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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., (© 2017 The Japan Society of Hepatology.)

Aim: To evaluate the clinical and virological features of acute hepatitis E (AH-E) in Gunma prefecture and focus on the hepatitis E virus (HEV) infection in immunocompromised patients., Methods: A total of 30 patients with AH-E diagnosed at our Gunma University Hospital, and located in 3-39-15 Showa-machi, Maebashi, Gunma 371-8511 Japan, and its affiliated hospitals from 2004 to 2015, were studied. We evaluated the detailed medical histories, laboratory examinations and virological features of these participants., Results: Of the 30 patients, 21 patients were men, with a median age of 61 years. Three of these patients had a history of recent oversea travel. A total of 14 patients had eaten raw or undercooked meat/viscera from animals, and two patients had contracted transfusion-transmitted AH-E. Eight patients were immunocompromised, including those with hematological disease, cancer receiving systemic chemotherapy and kidney transplant or connective tissue disease undergoing immunosuppressive medications. The alanine aminotransferase and total bilirubin levels were more significantly reduced in these immunocompromised patients than in the non-immunocompromised patients. Severe thrombocytopenia, an extra-hepatic manifestation of AH-E, occurred in one case. Among the 22 HEV strains whose subgenotype was determined, two were imported strains (1a and 1f), and 11 strains formed four distinct phylogenetic clusters within subgenotype 3b. The remaining nine strains differed from each other by 9.8-22.4%, and were classified into four subgenotypes (3a, 3b, 3e and 3f)., Conclusion: Markedly divergent HEV strains (3a, 3b, 3e and 3f) were found to circulate in Gunma. Although immunosuppression appears to play a crucial role in establishing chronic sequels, AH-E in eight immunocompromised patients, including transfusion-transmitted HEV infection in two patients, did not become chronic., (© 2016 The Japan Society of Hepatology.)

Aim: Amino acid transporters play an important role in tumor progression and survival of cancer cells. However, the prognostic significance of L-type amino acid transporter 1 (LAT1), system ASC amino acid transporter-2 (ASCT2) and xCT expression in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the clinicopathological significance of these amino acid transporters in patients with HCC., Methods: We examined 84 patients with surgically resected HCC. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67 and microvessel density (MVD) determined by CD34., Results: LAT1, 4F2hc, ASCT2 and xCT were positively expressed in 61% (50/84), 77% (65/84), 63% (53/84) and 65% (55/84), respectively. Positive LAT1 expression was significantly associated with 4F2hc expression, Ki-67 and the serum albumin. By univariate analysis, LAT1 expression, disease stage and albumin had a significant relationship with overall survival. Tumor size, disease stage, portal vein invasion, albumin and α-fetoprotein had a significant relationship with progression-free survival. Multivariate analysis confirmed that LAT1 expression is an independent and significant prognostic factor for predicting worse outcome after surgery., Conclusion: LAT1 can serve as a significant prognostic marker for predicting negative prognosis after surgery., (© 2014 The Japan Society of Hepatology.)

Aims:   Optimization of the duration of peginterferon-α/ribavirin therapy in patients with hepatitis C virus (HCV) genotype 2 and high viral loads remains to be established. We sought to prospectively optimize the treatment duration based on their virological responses., Methods:   Serum HCV RNA levels of less than 50 IU/mL at weeks 2 and 4, and of 50 IU/mL or more at week 4, were defined as a super-rapid virological response (SRVR), rapid virological response (RVR) and late virological response (LVR), respectively. Treatment for 12, 24 or 48 weeks was assigned to the patients with an SRVR, RVR or LVR, respectively. However, patients with an LVR who expressed a desire to receive the standard therapy duration were given the 24-week therapy., Results:   The overall sustained virological response (SVR) rate was 78.1% (118/151). The SVR rate in the SRVR group was 93.8% (15/16), which was comparable to the 93.0% (66/71) SVR rate in the RVR group. In the LVR patients, the 48-week treatment slightly increased the SVR rate to 76.5% (13/17) compared with the 51.1% (24/47) SVR rate in LVR patients who underwent the standard 24-week treatment. The relapse rate in LVR patients was significantly decreased in patients treated for 48 weeks compared with patients treated for 24 weeks. Multivariate analysis identified the predictive factors for SVR as RVR, prior interferon therapy and total peginterferon-α-2b adherence in patients treated for 24 weeks., Conclusion:   Response-guided therapy may be effective and useful for optimization of the treatment duration., (© 2012 The Japan Society of Hepatology.)