Masaharu Ando

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.

Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long-term prospective cohort study.

Background and Aims:  It still remains controversial whether gastric mucosal atrophy and intestinal metaplasia are reversible after eradication of Helicobacter pylori infection. The aims of this study were to evaluate the histological changes in gastric mucosa after H. pylori eradication during long‐term follow‐up periods, and to verify the propriety of H. pylori eradication for the elderly population.

Partial splenic embolization prior to combination therapy of interferon and ribavirin in chronic hepatitis C patients with thrombocytopenia

Aim:  A low platelet count leads to dose reduction of interferon (IFN) and is associated with failure to achieve a sustained virological response (SVR) in chronic hepatitis C patients. However, partial splenic embolization (PSE) is effective for treating thrombocytopenia resulting from hypersplenism.

Roles of alcohol consumption in fatty liver: A longitudinal study

BACKGROUND & AIMS Roles of alcohol consumption in non-alcoholic fatty liver disease are still controversial, although several cross-sectional studies have suggested the beneficial effect of light to moderate drinking on fatty liver. We analyzed the longitudinal relationship between drinking pattern and fatty liver. METHODS We included 5297 Japanese individuals (3773 men and 1524 women) who underwent a baseline study in 2003 and follow-up at least once from 2004 to 2006. Generalized estimating equation was used to estimate any association between drinking pattern and fatty liver assessed by ultrasonography. RESULTS At baseline, 1179 men (31.2%) and 235 women (15.4%) had fatty liver; 2802 men (74.2%) and 436 women (28.6%) reported alcohol consumption. At the latest follow-up, 348 of 2594 men (13.4%) and 101 of 1289 women (7.8%) had newly developed fatty liver; 285 of 1179 men (24.2%) and 70 of 235 women (29.8%) demonstrated a remission of fatty liver. In men, drinking 0.1-69.9 g/week (odds ratio, 0.79 [95% confidence interval, 0.68-0.90]), drinking 70.0-139.9 g/week (0.73 [0.63-0.84]), drinking 140.0-279.9 g/week (0.69 [0.60-0.79]), and drinking ⩾280.0 g/week (0.68 [0.58-0.79]) were inversely associated with fatty liver after adjusting for obesity, exercise, and smoking. In women, drinking 0.1-69.9 g/week (0.71 [0.52-0.96]) and drinking 70.0-139.9 g/week (0.67 [0.45-0.98]) were inversely associated with fatty liver after the adjustment. CONCLUSIONS Light to moderate alcohol consumption, or even somewhat excessive amounts especially in men, was likely to protect most individuals against fatty liver over time.

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.

New prognostic scoring model for liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure.

Background. Many patients with fulminant hepatic failure die before receiving liver transplantation because of the difficulty of pinpointing the suitable timing for liver transplantation. The revised Kings College criteria are useful for patients with acetaminophen-related fulminant hepatic failure; however, in those with non-acetaminophen-related fulminant hepatic failure, a new prognostic system that can accurately identify the suitable timing for liver transplantation is required. Methods. Using the first sample consisted of eighty patients with fulminant hepatic failure, we examined 2-week poor prognostic parameters at the time of diagnosis of fulminant hepatic failure (day 1) and on days 4, 8, and 15, respectively, and a 2-week prognostic scoring model was constructed. To confirm the accuracy of this model, validation was performed in the second sample consisting of 26 patients. Results. Cause of fulminant hepatic failure (hepatitis B virus or indeterminate), hepatic coma grade (III or IV), systemic inflammatory response syndrome (yes) and ratio of total to direct bilirubin (> 2.0) were associated with 2-week outcomes during days 1-15. Each of these four parameters was valued at +1. The 2-week survival rate in patients scoring <3 was ≥80% in contrast to less than 30% in patients scoring ≥3. When this scoring model was applied to the second sample, the sensitivity, specificity, and positive and negative predictive values were 87.5%, 90.0%, 93.3%, and 81.8%, respectively. Conclusions. This scoring model may be useful for predicting 2-week outcomes and determining the suitable timing for liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure.

Factors associated with adherence to combination therapy of interferon and ribavirin for patients with chronic hepatitis C: Importance of patient's motivation and physician's treatment experience

Background/Aims: Adherence to combination therapy with interferon (IFN) or pegylated IFN plus ribavirin for chronic hepatitis C patients is important for a better virological response. However, the impact of the patients treatment experience and treatment centre on adherence to combination therapy has not been fully analysed. In this prospective study, we analysed the factors that might have an effect on adherence to therapy in patients who had initial or retreatment IFN therapy.

Large waist circumference is a risk factor for reflux esophagitis in Japanese males.

Background/Aims: The prevalence of reflux esophagitis, which might lead to development of Barrett’s esophagus and esophageal adenocarcinoma, has been increasing. The aim of this study was to assess risk factors for reflux esophagitis. Methods: We conducted a cross-sectional study of 1,495 Japanese subjects undergoing health checkups (822 males and 673 females; median age 50 years) at a tertiary care center. Results: One hundred and twenty-seven subjects (8%) had reflux esophagitis and hiatal hernia was observed in 292 subjects (20%). Reflux esophagitis (13 vs. 3%) and hiatal hernia (28 vs. 9%) were more frequent in males than females. Significant differences in clinical backgrounds were observed between females and males. Multivariate logistic regression analyses revealed that hiatal hernia (OR 6.63, 95% CI 2.47–17.8; p = 0.0002) was associated with reflux esophagitis in females. In males, age (per 1-year increment: OR 0.96, 95% CI 0.94–0.99; p = 0.007), hiatal hernia (OR 3.16, 95% CI 2.05–4.87; p < 0.0001) and waist circumference (per 1-cm increase: OR 1.09, 95% CI 1.02–1.15; p = 0.006) were associated with reflux esophagitis. Conclusions: Abdominal obesity may be an important risk factor for reflux esophagitis in males compared with females.

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.