Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection.

AIM: This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS: A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS: All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P < 0.01); however, the serum bilirubin level and encephalopathy did not improve. Among patients who achieved SVR12, 75.0% showed an improvement in their CP score, while 5.9% showed a worsening. The presence of large portosystemic shunt (diameter ≥6 mm) and hyperbilirubinemia (≥2.0 mg/dL) were independent factors that interfered with the improvement in the CP score (P < 0.05). The most common AEs were encephalopathy (15.3%) and skin symptoms (7.9%). Two patients discontinued SOF/VEL due to AEs. CONCLUSIONS: Treatment with SOF/VEL for 12 weeks was relatively safe and effective for patients with decompensated cirrhosis. An SVR provided an improvement of the liver function in the majority of patients. However, large portosystemic shunt and hyperbilirubinemia were independent factors that interfered with the improvement in the CP score.

Elevated serum uric acid level was a notable adverse event during combination therapy with sofosbuvir and ribavirin.

AIM: Combination therapy with sofosbuvir and ribavirin (SOF/RBV) has been recently available for chronic hepatitis C patients with genotype 2 (CHG2) in Japan. The domestic phase III clinical trial showed a high antiviral effect with a relatively safe adverse event (AE) profile. Our aim was to report an important AE detected during treatment. METHODS: A prospective multi-institutional study of 12-week combination therapy with SOF/RBV for CHG2 was carried out to evaluate efficacy and safety. RESULTS: The eligible subjects included 142 patients. Out of 50 assessable patients, 16% of the patients were diagnosed with hyperuricemia. The proportions of subjects with grade 1, grade 3, and grade 4 hyperuricemia were 12, 2, and 2%, respectively. Serum uric acid (UA) levels at week 1 of the therapy (W1) were numerically the highest during therapy in patients with hyperuricemia, and the ratio of W1/baseline serum UA levels was significantly higher than that of post-treatment week 4 or 8/baseline serum UA levels in assessable patients. Serum UA levels at W1 were significantly correlated with body mass index. The difference between serum UA levels at W1 and baseline serum UA levels was significantly correlated with the difference between serum creatinine levels at W1 and baseline serum creatinine levels. CONCLUSIONS: Elevated serum UA level was a notable AE associated with SOF/RBV therapy for CHG2. However, because of the small number of subjects, the exact frequency of AEs should be re-evaluated with larger cohorts. We need to remember that elevated serum UA level might develop during the therapy, especially at W1.

Computed tomography-guided transpulmonary radiofrequency ablation for hepatocellular carcinoma located in hepatic dome.

AIM: To determine the feasibility of performing computed tomography (CT)-guided transpulmonary radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) located in the hepatic dome. METHODS: A total of seven patients with HCC comprising seven nodules located in the hepatic dome were treated from April 2004 to December 2004. CT-guided transpulmonary RFA was performed using a cool-tip type electrode (Radionics Company) based on a standardized energy protocol. All tumors located in the hepatic dome were not detectable by the usual ultrasound (US) methods. The lesion diameters ranged from 15 to 27 mm. RESULTS: RFA was technically feasible in all the patients. The puncture procedure was performed twice or less and the total average performance time was 40.6 min. Local tumor control was achieved in all the patients. The necrosis diameter ranged from 25 to 35 mm. The mean follow-up period was 9.6 (7-14 mo) mo. There was no local recurrence at the follow-up points. Pneumothorax requiring pleural drainage was the main complication, which was observed in two of the seven patients (28.6%). However, it improved with chest drainage tube, and the tube could be removed within 2-3 d. No other major complications were observed. CONCLUSION: CT-guided puncture is useful for the treatment of tumors located in the hepatic dome which are hardly detectable by US, even though pneumothorax sometimes may occur as a complication. In the cases with adhesion in the pleura for which artificial pleural effusion methods are not appropriate, CT-guided RFA is thus considered to be an alternative treatment for HCC located in the hepatic dome.

Hepatocellular carcinoma in extremely elderly patients: an analysis of clinical characteristics, prognosis and patient survival.

AIM: To identify the clinical and prognostic features of patients with hepatocellular carcinoma (HCC) aged 80 years or more. METHODS: A total of 1310 patients with HCC were included in this study. Ninety-one patients aged 80 years or more at the time of diagnosis of HCC were defined as the extremely elderly group. Two hundred and thirty-four patients aged > or = 50 years but less than 60 years were regarded as the non-elderly group. RESULTS: The sex ratio (male to female) was significantly lower in the extremely elderly group (0.90:1) than in the non-elderly group (3.9:1, P < 0.001). The positive rate for HBsAg was significantly lower in the extremely elderly group and the proportion of patients negative for HBsAg and HCVAb obviously increased in the extremely elderly group (P < 0.001). There were no significant differences in the following parameters: diameter and number of tumors, Child-Pugh grading, tumor staging, presence of portal thrombosis or ascites, and positive rate for HCVAb. Extremely elderly patients did not often receive surgical treatment (P < 0.001) and they were more likely to receive conservative treatment (P < 0.01). There were no significant differences in survival curves based on the Kaplan-Meier methods in comparison with the overall patients between the two groups. However, the survival curves were significantly worse in the extremely elderly patients with stage I/II, stage I/II and Child-Pugh grade A cirrhosis in comparison with the non-elderly group. The causes of death did not differ among the patients, and most cases died of liver-related diseases even in the extremely elderly patients. CONCLUSION: In the patients with good liver functions and good performance status, aggressive treatment for HCC might improve the survival rate, even in the extremely elderly patients.

Evaluation of abdominal circumference and salivary amylase activities after unsedated colonoscopy using carbon dioxide and air insufflations.

OBJECTIVE: To assess and compare abdominal distention and stress in unsedated colonoscopy using carbon dioxide (CO2 ) and air insufflations. METHODS: Two hundred and five patients underwent colonoscopic examinations without sedation using either CO2 or air insufflation. Abdominal circumference and salivary amylase (sAMY) activities before and 0 and 15 min after colonoscopy were measured by a nurse who was blinded to the grouping of the patients. RESULTS: In all, 102 and 103 patients were randomly recruited in the CO2 and air insufflation groups, respectively. sAMY activities before and 0 and 15 min after colonoscopy were not significantly different between the two groups. Abdominal circumference measured immediately and 15 min after colonoscopy was significantly smaller in CO2 insufflation group than in the air insufflation group (81.2 cm vs 84.0 cm, and 79.7 cm vs 83.6 cm, respectively; P <0.05). The increasing ratio of abdominal circumference immediately after colonoscopy was not significantly different between the two groups; however, the ratio at 15 min after colonoscopy using CO2 insufflation was significantly lower than that in the air insufflation group (1.007 vs 1.028, P <0.001). CONCLUSION: sAMY activities after unsedated colonoscopy using CO2 insufflation were not improved; however, CO2 insufflation decreases abdominal circumference after colonoscopy compared with air insufflation.

A case of diffuse neuronal hypertrophy in acute appendicitis.

We report a case of neuronal hypertrophy associated with acute appendicitis in which significant neuronal fibers and the number of ganglion cells increased in the absence of inflammatory cells. Differential diagnosis from diffuse ganglioneuromatosis by the pathologic findings of resected specimen was difficult. A 33-year-old Japanese female visited our hospital complaining of acute abdominal pain. The patient underwent appendectomy upon the diagnosis of acute appendicitis on the day of admission. Postoperative examinations found no neoplastic lesions in other organs or inherited disorders such as multiple endocrine neoplasia (MEN) type 2b and von Recklinghausen's disease (VRD). The pathologic diagnosis was neuronal hypertrophy of the appendix. Because the clinical outcomes of diffuse ganglioneuromatosis and neuronal hypertrophy of the gastrointestinal tract are quite different, clinical and pathologic examination should be carefully carried out for lesions in which significant proliferation of neuronal components is seen.

Ectopic Sebaceous Glands in the Esophagus: Endoscopic Findings over Three Years.

Sebaceous glands in the esophagus are rare and are of particular interest because of their as yet unknown origin. We report a case with ectopic sebaceous glands diagnosed by esophageal endoscopy and biopsy, with follow-up endoscopic examinations for 3 years. Few cases with follow-up endoscopic findings have been reported. In our case, there were no significant overall changes during 3 years of follow-up, but the lesions fluctuated over time. While taking the endoscopic findings of the present or past cases into account, we discuss the possible pathogenic mechanisms of this condition.

A retrospective cohort study of partial splenic embolization for antiviral therapy in chronic hepatitis C with thrombocytopenia.

BACKGROUND: Although partial splenic embolization (PSE) is reportedly effective prior to interferon (IFN)-based therapy, the number of subjects in these studies is small, and the appropriate candidates and disease prognosis remain unknown. METHODS: PSE was performed in 30 patients with advanced hepatitis C who could not receive IFN-based therapy because of thrombocytopenia, platelet counts of ≤100,000/mm(3), and hypersplenism. Also, we compared 25 PSE-treated patients with 23 PSE-untreated patients with thrombocytopenia receiving pegylated IFN (PEG-IFN)-alpha 2b plus ribavirin over the same period. RESULTS: PSE significantly increased platelet and leukocyte counts. PSE was well tolerated with no severe complications. All the patients could receive IFN-based therapy. Discontinuation of therapy in the total cohort of PSE-treated patients was not due to thrombocytopenia. Although PSE did not significantly increase the sustained virological response (SVR) rate, it significantly maintained higher platelet counts throughout the observation period and increased the percentage of patients with 100% adherence to PEG-IFN in the total controlled study population and in subjects with genotype 2. In PSE-treated patients with genotype 2, a trend towards increased SVR was noted. Four patients developed hepatocellular carcinoma (HCC) at a median of 14.5 months after PSE, even though two of these patients had achieved an SVR. CONCLUSIONS: IFN-based therapy following PSE had an advantage in the maintenance of higher platelet counts, and PSE possibly caused an increase in adherence to PEG-IFN. Although patients with genotype 2 might be better candidates for PSE, further evaluation is needed. Careful follow-up of PSE-treated patients, even though they may have achieved an SVR, is needed to detect HCC.

Marked eosinophilia as the first manifestation of sclerosing cholangitis.

We encountered a 45-year-old man who presented with marked eosinophilia as the first manifestation of sclerosing cholangitis. He was found to have a liver dysfunction during a regular physical check up and thereafter consulted our hospital. The laboratory data on admission indicated an elevation of AST (96 IU/L), ALT (136 IU/L) and ALP (1,025 IU/L). Furthermore, the leukocyte count was 18,190/mm(3) and he also showed marked eosinophilia (54.5%, 9,914/mm(3)). There were no atypical findings in the eosinophils. Other diseases causing eosinophilia, including parasite infection, allergic disorders, hypereosinophilic syndromes, drug-induced eosinophilia, malignancies, etc. were all investigated and ruled out. A liver biopsy revealed marked eosinophilic infiltration in the portal area and interlobular bile duct injury. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a slight dilatation of the left intrahepatic bile ducts, but no clear diagnosis could be made at that time. A follow-up liver biopsy and endoscopic retrograde cholangiopancreatography (ERCP) finally revealed a diagnosis of secondary sclerosing cholangitis due to eosinophilic cholangiopathy. According to previous Japanese reports, eosinophilia of more than 5% was reported in 39 of 142 (27.0%) primary sclerosing cholangitis (PSC) patients. Eosinophilic cholangiopathy could cause a condition mimicking PSC and it might be confused as PSC with eosinophilia. The literature contains only about 40 case reports on eosinophilic cholangiopathy, and therefore, to date little attention has been paid to this condition. We should therefore pay attention to this condition when making a differential diagnosis of either PSC or IgG4-related sclerosing cholangitis.