Potential for differential diagnosis of autoimmune pancreatitis and pancreatic cancer using carbonic anhydrase II antibody.

OBJECTIVES: Pancreatic ductal epithelia contain an abundance of carbonic anhydrase (CA), and the presence of antibodies to this enzyme has been described in autoimmune disorders. We previously found a small amount of an immunoglobulin G-like material in purchased CAII reagents, which led to pseudopositive reactions. METHODS: We determined the optimum measurement conditions for detecting anti-CAII antibody using an enzyme-linked immunosorbent assay and sera from 140 patients with pancreatic diseases. RESULTS: Compared with the prevalence of anti-CAII antibody in healthy subjects, a significantly higher seroprevalence of the antibody was detected in patients with autoimmune pancreatitis (AIP) (88.9%, P < 0.02), Sjögren syndrome (67.6%, P < 0.01), and alcoholic chronic pancreatitis (45.8%, P < 0.01). No positive results were obtained among patients with pancreatic cancer. Moreover, the antibody value obtained in the pancreatic cancer patients was actually lower than that obtained in healthy subjects. CONCLUSIONS: The anti-CAII antibody is probably not a specific marker of AIP because it was present at a higher frequency in the sera of patients with other pancreatic diseases. Nevertheless, the anti-CAII antibody may be a useful tool for the differential diagnosis of AIP and pancreatic cancer.

Postmarketing surveillance of rabeprazole in upper gastrointestinal peptic lesions in Japanese patients with coexisting hepatic disorders.

BACKGROUND: Many Japanese patients with hepatic disorders confirmed on diagnostic imaging and coexisting upper gastrointestinal (GI) peptic lesions receive treatment with proton pump inhibitors. Some pharmacotherapies used to treat peptic ulcers have been associated with adverse drug reactions (ADRs), including elevated liver enzyme levels. OBJECTIVE: The aim of this study was to determine the tolerability and effectiveness of rabeprazole sodium in treating peptic lesions in patients with coexisting hepatic disorders. METHODS: This open-label, practice-based, postmarketing surveillance investigation was conducted at 15 centers across Japan. Male and female patients aged ≥18 years with peptic lesions confirmed on upper GI endoscopy and with underlying hepatic disease were enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using monitoring of the incidence of ADRs determined by direct patient questioning, spontaneous reporting, and laboratory assessment. All patients who received at least 1 dose of study drug were included in the tolerability assessment. Effectiveness was assessed at baseline and study end using the rates of achievement of improvement on endoscopy, relief of subjective/objective symptoms (rates of improvement in epigastric pain and heartburn), and global improvement. The effectiveness analysis included all patients with complete data before and after treatment. Subanalyses were conducted to determine the effectiveness of drug by identification of the proportion of patients with coexisting hepatic disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg, alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement. RESULTS: A total of 114 patients were enrolled; 108 patients were included in the tolerability analysis (81 men, 27 women; mean age, 59.9 years; 10-mg dose, 90 patients; 20-mg dose, 18 patients) and 98 patients were included in the analysis of effectiveness. Twenty-one ADRs occurred in 11 (10.2%) patients. Serious ADRs occurred in 2 patients (elevated bilirubin level and hepatic encephalopathy, 1 patient each). Administration of rabeprazole was discontinued in 5 patients due to the occurrence of the following ADRs: constipation (1 patient); epigastric pain (1); dyslalia, disorientation, tremor, sleep disorder, and hepatic encephalopathy (1); diarrhea (1); and elevated alkaline phosphatase and y-glutamyl transpeptidase levels (1). On endoscopy, the proportion of patients achieving improvement with either dose was 30/33 (90.9%). The relief rates assessed using subjective symptoms were 47/55 (85.5%) and 47/56 (83.9%) for epigastric pain and heartburn, respectively. The proportion of patients achieving global improvement with either dose was 80/98 (81.6%) patients (49/62 [79.0%] for cirrhosis, 11/16 [68.8%] for chronic hepatitis, and 20/20 [100.0%] for other hepatic diseases [alcoholic hepatitis, fatty liver]). CONCLUSION: In this study in Japanese patients with hepatic disorders, rabeprazole was well tolerated and appeared effective for the treatment of upper GI peptic lesions.

Detection of autoantibody against carbonic anhydrase II in various liver diseases by enzyme-linked immunosorbent assay using appropriate conditions.

BACKGROUND: Immunoglobulin G autoantibody against carbonic anhydrase (CA) II has been detected in the sera of patients with a variety of autoimmune diseases. Antibody against CAII has also been described as a serological marker for distinguishing between cases of autoimmune cholangitis (AIC) and those of primary biliary cirrhosis (PBC). However, the optimal antibody measurement conditions (enzyme-linked immunosorbent assay: ELISA) have not yet been established. Moreover, we also found that a small amount of an IgG-like material exists in purchased CAII reagents, which causes pseudopositive reactions. METHODS: The sera of 96 patients with liver disease were examined for the presence of anti-CAII antibody using antigen (CAII) not containing the IgG-like material as the most suitable measurement conditions. Compared with the anti-CAII antibody prevalence of 3.8% found in normal subjects, a significantly higher seroprevalence of the antibody was detected in patients with PBC (31.0%, P<0.02), autoimmune hepatitis (AIH) (50.0%, P<0.01) and chronic viral hepatitis (27.5%, P<0.01). But, in cases of PBC, no significant correlation was noted between the level of anti-CAII antibody and the presence of anti-mitochondrial antibodies (AMA). CONCLUSIONS: While CAII may be a target antigen in autoimmune diseases, the anti-CAII antibody is not likely to be a specific marker of AIC. The optimum measurement conditions for the ELISA for anti-CAII antibody would provide us with valuable information to elucidate the underlying immunological abnormalities in liver diseases.

Efficacy of Stronger Neo-Minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis.

BACKGROUND: A daily injection of glycyrrhizin (Stronger Neo-Minophagen C (SNMC) containing 40 mg glycyrrhizin in a 20 mL ampoule) lowers alanine aminotransferase (ALT) levels in patients with chronic viral hepatitis. METHODS: The therapeutic effects of intermittent administration of SNMC three times a week for 12 weeks were evaluated and compared between two doses (40 and 100 mL) in a randomized clinical trial. RESULTS: Overall, the therapeutic response was better in the 53 patients allocated 100 mL than the 59 who were allocated to have 40 mL SNMC (P = 0.0243). At the completion of SNMC treatment, ALT levels decreased more extensively in the patients on 100 mL than those on 40 mL SNMC (-29 vs-50% in comparison with the baseline value, P = 0.0002). Minor side-effects occurred in both the patients on 100 mL (20%) and those on 40 mL (12%), but they did not require any therapies. CONCLUSIONS: Intermittent SNMC would be efficient in suppressing ALT levels in patients with chronic viral hepatitis in a dose-dependent manner. Taken along with infrequent and very mild side-effects, long-term intermittent SNMC would benefit patients with chronic hepatitis by maintaining their quality of life with easier compliance.

Differentiation of subtypes B and E of human immunodeficiency virus type 1 by polymerase chain reaction using novel env gene primers.

Novel sets of env gene PCR primers for distinguishing human immunodeficiency virus type 1 (HIV-1) subtypes B and E were designed. These primers anneal to different regions of the env gene and amplify DNA fragments of distinct sizes in a subtype-specific manner. Blood samples from 11 HIV-1 carriers in Thailand and 46 carriers in Japan were examined by PCR. The new env primers detected HIV-1 proviral DNA in 100% (11/11) and 88% (37/42) of the subtype B and E infection cases, respectively. The env primers also detected proviral DNA in saliva and breast milk samples in seven of 11 cases and two of three cases, respectively. The PCR subtyping results matched completely with those obtained by nucleotide sequencing of the env V3 region. The results suggest that the PCR using the env primers designed in this study may be an accurate and cost-effective method for differentiating subtypes B and E of HIV-1 in a large number of clinical samples. However, subtype E specific primer cross-react with subtype A, C, G, the new primer in this study is useful for regions in South East Asia where subtype E is predominant.