Development of the Anger Children's Cognitive Error Scale and the Anger Children's Automatic Thought Scale.

BACKGROUND: Empirical studies between anger and anger-provoking cognitive variables in children and adolescents are lacking, despite numerous studies on internalising and externalising problems. AIM: The purpose of this study was to develop new questionnaires for anger-provoking cognitive errors and automatic thoughts, and examine relationships between anger, cognitive errors, and automatic thoughts in children and adolescents. METHOD: Participants were 485 Japanese children and adolescents aged 9-15 years old (254 females; average age 12.07; SD = 1.81). They completed the Anger Children's Cognitive Error Scale (A-CCES) and the Anger Children's Automatic Thought Scale (A-CATS), which were developed in this study, as well as the Anger Scale for Children and Adolescents and the Japanese version of Short Spence Children's Anxiety Scale. RESULTS: Both the A-CCES and the A-CATS had adequate reliability (internal consistency) and validity (face validity, structural validity and construct validity). A hierarchal regression analysis indicated that automatic thoughts were positively and moderately related to anger (ß = .37) after controlling for age, gender, anxiety symptoms, cognitive errors and interaction term. Moreover, a mediation analysis indicated that automatic thoughts significantly mediated the relationship between cognitive errors and anger (indirect effect, 0.24; 95% CI: .020 to .036). CONCLUSIONS: This study developed the new questionnaires to assess anger-provoking cognitive errors and automatic thoughts. In addition, this study revealed that automatic thoughts rather than cognitive errors are associated with anger in children and adolescents.

Pain sensitivity after low-level clenching is influenced by preloading eccentric exercise.

PURPOSE: To examine the effect of preloading eccentric exercise on pain sensitivity in healthy volunteers. METHODS: In 20 healthy volunteers, pain-related sensations (6 items: pain, unpleasantness, fatigue, stiffness, tension, and soreness during maximum biting), and pain intensities induced by repeated electrical stimuli on the masseter and the hand palm were evaluated using a visual analog scale (VAS) of 0-100 mm. Eccentric exercise (6 min-test) or gum chewing (6 min-control) was used as preloading exercise to evaluate the effect on pain sensitivities before and after low-level clenching (15 min) performed 2 days after the preloading exercise. RESULTS: Eccentric exercise induced only low levels of pain-related sensations 2 days later. However, the time course of temporal summation induced by four repeated electrical stimuli on the masseter was influenced by the type of preloading exercise, i.e., temporal summation increased after the low-level clenching (P = 0.016) when preloading was done by the eccentric exercise, while no significant change was observed when preloading was done by the gum chewing. CONCLUSIONS: Eccentric exercise may facilitate pain sensitivity induced by subsequent low-level clenching via the central nervous system. In addition, it was demonstrated that pain sensitivity after the low-level clenching could be influenced by the type of preloading exercise. These experimental results may suggest that eccentric exercise could act as one of the triggering factors in the mechanism by which tooth clenching leads to a chronic pain condition in susceptible individuals.

The influence of thickeners of food on the particle size of boluses: a consideration for swallowing.

The purpose of this study was to examine the influence of thickeners with different levels of thickness on the sizes of particles in food boluses. In medical and nursing care, thickeners are used to make food safe for patients with dysphagia. However, the effect of thickeners on the foods they are added to, especially during swallowing, is still unclear. The bolus particles of 20 healthy volunteers were photographed, and the digital images were used to estimate the sizes of particles in them. Eight test samples with thickeners with different levels of thickness were tested: six grades of thickened carrot juice with raw carrots in it, raw carrot with banana, and raw carrot alone. The particle homogeneity index (HI) and particle size index (SI) just before swallowing were calculated. The viscosities of the liquid part of the test samples were also measured. The number of mastication cycles across the test samples was not significantly different. However, significant differences were found in SI and HI across the test samples: the absolute values of SI and HI tended to rise as the thickness of the test sample increased. The viscosity of the liquid part of the test sample also increased as the thickness increased. The differences in the thickness of food had an influence on the bolus particle sizes just before swallowing.

Efficacy of interferon-beta plus ribavirin combination treatment on the development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C.

AIM: Although there is much evidence of an antitumor effect of pegylated interferon (IFN)-α-based treatment, limited data is available about that of IFN-ß-based treatment. Our goal was to evaluate the impact of IFN-ß plus ribavirin (RBV) treatment on the suppression of hepatocellular carcinoma (HCC). METHODS: This retrospective, multicenter study consisted of 124 chronic hepatitis C patients who were treated with IFN-ß plus RBV treatment, including 61 with advanced fibrosis and five with pretreatment HCC. All participants were followed for a median of 2.8 years (range, 2.2-3.2) after the end of their antiviral treatment. The data of 112 patients who finished the treatment were available for analysis. Cox proportional hazard analyses were performed to determine factors significantly associated with HCC development. Cumulative incidence curves for HCC were plotted using the Kaplan-Meier method and differences between groups were assessed using the log-rank test. RESULTS: The 2.9% rate of HCC development of patients with sustained virological response (SVR) was significantly lower (P = 0.027) than the 15.9% of non-SVR patients. Interestingly, no significant difference was observed between the rates of HCC development of patients with and without advanced fibrosis (P = 0.733), even though the SVR rate of patients with advanced fibrosis was significantly lower than that of those without advanced fibrosis (P < 0.001). Stepwise multivariable Cox analysis extracted that only SVR was significantly associated with HCC development (hazard ratio, 0.20; 95% confidence interval, 0.03-0.84, P = 0.027). CONCLUSION: SVR was significantly associated with a lower risk of HCC development after IFN-ß plus RBV treatment.

Efficacy and safety of splenectomy in telaprevir-based triple therapy for chronic hepatitis C patients with thrombocytopenia and advanced fibrosis.

BACKGROUND AND AIM: Thrombocytopenia (TCP) of chronic hepatitis C patients with cirrhosis has a negative impact on the management of interferon-based treatment. The aim of this study is to evaluate the efficacy and safety of telaprevir-based triple therapy for patients who have undergone splenectomy (Spx). METHODS: This prospective, multicenter study consisted of 80 patients, including 32 Spx and 48 non-Spx/TCP (platelet count: 60-99 × 10(9) /L) patients with advanced fibrosis infected with hepatitis C virus genotype 1b. All received 12 weeks of telaprevir in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin. RESULTS: The sustained virological response (SVR) rate of the Spx group (75.0%) was significantly higher than that of the non-Spx/TCP group (52.1%) (P < 0.05). Under favorable conditions such as treatment-naïve/prior relapse and interleukin-28B (IL28B) TT allele (rs8099917), the SVR rates of the Spx group were significantly higher than those of the non-Spx/moderate TCP (60-79 × 10(9) /L) groups (91.3% vs 50.0% and 93.8% vs 37.5%, respectively; both P < 0.05). Adequate PEG-IFNα2b adherence was associated with SVR. However, the percentage of patients who achieved 80% adherence to PEG-IFNα2b in the non-Spx/moderate TCP (42.9%) group was significantly lower than that of the Spx (79.3%) and non-Spx/mild TCP (80-99 × 10(9) /L) (80.0%) groups. Treatment discontinuation due to adverse effects and the development of bacterial infection did not differ between the Spx and non-Spx/TCP groups. CONCLUSION: The increase of platelet count after Spx contributed to treatment success, especially for moderate to severe TCP patients who are treatment-naïve/prior relapse or IL28B TT allele.

Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: a prospective, multicenter study.

BACKGROUND & AIMS: The effects of pegylated interferon (PegIFN) α and ribavirin (RBV) treatment of chronic hepatitis C on the incidence of hepatocellular carcinoma (HCC) have not been well established. This study investigated the impact of treatment outcome on the development of HCC by chronic hepatitis C patients treated with PegIFNα2b and RBV. METHODS: This large-scale, prospective, multicenter study consisted of 1013 Japanese chronic hepatitis C patients with no history of HCC (non-cirrhosis, n=863 and cirrhosis, n=150). All patients were treated with PegIFNα2b and RBV and the follow-up period started at the end of the antiviral treatment (median observation period of 3.6 years). The cumulative incidence rate of HCC was estimated using the Kaplan-Meier method, according to treatment outcome. RESULTS: Forty-seven patients (4.6%) developed HCC during the observation period. In the non-cirrhosis group, the 5-year cumulative incidence rates of HCC for the sustained virological response (SVR) (1.7%) and transient virological response (3.2%) (TVR: defined as relapse or breakthrough) groups were significantly lower than those of the non-virological response (NVR) group (7.6%) (p=0.003 and p=0.03, respectively). A significantly low rate of incidence of HCC by TVR patients in comparison with NVR patients was found for patients aged 60 years and over, but not for those under 60 years of age. In the cirrhosis group, the 5-year cumulative incidence rates of HCC for the SVR (18.9%) and TVR groups (20.8%) were also significantly lower than those of the NVR group (39.4%) (p=0.03 and p=0.04, respectively). CONCLUSIONS: SVR and complete viral suppression during treatment with relapse (TVR) were associated with a lower risk of HCC development when compared with NVR.

Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy.

BACKGROUND & AIMS: Anemia is a common adverse effect of telaprevir (TVR) in combination with pegylated interferon (PegIFN)α and ribavirin (RBV) therapy. It occurs at a higher incidence with the TVR relative to PegIFNα and RBV alone. We herein evaluate the baseline and on-treatment predictors of the development of severe anemia by chronic hepatitis C virus (HCV) patients receiving TVR-based triple therapy. METHODS: This prospective, multicenter study consisted of 292 patients (median age: 62 years) infected with HCV genotype 1. All received 12 weeks of TVR in combination with 24 weeks of PegIFNα2b and RBV. The definition of severe anemia during antiviral treatment is hemoglobin (Hb)<85 g/L. RESULTS: 101 (34.6%) patients developed severe anemia during the treatment period. Multivariable logistic regression analysis of possible pretreatment predictors of the development of severe anemia extracted baseline Hb < 135 g/L (Hazard ratio [HR], 2.53; p = 0.0013), estimated glomerular filtration rate <80 ml/min/1.73 m(2) (HR, 1.83; p = 0.0265), and inosine triphosphatase (ITPA) CC genotype (rs1127354) (HR, 2.91; p = 0.0024). For patients with ITPA CC (n = 227), multivariable logistic regression analysis of possible pretreatment and on-treatment predictors of the development of severe anemia extracted Hb level at week 2 (HR, 0.96; p = 0.0085) and the initial four weeks of weight-adjusted TVR (HR, 1.05; p = 0.0281). CONCLUSIONS: Anemia remains a risk for all patients treated with TVR-based triple therapy. However, ITPA polymorphism (rs1127354) is useful for predicting the development of severe anemia and will be helpful in the management of treatment.

Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C.

BACKGROUND & AIMS: This study was performed to evaluate the efficacy of a triple therapy in older Japanese patients; telaprevir (TVR) was added to pegylated interferon α2b and ribavirin. METHODS: This prospective study enrolled 120 genotype 1b patients with chronic hepatitis C who received 12 weeks of triple therapy followed by a 12-week dual therapy that included pegylated interferon α2b and ribavirin. Patients were categorized according to age: group A, 64 patients aged >60 and group B, 56 patients aged ⩽60. Serum HCV RNA levels were monitored by COBAS TaqMan HCV test. RESULTS: The rates of undetectable HCV RNA at week 4 (rapid virological response, RVR) were 73.4% in group A and 73.2% in group B. No significant difference in sustained virological response (SVR) was found between groups A (76.6%) and B (83.9%) (p=0.314). The SVR rates for patients with interleukin 28B (IL28B) (rs8099917) TT allele (89.4% and 91.9% for groups A and B) were significantly higher than for those with the IL28B TG/GG allele (41.2% and 68.4%, respectively) (both p<0.05). Multivariate analysis extracted IL28B TT and RVR as independent factors associated with SVR. Adverse effects resulted in treatment discontinuation by 12.5% in each group. Hemoglobin decrease significantly differed between groups A and B: the decrease to ≤100 g/L, to 85 - <100g/L, and to <85 g/L, was 9.4%, 40.6%, and 50% in group A patients, respectively, and 41.1%, 25%, and 33.9% in group B patients, respectively (p=0.0006). CONCLUSIONS: TVR-based triple therapy can be successfully used to treat older patients with genotype 1b chronic hepatitis C.

Mitochondrial DNA data indicate an introduction through Mainland Southeast Asia for Australian dingoes and Polynesian domestic dogs.

In the late stages of the global dispersal of dogs, dingoes appear in the Australian archaeological record 3500 years BP, and dogs were one of three domesticates brought with the colonization of Polynesia, but the introduction routes to this region remain unknown. This also relates to questions about human history, such as to what extent the Polynesian culture was introduced with the Austronesian expansion from Taiwan or adopted en route, and whether pre-Neolithic Australia was culturally influenced by the surrounding Neolithic world. We investigate these questions by mapping the distribution of the mtDNA founder haplotypes for dingoes (A29) and ancient Polynesian dogs (Arc1 and Arc2) in samples across Southern East Asia (n = 424) and Island Southeast Asia (n = 219). All three haplotypes were found in South China, Mainland Southeast Asia and Indonesia but absent in Taiwan and the Philippines, and the mtDNA diversity among dingoes indicates an introduction to Australia 4600-18 300 years BP. These results suggest that Australian dingoes and Polynesian dogs originate from dogs introduced to Indonesia via Mainland Southeast Asia before the Neolithic, and not from Taiwan together with the Austronesian expansion. This underscores the complex origins of Polynesian culture and the isolation from Neolithic influence of the pre-Neolithic Australian culture.

Evaluation of the adverse effect of premature discontinuation of pegylated interferon α-2b and ribavirin treatment for chronic hepatitis C virus infection: results from Kyushu University Liver Disease Study.

BACKGROUND AND AIMS: Pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) treatment of chronic hepatitis C virus (HCV) infection is associated with a substantially elevated risk of discontinuation. The aim of this study is to evaluate the reason for premature discontinuation during PEG-IFN α-2b and RBV treatment due to adverse effects in patients with chronic HCV infection. METHODS: A total of 2871 Japanese patients who had chronic HCV infection treated with PEG-IFN α-2b and RBV were screened. We prospectively investigated the reasons for premature discontinuation of treatment classified by sex and age, and analyzed the timing of discontinuation. RESULTS: Of the 2871 patients, 250 (8.7%) discontinued treatment because of adverse effects. The main reasons for premature discontinuation were neurovegetative symptoms (n = 77, 30.8%), depression-related syndrome (n = 46, 18.4%), hematologic effects (n = 41, 16.4%) and dermatologic effects (n = 27, 10.8%). The rate of discontinuation of treatment for patients aged ≥ 65 years was significantly higher than for patients aged < 65 years, for both men (P < 0.0001) and women (P = 0.0121). Moreover, the frequency of discontinuation due to neurovegetative symptoms, depression-related syndrome, and hematologic effects for men aged ≥ 65 years was significantly higher than for those aged < 65 years (P = 0.0001, P = 0.0016, and P = 0.0170, respectively), but not for women. CONCLUSION: Premature discontinuation due to the adverse effects of PEG-IFN α-2b and RBV treatment by patients with chronic HCV infection is mainly due to neuropsychiatric symptoms and is more common for older than for younger patients.

An inadequate dose of ribavirin is related to virological relapse by chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin.

The aim of this large-scale analysis was to assess the effect of 48-week pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) therapy on virological relapse by patients infected with hepatitis C virus (HCV) genotype 1. The relationship between virological relapse and the dose of PEG-IFNα-2b and RBV was investigated in 619 patients who had once cleared HCV RNA during PEG-IFNα-2b and RBV treatment for 48 weeks. The overall virological relapse rate was 34.1% (211 of 619). The relapse rate was 59.5% (22 of 37) for patients who received <6 mg/kg/day of RBV, even if a sufficient dose of PEG-IFNα-2b (≥1.5 µg/kg/day) was received. In contrast, the relapse rate was 28.1% (16 of 57) for patients who received ≥12 mg/kg/day of RBV, irrespective of the PEG-IFNα-2b dose. The relapse rates were significantly increased with the reduction of the RBV dose for both PEG-IFNα-2b doses of ≥1.2 and <1.2 µg/kg/week (P < 0.0001 and P = 0.0006, respectively). Moreover, the relapse rate was 41.2% (35 of 85) for patients with an early virological response (EVR) who received <6 mg/kg/day of RBV. The relapse rates were significantly increased with the reduction of the RBV dose in both those patients with an EVR and those with a late virological response (P = 0.0006 and P = 0.0088, respectively). To summarize, for HCV genotype 1 patients treated with PEG-IFNα-2b and RBV, the virological relapse of HCV was RBV dose-dependent, irrespective of the dose of PEG-IFNα or the effect of early viral kinetics.

Polymorphism of the apolipoprotein B gene and association with plasma lipid and lipoprotein levels in the Mongolian Buryat.

Allele frequencies at six RFLP sites (Ins/Del, ApaLI, AluI, XbaI, MspI, and EcoRI) of the apolipoprotein B gene (APOB) and the relationship of genotypes with plasma lipid and lipoprotein levels in the Mongolian Buryat were investigated. Common alleles at these sites in 110 Buryat subjects were I, G, A-, X-, M+, and E+; the frequencies of 0.809-0.991 differed strikingly from those of a few Asians and most Europeans. Five unambiguous haplotypes of all sites were revealed at 74%; haplotype IGA-X-M+E+ (000000) was the most frequent (67%), followed by IGA+X-M+E+ (001000) (19%). The frequency constitution differed significantly from the Chinese, Malaysians, and Caucasians but resembled the Indians. No APOB polymorphisms were associated with cholesterol levels (total, HDL and LDL). Significant associations of genotypes were shown with the triglyceride level only at the AluI and XbaI sites. The lipid level of A-A+ females or X-X+ males was higher than that of A-A- females or X-X- males, respectively.

Laparoscopic splenectomy may be a superior supportive intervention for cirrhotic patients with hypersplenism.

BACKGROUND AND AIMS: To evaluate and compare laparoscopic splenectomy and partial splenic embolization as supportive intervention for cirrhotic patients with hypersplenism to overcome peripheral cytopenia before the initiation of and during interferon therapy or anticancer therapy for hepatocellular carcinoma. METHODS: Between December 2000 and April 2008, 43 Japanese cirrhotic patients with hypersplenism underwent either laparoscopic splenectomy or partial splenic embolization as a supportive intervention to facilitate the initiation and completion of either interferon therapy or anticancer therapy for hepatocellular carcinoma. We reviewed the peri- and post-intervention outcomes and details of the subsequent planned main therapies. For interferon therapy, the rate of completion, the rate of treatment cessation and virological responses were evaluated. Anti-cancer therapies for hepatocellular carcinoma included liver resection, ablation therapy, intra-arterial chemotherapy, and transarterial chemoembolization. RESULTS: All patients tolerated the operations well with no significant complications. The platelet count was significantly higher in the laparoscopic splenectomy group than in the partial splenic embolization group at 1 and 2 weeks after the intervention. Interferon therapy was stopped in two patients in the partial splenic embolization group due to recurrent thrombocytopenia whereas all patients in the laparoscopic splenectomy group completed interferon therapy. The planned anticancer therapies were performed in all patients, and were completed in all patients without any problems or major complications. CONCLUSION: Laparoscopic splenectomy may be superior to partial splenic embolization as a supportive intervention for cirrhotic patients with hypersplenism. Future prospective, randomized controlled patient studies are required to confirm these findings.

Association between the treatment length and cumulative dose of pegylated interferon alpha-2b plus ribavirin and their effectiveness as a combination treatment for Japanese chronic hepatitis C patients: project of the Kyushu University Liver Disease Study Group.

AIM: The aim of the present study was to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2b (peg-IFN alpha-2b) plus ribavirin (RBV) and their effectiveness in the treatment of chronic hepatitis C. METHODS: Seven hundred and fifteen patients received peg-IFN alpha-2b plus RBV treatment for 48 weeks and 24 weeks for genotypes 1 (n = 586) and 2 (n = 129), respectively. RESULTS: Sustained virological responses (SVR), defined as serum hepatitis C virus (HCV)-RNA undetectable at 24 weeks after the end of treatment, were 42.4% and 74.4% in genotypes 1 and 2, respectively, on an intention-to-treat analysis. SVR significantly increased with treatment length (4.7%, 36.4%, and 51.8% for < 24 weeks, 24-47 weeks, and 48 weeks, respectively, for genotype 1; and 28.6%, 57.1%, 78.3% for < 12 weeks, 12-23 weeks, and 24 weeks, respectively, for genotype 2). SVR significantly increased with total cumulative treatment dose (21.1%, 36.5%, and 52.9% with < 60%, 60-79%, and >or= 80% in peg-IFN dose; 29.6%, 51.1%, and 59.2% with < 60%, 60-79%, and >or= 80% in RBV dose) in genotype 1, although it did not differ significantly for genotype 2. CONCLUSIONS: In peg-IFN alpha-2b plus RBV treatment for chronic hepatitis C, it is important to complete the target length of treatment and to continue the target dosage to achieve SVR, especially for genotype 1 patients.

Effects of lamivudine on serum albumin levels correlate with pretreatment HBV-DNA levels in cirrhotic patients.

BACKGROUND: Lamivudine treatment has been recently demonstrated to increase the serum albumin levels in cirrhotic patients with hepatitis B virus (HBV) infection, but the precise mechanism remains unclear. We hypothesized that the improvement of hypoalbuminemia by lamivudine may be attributable to the reduction of HBV replication itself, rather than to cessation of hepatitis. In order to confirm this hypothesis, in this study we evaluated factors which correlated with the increase in serum albumin levels. Fifty-four patients (Child-Pugh A/B/C, 35/9/10) with HBV-related liver cirrhosis who had been treated with lamivudine for more than 12 months were evaluated. We analyzed the correlation between the increase in serum albumin levels at month 12 after starting treatment (Delta-albumin) and various pretreatment variables. We also analyzed the correlation between Delta-albumin and the reduction in serum levels of HBV-DNA (Delta-HBV-DNA) or alanine aminotransferase (Delta-ALT) at month 12. RESULTS: The average Delta-albumin was 0.38 g/dL and only serum HBV-DNA levels before treatment correlated significantly with Delta-albumin. We also analyzed the correlation in patients whose alanine aminotransferase levels were normalized after 12 months so that the possible influence of breakthrough hepatitis could be excluded. Even among this subgroup of patients, there was no significant correlation between Delta-albumin and either pretreatment alanine aminotransferase levels or Delta-ALT. In contrast, in patients whose serum HBV-DNA was undetectable at month 12, we found a significant correlation between Delta-albumin and both pretreatment serum HBV-DNA levels and Delta-HBV-DNA. CONCLUSION: Our results demonstrated that albumin levels are associated with pretreatment HBV-DNA but not with alanine aminotransferase levels.

Long-term lamivudine treatment for chronic hepatitis B in Japanese patients: a project of Kyushu University Liver Disease Study.

AIM: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS: Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P<0.0001), HBeAg negativity (P<0.0001), a platelet count of 100 x 10(9)/L or more (P=0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P=0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at >=5 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION: Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2: a project of the Kyushu University Liver Disease Study Group.

AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2, a multi-center study was retrospectively analyzed. METHODS: In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9% vs 92.9%), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8% vs 92.0%). CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16 weeks.

Body surface area is an independent factor contributing to the effects of lamivudine treatment.

BACKGROUND:: It has been suggested that lamivudine therapy may be even more effective if administered at higher doses than is dictated by the current standard regimen. We analyzed the correlation between the effects of lamivudine and body surface area (BSA). METHOD:: We evaluated 134 patients with chronic hepatitis B who had been treated with lamivudine for more than 12 months. The effect of the treatment was evaluated from the levels of serum alanine aminotransferase (ALT) and HBV-DNA. Several variables that could influence the response to treatment, including ALT, albumin, and bilirubin levels, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed. RESULTS:: Univariate logistic analysis selected platelet counts, BSA, HBV-DNA and HBeAg in the biological evaluation, and bilirubin, BSA, HBV-DNA and HBeAg in the virological evaluation (chi(2)>1.0). Using these factors, multivariate analysis revealed that BSA (chi(2)=12.8, p=0.0004) was the only factor that could contribute significantly to the improvement of ALT levels, and that BSA (chi(2)=4.4, p=0.0354) and HBeAg (chi(2)=8.1, p=0.0044) were independent factors that could influence the suppression of HBV-DNA. CONCLUSION:: We revealed that BSA is a significantly predictor of the effect of lamivudine therapy, suggesting that lamivudine dosage should be based on the individual BSA.

Relationship between body surface area and ALT normalization after long-term lamivudine treatment.

AIM: To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS: We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year (n = 249), two years (n = 147), and three years (n = 72) were evaluated from the levels of serum ALT and HBV-DNA, as biological and virological effects (undetectable levels by PCR), respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed. RESULTS: For 1-year treatment, multivariate analysis revealed that BSA (P = 0.0002) was the only factor for the biological effect, and that ALT (P = 0.0017), HBV-DNA (P = 0.0004), and HBeAg (P = 0.0021) were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA (P = 0.0147) was the only factor for the biological effect, and that ALT (P = 0.0192) and HBeAg (P = 0.0428) were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA (P = 0.0730) as a factor for the normalization of ALT levels. CONCLUSION: BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.