Suspected Hepatically Localized Granulomatosis with Polyangiitis.

The patient was a 72-year-old woman whose alkaline phosphatase levels had been elevated since she was 56 years old. Liver biopsies obtained when the patient was 64 and 66 years of age led to a suspicion of cholangitis caused by vasculitis. Furthermore, proteinase-3 anti-neutrophil cytoplasmic antibody positivity led to a suspicion of granulomatosis with polyangiitis, but subjective symptoms and disorders in other organs were absent, so this suspicion was not confirmed. Cholangitis caused by vasculitis rarely occurs without vasculitis in other organs. We herein report this case in which we obtained distinctive laparoscopic and imaging findings that raised suspicions of liver circulatory failure.

Contrast-Induced Nephropathy and Oxygen Pretreatment in Patients With Impaired Renal Function.

INTRODUCTION: Contrast-induced nephropathy is a complication following coronary angiography and percutaneous coronary intervention. Because contrast-induced nephropathy is a predictor of long-term mortality in patients with ischemic heart disease undergoing percutaneous coronary intervention, preventive strategies are required. We assessed the effects of periprocedural oxygenation on contrast-induced nephropathy among patients with pre-existing renal dysfunction. METHODS: A total of 200 consecutive patients with impaired renal function (estimated glomerular filtration < 60 ml/min per 1.73 m2) undergoing elective cardiovascular angiography were randomly assigned to an oxygenation treatment (n = 100) or control group (n = 100). In oxygenation treatment, pure oxygen (2 L/min) was administered for 10 minutes before exposure to contrast medium. The primary endpoint was the incidence of contrast-induced nephropathy, defined as a ≥ 25% increase in serum creatinine levels from baseline within 48 hours of exposure. RESULTS: In the oxygenation treatment group, partial pressure of arterial oxygen was higher (135 ± 25 mm Hg vs. 84 ± 10 mm Hg, P < 0.001); contrast-induced nephropathy incidence was lower (1% vs. 8%, odds ratio [OR] = 0.12, 95% confidence interval [CI] = 0.01-0.95, P = 0.02); and partial pressure of arterial carbon dioxide and bicarbonate base lactate levels were similar compared with those in the control group. Upon univariate analysis, excess and absence of oxygenation treatment (OR = 9.18, CI = 1.13-74.86, P = 0.03) and anemia (OR = 4.30, CI = 1.04-17.78, P = 0.04) were shown to be associated with contrast-induced nephropathy incidence. CONCLUSION: Oxygenation, a simple, nonpharmacological strategy, may be beneficial when using contrast media in patients with impaired renal function from noninvasive angiography to emergency catheterization.

Efficacy of a microballoon catheter in transarterial chemoembolization of hepatocellular carcinoma using miriplatin, a lipophilic anticancer drug: Short-term results.

AIM: The goal of the study was to evaluate the efficacy and safety of balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma (HCC) using miriplatin (a lipophilic anticancer drug) and gelatin particles. METHODS: B-TACE was performed for 62 HCC nodules in 33 patients who could not be treated by surgical resection or radiofrequency ablation. All 33 patients had a history of transarterial chemoembolization (TACE) treatment prior to B-TACE. As a historical comparison, we investigated 40 nodules in 28 patients treated by TACE using a conventional microcatheter (C-TACE), miriplatin and gelatin particles. The therapeutic effect per tumor was compared between the groups based on the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL) and side-effects were compared based on the Common Terminology Criteria for Adverse Events (ver. 4.0). RESULTS: The therapeutic efficacy after 4-12 weeks was evaluated in 59 nodules in the B-TACE group and in 37 nodules in the C-TACE group. Of these nodules, TE4 occurred in 29 (49.2%) in the B-TACE group and in 10 (27%) in the C-TACE group. Local efficacy was significantly higher in nodules treated by B-TACE than by C-TACE. The side-effects on hepatic function were similar in the two groups. CONCLUSION: Our results suggest that B-TACE with miriplatin is a useful treatment for hepatocellular carcinoma.

Histopathology of type C liver disease for determining hepatocellular carcinoma risk factors.

AIM: To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma (HCC). METHODS: We studied 232 patients, who underwent liver biopsy for type C chronic liver disease between 1992 and 2009, with sustained virological response (SVR) after interferon therapy. The patients were divided into two groups according to the F stage 0 + 1 + 2 group (n = 182) and F3 + 4 group (n = 50). We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0 + 1 + 2 and F3 + 4 groups. Then, the background factors and liver histopathological findings, including the degree of fibrosis, F stage, inflammation, necrosis, bile duct obstruction, fat deposition, and degree of irregular regeneration (IR) of hepatocytes, were correlated with the risk of developing HCC. RESULTS: HCC developed in three of 182 (1.6%) patients in the F0 + 1 + 2 group, and four of 50 (8.0%) in the F3 + 4 group. The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3 + 4 group (log rank test P = 0.0224). The presence of atypical hepatocytes among IR of hepatocytes in the F3 + 4 group resulted in a higher cumulative incidence of HCC, and was significantly correlated with risk of HCC development (RR = 20.748, 95%CI: 1.335-322.5, P = 0.0303). CONCLUSION: Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.

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.

Zinc supplementation therapy improves the outcome of patients with chronic hepatitis C.

We administered zinc supplementation therapy over three years to patients with chronic hepatitis C and reported and that the aspartate aminotransferase (AST) and alanine aminotaransferase (ALT) levels decreased, and platelet counts increased, significantly in the group with increased serum zinc concentrations. We are continuing this treatment to clarify the long-term consequences and report here the changes in serum zinc concentrations over seven years and compare the cumulative incidence of hepatocellular carcinoma (HCC). We administered polaprezinc to 32 patients, randomly selected for zinc therapy (treatment group), while another 30 formed the control group. We measured the serum zinc and albumin concentrations and conducted a prospective study to determine long-term outcomes. The changes and rates of change of serum zinc concentrations after seven years were 76.7 ± 18.2 µg/dl and +0.302 ± 0.30% in the treatment group and 56.7 ± 12.4 µg/dl and +0.033 ± 0.21% in the control group and had increased significantly (p = 0.0002, p = 0.0036). Progression of liver disease seemed to vary, depending on serum albumin concentrations. In the group with baseline serum albumin concentrations of 4.0 g/dl or more, the change and rate of change of serum zinc concentrations increased significantly, and the cumulative incidence of HCC tended to decrease, in the treated group. According to multivariate analysis, the factors that contribute to a reduction in the incidence of HCC are zinc therapy (risk ratio: 0.113, 95% CI: 0.015-0.870, p = 0.0362), and platelet counts (0.766, 0.594-0.989, 0.0409). Zinc supplementation therapy seems to improve liver pathology and reduce the incidence of HCC.

Zinc supplementation improves the outcome of chronic hepatitis C and liver cirrhosis.

We treated patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) with polaprezinc and determined prospectively the effect on long-term outcome. 62 patients were enrolled. Of these, 32 were administered 1.0 g polaprezinc and the remainder were not administered polaprezinc. We measured the serum zinc concentrations using conventional atomic absorption spectrometry and conducted a prospective study to determine the long-term outcome of the polaprezinc therapy. Changes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the polaprezinc administration group were significantly lower than those of the untreated group. The decrease in platelet count was clearly less than that of the untreated group. The factors that inhibited increases in serum zinc concentrations following administration of polaprezinc included low serum zinc concentration states. Furthermore, the reductions of AST and ALT levels in the low zinc group were significantly greater than those of the high zinc group. When the patients who were administered polaprezinc were divided into two groups whose zinc concentrations increased (zinc responders) or remained stable or decreased (zinc non-responders), the zinc responders had a clearly lower cumulative incidence of HCC than the zinc non-responders. We conclude zinc supplementation improved the long-term outcome in C-viral CH and LC patients.

Expression of intercellular adhesion molecule-1 in the livers of rats treated with diethylnitrosamine.

It has been reported that levels of soluble intercellular adhesion molecule-1 (ICAM-1) in the blood are elevated in hepatocellular carcinoma patients. In the present study, serial observations of the localization of ICAM-1 in the liver were made by light and electron microscopy in rats with carcinogen-induced cancer. Male Fisher rats were given diethylnitrosamine (DEN) orally in their drinking water. Rats were sacrificed at 6, 8, 12, or 14 weeks after the start of DEN administration and the liver tissue was collected. ICAM-1 expression in liver was assessed using indirect immunoperoxidase staining with anti-rat ICAM-1 antibody. Although ICAM-1 expression by endothelial cells in livers of DEN-treated rats was lower than in the control group at 8 weeks, it was higher in the membrane and cytoplasm of hepatocytes. The expression of ICAM-1 in mesenchymal cells was decreased, paralleling development of cellular atypia, whereas in hepatocyte membranes and cytoplasm it was increased in these atypia. ICAM-1 was localized to the cytoplasm of cancer cells, but to the membrane of hepatocytes in the treated livers at 14 weeks. Furthermore, the levels of ICAM-1 in mesenchymal cells tended to be lower in the cancerous area than in the atypical hyperplastic nodule, and were reduced as the density of cell atypia increased, in comparison to cells in areas without cancerous nodules. We concluded that ICAM-1 may be influenced the development of cancer induced in the rat liver by a chemical carcinogen.

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.

[A case of alpha-fetoprotein-producing gastric cancer with hepatic metastasis successfully treated with combination chemotherapy].

The patient was a 79-year-old woman. We became introduction consultation than a nearby doctor in alpha-fetoprotein(AFP)high level. Abdominal ultrasonography showed 30mm great tumor in liver lateral segment area and gastric fiber showed type2 tumor which is AFP producing gastric cancer. On admission AFP level is high(403ng/ml). Multiple liver metastases were noted it by abdominal angiography. We started FLAP(5-fluorouracil, leucovorin, etoposide, cisplatin)combination chemotherapy by a diagnosis of AFP producing gastric cancer StageIV. It is reduction of a liver tumor after one course, and the stomach lesion almost disappeared after three courses end points.

Endoscope images of Schönlein-Henoch purpura.

BACKGROUND/AIMS: Schönlein-Henoch purpura (SHP) is a systemic condition characterized by purpura associated with leukocytoclastic vasculitis. SHP diagnosis is more difficult in infrequent cases where gastrointestinal (GI) symptoms precede purpura. This report examines 11 cases of SHP at our hospital with specific regard to the incidences and details of GI symptoms. METHODS: The clinical manifestations and endoscopic findings were investigated for their utility in SHP diagnosis. RESULTS: Among the 11 cases, 3 showed GI symptoms prior to other manifestations. In terms of GI symptoms, abdominal pain was reported in all 11 cases, diarrhea in 4 cases, and bloody stools in 3 cases. Endoscopic findings were seen in the stomach in 7/10 cases, in the small intestine including the duodenum in 10/11 cases, and in the large intestine in 6/10 cases. The frequency of ulcer formation was significantly higher in the small intestine (including the duodenum) than in the stomach. Multiple specific erythematosus lesions were observed in the stomach and large intestine. CONCLUSION: Familiarity with characteristic endoscopic findings and careful observation of all GI findings are essential for diagnosing SHP in cases in which GI tract symptoms precede cutaneous findings.

Influence of occult hepatitis B virus coinfection on the incidence of fibrosis and hepatocellular carcinoma in chronic hepatitis C.

We examined prospectively the influence of occult hepatitis B virus (HBV) infection on the histopathological features and clinical outcome of HCV RNA-positive chronic hepatitis (CH-C) and detected hepatitis B core (HBc) particles in hepatocytes. The subjects were 468 patients with CH-C or liver cirrhosis (LC) who were negative for serum hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay. HBV DNA was detected in serum by nested PCR. HBsAg and HBc antigen (HBcAg) in liver were investigated using immunohistochemical techniques and light (LM) and electron microscopy (EM). Serum HBV DNA was detected in 43.6% of the patients studied. There were no significant differences between HBV DNA-positive and DNA-negative patients in terms of their clinical profiles. For HBV DNA-positive patients, the degree of inflammatory cell infiltration and irregular regeneration of hepatocytes was significantly greater than for HBV DNA-negative patients. The cumulative probability of development of hepatocellular carcinoma (HCC) was significantly higher for HBV DNA-positive patients than for HBV DNA-negative patients. HBV DNA positivity was a risk factor for the occurrence of HCC according to multivariate analysis. HBsAg and HBcAg were detected in 8.5 and 72.3%, respectively, of the livers of serum HBV DNA-positive individuals. Core particles were detected in the nuclei of the hepatocytes by IEM. The histopathological features and long-term outcome of CH-C or LC could be affected by occult HBV infection.

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.

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.

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.

Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1.

BACKGROUND: Hepatitis C virus (HCV) RNA titer and HCV genotype are two major determinants of the outcome of interferon (IFN) monotherapy. To clarify the usefulness of combination therapy with IFN and ribavirin in Japanese hepatitis C patients, we treated patients with a relatively high dose of IFN in combination with ribavirin for 24 weeks and examined the effects in relation to the viral parameters. METHODS: Two hundred and ninety-five patients were enrolled in the study. The patients received either 6 or 10 million units (MU) of interferon alpha-2b every day for 2 weeks and then three times a week for 22 weeks with a daily dose of either 600 or 800 mg of ribavirin. The treatment response and safety of this treatment were examined. RESULTS: The sustained virologic response (SVR) rates were 26.8% in genotype 1 and 76.5% in genotype 2 (P < 0.001), and 36.1% with the 6 MU group and 45.8% with the 10 MU group (P = 0.09). Multivariate analysis indicated that SVR was associated with genotype 2, HCV RNA <500 kilointernational unit/ml (kIU/ml), and HCV RNA undetectability at week 8 of treatment. CONCLUSION: Our current study showed that a 24-week course of IFN plus ribavirin combination therapy was effective with respect to virologic response in Japanese hepatitis C patients, particularly in patients with HCV genotype 2.

Coronary angioplasty in a patient with a prior Bentall procedure.

We reported a case of percutaneous coronary intervention in a patient with a prior Bentall procedure. We observed a neointimal layer with intracoronary ultrasound during a successful intervention procedure through a composite graft 11 years after the Bentall operation.