Ropeginterferon Alfa-2b administered every two weeks for patients with genotype 2 chronic hepatitis C.

BACKGROUND: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. METHODS: Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg-IFN-α2a) at 180 µg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 µg (n = 23), 360 µg (n = 21), 450 µg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). RESULTS: SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg-IFN-α2a 180 µg, Ropeginterferon alfa-2b 270 µg, 360 µg, and 450 µg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. CONCLUSION: Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg-IFN-α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

A prospective, randomized trial of thrombin versus cyanoacrylate injection in the control of acute gastric variceal hemorrhage.

BACKGROUND: Acute gastric variceal hemorrhage (AGVH) is a serious complication of portal hypertension. Endoscopic cyanoacrylate glue injection is standard therapy for acute hemostasis; however, it may be associated with serious complications. The role of thrombin injection has not been confirmed. This study compared endoscopic thrombin and glue injections in the hemostasis of AGVH. METHODS: 68 eligible patients with AGVH were randomized to receive thrombin injection (33 patients) or glue injection (35 patients). The primary end point was injection-induced gastric ulcers. Secondary end points were acute hemostasis, rebleeding, and mortality within 42 days. RESULTS: Both groups had comparable baseline data. Hemostasis of active bleeding at endoscopy was 90.0 % (9/10) in the thrombin group and 90.9 % (10/11) in the glue group (P = 0.58), and 48-hour hemostasis was achieved in 93.9 % (31/33) and 97.1 % (34/35), respectively (P = 0.60). Treatment failure at 5 days occurred in two patients (6.1 %) in the thrombin group and two patients (5.7 %) in the glue group (P > 0.99). Gastric ulcers occurred in none of the thrombin group and 11/30 (36.7 %) of the glue group (P < 0.001, 95 % confidence interval [CI] 8 % - 27 %). Complications occurred in 4 (12.1 %) and 18 (51.4 %) patients in the thrombin and glue groups, respectively (P < 0.001, 95 %CI 22 % - 45 %). Two patients who received glue had post-treatment gastric ulcer bleeding. One patient in each group died. CONCLUSIONS: Endoscopic thrombin injection was similar to glue injection in achieving successful hemostasis of AGVH. However, a higher incidence of complications may be associated with glue injection.

A retrospective comparative study of histoacryl injection and banding ligation in the treatment of acute type 1 gastric variceal hemorrhage.

BACKGROUND. Esophageal varices extending along lesser curvature side of stomach is classified as GOV1. The optimal therapy for GOV1 bleeding is still undetermined. METHODS. One hundred and sixty-two patients diagnosed as acute hemorrhage from GOV1 were enrolled. At endoscopists' discretion, 118 patients received glue injection (Glue group) and 44 patients received ligation to arrest bleeding [endoscopic variceal ligation (EVL) group]. This study aimed to compare hemostasis, rebleeding, complications and mortality within 42 days. RESULTS. Both groups were comparable in baseline data. In 109 patients (92%) in the Glue group and 36 patients (82%) in the EVL group (p = 0.07) 48-h hemostasis was achieved . Hemostasis of active bleeding was achieved in 49 of 55 patients (89%) in the Glue group and 24 of 28 patients (85%) in the EVL group (p = 0.70). Treatment failure was noted in 14% of the Glue group and 23% in the EVL group (p = 0.22). Eight patients in the Glue group and four patients in the EVL group rebled between 5 and 42 days (p = 0.73). A total of 48 and 19 adverse events occurred in the Glue and EVL groups, respectively (p = 0.85). Six patients in the Glue group and seven patients in the EVL group encountered posttreatment gastric ulcer bleeding (p = 0.04). Seventeen patients (14%) in the Glue group and 10 (23%) patients in the EVL group died within 42 days (p < 0.001). CONCLUSIONS. Banding ligation was similar to glue injection in achieving successful hemostasis of acute bleeding from GOV1. However, a higher incidence of posttreatment ulcer bleeding and mortality may be associated with banding ligation.

Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

Endoscopic treatments for portal hypertension.

Acute esophageal variceal hemorrhage is a dreaded complication of portal hypertension. Its management has evolved rapidly in recent years. Endoscopic therapy is often employed to arrest bleeding varices as well as to prevent early rebleeding. The combination of vasoconstrictor and endoscopic therapy is superior to vasoconstrictor or endoscopic therapy alone for control of acute esophageal variceal hemorrhage. After control of acute variceal bleeding, combination of banding ligation and beta-blockers is generally recommended to prevent variceal rebleeding. To prevent the catastrophic event of acute variceal bleeding, endoscopic banding ligation is an important tool in the prophylaxis of first bleeding. Endoscopic obturation with cyanoacrylate is usually utilized to arrest acute gastric variceal hemorrhage as well as to prevent rebleeding. It can be concluded that endoscopic therapies play a pivotal role in management of portal hypertensive bleeding.

Salivary immunoreactive endothelin in patients with upper gastrointestinal diseases.

Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Furthermore, clinical reports also show elevated gastric mucosal endothelin-1 levels in patients suffering from peptic ulcer diseases. We have demonstrated, first, the presence of immunoreactive endothelin (IR-ET) in human saliva. We also show that endothelins are rather stable in human saliva. The present study was undertaken to determine whether patients with endoscopically proven upper gastrointestinal diseases have a salivary excess of IR-ET, compared with patients with a normal esophagogastroduodenoscopy. Saliva was collected from fasting subjects prior to esophagogastroduodenoscopy. The levels of IR-ET were measured by the radioimmunoassay method. The salivary concentrations of IR-ET in the studied subjects were as follows: 8.9 +/- 1.0 fmol/mL (mean +/- standard error of the mean) for patients with gastric ulcers (n = 18); 7.3 +/- 1.0 fmol/mL for patients with duodenal ulcers (n = 22); and 6.8 +/- 0.6 fmol/mL for patients with gastritis (n = 28). These values are all higher than that of normal subjects (4.4 +/- 0.5 fmol/mL, n = 20; P < 0.001, P < 0.01, and P < 0.05, respectively). No significant differences in salivary IR-ET were noted between patients with a normal esophagogastroduodenoscopy and patients with esophagitis (3.8 +/- 0.7 fmol/mL, n = 4) or gastric cancer (5.3 +/- 1.4 fmol/mL, n = 4). There were no significant differences in the salivary IR-ET levels between males and females. However, the salivary IR-ET levels in the smokers (8.0 +/- 0.6 fmol/mL, n = 38) were significantly higher (P < 0.01) than those of the non-smokers (6.0 +/- 0.4 fmol/mL, n = 58). There was no correlation of IR-ET levels with age. Our findings suggest that salivary endothelin may have a contributing role in certain gastroduodenal diseases.