Search

Lamivudine (100mg/日) が投与されたB型慢性肝炎患者34例の治療終了後の長期経過を検討した. 投与期間は16～52週間, 治療後の平均観察期間は151週 (42～172週) であった. 34例中8例 (24%) は最終観察時点でALT値が正常であった. 8例中の3例は投与前のHBV DNA量が低値であったが, この3例はいずれもALT値が投与中に正常化し, 投与終了後も正常値を維持した. 他の5例は, 投与終了後にALT値が一過性に上昇した後に正常化した. 他の26例はいずれもALT値の異常変動が持続しており, Lamivudine によって肝機能の正常, 安定化を得るには長期投与が必要と考えられた. また Lamivudine 投与終了の必要条件は治療前のHBV DNA量が低値であること, 治療中のHBe抗体の出現及びHBV DNAの持続陰性化を得ることなどが考えられたが投与中止の条件については, 今後さらに症例数を増やし検討する必要があると考えられた.

A 68-year-old woman developed acute pulmonary embolism after hepatic arterial infusion therapy for advanced hepatocellular carcinoma. Because the platelet count was significantly reduced, heparin-induced thrombocytopenia (HIT) due to heparin usage in hepatic arterial infusion therapy was clinically suspected. Subsequently, the patient tested positively for HIT antibodies, and a definitive diagnosis was obtained. Antithrombotic therapy with heparin was discontinued and treatment with argatroban was started. After the heparinized hydrophilic catheter was removed, the platelet count improved immediately. HIT should be considered when a decrease in platelet count and thrombosis are involved with the usage of heparin.

B型および非A非B型慢性肝炎患者129例でインターフェロン(IFN)投与中の蛋白尿の出現について検討を行った.蛋白尿は26例(20.2%)に認められた.1日尿蛋白量はほとんどの症例で3g以下であったが,1例のみはネフローゼ症候群を呈した.しかしながら,尿沈査異常や腎機能低下をきたした症例は1例もなく,尿蛋白は投与終了後速やかに消失した.IFNの種類ではαよりβで蛋白尿の出現率が有意に高く,また,一回投与量においても総投与量においても,高用量群で出現率が高い傾向が認められた.血清アルブミン値は,蛋白尿出現の有無にかかわらずIFN投与により低下したが,特に蛋白尿出現群で著しく,尿中への蛋白の喪失が血清アルブミン低下の一因であることが推測された.尿蛋白はアルブミンが主体で,可逆性であり,かつ尿沈査異常および腎機能障害を伴わないことなどから,腎糸球体基底膜のcharge barrierの消失による蛋白尿出現の可能性が示唆された.

インターフェロン(IFN)治療中に精神症状を呈したC型慢性活動性肝炎の2例を報告した.症例1は44歳,男性.トランスアミナーゼの異常,HCV抗体陽性を認めたためHLBIを投与した.開始当初,発熱,食欲不振が出現,遅れて13日目より不眠,抑鬱症状が出現し,さらに自殺企図,被害妄想も認めた.それ故,投与を中止し,抗精神薬で徐々に改善した.症例2は34歳,女性.トランスアミナーゼの異常,HCV-RNA陽性を認めたため,IFN-α投与を関始した.当初,発熱,悪寒,倦怠感,食思不振が出現し,4日目から不眠,焦燥感も出現した.精神安定剤を併用したところ,症状は改善し,IFN投与を終了しえた.IFNは,慢性肝炎に対する通常量でも,稀ながら精神症状を呈する例もあるため,IFN治療中は充分な注意が必要である.

The patients was a 54-year-old woman. In the liver, a high-echo phyma was detected. The lesion increased from 5 to 23mm over 2 years and 4 months. On CT and MRI, it was difficult to differentiate the phyma from hepatocellular carcinoma. However, angiography revealed early outflow to the hepatic vein. In the late CTHA phase of angio-CT, there was no ring-like dark staining reaction (corona), as observed in hepatocellular carcinoma patients, outside the tumor. Hepatectomy was performed, suggesting angiomyolipoma. The course of enlargement could be followed-up, and we present findings that may be useful for differentiating this tumor from hepatocellular carcinoma.

Possible short-term interferon therapy was investigated in chronic hepatitis C patients with genotype 2a or 2b and low viral-loads. Furthermore, initial changes of hepatic C virus RNA levels in early phase interferon therapy, and the number of pretreatment mutated clones at hypervariable region-1 were determined in order to upgrade interferon therapy efficacy prediction rates.Study subjects were 31 patients with histologically proven chronic hepatitis C, having less than 1 Meq/mL of hepatic C virus RNA levels. Daily dose was defined as 9 MU of interferon; patients with genotype lb were treated for 26 weeks, while those with genotype 2a or 2b were treated for 16 weeks.Sustained response rates showed no difference in efficacy between the 2 groups (66.7% vs. 62.5%). Response rates based on the number of hypervariable region-1 clones indicated that the fewer the number of mutated clones, more significant was the increase in efficacy. Efficacy as hepatic C virus RNA in early phase treatment showed no difference in response rates between negative and positive groups at any time point from day 1.In a low viral-load group, the number of hypervariable region-1 clones was a critical factor influencing interferon therapy efficacy. Thus, 16-week interferon therapy was effective and economical.

Twenty-four weeks administration of interferon-alpha has been performed to 23 patients of chronic hepatitis B. As the result, complete or partial responders reached to 47.8%, so that it was considered to be effective therapy for chronic hepatitis B. By the investigation of behaviors of HBV-DNA, the reduction of HBV-DNA below 4 x 10(2) copy/ml during the administration of interferon was considered to be one essential factor for inducing the effectiveness of interferon. Though lamivudine, which has a strong anti-viral effect, has been permitted, interferon is still considered as the good indication for relative young patients who do not have advanced hepatic fibrosis. As a newly strategy for the patients with high titer of HBV-DNA or breakthrough hepatitis, the combination therapy of interferon and lamivudine will be expected.

Titrations of anti-hepatitis C core (anti-HCc) immunoglobulin G (IgG) antibodies and its subclasses were studied in 90 patients with acute and chronic hepatitis C virus (HCV) infection, including 27 patients who underwent interferon (IFN) therapy. The positivity rates for each anti-HCc subclass were as follows: 95.2% for IgG1, 12.0% for IgG2, 69.9% for IgG3 and 19.3% for IgG4. The total anti-HCc IgG titre correlated well with the IgG1, titre, indicating that IgG1 was the main virus-specific IgG. Changes of IgG1 production mainly contributed to fluctuations of the anti-HCc IgG titre and corresponded well to positivity for HCV-RNA during and after IFN therapy. IgG3 was detected prior to IgG1 during the early phase of acute hepatitis in some cases and also appeared with relapse after IFN therapy. The serial assay of anti-HCc subclasses showed the patients' humoral immune response to HCV infection, and might be useful for evaluation of anti-viral immunity influenced by IFN therapy.

Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P

The clinical utility of a new JCC-2 enzyme-linked immunosorbent assay kit that detects and quantitates anti-hepatitis C virus (anti-HCV) core antibodies (anti-HCc) was investigated. Serum samples were obtained from 102 patients with various non-A, non-B liver diseases, including 19 cases of chronic hepatitis type C who had been treated with interferon (IFN). The results of the anti-JCC-2 assay were significantly correlated with serum HCV-RNA positivity. Patients who were HCV-RNA positive exhibited a high rate of positivity for anti-JCC-2 (72.2% in acute hepatitis, > 90% in chronic liver diseases). The geometric mean of the anti-JCC-2 titre was not significantly different among different stages of chronic liver disease (among CPH, CAH and LC). The anti-JCC-2 titre decreased gradually in cases that became HCV-RNA negative after IFN therapy. If HCV-RNA positivity recurred, the anti-JCC-2 titre increased, indicating that serial measurements of the anti-JCC-2 titre are useful for monitoring the antiviral effect of IFN treatment. These results suggest that quantification of anti-HCc by the anti-JCC-2 assay is superior to the semi-quantification of circulating HCV-RNA provided by monitoring of IFN therapy. Monitoring of HCV-RNA status using reverse transcription-nested polymerase chain reaction (RT-nested PCR) is possible, but it is technically demanding and too expensive for routine clinical use.

To clarify the involvement of atrial natriuretic peptide (ANP) in the pathogenesis of liver cirrhosis, we measured plasma ANP in patients with various stages of cirrhosis and in age-matched normal subjects. Urinary cyclic guanosine monophosphate (cGMP) was also measured as a marker of active biological ANP. In addition, effects of exogenous synthetic human ANP (0.5 micrograms/kg) on renal functions were examined in normal subjects and in cirrhotics without ascites or with mild ascites. Plasma ANP levels were not significantly different among these 3 groups. Urinary cGMP concentrations were significantly higher in both cirrhotics without ascites and cirrhotics with mild ascites, (340 pmol/ml, P less than 0.05 and 496 pmol/ml, P less than 0.01 respectively) than normal subjects (95 pmol/ml). In normal subjects, marked increases in urinary volume (UV), sodium excretion (UNaV), fraction excretion of sodium (FENa) and free water clearance (CH2O) were induced after ANP infusion, and significant recoveries were subsequently observed in these parameters. However, in cirrhotics, the responses to ANP infusion of UV, FENa and CH2O were far less dramatic. The response of UV, UNaV and FENa in cirrhotics with mild ascites was delayed compared to cirrhotics without ascites. These results suggest that the blunted natriuretic responsiveness to ANP is contributory to the pathogenesis of initial sodium retention in cirrhotics.