Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open‐label,phase 3 trial

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open‐label study to assess the efficacy and safety of an all‐oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment‐naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight‐based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment‐naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment‐naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.     

The Reverse-Direction Method Links Mass Experimental Data to Human Diseases

Genome-wide analyses such as DNA microarray, RNA sequencing and RNA interference-based high-throughput screening are prevalent to decipher a biological process of interest, and provide a large quantity of data to be processed. An ultimate goal for researchers must be extrapolation of their data to human diseases. We have conducted functional genome-wide screenings to elucidate molecular mechanisms of the inflammation amplifier, a NFκB/STAT3-dependent machinery that potently drives recruitment of immune cells to promote inflammation. Using a public database of genome-wide association studies (GWAS), we recently reported the reverse-direction method by which our mass screening data were successfully linked to many human diseases. As an example, the epiregulin–epidermal growth factor receptor pathway was identified as a regulator of the inflammation amplifier, and associated with human diseases by GWAS. In fact, serum epiregulin levels were higher in patients with chronic inflammatory disorders. The reverse-direction method can be a useful tool to narrow mass data down to focus on human disease-related genes.     

An analysis of and new risk factors for reexpansion pulmonary edema following spontaneous pneumothorax

Background

The major risk factor for reexpansion pulmonary edema (RPE) following the treatment of spontaneous pneumothorax is thought to be chronic lung collapse. However, a long-term collapsed lung does not always cause RPE. The purpose of this study was to define other risk factors for RPE among patients undergoing drainage for the treatment of spontaneous pneumothorax.

Methods

We retrospectively reviewed all the patients with spontaneous pneumothorax who had been treated at our hospital during a 5-year period. The duration of symptoms, location and size of the pneumothorax, size of the chest tube, and pleural effusion, which can occur coincidentally with pneumothorax, were compared in patients who did and did not experience RPE.

Results

Forty patients were underwent drainage for the treatment of a spontaneous pneumothorax between January 2007 and December 2012. RPE developed in 13 of the 40 (32.5%) patients. In the multivariate analysis, the presence of pleural effusion coincident with pneumothorax contributed to the risk for RPE [odds ratios (OR), 1.557; 95% confidence intervals (CI), 1.290-1.880]. The duration of symptoms, location and size of the pneumothorax and size of the chest tube were similar between the groups. Symptomatic RPE was associated with a larger pneumothorax size.

Conclusions

The rate of RPE following spontaneous pneumothorax is higher than was previously reported. Our findings suggest the presence of pleural effusion coincidentally with pneumothorax may therefore be a new risk factor for RPE.     

D-index dose not predict the development of pulmonary infection in acute myeloid leukemia patients undergoing consolidation chemotherapy with high-dose cytarabine

The D-index is calculated as the area over the neutrophil curve during neutropenia. We investigated the impact of the D-index on pulmonary infection in 33 acute myeloid leukemia patients undergoing consolidation chemotherapy with high-dose cytarabine. There was no difference in the D-index between chemotherapies with and without pulmonary infection. The cumulative D-index (c-D-index) until the development of infection exceeded 4000 in four of five patients with pulmonary infection. Although there was no difference in the total D-index throughout the overall consolidation chemotherapy, the total D-index from induction to consolidation and the D-index at induction chemotherapy were higher in patients with pulmonary infection during consolidation than in those without it (P = 0.014 and 0.019, respectively). Our results showed that the cumulative effect of neutropenia might determine the risk of pulmonary infection in consolidation chemotherapy. We are planning a clinical trial of c-D-index-guided preemptive antifungal therapy.     

Biliary adenofibroma with ominous features of imminent malignant changes

Biliary adenofibroma (BAF) is a rare, benign liver tumor. Herein, we report a case of BAF with histological features of imminent malignant changes. Ultrasound and CT revealed a solid 2.5-cm mass in the right liver lobe. The patient was asymptomatic and had no past medical history including liver disease. A general examination that included the abdomen and the laboratory data were normal. Because of the increase of its size, this tumor was surgically resected. Grossly, a 3.5-cm nodular mass abutted on the hepatic capsule was found, and its cut surface showed a well-circumscribed, whitish, and firm lesion that showed microcystic changes in the periphery and solid changes in the central parts. Histologically, the tumor showed a proliferation of tubulocystic structures embedded in a fibrous stroma. Microcysts were prevalent in the periphery, while tubular components with abundant fibrous stroma were in the central parts. The tubules were variably dilated and branched. This case closely resembled the previously reported cases of BAF, except that there were complicated papillary projections with fine fibrovascular cores in some of the microcysts and that the epithelial component in papillary projections showed dysplastic changes and increased cellular proliferative activities, implicating ominous features of imminent malignant changes. These dysplastic and papillary changes may be an intermediate lesion leading to malignancy, which have occasionally been reported in BAF.