suppressed this increased proliferation. H. pylori infection increased apoptotic cells in both the antrum and the corpus in comparison with controls. This increase was not seen in H. pylori-infected mice given polyphenols. We conclude the administration with polyphenols might suppress gastric carcinogenesis that is in part related to H. pylori infection.

Evaluation of malignancy of hepatocellular carcinoma using the ultrasonic B-mode method: clinical significance of extracapsular invasion of hepatocellular carcinoma using ultrasonography.

PURPOSE: To determine the influence of capsule formation or presence of capsular invasion on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The patient group consisted of 70 patients with 74 HCC lesions who had been examined by US and undergone surgical tumor resection at our institution. For these patients, we conducted the following comparative studies: (a) comparison between halo findings on US and microscopic capsular results; (b) comparison between halo findings on US and tumor diameter, tumor histological differentiation, and serum value of each tumor marker; and (c) comparison between halo findings on US and tumor recurrence. RESULTS: (a) The corresponding value between sonographic halo and histological capsule was 90.1%, and that between presence of extracapsular invasion on US and that seen by histology was 88.0%. (b) There was no relation between US images and histological differentiation of tumors. (c) Presence of extracapsular invasion on US was a predisposing factor for the development of tumor recurrence. CONCLUSION: (1) Globally speaking, sonographic halo corresponded to the histological tumor capsule. (2) In patients with extracapsular invasion, tumor recurrence after treatment increased. Thus, a better understanding of sonographic halo findings helps determine diagnostic and therapeutic strategies in HCC patients.

Clinical efficacy of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC).

PURPOSE: To evaluate the role of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC). METHODS: CEUS and angiography were performed in ten cases of ruptured HCC. We evaluated whether this technique allowed us to determine the bleeding point by observing an extravasation of contrast media into the ascites. RESULTS: In four of the ten cases, CEUS demonstrated an extravasation of Levovist into ascites. Angiography showed an extravasation of contrast medium in three of these four cases. In three of the remaining six cases, in which CEUS did not show the presence of contrast medium in ascites, angiography demonstrated an extravasation. In eight cases, it yielded cessation of bleeding. In two cases, embolization was not successful. The bleeding point was not determined by CEUS or angiography in one case. CONCLUSION: CEUS allows us to differentiate active bleeding (presence of contrast medium in the ascites) from nonactive bleeding.

Interferon therapy improves the irregular regeneration of hepatocytes in liver in patients with C-viral chronic hepatitis and liver cirrhosis.

We examined changes in the degree of irregular regeneration (IR) of hepatocytes and the F stage in patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) who received interferon (IFN) therapy. The IFN-treated group consisted of 148 C-viral CH and LC patients; the IFN-untreated (UT) group consisted of 42 patients. The liver biopsy specimens were examined histologically, followed by a separate scoring of the degree of IR of hepatocytes which was classified into the following 5 grades and scored (IR score): score 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe). The annual rates of the IR score were -0.593 in sustained virologic responders, -0.188 in sustained biochemical responders, 0.071 in nonresponders and 0.121 in UT patients. The annual rates of the F stage were -0.218 in sustained virologic responders, -0.061 in sustained biochemical responders, 0.123 in nonresponders and 0.157 in UT patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence was significantly higher in groups of IFN-treated patients without improvement of IR scores than in groups with improvement of IR scores. Multivariate analyses revealed that a lack of improvement in the IR score was a cardinal risk factor for the development of HCC in C-viral CH and LC patients. Our data suggest that IFN therapy leads to an improvement in the degree of IR of hepatocytes and thereby influences the development of HCC in patients with CH and LC.

The protective effect of the soybean polyphenol genistein against stress-induced gastric mucosal lesions in rats, and its hormonal mechanisms.

The present study investigated the effect of the soybean polyphenol genistein on the stomach using a water immersion restraint (WIR) stress model. Male Wistar rats were administered 50 or 100 mg/kg/d of genistein for 2 wk or were not given any drug. Rats were subjected to WIR stress for 4 h. At the end of the WIR period, rats were sacrificed. Subsequently, rats underwent measurement of the ratio of the mucosal hemorrhagic erosion area to the whole stomach body area, myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, thiobarbituric acid reactive substances (TBARS) level, and proinflammatory cytokines (tumor necrosis factor (TNF)-a and cytokine-induced neutrophil chemoattractant (CINC)-1) levels in the gastric tissue. Furthermore, an isolated rat stomach infusion model was employed for the endocrinological investigation of the effect of genistein. The extracted stomach canal and the vascular system, which comprised the experimental model, were subjected to perfusion. After 20 min of perfusion, the perfusate from the portal vein was collected, and the concentrations of histamine, gastrin, and somatostatin in the perfusate were measured. Experiments demonstrated that genistein administration resulted in significant suppression of WIR stress-induced gastric mucosal injury and MPO activity, Further, genistein significantly elevated SOD activity and significantly suppressed the TBARS level, production of TNF-alpha and CINC-1, and secretion of gastrin, histamine, and somatostatin. These data suggest that genistein protected against gastric mucosal injury, likely via its ability to inhibit oxidation, inflammation, and secretion of gastrin and histamine.

Genetic variants of the IgA Fc receptor (FcalphaR, CD89) promoter in chronic hepatitis C patients.

Fc receptor for IgA (FcalphaR, CD89) is capable of triggering IgA-mediated immune responses to pathogens and has been proposed to function in circulating IgA clearance. Because inheritable variations modifying individual immune responses or immunoglobulin catabolism may affect the chronicity of viral infection, we investigated whether promoter polymorphisms of the FcalphaR gene (FCAR) affect chronic hepatitis C virus (HCV) infection and its disease progression. The two -311T/C and -142T/C single-nucleotide polymorphisms (SNPs) were studied by direct DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both -311CC and -142CC genotypes were more frequent in CHC patients (15.9 and 18.6%) compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) = 3.10, 95% confidence interval CI) = 1.53-6.30 and p = 0.014, OR = 2.06, 95% CI = 1.14-3.72, respectively], and were associated with infection with HCV genotype 2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, -311CC and -142CC were decreased in 59 patients at advanced stages of disease as assessed on the basis of hepatic fibrosis markers such as decreased platelet count (PLT) (< 150,000/microl) (5.1 and 8.5%) compared with 91 patients with normal PLT (> or = 150,000/microl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively). Moreover, among the patients with normal PLT (but not with decreased PLT), -311CC or -142CC was significantly associated with decreased serum IgA levels (p = 0.023 or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs may be related to chronic HCV infection and disease progression in Japanese CHC, which might be explained by altered FcalphaR expression affecting IgA-mediated immune responses and/or IgA catabolism.

Clinical significance of evaluation of serum zinc concentrations in C-viral chronic liver disease.

We evaluated zinc concentrations in patients with hepatitis C virus (HCV)-positive chronic liver disease and correlated them with the clinical profiles of the patients. A total of 100 patients with chronic hepatitis (CH), 29 with liver cirrhosis (LC), and 6 who were asymptomatic HCV carriers (ASC) were examined. All of the patients were positive for serum HCV RNA. One hundred eighteen HCV antibody-positive hepatocellear carcinoma (HCC) patients and 11 healthy subjects also were included in this study. Serum zinc concentrations were evaluated using conventional atomic absorption spectrometry. The median concentration of zinc in patients with CH was statistically lower than that in healthy control subjects. The median zinc concentrations of the LC and HCC groups were significantly lower than that of the CH group. A significant correlation was observed between the zinc concentrations and the platelet counts and albumin concentrations. The zinc concentrations did not correlate with tumor size and number and decreased with the development of Child-Pugh stage. The cumulative survival rate after therapy for HCC nodules in the low zinc concentration group was significantly lower than in the high group. We conclude that the serum concentration of zinc influences the clinical profiles in patients with C-viral chronic liver disease.

Measurement of human intercellular adhesion molecule 1 in the blood is useful for predicting the occurrence of hepatocellular carcinomas from chronic hepatitis C and liver cirrhosis.

OBJECTIVE: We measured the concentrations of serum intercellular adhesion molecule 1 (sICAM-1) in patients with C-viral chronic liver diseases and started prospective studies immediately thereafter, in order to determine whether the concentration of sICAM-1 is useful for predicting the occurrence of hepatocellular carcinoma (HCC) following C-viral chronic hepatitis (CH) and liver cirrhosis (LC). METHODS: We studied 74 patients with CH, 18 with LC, and 28 patients with HCC who visited our institute from 1993 through 1996. All were positive for hepatitis C virus RNA in the blood. The concentrations of sICAM-1 were measured using enzyme-linked immunosorbent assay kits. The expression of ICAM-1 in the liver was detected by indirect immunoperoxidase staining. RESULTS: The concentrations of sICAM-1 were significantly higher in patients with LC and HCC than in patients with CH. The sICAM-1 concentrations were high in patients whose platelet counts were low. ICAM-1 in the liver was localized to the endoplasmic reticulum or the membrane of cancer cells. The cumulative rate of occurrence of HCC from CH or LC was significantly higher in the high-sICAM-1 group (>400 ng/ml) than in the low-sICAM-1 group. Multivariate analysis revealed that elevation of the sICAM-1 concentration is a significant risk factor for the occurrence of HCC. CONCLUSION: Evaluation of the sICAM-1 concentration is useful for prediction of the occurrence of HCC in patients with C-viral CH or LC.