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AIM: To study the therapeutic effect of interferon (IFN) and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection. METHODS: A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFNalpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defi ned as negative HCV-RNA in the serum 6 mo after treatment. RESULTS: There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P < 0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P = 0.019). CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.

The etiology of inflammatory bowel disease is multifactorial and appears to combine both genetic and environmental factors. We experienced here a rare occurrence of woman monozygotic twins with ulcerative colitis (UC). A 45-year-old woman (the elder monozygotic twin) was admitted to our hospital because of bloody diarrhea occurring over 10 times per day, abdominal pain and fever. She was diagnosed as UC at the age of 22, and repeated the relapse and remission. She was diagnosed as relapse of UC and total colitis type. Her younger monozygotic twin sister also suffered from UC at the age of 22. Human leukocyte antigen was examined serologically with DNA type in both patients. DRB1*1502, which was previously shown to be dominant in Japanese patients with UC, was not observed in this case. Although the concordance in monozygotic twin in UC is reported to be 6.3-18.8%, the concordant case like this is relatively rare. We report this rare case of UC and the previously reported cases are also discussed.

AIM: To investigate the precise roles of CAR in CCl4-induced acute hepatotoxicity. METHODS: To prepare an acute liver injury model, CCl4- induced was intraperitoneally injected in CAR+/+ and CAR-/- mice. RESULTS: Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR-mice compared to CAR+/+ mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR-/- mice compared with CAR+/+ mice. On the other hand, androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR+/+ but not in CAR-/- mice. Thus, CAR activation caused CCl4- induced hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity.There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR+/+ and CAR-/- mice. However, the expression of other CCl4-metabolizing enzymes, such as CYP2B10 and 3A11, was induced by PB in CAR+/+ but not in CAR-/- mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and3A11 in the presence of activator or inhibitor. CONCLUSION: The nuclear receptor CAR modulates CCl4-induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drug-drug interaction even though such drugs themselves are not hepatotoxic.

AIM: To define the clinical characteristics, and to assess the management of colonoscopic complications at a local clinic. METHODS: A retrospective review of the medical records was performed for the patients with iatrogenic colon perforations after endoscopy at a local clinic between April 2006 and December 2010. Data obtained from a tertiary hospital in the same region were also analyzed. The underlying conditions, clinical presentations, perforation locations, treatment types (operative or conservative) and outcome data for patients at the local clinic and the tertiary hospital were compared. RESULTS: A total of 10 826 colonoscopies, and 2625 therapeutic procedures were performed at a local clinic and 32 148 colonoscopies, and 7787 therapeutic procedures were performed at the tertiary hospital. The clinic had no perforations during diagnostic colonoscopy and 8 (0.3%) perforations were determined to be related to therapeutic procedures. The perforation rates in each therapeutic procedure were 0.06% (1/1609) in polypectomy, 0.2% (2/885) in endoscopic mucosal resection (EMR), and 3.8% (5/131) in endoscopic submucosal dissection (ESD). Perforation rates for ESD were significantly higher than those for polypectomy or EMR (P < 0.01). All of these patients were treated conservatively. On the other hand, three (0.01%) perforation cases were observed among the 24 361 diagnostic procedures performed, and these cases were treated with surgery in a tertiary hospital. Six perforations occurred with therapeutic endoscopy (perforation rate, 0.08%; 1 per 1298 procedures). Perforation rates for specific procedure types were 0.02% (1 per 5500) for polypectomy, 0.17% (1 per 561) for EMR, 2.3% (1 per 43) for ESD in the tertiary hospital. There were no differences in the perforation rates for each therapeutic procedure between the clinic and the tertiary hospital. The incidence of iatrogenic perforation requiring surgical treatment was quite low in both the clinic and the tertiary hospital. No procedure-related mortalities occurred. Performing closure with endoscopic clipping reduced the C-reactive protein (CRP) titers. The mean maximum CRP titer was 2.9 ± 1.6 mg/dL with clipping and 9.7 ± 6.2 mg/dL without clipping, respectively (P < 0.05). An operation is indicated in the presence of a large perforation, and in the setting of generalized peritonitis or ongoing sepsis. Although we did not experience such case in the clinic, patients with large perforations should be immediately transferred to a tertiary hospital. Good relationships between local clinics and nearby tertiary hospitals should therefore be maintained. CONCLUSION: It was therefore found to be possible to perform endoscopic treatment at a local clinic when sufficient back up was available at a nearby tertiary hospital.

AIM: To evaluate the value of ABC (D) stratification [combination of serum pepsinogen and Helicobacter pylori (H. pylori) antibody] of patients with gastric cancer. METHODS: Ninety-five consecutive patients with gastric cancer were enrolled into the study. The serum pepsinogen I (PG I)/pepsinogen II (PG II) and H. pylori antibody levels were measured. Patients were classified into five groups of ABC (D) stratification according to their serological status. Endoscopic findings of atrophic gastritis and histological differentiation were also analyzed in relation to the ABC (D) stratification. RESULTS: The mean patient age was (67.9 ± 8.9) years. Three patients (3.2%) were classified into group A, 7 patients (7.4%) into group A’, 27 patients (28.4%) into group B, 54 patients (56.8%) into group C, and 4 patients (4.2%) into group D, respectively. There were only three cases in group A when the patients taking acid proton pump inhibitors and those who had undergone eradication therapy for H. pylori (group A’) were excluded. These three cases had mucosal atrophy in the grey zone according to the diagnostic manual of ABC (D) stratification. Histologically, the mean age of the patients with well differentiated adenocarcinoma was significantly higher than that of the patients with poorly differentiated adenocarcinoma (P < 0.05). There were no differences in the pattern of atrophy in the endoscopies between the well differentiated and poorly differentiated groups. CONCLUSION: ABC (D) stratification is a good method for screening patients with gastric cancers. Endoscopy is needed for grey zone cases to check the extent of mucosal atrophy.

AIM: To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC). METHODS: Experimental colitis was induced by oral administration of dextran sodium sulfate. Rats with colitis were intrarectally administered GL-p or saline. The extent of colitis was evaluated based on body weight gain, colon wet weight, and macroscopic damage score. The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis. The effect of GL-p on myeloperoxidase (MPO) activity in the inflamed mucosa and purified enzyme was assayed. RESULTS: GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline. Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant-2, and monocyte chemoattractant protein-1 in the inflamed mucosa. Furthermore, GL-p inhibited the oxidative activity of mucosal and purified MPO. CONCLUSION: GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

We have reported a case of hepatic adenomatosis associated with hormone replacement therapy (estrogen and progesterone) and hemosiderosis caused by excessive blood transfusion for the treatment of chronic myeloid leukemia. A 34-year-old woman was found to have several hepatic tumors on a routine medical examination. The general condition was good. Laboratory studies showed iron overload. Abdominal computed tomography and selective hepatic angiography showed several hypervascular tumors in the right lobe of the liver (up to 20 mm in diameter). Since hepatocellular carcinoma could not be ruled out, subsegmental hepatectomy was performed. Histopathological examination of the surgical specimen showed hepatic adenomatosis with hemosiderosis. Both hormone replacement therapy and iron overload could be the cause of hepatic adenomatosis.

The beneficial effect of zinc supplementation on the efficacy of interferon as a treatment for chronic hepatitis C had been demonstrated in hepatitis virus genotype 1b of high viral load. This study focused on patients with genotype 2, which is more sensitive to interferon than genotype 1b, and used consensus interferon (CIFN) with or without zinc.We randomized 83 patients with chronic hepatitis C to CIFN at 18 MIU six times/wk for 4 wk, followed by CIFN at 18 MIU six times/wk for another 20 wk, in combination with polaprezinc 300 mg (regimen A, n=41) or as monotherapy (regimen B, n=42). Thirty-one patients in regimen A and 33 patients in regimen B completed the clinical trial; the remaining patients withdrew because of side effects or a transfer to another hospital.Sustained biochemical response, defined as a normal aminotransferase level at the end of the 6-mo post-treatment observation, was 68% and 69%, and sustained virological response, defined as undetectable HCV-RNA at the end of the 6-mo post-treatment observation, was 54% and 67% for regimens A and B, respectively.CIFN treatment combined with zinc did not enhance the effect of CIFN as shown by biochemical, virological criteria. No side effects related to polaprezinc were noted.

AIM: To examine the hepatitis C virus (HCV) levels and immunological markers in cirrhotic patients after splenectomy. METHODS: HCV RNA titers as well as cellular and humoral immune markers were determined in 20 cirrhotic patients after splenectomy and in 32 cirrhotic controls with an intact spleen. RESULTS: Serum HCV RNA titers were lower in the splenectomized patients than in the controls (186 ± 225 × 103 copies/mL vs 541 ± 417 × 103 copies/mL, P

Prompt treatment in tumor-associated encephalopathy may prolong survival. We describe a 69-year-old male patient who was presented with fulminant hepatic failure, secondary to small-cell lung carcinoma with rapidly progressing encephalopathy. Both symptoms remitted following chemotherapy, suggesting swift diagnosis and administration of chemotherapy to be effective in treatment of fulminant hepatic failure and encephalopathy.

Hepatic inflammatory pseudotumor (IPT) is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis (PBC). To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasono-graphy. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis (type C cirrhosis), we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G (PAIgG) levels and platelet numbers.PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen.Thrombocytopenia (PLT15 x 10(4)/microL) in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/10(7) cells were detected in all cirrhotic patients except for one splenectomized patient. PAIgG titers (ng/10(7) cells) were significantly higher in the type C cirrhosis with an intact spleen (247.9+/-197.0) compared with the splenectomized patients (125.6+/-87.8) or non-C cirrhosis (152.4+/-127.4). PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index (cm2) was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis.Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition, splenectomy may impair T cells function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production.

AIM: To evaluate the effect of three interventional treatments involving transvenous obliteration for the treatment of gastric varices, and to compare the efficacy and adverse effects of these methods. METHODS: From 1995 to 2004, 93 patients with gastric fundal varices underwent interventional radiologic embolotherapy at our hospital. Of the 93 patients, 75 were treated with the balloon-occluded retrograde transvenous obliteration (BRTO) procedure; 8 were with the percutaneous transhepatic obliteration (PTO) procedure; and 10 were with the combined BRTO and PTO therapy. A follow-up evaluation examined the rates of survival, recurrence and rebleeding of the gastric varices, worsening of esophageal varices and complications in each group. RESULTS: The BRTO, PTO, and combined therapy were technically successful in 81% (75/93), 44% (8/18), and 100% (10/10) patients, respectively. Recurrence of gastric varices was found in 3 patients in the BRTO group and in 3 patients in the PTO group. Rebleeding was observed in 1 patient in the BRTO group and in 1 patient in the PTO group. The 1- and 3-year survival rates were 98% and 87% in the patients without hepatocellular carcinoma (HCC) in the BRTO group, 100% and 100% in the PTO group, and 90% and 75% in the combined therapy group, respectively. CONCLUSION: Combined BRTO and PTO therapy may rescue cases with uncontrollable gastric fundal varices that remained even after treatment with BRTO and/or PTO, though there were limitations of our study, including retrospective nature and discrepancy in sample size between the BRTO, PTO and combined therapy groups.