Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study.

Background and aim: In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. Methods: This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. Results: The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). Conclusion: GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.

Radially asymmetric gastroesophageal acid reflux in the distal esophagus: examinations with novel pH sensor catheter equipped with 8 pH sensors.

BACKGROUND: Esophageal mucosal breaks in patients with Los Angeles (LA) grade A or B esophagitis are mainly found in the right anterior wall of the distal esophagus. The aim of this study was to reveal radial acid exposure in the distal esophagus and determine whether radial asymmetry of acid exposure is a possible cause of radially asymmetric distribution of the lesions. METHODS: We developed a novel pH sensor catheter using a polyvinyl chloride catheter equipped with 8 antimony pH sensors radially arrayed at the same level. Four healthy volunteers, 5 patients with non-erosive reflux disease (NERD), and 10 with LA grade A or B esophagitis were enrolled. The sensors were set 2 cm above the upper limit of the lower esophageal sphincter, and post-prandial gastroesophageal acid reflux was monitored for 3 h with the subjects in a sitting position. RESULTS: We successfully examined radial acid exposure in the distal esophagus in all subjects using our novel pH sensor catheter. Radial variations of acid exposure in the distal esophagus were not observed in the healthy subjects. In contrast, the patients with NERD and those with reflux esophagitis had radial asymmetric acid exposure that was predominant on the right wall of the distal esophagus. In the majority of patients with reflux esophagitis, the directions of longer acid exposure coincided with the locations of mucosal breaks. CONCLUSIONS: Radial acid exposure could be examined using our novel 8-channel pH sensor catheter. We found that the directions of longer acid exposure were associated with the locations of mucosal breaks.

Evaluation of virtual CT sonography for enhanced detection of small hepatic nodules: a prospective pilot study.

OBJECTIVE: Virtual CT sonography is a system for synchronizing multiplanar reconstructed CT scans with corresponding conventional ultrasound images in real time. The aim of this study was to prospectively evaluate the feasibility of virtual CT sonography for detection of nodules difficult to detect with conventional sonography alone. SUBJECTS AND METHODS: Fifty-nine patients with 140 nodules were included in the study. All patients underwent CT angiography then conventional sonography and finally virtual CT sonography. The number, location, and echogenicity of nodules and parenchyma were assessed. RESULTS: Among 140 nodules detected with CT angiography, 71 were detected with conventional sonography and another 46 were detected with virtual CT sonography, increasing the overall sensitivity from 50.7% to 83.57%. The average diameter of nodules detected only with virtual CT sonography (9.7 +/- 3.3 mm) was significantly smaller than that of nodules detected with conventional sonography (16.6 +/- 6.2 mm). The results of multivariate analysis suggested that nodule size (p < 0.001), echo pattern (p = 0.004), and location (p = 0.028) are associated with the difference in detection. Interestingly, 87% of the nodules 10 mm in diameter or smaller were already dysplastic or malignant. CONCLUSION: Nodules 10 mm in diameter or smaller have significant malignant potential and therefore are clinically important. Even though we do not consider virtual CT sonography a screening tool, we conclude it superior to conventional sonography for detection of small hepatic nodules, allowing bedside percutaneous ultrasound-guided biopsy and treatment that would not be possible with conventional sonography alone.

Prophylactic administration of antibiotics unnecessary following ultrasound-guided biopsy and ablation therapy for liver tumors: Open-labeled randomized prospective study.

AIM: To determine the prophylactic effect of antibiotics administration in the prevention of infection following an ultrasound-guided percutaneous liver biopsy or treatment of liver tumors, we performed an open-labeled randomized prospective study of patients who received prophylactic antibiotics after undergoing those procedures. METHODS: We studied 101 patients, with ultrasound-guided percutaneous aspiration biopsies of the liver performed in 48 to diagnose diffuse liver diseases or liver tumors, while percutaneous ethanol-injection therapy was performed in two patients with malignant liver tumors and percutaneous radiofrequency ablation was performed in 51 patients. An oral administration of levofloxacin at 400 mg/day was given to 50 of the enrolled patients from the morning of the treatment day for three days. Preventive antibiotics were not administered to the remaining 51 patients. Body temperature, peripheral blood leukocyte number, c-reactive protein, alanine aminotransferase, and lactic dehydrogenase were measured daily for three days after treatment. RESULTS: Most parameters changed following percutaneous treatments of liver tumors, though no significant differences were seen between the patients treated with antibiotics and those untreated. Most significantly, there was no difference in the frequency of post-procedure infection between the groups. CONCLUSION: Our results suggest that prophylactic administration of antibiotics following a percutaneous liver biopsy and treatment of liver tumors does not have a significant impact on the post-procedure results or incidence of infection.

Does gastroesophageal reflux have an influence on bleeding from esophageal varices?

BACKGROUND: Mucosal breaks induced by gastroesophageal reflux of gastric contents were more frequently found on the right anterior wall of the lower esophagus. Bleeding from esophageal varices may be also derived from gastroesophageal reflux. The circumferential location of the ruptured esophageal varices was evaluated to elucidate the relationship between gastroesophageal reflux and variceal rupture. METHODS: Between January 2004 and December 2006, 26 patients who had primary bleeding from esophageal varices and 74 patients without evidence of bleeding with positive red color signs on varices were enrolled in this study retrospectively. Locations of bleeding spots and nonbleeding red color signs of esophageal varices were retrospectively evaluated by endoscopic photographs, and the relationship between the location of red color signs and the risk of bleeding was evaluated. Other possible predictors for bleeding were also investigated by multivariate regression analysis. RESULTS: Red color signs were frequently found in the right posterior wall of the lower esophagus. However, bleeding spots of esophageal varices were more frequently seen in the right anterior side (64.0%) than in others. The positive predictor for bleeding from esophageal varices was the presence of red color sign in the right anterior wall of the esophagus, and the administration of proton pomp inhibitor was the negative predictor. CONCLUSIONS: Gastroesophageal acid reflex may be a risk factor of bleeding from esophageal varices. Attention should be paid to the circumferential location of red color signs in endoscopic screening of patients with esophageal varices to predict future bleeding.

Anti-tumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosamine-treated rats.

Cimetidine is known to have an anti-tumor effect on certain types of malignancies, though on hepatocellular carcinomas (HCCs), its effect remains unclear. We studied the anti-tumor effects of cimetidine on chemically-induced HCCs in rats. Four-week-old male Wistar rats (n=105) were divided into 4 groups. Those in groups A and B were administered diethylnitrosamine (DEN) intraperitoneally at 100 mg/kg body weight every week for 6 weeks, during which rats in group A were given tap water and those in group B received cimetidine (100 mg/kg/day) in their drinking water. Rats in groups C and D were administered saline instead of DEN and given tap water with 100 mg/kg/day of cimetidine, respectively. The animals were sacrificed at 7, 12, 22 and 32 weeks after the first administration of drugs and examined. Liver nodules were observed only in groups A and B, with the number of nodules, maximum diameter of the largest nodule, and liver weight significantly lower in group B. Immunohistochemistry findings showed that glutathione S-transferase placental-positive preneoplastic foci were significantly decreased in group B. Cimetidine treatment decreased the number of proliferating cell nuclear antigen-positive hepatocytes and tended to enhance natural killer (NK) cell activity in splenic lymphocytes. In addition, flow cytometry revealed that the proportion of NK cells among total splenic lymphocytes was not affected by cimetidine treatment. Our results showed that cimetidine has an inhibiting effect on hepatocarcinogenesis.

Ferucarbotran expands area treated by radiofrequency ablation in rabbit livers.

BACKGROUND AND AIM: Several studies have examined the factors involved with expansion of the coagulation volume following radiofrequency ablation (RFA). Ferucarbotran contains superparamagnetic iron oxide that generates heat in a radiofrequency electric field and may have an effect on the area affected by RFA. We attempted to determine whether ferucarbotran administration expands radiofrequency-ablated volume using a rabbit model. METHODS: A total of 15 male Japanese white rabbits (16 weeks old) were used and divided into three groups of five each. A 1-mL saline solution was given intravenously into a dorsal ear vein in the control group, whereas 1 mL ferucarbotran solution (0.016 mL/kg bodyweight) was given to the common-dose group and 1 mL of a twofold concentrated ferucarbotran solution (0.032 mL/kg bodyweight) was given to the high-dose group. RFA was performed with a cool-tip electrode 4 h after the administration and immediately thereafter the rabbits were killed, and the volume of the ablated area measured using magnetic resonance imaging (MRI). Following the MRI analysis, the rabbit's livers were resected, and the maximum short axis diameter of the ablated area in each was measured. RESULTS: None of the rabbits died during the RFA procedure. The volume of the ablated area estimated on MR images in the ferucarbotran-administered groups was larger than that in the control group. Further, our macroscopic assessment showed that the maximum short axis diameter had a tendency to increase with ferucarbotran administration. CONCLUSION: Ferucarbotran may expand the area treated by RFA.