妊娠を契機に血小板減少を来たし，子宮内胎児死亡に至った全身性エリテマトーデス及び抗リン脂質抗体症候群の一例

　抗リン脂質抗体症候群は，抗リン脂質抗体が産生されることで血栓症を主体とする病態を引き起こす自己免疫疾患である．動静脈血栓症に加え，習慣性流産，早産，妊娠高血圧症候群，胎児発育遅延，胎児機能不全などの妊娠合併症を高率に引き起こすとされている．また患者のうち約半数は全身性エリテマトーデスが併存していると言われている．我々は妊娠を契機に血小板減少を来たし，子宮内胎児死亡に至った全身性エリテマトーデス及び抗リン脂質抗体症候群の症例を経験した．　患者は20歳代女性，未経妊未経産．５年前に全身性エリテマトーデス及び抗リン脂質抗体症候群と診断された．プレドニゾロンとタクロリムス，アザチオプリンによる免疫抑制療法及び低用量アスピリン療法を開始され，数年間に渡りプレドニゾロン５mg/ 日＋タクロリムス３mg/ 日＋アザチオプリン50mg/ 日で病態は安定していた．妊娠を契機にプレドニゾロン10mg/ 日の単独治療に切り替えたが，徐々に血小板減少が進行してきたため入院し，プレドニゾロン30mg/ 日への増量及びタクロリムス３mg/ 日を再開した．また血栓予防治療として，低用量アスピリンに加えヘパリン療法を開始した．しかし妊娠16週５日で子宮内胎児死亡が判明したため，血栓予防治療を中止し児の娩出に至った．　抗リン脂質抗体症候群合併妊娠は，周産期管理に慎重を要する例も存在することを念頭に置き，特にハイリスク症例に対しては妊娠成立前から産婦人科と連携して治療にあたる必要がある．　Antiphospholipid syndrome is an autoimmune disease characterized by episodes of recurrent thrombosis. This syndrome is associated with not only recurrent arteriovenous thrombosis but also recurrent pregnancy loss, premature birth, pregnancyinduced hypertension, and fetal growth restriction. It has been reported that systemic lupus erythematosus coexists with antiphospholipid syndrome in as many as about 50% of patients. We report a case of intrauterine fetal death (IUFD) following thrombocytopenia in a patient with systemic lupus erythematosus and antiphospholipid syndrome. A woman in her 20s had difficulty conceiving and had been diagnosed as having systemic lupus erythematosus and antiphospholipid syndrome 5 years earlier. She was started on immunosuppressive therapy with prednisolone 5 mg/day, tacrolimus 3 mg/day, and azathioprine 50 mg/day, with low-dose aspirin therapy. Her disease was stable for several years. Thrombopenia gradually developed after treatment was changed to prednisolone 10 mg/day during pregnancy. She was admitted to hospital and treatment was started with prednisolone 30 mg/day, tacrolimus 3 mg/day, and heparin therapy in addition to low-dose aspirin therapy. However, IUFD was detected at a gestational age of 16 weeks 5 days, so we discontinued thromboprophylaxis treatment and administered a therapeutic abortion. In patients with antiphospholipid syndrome who need meticulous perinatal management, it is important to consult with the obstetrics and gynecology specialists before proceeding with a potentially high-risk pregnancy

ステロイド抵抗性のループス関連蛋白漏出性胃腸症にシクロホスファミドパルス療法が有効であった１例

全身性エリテマトーデスは，全身の多臓器に炎症を起こし多彩な症状を引き起こす全身性自己免疫疾患である．消化器病変としては，ループス腸炎や腸間膜血管炎が多く，蛋白漏出性胃腸症を呈するのは稀である．我々はシクロホスファミドパルス療法が著効したループス関連蛋白漏出胃腸症の症例を経験した．　患者は20歳代女性．全身の浮腫と喉頭浮腫による呼吸困難感で当院に搬送され，血液検査で低アルブミン血症，抗核抗体陽性，抗SS-A 抗体陽性，低補体血症を認めた．99mTc 標識ヒト血清アルブミンによる消化管シンチグラフィにて，胃から小腸の広範囲で蛋白漏出が認められた．ループス関連蛋白漏出性胃腸症と診断し，ステロイドパルス療法を含め２週間以上のステロイド大量療法を行うも症状の改善を認めなかった．ステロイド治療に併用してシクロホスファミド700 mg の点滴を施行したところ，翌日より大量の尿排泄（5,000 ml/ 日以上）を認め，速やかに全身状態は改善した．ループス関連蛋白漏出性胃腸症は，ステロイドが奏効しない例も存在することを念頭に置き，免疫抑制薬を早期から併用することも重要である．Systemic lupus erythematosus is an autoimmune disease that can cause wide-spread inflammation affecting multiple organs. Most gastrointestinal involvement in systemic lupus erythematosus is lupus enteritis and lupus mesenteric vasculitis; proteinlosing gastroenteropathy is rare. We report a patient with protein-losing gastroenteropathy in association with steroid-resistant systemic lupus erythematosus who was successfully treated with cyclophosphamide pulse therapy. A woman in her 20s was referred to our hospital because of systemic edema and dyspnea from laryngeal edema. Laboratory tests showed hypoalbuminemia, positive ANA and anti-SSA tests, and low serum levels of complement. 99mTc-human serum albumin scintigraphy showed a localized area of protein loss in the gastrointestinal tract. A diagnosis of protein-losing gastroenteropathy in association with systemic lupus erythematosus was made. She was started on high-dose corticosteroid therapy including methylprednisolone pulse therapy for over 2 weeks, but therapy was not effective. We then started intravenous administration of cyclophosphamide (700 mg) with prednisolone and the patient’s general status improved as evidenced by increased urine output. In patients with protein-losing gastroenteropathy associated with systemic lupus erythematosus who are not responsive to high-dose corticosteroid therapy, it is important to use an immunosuppressive agent in combination with prednisolone at an early stage

Change in Fibrosis 4 Index as Predictor of High Risk of Incident Hepatocellular Carcinoma After Eradication of Hepatitis C Virus.

BackgroundIt is unclear whether the fibrosis 4 index (FIB-4), a marker of liver fibrosis, at baseline and change in FIB-4 after sustained virological response (SVR) is associated with incident hepatocellular carcinoma (HCC) risk. In this study, we examined the association of incident HCC risk with baseline FIB-4 and sustained high FIB-4 (>3.25) at any time point after SVR.MethodsA total of 3823 patients who received direct-acting antiviral treatment and achieved SVR were enrolled. The FIB-4 was measured 24 weeks after the end of direct-acting antiviral treatment and achievement of SVR (SVR24), and 1, 2, and 3 years after SVR24, after which subsequent HCC development was investigated.ResultsIn patients with an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years after SVR24, subsequent HCC development was significantly higher than in those with an FIB-4 ≤3.25 at each point. The rates of HCC development 1, 2, 3, and 4 years after SVR24 were significantly higher in patients with sustained FIB-4 >3.25 than in those whose FIB-4 decreased to ≤3.25 (5.4%, 9.2%, 11.7%, and 16.0%, respectively, vs 2.2%, 3.1%, 3.7%, and 4.4%; P < .001). The adjusted hazard ratios (95% confidence intervals) for an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years later were 3.38 (2.4-4.8), 2.95 (1.9-4.7), 2.62 (1.3-5.1), and 3.37 (1.4-9.8), respectively.ConclusionsThe FIB-4 could be used to assess HCC development risk at any time after SVR, and changes in FIB-4 were associated with changes in the HCC development risk. Repeated assessments of FIB-4 could serve as a prognostic indicator of a high-risk HCC cohort that may require more intensive HCC surveillance strategy

Hepatocellular Carcinoma Risk Assessment for Patients With Advanced Fibrosis After Eradication of Hepatitis C Virus.

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase < 28 IU/L, alpha-fetoprotein < 4.0 ng/mL, and Fibrosis-4 Index < 4.28) were classified as low-risk and others were classified as high-risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low-risk patients (0.5-1.1 per 100 person-years in the derivation cohort and 0.9-1.1 per 100 person-years in the validation cohort) than in high-risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high-risk to low-risk (HCC incidence: 0.6 per 100 person-years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person-years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance