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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-β-based treatment. Our goal was to evaluate the impact of IFN-β 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-β 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

肝細胞癌に対する経皮的ラジオ波焼灼術（RFA）後に発症した右横隔膜ヘルニアの2症例を経験した．横隔膜の欠損は治療部位に接して生じており，ラジオ波焼灼術による合併症と判断した．RFA治療から発症までの期間は症例1で78週，症例2で112週であった．しかし，横隔膜の断裂は症例1では65週の時点で，症例2では42週の時点でCT上明らかになっていた．横隔膜断裂に加え，肝委縮・腹水貯留・腹圧上昇などにより腸管が横隔膜下腔に入り込むことがヘルニア発症の誘引と考えられた．右葉横隔膜直下の腫瘍に対するラジオ波焼灼術においては，十分量の人工腹水注入や腹腔鏡あるいは開腹下などの横隔膜を損傷しない工夫と治療後の経過観察が重要であると考えられた．

Interferon monotherapy is considered to have limited effectiveness in patients with HCV of a high viral load. Here, we reported a 21-year old male of chronic hepatitis C with a high viral load of HCV genotype 1b. He received both peg-interferon α-2b plus ribavirin and peg-interferon α-2a plus ribavirin combination therapy. But there were no virological response. Nevertheless, after starting natural interferon α(human lymphoblastoid interferon (HLBI), Sumiferon; Dainippon Sumitomo Pharmaceutical Co., Osaka, Japan), he became HCV-RNA negative at 4 week. The therapy is continued and HCV-RNA negativity is sustained for over 40 weeks. Eradication of HCV might be expected. Natural IFN α contains more than 20 subtypes, and one or more of them may have therapeutic effect against HCV virus of this patient.

We examined the protective effects of α-tocopherol against glucose intolerance and mitochondrial damage in rat liver after partial in vivo ischemia and reperfusion, while glucose was intravascularly supplemented. Rats were given α-tocopherol or vehicle for three consecutive days before the experiment. Left and median lobes of the liver received 90-min ischemia and 60-min reperfusion. Besides plasma levels of glucose, insulin, and lipid peroxide, we also measured oxidative phosphorylation, cytochrome c oxidase (CCO) activity, and lipid peroxide levels in mitochondria in both ischemic and non-ischemic lobes of the liver in control and α-tocopherol groups before and at the end of ischemia and after reperfusion. Both plasma glucose and insulin levels after reperfusion were lower in the α-tocopherol-treated group than in the control group. Ischemia markedly suppressed both mitochondrial respiration supported by succinate and CCO activity in the ischemic lobes in both groups. Reperfusion recovered mitochondrial function and CCO activity better in the α-tocopherol-treated group than in the control group, whereas the lipid peroxide levels in both plasma and mitochondria were significantly lower in the α-tocopherol-treated group. In non-ischemic lobes, ischemia-reperfusion slightly accelerated both the oxidative phosphorylation rate (OPR) and CCO activity, whereas lipid peroxide levels were unaffected. The results suggest that glucose intolerance during the early phase of reperfusion was not due to lowered plasma insulin level, but might be related to liver damage, as assessed in terms of mitochondrial functions, in the ischemic lobes. α-Tocopherol could protect against mitochondrial damage and glucose intolerance. Oxidative phosphorylation in non-ischemic lobes likely compensated for the decreased mitochondrial activity in the ischemic lobes during ischemia and reperfusion.

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co-infection with the human T-lymphotropic virus type I (HTLV-I) might be associated with this transition in a cross-sectional analysis of 127 patients with HCV-chronic hepatitis (mean age = 51.7) and 43 patients with HCV-associated HCC (mean age = 62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) (P = 0.001). The relative risk (RR) of association was 12.8 (P = 0.0004) among the males, however, no association was evident among the females, RR = 1.3 (P = 0.80). The increased prevalence of HTLV-I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co-infection with HTLV-I may contribute to the development of HCC among patients with HCV-induced chronic liver diseases in a highly HTLV-I-endemic area.

AIM: To analyze the efficacy and safety of a combination therapy of pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) in older Japanese patients (65 years or older) infected with hepatitis C virus (HCV). METHODS: This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk. RESULTS: At 24 wk after the end of combination therapy, the overall sustained virological response (SVR) for genotypes 1 and 2 were 40.7% and 79.6%, respectively. The SVR rate decreased significantly with age in each genotype, and was markedly reduced in genotype 1 (P < 0.001). Moreover, the SVR was significantly higher in patients with genotype 1 who were less than 65 years (47.3% of 685) than in those 65 years or older (22.9% of 253) (P < 0.001) and was higher in patients with genotype 2 who were less than 65 years (82.9% of 252) than in those 65 years or older (65.6% of 61) (P = 0.004). When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV, the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older (P < 0.001). Adverse effects resulted in treatment discontinuation more often in patients with genotype 1 (14.4%) than in patients with genotype 2 (7.3%), especially by patients 65 years or older (24.1%). CONCLUSION: PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.

Preparation de polystyrenes reticules contenant des groupes chiraux aminoalcool primaires par fixation du groupe chiral lateral sur un polystyrene reactif ou par terpolymerisation d'un monomere chiral avec le styrene et un reticulant. Utilisation comme catalyseurs de l'alkylation enantioselective d'aldehydes par des dialkylzinc. Adaptation de la methode a un systeme de reaction en continu

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

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.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.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.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.

症例は53歳,男性.全身倦怠感と露出部の皮膚症状を主訴として来院した.検査所見では軽度の肝機能障害ならびに尿中ポルフィリン体の排泄増加がみられた.腹腔鏡検査では肝表面に灰青色斑がみられ,生検肝は紫外線の照射によって赤色蛍光を発した.肝組織像では軽度のリンパ球浸潤,ヘモジデリンの沈着および多数の細胞質内針状結晶を認めた.症候性晩発性皮膚ポルフィリン症と診断し,昭和56年12月より4～8週おきに1回250～300ml,総量3,000mlの瀉血療法を行った.治療にほぼ平行して自覚症状の軽減,尿中ポルフィリン体排泄量の正常化がみられたが,肝機能検査成績はほとんど不変であった.治療終了6カ月後に行われた腹腔鏡検査では,肝の灰青色斑は消失し,生検肝の赤色蛍光もみられなくなったが,肝組織の炎症像および針状結晶については不変であった.本例において瀉血療法は体内の過剰な蓄積ポルフィリン体の減少と,皮膚所見および自覚症状の軽減という点では著効を示したといえよう.

生前異所性ACTH, β-MSH産生悪性胸腺腫と診断し,試験切除による一部腫瘍切片の光顕および電顕的検索から悪性胸腺carcinoidと診断された興味ある症例を経験したので,剖検所見と共に症例の概要を紹介し,文献的考察を加えた.症例は68才,男子で胸部X線異常陰影の精査と下腿浮腫を訴え入院.典型的Gushing症候群やcarcinoid症候群を示唆する所見はない.胸部X線縁で左側上前縦隔に直1Ocmの巨大な腫瘤陰影を認め,選択的胸腺静脈撮影により悪性胸腺腫が示唆された.尿中17-OHCS, 17-KS共に著増し,血中cortisol, ACTH, β-MSH (9am)も共に高値で日内変動を認めず, dexamethasone lmg, 4mg法の抑制試験は共に陽性, rapid ACTH試験で過大反応を示す.入院40日後突然,低K血性アルカローシス,尿糖,高血糖,高血圧などが出現し,異所性ACTH, β-MSH産生悪性胸腺腫の診断のもとに開胸手術を行なうも高度の癒着のため試験切除の施行にとどめた.術後9日目に肺水腫を来たし死亡した.病理組織学的に原発腫瘍は神経細胞由来の腫瘍に酷似し,索状配列,中心壊死,石灰沈着,ロゼット形成を示し, argyrophil顆粒陽性,電顕的にも豊富な分泌穎粒が確認され,胸腺carcinoidと診断された.また本腫瘍中よりACTH, β-MSHおよびserotoninが証明され,剖検で副腎の結節性過形成および下垂体β細胞のCrooke変性とACTH含量の著減が証明された.異所性ACTH産生腫瘍とPearseのAPUD系細胞由来carcinoidとの関連,および異所性ACTH産生胸腺腫瘍の本邦報告例をまとめ考察を加えた.

When THF–borane (1/1) and aromatic ketone were supplied continuously to the column containing polymer-supported (S)-(−)-2-amino-3-(p-hydroxyphenyl)-1,1-diphenyl-1-propanol, the chiral product, secondary benzylic alcohol, could be obtained successfully (>90% ee). Large quantities of highly optically pure alcohol could be produced by the continuous flow system by the use of only a small amount of polymeric auxiliary.

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 (Δ-albumin) and various pretreatment variables. We also analyzed the correlation between Δ-albumin and the reduction in serum levels of HBV-DNA (Δ-HBV-DNA) or alanine aminotransferase (Δ-ALT) at month 12. Results The average Δ-albumin was 0.38 g/dL and only serum HBV-DNA levels before treatment correlated significantly with Δ-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 Δ-albumin and either pretreatment alanine aminotransferase levels or Δ-ALT. In contrast, in patients whose serum HBV-DNA was undetectable at month 12, we found a significant correlation between Δ-albumin and both pretreatment serum HBV-DNA levels and Δ-HBV-DNA. Conclusion Our results demonstrated that albumin levels are associated with pretreatment HBV-DNA but not with alanine aminotransferase levels.