Artificial Liver Support Therapy Research Articles

Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute liver failure: A single center experience from China.

To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF). In this retrospective study, we enrolled patients with ALF (serum total bilirubin >10 mg/dL or Model for End-Stage Liver Disease [MELD] Score >18) hospitalized between August 2017 and August 2022. All patients had at least two sessions of FPSA-CVVH. The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH. Seventy-eight patients with ALF were enrolled. The MELD score at baseline was 22.9 ± 7.5. The mean total bilirubin was 22.05 ± 5.94 mg/dL, direct bilirubin was 16.33 ± 4.60 mg/dL and indirect bilirubin was 3.43 ± 1.60 mg/dL. One hundred and eighty seven sessions of FPSA-CVVH treatment lasting 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs were 52.0% ± 7.6% for total bilirubin, 59.4% ± 13.0% for direct bilirubin and 36.9% ± 15.4% for indirect bilirubin. Twenty nine patients (37.2%) survived and were discharged from the hospital, 12 of them recovered their liver function while the remaining 17 patients needed intermittent artificial liver support therapy. FPSA-CVVH therapy is an effective artificial liver support therapy in patients with ALF. It may be considered as a "bridge technique" to the recovery of liver function in critical ill patients with ALF.

Single-center experience in 127 adult patients, mono or dual artificial liver support therapy, in patients with acute liver failure.

Acute liver failure (ALF) is a serious condition characterized by sudden liver dysfunction, jaundice and hepatic encephalopathy. Its mortality rate of approximately 80% underscores the urgent need for effective treatments. Supportive extracorporeal therapies (SET), which temporarily support liver function and remove toxins, have shown promise in improving outcomes in acute liver failure (ALF). The aim of this study was to compare the outcomes of dual supportive extracorporeal therapy (SET) and mono supportive extracorporeal therapy in patients with acute liver failure. A total of 127 patients with acute liver failure were included in this retrospective, single-center study. Of these, 62 patients received dual supportive extracorporeal therapy and 65 patients received mono supportive extracorporeal therapy. Primary endpoints were survival without the need for liver transplantation and mortality. Secondary endpoints included resolution of encephalopathy and normalization of International Normalized Ratio (INR). In the dual supportive extracorporeal therapy group, 59.6% of patients survived without the need for liver transplantation, while 27.4% achieved recovery with liver transplantation. The mortality rate in this group was 12.9%. Significant regression of encephalopathy grade was observed in 87% of patients, and the 1 year mortality rate for liver transplant recipients was 10.7%. In the mono supportive extracorporeal therapy group, 61.5% of patients experienced a successful recovery without the need for liver transplantation, with a mortality rate of 29.2%. Significant improvement in the grade of encephalopathy was observed in 70.7% of patients. Both dual supportive extracorporeal therapy (CVVHDF and PE) and mono supportive extracorporeal therapy (PE) were associated with significant improvements in renal and hepatic biochemical parameters, blood ammonia levels, and neurological status in patients with acute liver failure associated with grade III-IV hepatic encephalopathy. In particular, dual support was associated with improved hemodynamic stability, lactic acidosis and acid-base balance. Survival in acute liver failure in our retrospective cohort using a protocolized approach to extracorporeal therapies is higher compared to previously published large ALF studies. This protocolized approach warrants further prospective studies.

#4074 FRACTIONATED PLASMA SEPARATION AND ADSORPTION INTEGRATED WITH CONTINUOUS VENO-VENOUS HEMOFILTRATION IN PATIENTS WITH ACUTE LIVER FAILURE

Abstract Background and Aims To observe the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF). Method In this retrospective study, we enrolled patients with ALF (serum total bilirubin>10mg/dl or Model for End-Stage Liver Disease (MELD) Score>18) hospitalized from 2017 to 2022.All patients received the treatment of FPSA-CVVH.The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH. Results 8 patients (68 males and 10 females) with ALF were enrolled. 66 patients (84.6%) exhibited acute kidney injury and required renal replacement therapy (RRT). The score of MELD at baseline was 22.9±7.5. The concentration of serum total bilirubin was 22.05±5.94mg/dL, direct bilirubin was 16.33±4.60mg/dL and indirect bilirubin was 3.43±1.60mg/dL.187 sessions of FPSA-CVVH treatment with 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs was 52.0±7.6% for total bilirubin, 59.4±13.0% for direct bilirubin and 36.9±15.4% for indirect bilirubin. 2 patients changed the filters due to blood coagulation. And other 2 patients exhibited bleeding, including gastrointestinal bleeding and Oozing bleeding. 29 patients (37.2%) survived in discharging from hospital, 12 patients recovered with their liver function, and the remaining 17 patients still needed intermittent artificial liver support therapy. Conclusion FPSA-CVVH therapy was a novol and effective artificial liver support therapy in patients with ALF. It may be considered as a “bridge technique” to the recovery of liver function in critical ill patients with ALF.

レジオネラ肺炎を契機に発症したAcute–on–chronic liver failureの救命例(A case of acute–on–chronic liver failure caused by Legionella pneumonia)

レジオネラ肺炎は，多臓器不全を合併し致死的な経過をたどることがある。今回，ACLFに伴う肝性脳症を合併するも，人工肝補助療法を導入し，救命し得た症例を経験したので報告する。症例は50歳の男性で，高度意識障害と多臓器不全のため近隣病院から転院搬送された。搬入時より意識レベルはJCS III–300であり，血液検査でアンモニアが高値であった。肝性脳症と診断し，直ちにon–line HDFによる人工肝補助療法を開始した。第2病日に尿中レジオネラ抗原が陽性となったことから，レジオネラ肺炎と診断し，それに伴って多臓器不全を発症した状態であると判断した。抗生剤については，メロペネム，レボフロキサシン，アジスロマイシンを投与した。凝固障害に対しては，適宜輸血を実施した。合計3回のon–line HDFとCHDFを交互に実施し，緩徐に意識レベルの改善が得られ，第5病日には意識清明となった。第8病日にICUを退出し，第20病日に転院した。ACLFは，最近定義された新しい疾患概念であり，代償性あるいは非代償性肝硬変に増悪因子が加わって，高度の肝機能異常を呈する病態である。治療については症候に対する対症療法が中心であり，本症例では人工肝補助療法を導入したことで覚醒が得られ，救命に寄与したと考えられた。 Legionella pneumonia may be complicated by multiple organ failure and may result in death. We herein report a case of hepatic encephalopathy associated with acute–on–chronic liver failure, which was successfully rescued by artificial liver support therapy. A 50–year–old man was transferred from a nearby hospital due to severe disturbance of consciousness and multiple organ failure. His level of consciousness was Japan coma scale III–300, and a blood test revealed a high level of ammonia. Hepatic encephalopathy was diagnosed as the cause of consciousness disturbance, and artificial liver support therapy with on–line hemodiafiltration was started immediately. On Day 2, Legionella pneumonia was diagnosed because urinary Legionella antigen was positive. For antibiotics, meropenem, levofloxacin, and azithromycin were administered. Blood transfusion was performed as needed for coagulopathy. The patient’s level of consciousness gradually improved, and he became lucid on Day 5. He was discharged from the intensive care unit on Day 8 and transferred to another hospital on Day 20. We believe that the rapid introduction of artificial liver support therapy enabled the patient to regain consciousness. レジオネラ肺炎は，多臓器不全を合併することで，致死的な経過をたどることがある。アルコール多飲歴が感染のリスクであるため，大酒家であればその発症に注意を払う必要がある。一方，大酒家は肝硬変に罹患していることが多く，acute–on–chronic liver failure（ACLF）を発症することで，慢性肝不全が急激に進行する可能性がある。今回，レジオネラ肺炎の感染を契機にACLFを発症し肝性脳症に陥るも，on–line hemodiafiltration（HDF）による人工肝補助療法を導入することで，覚醒が得られた症例を経験したので報告する。 本論文に倫理委員会の承諾は必要がない。また本論文は個人情報保護法に基づいて匿名化がなされ，患者またはその家族より論文の出版に関する同意を得ている。 患 者：50歳の男性 主 訴：なし（高度意識障害） 既往歴：急性腹膜炎で手術歴あり，C型肝炎ウイルス（hepatitis C virus: HCV）感染後 sustained virological response，アルコール依存症（精神科病院に入院歴あるも通院は自己中断） 内服歴：常用薬なし。健康食品，サプリメントや漢方薬の使用なし 家族歴：肝疾患の家族歴なし 生活歴：温泉や循環式風呂の入浴なし。加湿器の使用なし。飲酒はアルコール度数9%の缶チューハイ2,500mL/day。喫煙は20本/dayを30年間。アレルギー歴なし。生肉の摂取なし。職業は土木建築業。両肩から両前腕にかけて刺青あり 現病歴：搬送数日前から車上生活を送っていた。搬送当日，河川敷に本人の車両が放置されており，警察官が周囲を捜索したところ，車両から約400m離れた土手で倒れている本人を発見し救急要請された。全身に明らかな外傷は認めず，車内には飲酒後と思われる空き缶が散在していた。過量服薬や違法薬物の使用の痕跡はなかった。直近二次病院に搬送されたが，Japan Coma Scale（JCS）III–300の高度意識障害と黄疸があり，採血では肝機能障害，腎機能障害，凝固障害，電解質異常を認めた。体幹部の単純computed tomography（CT）では両側スリガラス陰影と脂肪肝を疑わせる肝臓の斑状低吸収域を認めたが，明らかな胸腹水は認めなかった。前医では対応困難であり，多臓器不全に対する集中治療目的に当院の救命救急センターに緊急転院搬送となった。 入院時現症：身長168cm，体重70.7kg，body mass index 25.0kg/m2，意識レベル Glasgow Coma Scale（GCS）E1V1M1，体温36.9度，血圧135/81mmHg，脈拍110/min・整，呼吸数30/min，SpO2 98%（酸素マスク5L/min）であった。瞳孔は左右同大5mmで対光反射は両側迅速，眼球結膜に黄染を認めた。胸部聴診では，心音は整で雑音はなく，両側胸部でcoarse cracklesを聴取した。腹部は膨満，軟で腹部正中に手術痕あり，右季肋部に肝臓を三横指触知し，波動は認めず，クモ状血管腫や女性化乳房も認めなかった。両側下腿に軽度の圧痕性浮腫を認めた。 入院時検査所見：当院で再検した血液検査（Table 1）では，貧血，凝固障害，肝機能障害，腎機能障害，電解質異常と多臓器不全を呈していた。新型コロナウイルス感染症の迅速抗原検査およびpolymerase chain reaction（PCR）検査は陰性であった。HCV ribonucleic acid（RNA）は陰性であった。また，尿中薬物検査キットもすべて陰性であった。頭部CTでは意識障害を来しうる脳出血や腫瘤性病変は認めなかった。体幹部単純CT（Fig. 1）では，両側上葉優位に浸潤影や網状影を認め，下葉に淡い濃度上昇を伴う陰影を認めたが，明らかな胸水貯留は指摘できなかった。肝形態は保たれており，肝臓周囲には腹水は認めず，胆嚢の浮腫性変化も認めなかった。入院時の血液検査結果では，FIB–4スコアは20.9点で，C型肝硬変の判別式は20点であった。 CT scans of the patient. A: Day 1, B: Day 7, C: Day 15 The abnormal chest opacity gradually improved. B showed ascites accumulation (white arrow), but C showed improvement. 入院後経過（Fig. 2）：病歴や所見からは元々アルコール性慢性肝硬変が背景にあり，何らかの要因で急性増悪し，ACLFおよび肝性脳症を来したものと考えた。肝性脳症については，犬山分類 grade Vであり，右内頸静脈からバスキュラーアクセスを確保し，直ちにon–line HDF（透析膜：FIX250E；ニプロ，血流量200mL/min，透析液流量500mL/min，補充液流量5,000mL/hour）を開始した。On–line HDFに伴い，血清カリウムとリンの低下が懸念され，適宜補正を行った。貧血と凝固障害に対しては，輸血を行い，ビタミンK製剤の投与を行った。消化管出血の懸念があったため，経鼻胃管は挿入せずに，経肛門的にラクツロースの注腸を開始した。分岐鎖アミノ酸製剤の投与については，窒素負荷につながり，肝性脳症を助長する可能性があると判断したため実施しなかった。On–line HDF終了後は，continuous hemodiafiltration（透析膜：セプザイリス；バクスター，血流量100mL/min，補充液流量400mL/min，排液量800mL/min，透析液流量400mL/min，以下CHDF）での血液浄化を開始した。敗血症の可能性は否定できず，各種培養を採取した後に，メロペネム（meropenem: MEPM）の投与を開始した。呼吸不全については，マスクでの酸素投与のみで酸素化が維持可能であり，努力呼吸も認めなかったことから，気管挿管や人工呼吸器管理は見送った。肺炎像の鑑別目的に，第2病日に実施した尿中レジオネラ抗原（リボテスト；旭化成ファーマ）が陽性となったため，レジオネラ肺炎と確定診断し，病態としてレジオネラ肺炎が契機となりACLFを発症したものと考えた。また，レボフロキサシン（levofloxacin: LVFX）の静注を開始した。培養検査については，当院ではbuffered charcoal yeast extract（BCYE）培地を常備しておらず，ヒメネス染色も外部発注の検査となること，尿中抗原陽性であれば，感染症法の四類感染症の定義を満たすことから実施しなかった。喀痰loop–mediated isothermal amplification（LAMP）法については外注であったが提出し，結果，良好な喀痰が得られなかったことと，LVFXを投与後に検体を採取した影響のためか陰性であった。一方で，第2病日のアンモニアが280μg/dLと増悪していたため，分岐鎖アミノ酸製剤は引き続き投与せず，2回目のon–line HDFを導入した。On–line HDF後の採血では，アンモニアが130μg/dLと改善しており，意識レベルも改善を認めた。第3病日に，重症のレジオネラ肺炎と判断し，LVFXに加えて，アジスロマイシン（azithromycin: AZM）の静注を開始し，AZMについては合計5日間投与した。同日の採血では，アンモニアは改善傾向であったが，依然として意識障害が残存していたため，3回目のon–line HDFを実施した。その後は乏尿が続いていたため，腎代替療法としてCHDFによる除水を継続した。3回目のon–line HDF施行後より，徐々に意識レベルは改善し，第4病日には軽度の見当識障害を認めるのみとなった。黄疸については，皮膚掻痒感の訴えに対し軟膏塗布での対症療法，経過観察とした。第6病日より食事（蛋白20g制限食）とリファキシミンの内服を開始した。第7病日に体幹部CTを再検査したところ，肺炎像については改善傾向を認め，新たに腹水が貯留していた。同日，自尿が増加傾向であったため，CHDFから離脱した。全身状態として経過が順調であったことから，第8病日にICUを退室した。また，入院時に採取した培養検査がすべて陰性であったことを確認し，MEPMの投与は終了した。第12病日にLVFXは内服へ移行し，静注と内服で合計21日間の抗生剤治療を予定した。一般床に転棟後は，羽ばたき振戦や異常行動を認めることなく経過した。第15病日に体幹部CTを再検し，肺炎像と腹水が消退傾向であることを確認した。第20病日に肝不全や黄疸に対する治療継続目的，およびリハビリテーション継続目的に，独歩で近隣病院に転院した。 Clinical course of the patient. i.v: intravenous drip, p.o: per os 今回，ACLFを合併し，肝性脳症により昏睡状態に陥るも，on–line HDFを用いた人工肝補助療法を導入することで，覚醒が得られたレジオネラ肺炎の1例を経験した。我々が渉猟し得た限りでは，本邦で類似症例の報告はなく，本症例はレジオネラ肺炎が契機となってACLFを合併し，on–line HDFを用いることで救命し得た初の報告である。 レジオネラ菌（Legionella pneumophilla）は，1976年の米国在郷軍人会で発生した重症肺炎の原因菌として，1977年に初めて同定された好気性ブドウ糖非発酵グラム陰性桿菌である1。世界中の土壌中や環境水中に存在し，埃やエアロゾルとして吸入することで感染が成立する。市中肺炎のみならず，院内肺炎の起因菌としても重要である。細胞内寄生菌のため，細胞内へ移行し効果を発揮するβ–ラクタム系の抗菌薬は無効であり，早期の治療介入のためには鑑別すべき疾患として挙げることが必要である。ところが，確定診断のためにはヒメネス染色やBCYE培地での細菌培養，喀痰LAMP法といった，施設によっては外部発注での検査が必要となることが課題であった。近年ではその報告件数は増加傾向となっており2，要因として，1999年に感染症法の四類感染症に指定されたことや，2003年に尿中抗原検査が保険適応となったことが挙げられる。 重症度という点に着目すると，レジオネラ肺炎はしばしば多臓器不全を合併し，致死的な経過をたどることがある2。高柳らの報告によれば，死亡は65例中6例で，死因として敗血症性ショックや腎不全，播種性血管内凝固，多臓器不全の併発によるものであった2。とくに，多臓器不全を合併した3例中2例が死亡しており，レジオネラ肺炎に多臓器不全を合併した場合の致死率は極めて高いことが推察される。また，レジオネラ肺炎の発症リスクとして，高齢，男性，免疫抑制状態，慢性肺疾患，アルコール多飲歴，悪性腫瘍，鉄過剰症，tumor necrosis factor–α（TNF–α）治療歴，および喫煙が挙げられている3。本症例では，アルコール多飲歴やアルコール依存症の既往歴を認めていたことから，確定診断はされていないものの，基礎疾患としてアルコール性慢性肝硬変の存在が示唆され，発症リスクが高かったと推測された。また，肝硬変による免疫不全状態と考えれば，重症化しやすい素因も併せ持っていたと推測された。すなわち，アルコール多飲歴，肝硬変，レジオネラ肺炎の三者が，相互に悪影響を及ぼしたため，重症化に至ったと考えられた。 そのような背景のなかで，本症例ではレジオネラ肺炎が契機となってACLFを発症したと考えた。そもそも肝不全とは，肝細胞の減少ないし機能低下によって生体の恒常性が維持できなくなることであり，発症から肝不全に至るまでの期間で，急性，遅発性，慢性に分類されている4。急性肝不全とは「肝炎の発症から8週間以内に，高度の肝機能障害に基づいて昏睡II度以上の昏睡を来し，プロトロンビン時間が40%以下を示すもの」と定義される4。一方で，ACLFとは，「Child–Pughスコアが5～9点の代償性ないし非代償性肝硬変に，アルコール多飲，感染症，消化管出血，原疾患増悪などの増悪因子が加わって，28日以内に高度の肝機能異常に基づいて，プロトロンビン時間INRが1.5以上ないし同活性が40%以下で，血清総ビリルビン値が5.0mg/dL以上を示す症例」と厚生労働省の研究班により2018年に定義された5。急性肝不全とACLFは，正常肝あるいは肝予備能が正常の慢性肝疾患が背景にあるかどうか，という点で差別化された。診断に至るまでの因果関係として，急性肝不全が先行し，全身状態が悪化した後にレジオネラ肺炎を二次的に合併した，という可能性についても考慮されたが，レジオネラ肺炎が多臓器不全を発症しうる2という点を根拠に，本症例では，元々アルコール多飲に伴った肝硬変が存在し，レジオネラ肺炎を契機にACLFを発症したものと考えた。 ACLFの治療については，肝移植を除けば特異的かつ決定的なものはない6。原因に対する治療や，症候に対する対症療法が基本となる7。アルコール性慢性肝炎に準じたステロイドの投与については考慮したが，本症例では実施しなかった。肺野の異常陰影が，間質性肺炎の急性増悪であった場合，なおのことステロイドの投与が考慮されたが，レジオネラ肺炎の診断に至ったためにその必要性が低下し，人工肝補助療法での治療が奏功しない場合に，その実施を検討する方針としていたためである。血漿交換（plasma exchange: PE）についても，まずはon–line HDFで肝性脳症治療を進め，覚醒が得られない場合に実施を検討する方針としていた。幸い，on–line HDFとCHDFによる治療が奏功したため，血漿交換の導入は不要であった。肝移植については，現実的な問題として多臓器不全を呈しており，全身麻酔に耐えうるかが不明であったこと，背景にアルコール依存症があり，断酒もできていないことから，適応はないと判断した。 急性肝不全の内科的治療における両輪は，蛋白合成能（とくに血液凝固因子）の補助と解毒能の代替である8。前者については，新鮮凍結血漿（fresh frozen plasma: FFP）の輸血やアルブミン投与，ビタミンK製剤の補充を行うことが基本となる。本症例では，プロトロンビン時間40%を目標に適宜FFPを投与した。後者については，解毒すべき物質，すなわち肝性脳症の原因物質の排除が必要となる。本邦では，欧米と比較して肝移植のドナーが見つかりにくいという背景から人工肝補助療法が発展してきた9。肝性脳症の原因物質の代表の一つにアンモニアがあり10，アンモニアは肝性脳症患者の主たる死亡原因である脳浮腫および脳ヘルニアを惹起する可能性が示唆されている11。すなわち，人工肝補助療法の最大の目的は，肝性脳症から覚醒させ，意識障害を改善させることにある。アンモニアは分子量17g/moLと低分子であるため，小分子除去に効率の良い血液透析（hemodialysis: HD）が有効と考えられるが，実際にはHDでの肝性脳症の覚醒率は40%程度である12。これは，アンモニア以外に中分子の肝性脳症物質が関与しているためと考えられている（中分子仮説）が，具体的な物質の同定までは至っていない13。ほか，PE，血液濾過（hemofiltration: HF）での覚醒率は37.5%，78%程度である12。単独での実施は効果に乏しく，両者の利点を併せ持ったHDFが有効と考えられる。とくに，中央配管から供給される純水を透析液と置換液として使用し，前希釈法によるon–line HDFが効率的かつ経済的であるという報告が挙がっている14。本邦では，PEとHDFによるコンビネーション法が主流とされる15が，本症例では，まずon–line HDFを実施し，効果が得られない場合にPEを併用する方針としていた。結果，PEは回避することができ，on–line HDF単独でも良好な覚醒が得られ，脳ヘルニアに至ることなく経過した。覚醒率が高いということは，ICU入室期間の短縮にもつながる。合併症や続発症の低減などによる要素が，救命に寄与したと考えられた。本症例を通して，急性肝不全による肝性脳症のみならず，ACLFによる肝性脳症に対しても，on–line HDFによる人工肝補助療法が効果的であることが示唆された。 人工肝補助療法におけるon–line HDFの注意すべき点の一つとして，透析液が腎不全用であることが挙げられる16。すなわち，カリウム，リンが透析液中に不足しており，重炭酸が過剰に含まれている。アンモニアと同様に，カリウムとリンも小分子であるため，on–line HDFの開始に伴い急激に低下する可能性があり，注意が必要である。本症例では，HDF開始前と開始後約2時間が経過した時点，終了後の3ポイントで血液検査を実施し，カリウムとリンの値を逐一確認し，適宜補正を行った。また，薬剤や栄養についても影響を受けるため注意が必要と考えられる。本症例では，とくに抗生剤治療において，濃度依存性のLVFXと腎機能に応じて調整不要のAZMが治療の主軸であったため，on–line HDFの影響を考慮することなく治療を進めることが可能であった。 レジオネラ肺炎を契機としてアルコール性慢性肝硬変を背景にACLFを合併し，肝性脳症に陥った症例を経験した。肝性脳症に対して，on–line HDFによる人工肝補助療法を導入したことで覚醒が得られ，救命し得たと考えられた。 本論文における利益相反はない。

Establishment of non-biological artificial liver support therapy suitable for the medical environment in Japan and current problems

Establishment of non-biological artificial liver support therapy suitable for the medical environment in Japan and current problems

Prognosis and adverse reactions of patients with acute-on-chronic liver failure receiving artificial liver support therapy stratified by international normalized ratio

Prognosis and adverse reactions of patients with acute-on-chronic liver failure receiving artificial liver support therapy stratified by international normalized ratio

Influencing factors for hypotension in patients undergoing double plasma molecular adsorption system artificial liver support therapy

Influencing factors for hypotension in patients undergoing double plasma molecular adsorption system artificial liver support therapy

Application of double plasma molecular adsorption system in children with acute liver failure

Objective To study the efficacy and safety of double plasma molecular absorption system (DPMAS) in the treatment of pediatric acute liver failure (PALF). Methods A prospective analysis was performed on the medical data of children with PALF who were hospitalized in the Intensive Care Unit (ICU), Hunan Children's Hospital, from March 2018 to June 2020. The children were randomly divided into two groups:plasma exchange group (PE group) and DPMAS group (n=18 each). The two groups were compared in terms of clinical indices after treatment, laboratory markers before and after treatment, and adverse events after treatment. Results Compared with the PE group, the DPMAS group had a significantly lower number of times of artificial liver support therapy and a significantly shorter duration of ICU stay (P 0.05). There was no significant difference in laboratory markers between the two groups before treatment (P > 0.05). After treatment, both groups had reductions in the levels of total bilirubin, interleukin-6, and tumor necrosis factor-α, and the DPMAS group had significantly greater reductions than the PE group (P 0.05). The PE group had a significant increase in albumin, while the DPMAS group had a significant reduction in albumin (P 0.05). Conclusions DPMAS is safe and effective in the treatment of PALF and can thus be used as an alternative to artificial liver support therapy.

Efficiency of Double Plasma Molecular Absorption System on the Acute Severe Cholestatic Hepatitis

Background: Cholestasis may lead to hepatic cirrhosis and a longer hospital stay. A part of the patients with cholestasis requires liver transplantation. However, most of the treatment efficiency of cholestatic hepatitis (CH) is not satisfactory. For the patients with severe CH after artificial liver support, there was a lack of systemic evaluation on the treatment efficiency of double plasma molecular absorption system (DPMAS) for acute severe CH. Objective: We aim to investigate the treatment efficiency of DPMAS on acute severe CH. Methods: This retrospective study involved 309 cases diagnosed with acute severe CH admitted to the First Affiliated Hospital, Zhejiang University. We compared the prognosis of patients received standard medical therapy (SMT) and SMT + DPMAS. Besides, the effects of DPMAS on total bilirubin (TBIL) and prothrombin time (PT) were investigated. Results: DPMAS could significantly reduce the requirements for liver transplantation in the CH patients. After DPMAS therapy, significant decline was noticed in the TBIL, direct bilirubin (DBIL), total bile acid, and cholesterol. The baseline ratio of neutrophil showed significant elevation in the patients received 4 or more DPMAS compared with those received less DPMAS. Conclusions: DPMAS could significantly eliminate the necessity of liver transplantation. The artificial liver support system should be conducted to bring down the bilirubin level and the ratio of cases with severe conditions. In general, DPMAS should be preferred as an artificial liver support therapy for the patients with acute severe CH.

Potential predictors for prognosis and postpartum recovery time of acute fatty liver of pregnancy

BackgroundAcute fatty liver of pregnancy (AFLP) is a potentially lethal condition of pregnant women with a high mortality rate. Potential predictors related to postpartum recovery time and prognostic factors of AFLP are still unclear. This study aimed to evaluate potential predictors for prognosis and postpartum recovery time of AFLP.MethodsWe retrospectively analyzed the clinical data of 76 AFLP patients in our hospital from 2002 to 2017 and investigated potential predictors using univariate analysis and multivariate logistic regression analysis.ResultsHepatic encephalopathy (HE) was found to be associated with prognosis in AFLP patients (P = 0.005, OR = 26.844). The postpartum recovery time analysis showed that AFLP patients with a age < 25 had the shortest recovery time, but no significant difference (P = 0.134, OR = 5.952). The postpartum recovery time of patients with liver failure (LF) was significantly prolonged compared to those without LF (P = 0.036, OR = 10.052). Cryoprecipitate, and plasma infusion showed no significant effect on prognosis or recovery time. Artificial liver support therapy (ALST) had no effect on prognosis, but it might affect postpartum recovery time with no statistical significance (P = 0.128, OR = 5.470).ConclusionHE is a potential predictor for prognosis of AFLP. LF is a potential predictor for postpartum recovery time.

Use of the Molecular Adsorbent Recirculating System in Acute Fatty Liver of Pregnancy: a Case Report

Acute fatty liver of pregnancy (AFLP) can cause liver failure in the third trimester and lead to fatal complications of mother and fetus. Prompt delivery has been known as the best treatment but the importance of the maternal care is also considered an option for accomplishing maternal recovery. We report a case of 28 year-old nullipara with 36+1 weeks who was clinically diagnosed AFLP. Although the patient had an uneventful delivery, she was suffered from acute hepatic failure, coagulopathy, hepatic encephalopathy, postpartum hemorrhage, and renal failure. We decided to assist the patient’s liver function by using artificial liver support therapy such as molecular adsorbent recirculating system (MARS). After the intensive care with MARS and continuous renal replacement therapy, she was discharged with good condition in general. In conclusion, MARS can be a treatment option for AFLP as well as for prompt delivery. However, more studies need to be done to better understand the role of MARS in assisting liver function for AFLP.

Treating acute fatty liver of pregnancy with artificial liver support therapy: Systematic review.

Acute fatty liver of pregnancy (AFLP) is a serious disease with high mortality. Recent data suggest that postpartum application of artificial liver support therapy (ALST) in AFLP management improves disease outcome. In current study, we tend to further evaluate whether the type, the timing, and the number of postpartum ALST sessions and other clinical factors including complications and liver and renal function will influence disease outcome in ALST era. Medical records of 15 AFLP patients having postpartum ALST in our hospital from 2010 to 2016 were first retrospectively reviewed. A systematic review and statistical analysis was then conducted with our cases and those having postpartum ALST reported in PubMed, Embase, Cochrane, and ClinicalTrials.gov till the end of June 2016. Nine relevant studies were identified in the public databases. A total of 104 cases were enrolled for analysis including 15 cases from our hospital and 89 cases from the identified 9 studies. Univariate analysis revealed that 2 complications, postpartum hemorrhage and multiple organ dysfunctions (MODS), were associated with the outcome of AFLP patients undergoing postpartum ALST. Binary logistic regression analysis further indicated that MODS was the only independent factor affecting disease outcome. Surprisingly, factors including pre-ALST serum levels of total bilirubin and creatinine, the type and number of postpartum ALST sessions, time interval between delivery and ALST were unrelated to disease outcome. Current data suggest that postpartum ALST improves the outcome of AFLP patients but more properly designed experiments are needed to confirm this point. Our study further indicates that occurrence of MODS carries a bad prognosis even in ALST era. Our study provides valuable information on guiding the clinical application of postpartum ALST in AFLP management.

Therapeutic plasma exchange: A prospective randomized trial to evaluate 2 strategies in patients with liver failure

ObjectiveTo compare two means of performing therapeutic plasma exchange (TPE) in patients with liver failure. MethodThis open-label monocentric randomized trial, conducted in a single prestigious general healthcare facility, recruited liver failure patients with an indication to receive artificial liver support therapy for TPE. All patients underwent TPE procedures and were administered in a random sequence: heparin-free or systemic heparinization with unfractionated heparin. The primary endpoint was completion of TPE sessions, and the secondary endpoints included the safety and efficacy. ResultsIn the period of the studying, there were 164 patients being recruited in and underwent total of 398 randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2 of them (0.87%) were switched from heparin-free to unfractionated heparin eventually. No significant differences were found between the two groups for either RRs or IRs (P > 0.05). ConclusionHeparin-free regimen is feasible and safer than systemic heparinization with unfractionated heparin in the process of TPEs in patients with liver failure.

N,N-dimethylformamide-induced acute hepatic failure: A case report and literature review.

N,N-dimethylformamide (DMF) is a major solvent predominantly used in the chemical industry. The main toxic effects following exposure to DMF are gastric irritation, skin eruption and hepatotoxicity. However, hepatic failure induced by DMF is rare. In this report, we present a case of acute hepatic failure following exposure to a toxic dose of DMF via respiratory tract inhalation and skin absorption with detailed abdominal computed tomography scan, sequential laboratory data and polymorphisms. The patient recovered satisfactorily following artificial liver support therapy and pharmacological agents to protect the liver in addition to plasma, blood platelet and albumin transfusions. In view of the high mortality rate and rare occurrence rate of acute hepatic failure, the clinical characteristics, polymorphisms and therapeutic strategy of DMF poisoning are discussed.

Prognostic factors of the short-term outcomes of patients with hepatitis B virus-associated acute-on-chronic liver failure

OBJECTIVE:To investigate the impact of the baseline status of patients with hepatitis B virus-associated acute-on-chronic liver failure on short-term outcomes.METHODS:A retrospective study was conducted that included a total of 138 patients with hepatitis B virus-associated acute-on-chronic liver failure admitted to the Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, from November 2013 to October 2016. The patients were divided into a poor prognosis group (74 patients) and a good prognosis group (64 patients) based on the disease outcome. General information, clinical indicators and prognostic scores of the patients’ baseline status were analyzed, and a prediction model was established accordingly.RESULTS:Elder age, treatment with artificial liver support systems and the frequency of such treatments, high levels of white blood cells, neutrophils, neutrophil count/lymphocyte count ratio, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin, urea, and prognostic scores as well as low levels of albumin and sodium were all significantly associated with the short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure. The predictive model showed that logit (p) = 3.068 + 1.003 × neutrophil count/lymphocyte count ratio - 0.892 × gamma-glutamyl transferase - 1.138 × albumin - 1.364 × sodium + 1.651 × artificial liver support therapy.CONCLUSION:The neutrophil count/lymphocyte count ratio and serum levels of gamma-glutamyl transferase, albumin and sodium were independent risk factors predicting short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure, and the administration of multiple treatments with artificial liver support therapy during the early stage is conducive to improved short-term outcomes.

多臓器不全を来したIII度熱中症の管理において持続脳波モニタリングが有用であった1例(Usefulness of continuous electroencephalography in severe heat stroke complicated with multi–organ failure: a case report)

要旨III度熱中症では，熱や循環障害などによる中枢神経障害や体腔臓器機能障害による代謝性脳症により意識障害を来す。しかし，いずれの病態により意識障害を呈しているかの判断は困難である。今回，持続脳波モニタリング（continuous electroencephalography: cEEG）を行い，三相波を認めたことから重症急性肝不全の診断に至り，人工肝補助療法を行い良好な転帰を得た症例を経験した。71歳の女性。意識障害のため搬送。III度熱中症と診断しICUに入室，cEEGを開始した。第2病日に肝機能障害を認め，第3病日に意識障害の増悪を認めた。第4病日にcEEGにて三相波を認め，急性肝不全による肝性脳症合併と判断し，人工肝補助療法を開始，その後意識障害の改善を認めた。熱中症においてcEEGは有用である。

Artificial liver support therapy in patients with liver failure

Despite a combination of all available treatment, the mortality of liver failure is very high,especially in children patients. Artificial liver support methods have been tested for over 50 years. Standard techniques of blood purification like hemodialysis, adsorption, hemo or plasma filtration as well as bioreactorbased approaches using liver cells or tissues have been used. It' s believed that the damaged liver has the ability to return to normal. Artificial liver support systems are expected to be useful for temporary support of liver function. If the liver does not regenerate to normal functions, an artificial liver support system may be useful as a bridge to liver transplantation. In conclusion, artificial liver support method appears to be a reliable therapy for advanced liver diseases and has significantly decreased the mortality of liver failure. Artificial liver support system has been used in children patients as well, but it still needs more researches. Key words: Artificial liver support system ; Liver failure

Preoperative risk factor analysis in orthotopic liver transplant-ation with pretransplant artificial liver support therapy

To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT). Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d) after OLT. In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30 d observation was: 28 kept alive and 6 patients died. Pre-operative SOFA, level of creatinine, INR, TNF-alpha, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantation can relieve these factors significantly.

Preoperation risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

Orthotopic liver transplantation (OLT) is an accepted therapy for selected patients with advanced liver diseases. However, the early mortality rate after OLT remains relatively high due to the poor selection of candidates with various serious conditions. The aim of this study is to assess the value of pretransplantation artificial liver support treatment in reducing the pre-operation risk factors relating to early mortality after OLT. 50 adult patients in various stages of different etiologies who underwent OLT procedures had been treated with molecular adsorbent recycling system (MARS) preoperatively. The study was designed in two parts: the first one was to evaluate the effectiveness of a single MARS therapy by using some clinical and laboratory parameters which were supposed to be therapeutical pretransplantation risk factors. The second part was to study the patients undergoing OLT by using the regression analysis on preoperation risk factors relating to early (within 30 d after OLT) mortality rate. Among the 50 patients, a statistically significant improvement of the biochemical parameters was observed (pretreatment vs posttreatment). 8 patients cancelled their scheduled LTXs due to significant improvements in their clinical conditions or recovery of their failing liver functions. 8 patients died and 34 patients successfully underwent LTX. The immediate outcome (within 30 postoperative days) of these 34 patients was that 28 were kept alive and 6 died. Preoperation sequential organ failure assessment (SOFA), level of creatinine, INR, TNFalpha, and IL-10 are the main preoperative risk factors relating to early death after an operation. MARS treatment before a transplant operation can relieve these factors significantly, hence improve survival rate of liver transplantation or even make the transplantation unnecessary.

Application of Molecular Adsorbents Recirculating System to remove NO and cytokines in severe liver failure patients with multiple organ dysfunction syndrome.

Molecular Adsorbents Recirculating System (MARS) is a new promising artificial liver support therapy, the aim of this study was to assess the effectiveness of MARS to remove nitrous oxide (NO) and cytokines in severe liver failure patients with multiple organ dysfunction syndrome (MODS). Sixty single MARS treatments were performed with length of 6-24 h on 24 severe liver failure patients (18 males/6 females) with MODS. The MARS therapy was associated with a significant removal of NO and certain cytokines such as TNF-alpha, IL-6, IL-8, and INF-gamma, together with marked reduction of other non-water-soluble albumin bound toxins and water-soluble toxins, these were associated with a improvement of the patients' clinical conditions including hepatic encephalopathy, deranged hemodynamic situation and as well as renal and respiratory function, thus resulted into marked decrease of Sequential Organ Failure Assessment (SOFA) score and improved outcome: nine patients were able to be discharged from the hospital or bridged to successful liver transplantation, the overall survival of 24 patients was 37.5%. We can confirm the positive therapeutic impact and safety to use MARS on liver failure patients with MODS associated with elevated levels of NO and cytokines.