Objective: Celecoxib has been reported to enhance the action of warfarin by inhibiting CYP2C9, its major hepatic drug-metabolizing enzyme, but sufficient information about the mechanism has not been obtained, especially in Japan.
Methods: A study was conducted to investigate the prothrombin time international normalized ratio (PT-INR) and the warfarin sensitivity index (WSI) before and after concurrent administration of celecoxib, as well as the Drug Interaction Probability Scale (DIPS) scores to determine causality with drug interactions, in patients commencing concurrent therapy with celecoxib and warfarin at Kanagawa Prefectural Keiyukai Keiyu Hospital during the 4-year period from October 2011 to September 2015.
Results: Analysis of 18 patients showed that the PT-INR increased significantly from 1.53±0.43 before concurrent therapy to 2.18±1.01 after concurrent therapy (p=0.0101).  The WSI also increased significantly from 0.76±0.50 before concurrent therapy to 1.01±0.65 after concurrent therapy (p=0.0044).  According to the DIPS scores, the causal relation was not rated as “Highly Probable” in any of the patients, while it was considered to be “Probable” in 3 patients, “Possible” in 10 patients, and “Doubtful” in 5 patients.
Conclusion: The findings of this study suggested that when celecoxib treatment is initiated in patients who are already taking warfarin, attention must be paid to changes of coagulation profile, especially in elderly patients.

Objective: The purpose of this study was to assess the treatment outcome in patients with chronic hepatitis C (CHC) using the current standard antiviral therapy when patient were treated in collaboration between hepatologists and primary care physicians (PCPs).Patients and Methods: One hundred and ten patients with CHC were treated with a combination therapy of peginterferon-alpha 2b and ribavirin. Among them, 25 patients were treated by a collaboration between hepatologists and PCPs (collaboration group), whereas 85 patients were treated with exclusively by hepatologists (noncollaboration group). The duration of the therapy was 48 weeks for 58 'difficult- to-treat' patients (genotype 1 with a high load of HCV-RNA; 1H patients) and 24 weeks for the remaining 52 patients (non-1H patients). In the collaboration group, antiviral therapy was initiated and adjusted, if needed, by hepatologists (visits every four weeks), whereas the weekly administration of peginterferon-alpha 2b was performed by PCPs. Clinical characteristics and the treatment outcome were compared between these two groups.Results: The two groups had similar baseline characteristics. By intention to treat, the two groups showed similar rates of treatment-related serious adverse effects (0% vs. 1%, respectively) and dropout rates for adverse effects (8% vs. 13%, respectively). Sustained virologic response rates were also similar between the two groups, being 42% vs. 39% in the 58 1H patients (NS) and 62% vs. 64% in the 52 non-1H patients (NS), respectively.Conclusions: Collaboration between hepatologists and PCPs may be a valid treatment alternative to treat patients with CHC using the current standard antiviral therapy.

The whole spectrum of patients infected with hepatitis C virus (HCV) who visited hospitals has not been fully clarified. It is also unknown whether such patients have visited the hospitals regularly thereafter for a long period. We studied 844 consecutive patients with liver diseases who visited our outpatient clinic located in the southern region of Ibaraki Prefecture. Five hundred eighty-three patients were HCV-infected. Among them, three patients were HBsAg-positive and another patient was IgM anti-HAV positive. Thus, 579 patients (68.6%) were considered to have HCV solely as a hepatotropic virus.Of these HCV patients, 60 were asymptomatic carriers and 15 others were unclassified because of the absence of either biopsy or imaging test records of the liver. As to the rest of the HCV patients, acute hepatitis was diagnosed in one patients, chronic hepatitis in 332 patients, cirrhosis in 130 patients and cancer of the liver in 41 patients.About half of the patients undergoing liver biopsy showed F1 in the degree of liver fibrosis. The rate of virological response to interferon mono-therapy in patients infected with genotype 2 was worse than the national average. The poor response was considered to be due to high viral load. It was suggested that the distribution of patients with each genotype was uneven in this region. After five years, the rate of patients still visiting our clinic were 68.1% for those with chronic hepatitis, and 50% for the healthy carriers. We deemed that it was important to clarify whether patients not visiting our clinic are followed up closely in other hospitals.
Hepatitis C virus ; Liver ; Clinic ; Infection as complication of medical care ; biopsy characteristics

It has been made known that there isn't any significant regional difference in the frequencies of cases of viral hepatitis C by subtypes in our country. In the present study we investigated the subtypes in hepatitis C virus carring patients without blood transfusion history in the southern region of Ibaraki Prefecture to clarify the occurrence ratio of each subtype of the virus. The results of interferon therapy were also examined in those patients with chronic hepatitis C. The frequencies of subtypes 2, 3 and 4 were found to be 71%, 16% and 10%, respectively. Although these ratios were the same as the national average, a significantly high frequency (P>0.01) of subtype 3 was observed in the patients from Tsuchiura in the region, suggesting that there may have existed some particular source of infection other than blood transfusion. The effectiveness of interferon therapy was significantly higher (P>0.01) in the patients with subtype 3 (75%) than in those patients with subtypes 2 and 4 (23% and 43%, raspectively), suggesting that interferon is a remedy specific to subtype 3.