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Background/aims: We designed a randomized trial to examine whether increase or preservation of serum albumin levels was attained with administration of branched-chain amino acid (BCAA) granules for compensated cirrhosis, compared with decompensated cirrhosis., Methodology: Sixty-five patients with HCV-related cirrhosis with serum albumin level less than 4.0 g/dl were enrolled in this study. Half of the patients were randomly assigned to receive 14.22 g/day of BCAA granules orally, and half were assigned to a control group. Patients were evaluated at entry and at 1-year intervals for at least 2 years. The parameters were divided into 3 categories. Class 1 was decompensated cirrhosis with serum albumin level less than 3.5 mg/dl. Class 2 was compensated cirrhosis with serum albumin level over 3.6 mg/dl and molar ratio of BCAA to tyrosine (BTR) less than 4. Class 3 was compensated cirrhosis with serum albumin level over 3.6 mg/dl and BTR over 4., Results: In class 1 and class 2, the BCAA group exhibited significantly higher rates of maintaining serum albumin level than the control group for 2 years. In contrast, there was no significant difference between the BCAA group and control group in rate of maintaining serum albumin levels in class 3., Conclusions: Those results suggested that if cirrhotic patients were in the compensated stage at the entry but with lower BTR, as for decompensated cirrhosis, oral BCAA supplementation might be effective in maintaining serum albumin level for 2 years.

Background/aims: Surgically resected hepatocellular carcinomas (HCC) in patients with non-alcoholic steatohepatitis (NASH) have rarely been described and the clinicopathological characteristics of HCC and non-cancerous liver tissue are still obscure., Methodology: From 1997 to 2004, 242 patients with HCC underwent hepatic resection at the Hiroshima Red Cross Hospital and Atomic Bomb Survivors' Hospital. Among this group, the diagnosis of NASH was made in 3 patients., Results: All 3 patients with HCC had cirrhosis. The tumor cells contained Mallory bodies and fat. The non-cancerous areas showed nodular regeneration with fatty changes, ballooning degeneration, and mild inflammatory infiltrates, as well as perivenular and perisinusoidal fibrosis., Conclusions: Patients with NASH and cirrhosis may progress to HCC, and careful follow-up based on tumor markers and imaging modalities, is essential to detect resectable HCC in patients with NASH and cirrhosis.

Background/aims: The purpose of this study was to validate the usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) in predicting degree of malignancy and prognosis, evaluated in terms of Japan Integrated Staging (JIS) score, in cirrhotic patients with hepatocellular carcinoma (HCC)., Methodology: FDG-PET was performed in 50 patients with HCC. The activity within regions of interest placed over tumors was measured, and standardized uptake values (SUVs) were calculated by dividing the tissue activity by injected dose of radioactivity per unit body weight. SUV ratio (SUVR) was expressed as tumor-to-nontumor ratio of SUV. Patients were allocated to 3 groups of similar size: group A, SUVR < or = 1.1; group B, 1.1 < SUVR < 1.6; and group C, 1.6 < or = SUVR., Results: SUVR significantly correlated with tumor node metastasis stage score (p < 0.001) or JIS score (p = 0.022). Survival rate in SUVR group C was significantly lower than that in group A (p < 0.001), and close to being significantly lower than that in group B. On multivariate analysis, JIS scores 2 and > or = 3, SUVR group C were significantly related to survival (All p < 0.05)., Conclusions: SUVR was well associated with a tumor staging which is the factor of JIS score and with survival, and indicated malignancy and prognosis of patients especially with high-grade HCC.

Background/aims: We simultaneously examined the reservoir function of the stomach as well as emptying by one single assessment for gastric emptying, and investigated their association in patients with functional dyspepsia (FD). Next, we examined the interaction between the association and abdominal symptoms., Methodology: Sixty-one FD patients according to the Rome III criteria were recruited for this study. We measured the radioactive changes of the proximal and the whole stomach by the scintigraphy until 120 min, and assessed the reservoir function and the respective half-emptying time. We assessed the symptoms by the previously validated questionnaires., Results: Disordered emptying was seen in 55.7% (34/61) of patients, delay in 67.6% (23/34), and acceleration in 32.4% (11/34). Impaired reservoir function was found in 49.2% (30/61) of patients, which had an association with delayed (p = 0.025) and disordered (delay+acceleration) emptying (p = 0.027). Through the period, the radioactive decrease was dynamic in the normal, but virtually unchanged in the impaired reservoir function group. Symptoms in the motility disordered group tended to be more severe than in the normal group., Conclusions: Gastric reservoir function was associated with emptying in FD patients. Abdominal symptoms of FD patients were partly derived from the impairment of coordinated gastric motility.

Background/aims: We propose a method, named US score, for semi-quantitative determination of the stage of chronic type C liver disease by ultrasonography., Methodology: The subjects were 454 patients with chronic type C liver disease. Of the patients with chronic hepatitis C, 208 underwent US-guided or laparoscopic liver biopsy. US score was the sum of the scores representing five morphological variables, to be evaluated semi-quantitatively, and change in US score with chronic liver disease progression was determined., Results: The average US score was 2.5 +/- 0.4 for F0, 2.8 +/- 0.6 for F1, 3.0 +/- 0.6 for F2, 3.7 +/- 0.9 for F3 and 5.5 +/- 0.8 for F4. There was a significant correlation between US score and the degree of fibrosis of chronic hepatitis C as assessed by the new European classification (p<0.0001). The average US score was 5.6 +/- 0.9 for Child A, 6.6 +/- 1.1 for Child B, and 7.8 +/- 0.7 for Child C. There was a significant correlation between US score and the results of classification by Child-Turcotte criteria (p<0.0001)., Conclusions: These results suggest that US score is a stable, convenient method of evaluating the degree of progression of chronic type C liver disease.

Background/aims: Conventional methods predicting survival in patients with primary biliary cirrhosis are based on the results of blood tests and on clinical condition, both of which may be affected by treatment. Portal circulation can be evaluated in a relatively noninvasive manner by per-rectal portal scintigraphy. We used this method to evaluate portal hemodynamics and assess prognosis in patients with primary biliary cirrhosis., Methodology: Per-rectal portal scintigraphy with Tc-99m pertechnetate was done in 51 patients with primary biliary cirrhosis. A solution containing Tc-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was calculated from the curves., Results: The shunt index was higher in patients with stage IV primary biliary cirrhosis than in those with stage I, II, or III primary biliary cirrhosis. On the basis of portal shunt index, the patients were divided into those with a shunt index of less than 18%, and those with a shunt index of 18% or more. The cumulative survival rate was lower among patients with the higher shunt index. On regression analysis, the portal shunt index was found to be significantly related to survival., Conclusions: Our results indicate that per-rectal portal scintigraphy with Tc-99m pertechnetate can be used to non-invasively evaluate the portal circulation of patients with primary biliary cirrhosis and is useful in establishing prognosis in such patients.

Background/aims: Hepatitis C virus is a major causative agent of chronic liver disease and hepatocellular carcinoma and is considered to be a hepatotropic virus. It remains controversial whether hepatitis C virus exists in peripheral blood mononuclear cells and replicates there. In order to resolve this issue, we performed nested RT-PCR (reverse transcription polymerase chain reaction) and RT-PCR in situ hybridization in peripheral blood mononuclear cells of patients with chronic hepatitis C., Methodology: We collected peripheral blood mononuclear cells from patients with chronic hepatitis C, extracted total RNA from the samples, and performed nested RT-PCR to detect hepatitis C virus RNA in the peripheral blood mononuclear cells lysates. We also fixed peripheral blood mononuclear cells of the patients in 4% paraformaldehyde and performed RT-PCR in situ hybridization with a digoxigenin-labeled RNA probe to detect hepatitis C virus RNA in the cells., Results: Using these methods, we detected both positive- and negative-stranded hepatitis C virus RNA in peripheral blood mononuclear cells of hepatitis C patients. To determine in which cell population of peripheral blood mononuclear cells hepatitis C virus is present, we performed PCR in situ hybridization after incubation with fluorescent latex microbeads which could be phagocytozed by monocytes. We obtained positive signals of the replicative hepatitis C virus genome not only in lymphocytes but also in monocytes., Conclusions: RT-PCR in situ hybridization with a nonradioactive probe was found to be useful for in situ detection of hepatitis C virus RNA. Our findings suggest that peripheral blood mononuclear cells may be extrahepatic replication sites for hepatitis C virus.

Background/aims: Portal circulation can be evaluated in a relatively noninvasive manner by per-rectal portal scintigraphy. We used this method to evaluate portal hemodynamics in patients with primary biliary cirrhosis and idiopathic portal hypertension. We did the procedures simultaneously in some patients to examine the relation between portal circulation and hepatic functional reserve in these diseases., Methodology: Per-rectal portal scintigraphy with Tc-99m pertechnetate was done in 17 healthy subjects, 154 patients with chronic hepatitis, 447 patients with cirrhosis, 40 patients with primary biliary cirrhosis, and 20 patients with idiopathic portal hypertension. Eighty-three patients (14 with hepatitis, 48 with cirrhosis, 16 with primary biliary cirrhosis, and 5 with idiopathic portal hypertension) also underwent scintigraphy with Tc-99m galactosyl human serum albumin with 2 weeks. A solution containing Tc-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was calculated from the curves. A receptor index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest 15 min after the injection of Tc-99m galactosyl human serum albumin. The index of blood clearance was calculated by dividing the radioactivity of the heart region of interest at 15 min by that of the heart region of interest at 3 min., Results: The shunt index was higher for more severe disorders, increasing in the order of chronic hepatitis, cirrhosis without varices, and cirrhosis with varices. The shunt indices in patients with primary biliary cirrhosis and idiopathic portal hypertension were higher than that in patients with chronic hepatitis. In terms of receptor index, the standard residuals were more than 0 in 10 of 16 patients with primary biliary cirrhosis and 4 of 5 patients with idiopathic portal hypertension. In terms of index of blood clearance, the standard residuals were more than 0 in 10 of 16 patients with primary biliary cirrhosis and 4 of 5 patients with idiopathic portal hypertension, Conclusions: Abnormalities of portal hemodynamics in patients with primary biliary cirrhosis or idiopathic portal hypertension occur while hepatic functional reserve is still satisfactory as compared with patients who have chronic hepatitis or cirrhosis.

Background/aims: Natural killer cells have an intrinsic ability to recognize and attack some tumor cells and infected cells. Natural killer cell cytotoxicity is depressed in patients with hepatocellular carcinoma. In particular, cell-mediated immunity is impaired after transcatheter arterial embolization, which is an effective therapy for hepatocellular carcinoma. There have been reports that cimetidine can activate cellular immunity and increase the survival time in patients with some cancers. Therefore, we investigated whether cimetidine could improve cellular immunity after transcatheter arterial embolization, especially in relation to natural killer activity., Methodology: Thirty-four patients with hepatocellular carcinoma and cirrhosis who underwent transcatheter arterial embolization at our hospital were studied prospectively after giving informed consent. The patients were divided into three groups. In group A, 14 patients were administered 800 mg of cimetidine a day. In group-B, 13 patients were administered 40 mg of famotidine or 300 mg of nizatidine a day. In group-C 7 patients did not receive histamine 2 receptor antagonists. Natural killer cell activity in peripheral blood was measured before transcatheter arterial embolization and on days 1 and 7., Results: The % natural killer cell activity on day 1 was 74 in group A, 52 in group B, and 52 in group. The % activity on day 7 was 98 in group A, 71 in group B, and 82 in group C. Cimetidine group showed the significant higher % natural killer cell activity on day 1 (p = 0.032)., Conclusions: Our study raises the possibility that cimetidine has the effect to preserve cell-mediated immune response during transcatheter arterial embolization.

Background/aims: Hepatocellular carcinoma is usually complicated with liver cirrhosis, which makes its treatment difficult. Also a high rate of recurrence exists after surgical resection. However, how the prognosis after surgical treatment is affected by the severity of coexisting cirrhosis has not been clarified., Methodology: We compared the postoperative longterm courses of hepatocellular carcinoma patients with cirrhosis according to the liver function. All 112 hepatocellular carcinoma patients in this study underwent curative hepatic resection, and were classified into three groups according to the severity of liver dysfunction. The ICG R15' (indocyanine green retention test) normal: < 10%) was used in this study. Patients whose ICG R15' was less than 20% were classified as group I of 62, patients equal to 20% or between 20% and 30% as group II of 24, and patients equal to and more than 30% as group III of 26., Results: In this series, 76 of 112 patients had recurrence (68%). A second hepatic resection was performed in six cases of group I and one case in group II. Fifty-eight of 76 recurrent cases (76%) were treated with transcatheter arterial chemoembolization. A total of eleven cases had no transcatheter arterial chemoembolization in the three groups: 3 cases in group I, 5 cases in group II, and 3 cases in group III; The three cases of group III had no treatment because of extremely poor liver dysfunction, whilst the 8 patients without transcatheter arterial chemoembolization in groups I and II had hepatocellular carcinoma itself and other diseases. The 1-, 3-, and 5-year survival rates after recurrence were 92%, 48%, and 14%, respectively, in group I; 83%, 37%, 12%, respectively, in group II; and 66%, 30%, 0%, respectively, in group III. The prognosis was significantly worse according to the degree of liver dysfunction (p = 0.0206)., Conclusions: The prognosis of hepatocellular carcinoma with liver cirrhosis is affected not only by hepatocellular carcinoma itself, but also by the severity of the coexisting cirrhosis. Moreover, the cirrhotic liver can decline due to surgery. Surgical resection of this disease should be performed after careful patient selection and using a less invasive technique.

Background/aims: Polyamines are essential for cell proliferation, differentiation, and transformation. Concentrations of polyamines are higher in some cancer tissue than in normal tissue. We examined erythrocyte-binding polyamines to evaluate the usefulness of polyamines as pathophysiological markers for hepatocellular carcinoma., Methodology: We measured erythrocyte-binding polyamine levels in peripheral blood samples obtained from 51 normal adult controls, 136 patients with chronic viral hepatitis, 104 patients with viral hepatic cirrhosis, and 130 patients with hepatocellular carcinoma., Results: We defined the concentration of spermidine plus spermine as the erythrocyte polyamine level, and designated the cut-off level for normal as the mean erythrocyte polyamine level +/- 2 SD in control. The erythrocyte polyamine level was abnormally elevated (positive) in 56 (43%) of 130 patients with hepatocellular carcinoma, 11 (8%) of 136 patients with chronic hepatitis, and 13 (13%) of 108 patients with cirrhosis. The level was higher in patients with a short tumor doubling time. In 27 patients with tumors, there was negative correlation between tumor doubling time and erythrocyte polyamine level (r = -0.46; P = 0.0147)., Conclusions: We conclude that erythrocyte polyamine may be a useful tumor growth marker in patients with hepatocellular carcinoma.

Background/aims: Small-bowel obstructions caused by persimmon bezoars are uncommon, and the diagnosis is difficult before operation. The aim of this study was to present computed tomography findings of persimmon bezoars in the small bowel., Methodology: We reviewed 3 cases diagnosed with small-bowel obstruction caused by persimmon bezoars between April 1997 and March 1999 at Chikamori Hospital., Results: The cause of the small-bowel obstruction was bezoars in the 3 patients. Abdominal computed tomography performed before operation revealed a well-defined, intraluminal inhomogeneous mottled mass containing gas bubbles., Conclusions: Computed tomography is useful for diagnosing obstructed small-bowel persimmon bezoars.

Portal circulation in patients with chronic liver disease was evaluated by per-rectal portal scintigraphy, and per-rectal portal shunt indices were calculated to estimate the extent of the portosystemic shunt. The purpose was to identify patients with cirrhosis at special risk of developing esophageal varices. The cumulative incidence of varices in 3 years of the study in patients whose shunt index was originally 20% or over, was significantly higher than that in patients whose shunt index was originally under 20%. The cumulative survival rate in 7 years of the study in patients whose shunt index was originally under 70% was significantly higher than that in patients whose shunt index was originally 70% or over. The information obtained by calculating the shunt index could be used by physicians in out-patient clinics when deciding the schedule with which to monitor patients using barium esophagogram or endoscopy, and choosing the examination method.