Kouichi Takaguchi

Limitation of combination therapy of interferon and ribavirin for older patients with chronic hepatitis C

In contrast to the United States, Japanese patients with chronic hepatitis C currently treated with interferon are generally 10 to 15 years older. Older patients, however, tend to experience more frequent adverse events. This study was conducted to clarify the effect of patient age on the efficacy and safety of combination therapy. We consecutively enrolled 208 patients with naïve chronic hepatitis C. Patients were classified into three groups according to age: younger than 50 years of age (n = 52); 50 to 59 years old (n = 83); and 60 years of age or older (n = 73). Interferon alpha‐2b therapy was administered daily for 2 weeks, followed by 3 times per week for 22 weeks, while ribavirin was administered daily. Of the 208 study patients, discontinuation of therapy or dose reduction was required in 116 (56%) and was more frequent in older patient groups: 38%, 48%, and 77% for the <50, 50–59, and ≥60‐year‐old patient groups, respectively (P < .001). Multivariate analysis showed patient age to be independently associated with adherence to therapy. A sustained virological response was achieved in 77 (37%) patients, with genotype, viral load, and adherence to therapy associated with this achievement. A tendency toward a lower sustained virological response rate was seen in the older patients. In conclusion, patient age is an important factor contributing to the safety of combination therapy. Thus, treatment schedule should be modified, or other therapeutic modalities should be considered for older patients with chronic hepatitis C. (HEPATOLOGY 2006;43:54–63.)

Risk factors for hepatocellular carcinoma in Hepatitis C patients with sustained virologic response to interferon therapy

Abstract: Background: Although a variety of papers demonstrated inhibited hepatocarcinogenesis with interferon (IFN) therapy for chronic hepatitis C, a small number of hepatocellular carcinomas (HCCs) were still observed even in sustained virologic responders.

A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis

Background and Aims:  A prospective, non‐randomized cohort study on long‐term lamivudine treatment, comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus (HBV)–related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease.

Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim:  In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3‐positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians.

Systemic inflammatory response syndrome strongly affects the prognosis of patients with fulminant hepatitis B.

BackgroundHepatitis B virus infection is the most frequent cause of fulminant hepatic failure. Recently, systemic inflammatory response syndrome has been reported to be important in patients with fulminant hepatic failure. However, prognostic factors for fulminant hepatitis B have not been fully examined. In this study, we analyzed prognostic factors for fulminant hepatitis B in order to accurately identify patients with fatal outcomes.MethodsOf 110 consecutive patients with fulminant hepatic failure, 36 (33%) were diagnosed with fulminant hepatitis B. Five of the 36 patients received liver transplants, and we analyzed prognostic factors associated with fatal outcomes in the other 31 patients, who consisted of 15 men and 16 women with a median age of 45 (range, 20–74) years.ResultsEleven patients (35%) survived without liver transplantation, and the remaining 20 (65%) died. Nonsurvivors were older and had a higher prevalence ratio of systemic inflammatory response syndrome than survivors. Treatments were similar between survivors and nonsurvivors. Using a multivariate Cox proportional hazard model, age (>45 years), systemic inflammatory response syndrome, and ratio of total to direct bilirubin (>2.0) were associated with fatal outcomes. In particular, 1-week and overall survival rates of patients with systemic inflammatory response syndrome at the time of diagnosis were 39% and 8%, respectively, while those of patients without systemic inflammatory response syndrome were 94% and 56%, respectively.ConclusionsSystemic inflammatory response syndrome strongly affects the short-term prognosis of patients with fulminant hepatitis B, and patients with systemic inflammatory response syndrome might need urgent liver transplantation.

Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: phase II clinical study in Japan.

Background and Aim:  Entecavir has demonstrated clinical efficacy for chronic hepatitis B. This study evaluated the efficacy and safety of entecavir in nucleoside‐naive Japanese chronic hepatitis B patients.

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis

Aim:  Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20–30% of patients are negative for ANA. We assessed the clinical features of ANA‐negative patients.

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

Background:We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods:In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results:Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21–2.81), and OS (HR, 1.95; 95% CI, 1.21–3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30–3.06) and OS (HR, 1.94; 95% CI, 1.19–3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion:High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

Prognostic factors for fatal outcomes prior to receiving liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure

Background and Aim:  Many patients continue to die due to the rapid development of cerebral edema and/or multiple organ failure prior to receiving a liver transplantation.

Human leukocyte antigen DR status and clinical features in Japanese patients with type 1 autoimmune hepatitis

Aim:  Human leukocyte antigen (HLA) DR status affects the clinical features of autoimmune hepatitis. In Caucasians, patients with DR3 have poorer outcomes. In Japan, the relationship between HLA DR status and clinical features has yet to be fully examined.