Vonoprazan prevents bleeding from endoscopic submucosal dissection-induced gastric ulcers.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is expected to improve the healing of endoscopic submucosal dissection (ESD)-induced gastric ulcers compared with proton pump inhibitors (PPIs). AIM: To compare the healing status of ESD-induced gastric ulcers and the incidence of post-ESD bleeding between subjects treated with vonoprazan for 5 weeks and those treated with PPIs for 8 weeks. METHODS: Patients in the vonoprazan group (n = 75) were prospectively enrolled, whereas patients in the PPI group (n = 150) were selected for a 2:1 matched historical control cohort according to baseline characteristics including gastric ulcer size immediately following ESD, age, sex and status of Helicobacter pylori infection. Two controls per case of vonoprazan-treated group were matched with a margin of 20% in terms of ulcer size and a margin of 5 years in terms of their age. RESULTS: Although a higher number of completely healed ulcers was observed in the PPI group (95/150, 63.3%) than that in the vonoprazan group (14/75, 18.7%; P < 0.001), the ulcer size reduction rates, which were 96.0 ± 6.7% in the vonoprazan group and 94.7 ± 11.6% in the PPI group, were not significantly different (P = 0.373). The post-ESD bleeding incidence in the vonoprazan group (1/75, 1.3%) was less than that in the PPI group (15/150, 10.0%; P = 0.01). The factors affecting post-ESD bleeding incidence were the type of acid secretion inhibitor (P = 0.016) and use of an anti-thrombotic agent (P = 0.014). CONCLUSION: Vonoprazan significantly reduced post-endoscopic submucosal dissection bleeding compared with PPIs.

Relationship of serum markers of hepatitis B and C virus replication in coinfected patients.

To evaluate viral interference between hepatitis B and C, we studied coinfected patients serologically and molecular biologically. Twenty-seven patients positive for hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) antibody, were classified into Groups BC-L and BC-H according to DNA-polymerase activity (less or greater than 100 cpm, respectively). Patients with hepatitis B or C alone were also enrolled as controls. HCV-RNA was detected more often in Group BC-L than in Group BC-H. Genotype 1b of HCV was determined in 75% of Group BC-H, 87.5% of Group BC-L, and 70.7% of hepatitis C-only patients. Activity of DNA-polymerase in coinfected patients was lower in patients positive for HCV-RNA as compared with those negative. HBsAg titers tended to be lower in coinfected patients than in patients with hepatitis B virus (HBV) alone. In conclusion, in coinfection, HBV may suppress the replication of HCV and HCV appears to reduce the expression of HBsAg and probably suppresses HBV replication.

Quantitation of hepatitis C virus RNA in liver tissue as a predictive marker of the response to interferon therapy in chronic hepatitis C.

Recently, factors predicting the response to interferon (IFN) therapy against hepatitis C virus (HCV) have received much attention. To evaluate the usefulness of the quantitation of intrahepatic HCV RNA as a predictive marker of the response to IFN therapy, we compared the amount of intrahepatic HCV RNA with serum levels in 16 patients. Eleven patients who had 10(10) copies/g or more of intrahepatic HCV RNA had increased level of serum alanine aminotransferase (ALT) after IFN therapy, while 4 of 5 patients who had less than 10(10) copies/g of intrahepatic HCV RNA achieved sustained normalization of serum ALT level and were designated as complete responders. Four complete responders possessed significantly less HCV RNA in the liver parenchyma than partial and nonresponders (P = 0.010, Mann-Whitney U-test), but the amount of HCV RNA in the serum was not significantly different between those groups. In conclusion, the results suggest that the quantitation of intrahepatic HCV RNA is a better indicator of the response to IFN therapy than serum HCV RNA.

Quantitative detection of hepatitis C virus genome in liver tissue and circulation by competitive reverse transcription-polymerase chain reaction.

We quantified hepatitis C virus RNA in 25 Japanese patients with chronic type C liver disease by competitive reverse transcription-polymerase chain reaction. The amount of the viral RNA in the serum (2 x 10(5)-2 x 10(8) copies/ml) correlated with that in the liver tissue (10(8)-10(11) copies/g) (N = 23, r = 0.727, P < 0.0001). One gram of the infected liver tissue contained 10(2)-10(4) (geometric mean, 10(3), N = 23) times as many copies of the viral RNA as did 1 ml of the serum. Liver tissues of chronic aggressive hepatitis contained significantly higher amounts of the viral RNA than those of chronic persistent hepatitis (P < 0.05). These observations suggested that this method is useful to evaluate viral amount, and the amount of the circulating hepatitis C virus RNA could be used as a marker of the intrahepatic viral amounts, which might contribute to disease activity.

Evaluation of antibody against AR142, a synthetic peptide derived from the core sequence of hepatitis C virus, in the diagnosis of non-A, non-B chronic liver disease.

We evaluated serum anti-hepatitis C virus (HCV) using a synthetic peptide (AR142) which includes an epitope in the core region of HCV. The incidence of anti-AR142 in 98 patients with type non-A, non-B chronic liver diseases (NANB-CLD) was 89.8%, while all the 28 patients with non-type C chronic liver diseases were negative for anti-AR142. Among 98 NANB-CLD patients, 74 were positive for both anti-AR142 and anti-C100-3, 23 showed discordant results, and one was positive for neither. Eighty-one NANB-CLD patients underwent reverse transcription-polymerase chain reaction assay to detect viremia and 76 (93.8%) had a detectable level of HCV-RNA. Titers of anti-AR142 were not different among groups of different disease activities, genotypes of HCV, nor amount of serum HCV-RNA. These observations suggest that anti-AR142 could be a useful marker for chronic HCV infection.

[An epidemiological study on chronicity and incidence of hepatocellular carcinoma in the sequence of epidemic hepatitis].

From November 1951 to 1954, 416 patients in Kumayama Town, Okayama Prefecture, suffered from epidemic hepatitis, so-called "Kumayama Hepatitis". The mortality rate was 13.98% in the first one year, and the rate of progress to chronic hepatitis after 10 years was 24.6%. In the present study surveyed in 1991, 720 residents in this area had 13.6% positive anti-HCV (C100-3), significantly higher than in control areas. The rate of positive anti-HBs and abnormal liver functions in the subjects with positive anti-HCV was 42.9% and 40.8%, respectively. In 29 patients with clinically typical "Kumayama Hepatitis", the positivity rate of anti-HA IgG, anti-HBs, and anti-HCV, and the prevalence of abnormal liver function was 82.8%, 41.4%, 34.5%, and 10.3%, respectively. In conclusion, it is suggested that the hepatitis epidemic in Kumayama Town was caused by HAV and superinfected by HCV and/or HBV, then its clinical manifestations became complicated.

Detection of negative strand RNA of hepatitis C virus in infected liver and serum.

The negative strand RNA of hepatitis C virus, supposed to be a replicative intermediate of the virus appears to indicate viral replication. In this study, we detected the negative strand RNA by using reverse transcription-polymerase chain reaction with RNase A digestion to degrade the remaining positive strand genomic sequence of the virus after complementary DNA (cDNA) synthesis. In vitro transcribed positive-stranded mutant RNA was not detected by this method. Sample sera and liver tissues of 16 patients with chronic hepatitis C virus infection (liver fibrosis, 1; chronic hepatitis, 13; liver cirrhosis, 2) were analysed for negative strand RNA of hepatitis C virus. The negative strand RNA sequence was detected in 15 (93%) of 16 liver tissues and in 11 (78%) of 14 sera. The study demonstrated that negative strand RNA of hepatitis C virus in serum and liver tissue could be specifically detected.

Disappearance of pulmonary metastases by OK-432 treatment in a case of hepatocellular carcinoma.

We report here a case of hepatocellular carcinoma (HCC) with multiple lung metastases, which were disappeared by treatment of OK-432. The patient was a 65-year-old man and was diagnosed in 1986 with a small (17 x 11 mm) HCC in the anterior-superior segment of the liver. A part of the right hepatic lobe including the tumor was surgically removed, and transarterial injections of adriamycin (10 mg/week) and subcutaneous injections of OK-432 (10 KE/week) were given. Two and a half years later, recurrence of HCC in the liver and its invasion to vena cava inferior (IVC) were found. OK-432 administration was then stopped and percutaneous ethanol injection therapy (PEIT) was performed 10 times. Six months later, the PEIT was effective and the liver tumor with IVC invasion diminished. However, multiple lung metastases were visible on roentgenograms of the chest, and serum alphafetoprotein (AFP) concentration increased to 50,000 ng/ml. The OK-432 treatment resumed. After 6 months of OK-432 treatment, the multiple lung metastases were disappeared and the serum AFP level decreased to 100 ng/ml. At present, the patient is surviving without any sign of recurrence in either the liver or the lung. The clinical course of this case suggests that OK-432 might have effectively treated lung metastases of HCC, although the exact mechanisms are at present unclear.

Anti-C100-3 antibody status, viral genomic sequences, and clinical features in chronic hepatitic patients with hepatitis C virus RNA in sera.

Since detection of hepatitis C virus RNA by the polymerase chain reaction (PCR) showed that there existed anti-C100-3 (anti-HCV) antibody negative patients infected with HCV, we attempted to find out whether there were any clinical or viral genomic differences between the anti-HCV antibody positive and negative groups. One hundred and fifty-nine patients with chronic liver diseases with hepatitis C virus RNA in their sera were selected. Anti-HCV antibody was tested for anti-C100-3 antibody by an enzyme linked immunosorbent assay. The incidence of anti-HCV antibody was 129/159. The concentration of serum gamma-globulin, the titier of ZTT, and the positive rate of the PCR with the primers of the NS3/4 region (NS3/4PCR) were significantly higher in the anti-HCV antibody positive group than in the negative group. However, the other data such as alanine aminotransferase activity or past history were not significantly different. Nucleotide sequence of the cDNA fragments of NS3/4 region amplified by the PCR did not differ significantly between isolates from anti-HCV antibody positive and negative sera. The sequences observed in the present study did not differ significantly from those reported previously. Although there remains the possibility that the variation of viral genomic sequences may cause the absence of anti-HCV antibody, these results suggested that the individual clinical backgrounds or immunoreactivity of the patients might influence the antibody development.