Bridging to transplantation in acute liver failure in a 7-month-old infant

BACKGROUND: Acute liver failure (ALF) in children is a rare but often fatal event. At present, liver transplantation is the only successful therapy in most cases. In the face of deteriorating hepatic encephalopathy in these children, some bridging therapy using artificial detoxification can be necessary to enable successful transplantation. In adults, albumin dialysis using the molecular absorbent recycling system (MARS) has been described as effective for bridging to liver transplantation. CASE REPORT: A previously healthy 7-month-old infant was admitted with ALF due to autoimmune hepatitis. King's College criteria for children with ALF indicated the need for transplantation (bilirubin 13.7 mg/dl, leukocytes 18,980/mm3, INR 5.83, age<2 years). Despite moderate hyperammonemia (75 microm/l) along with the development of pneumonia, the child deteriorated hemodynamically and neurologically, showing grade III encephalopathy proven by EEG. Albumin dialysis using MARS was used to bridge 36 hours to successful living-donor split-liver transplantation, and resulted in improvements in EEG, plasma levels of amino acids and hemodynamics. Twenty-four months after transplantation the child shows normal liver function and normal neuropsychological development. The explanted liver showed 80 % tissue destruction from autoimmune hepatitis. CONCLUSION: Albumin dialysis as described can be used successfully in infants < 1 year old for bridging to liver transplantation in cases of acute hepatic failure with deteriorating encephalopathy.     

High‐volume plasma exchange in a patient with acute liver failure due to non‐exertional heat stroke in a sauna

Heat stroke is a life‐threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non‐exercise‐induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non‐exercise‐induced heat stroke in a 73‐year‐old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high‐volume plasma exchange, and the patient recovered completely after treatment. J. Clin. Apheresis 29:281–283, 2014. © 2014 Wiley Periodicals, Inc.     

Acute liver failure caused by herpes simplex virus in a pregnant patient: Is there a potential role for therapeutic plasma exchange?

A young woman presented with a febrile illness in the third trimester of pregnancy. Laboratory investigation revealed severe acute hepatitis with thrombocytopenia and coagulopathy. Liver injury progressed despite emergent caesarian section and delivery of a healthy infant. Therefore, therapeutic plasma exchange (TPE) was performed on three consecutive days post‐partum for a presumed diagnosis of acute liver failure (ALF) associated with pregnancy due to hemolysis, elevated liver enzymes, and low platelets (HELLP) or acute fatty liver of pregnancy (AFLP). Treatment with TPE was followed by biochemical and clinical improvement but during her recovery herpes simplex virus type 2 (HSV‐2) infection was diagnosed serologically and confirmed histologically. Changes in the immune system during pregnancy make pregnant patients more susceptible to acute HSV hepatitis, HSV‐related ALF, and death. The disease is characterized by massive hepatic inflammation with hepatocyte necrosis, mediated by both direct viral cytotoxicity and the innate humoral immune response. TPE may have a therapeutic role in acute inflammatory disorders such as HSV hepatitis by reducing viral load and attenuating systemic inflammation and liver cell injury. Further investigation is needed to clarify this potential effect. The roles of vigilance, clinical suspicion, and currently accepted therapies are emphasized. J. Clin. Apheresis, 28:426–429, 2013. © 2013 Wiley Periodicals, Inc.     

Therapeutic plasma exchange in a critically ill Covid‐19 patient

Here we describe the effect of therapeutic plasma exchange with 5% albumin as sole replacement solution for the management of Covid‐19. A 74‐year‐old man was admitted for severe Covid‐19 acute respiratory distress syndrome. Based on the growing body of evidence that cytokine release syndrome, and especially interleukin‐6, plays a key role in critically ill Covid‐19 patients, we decided to implement therapeutic plasma exchange as a rescue therapy. The patient's clinical status rapidly improved, and biological records showed convincing results of decrease in interleukin‐6 and inflammatory parameters under treatment. This case presents a proof‐of‐concept for the use of therapeutic plasma exchange with 5% albumin as sole replacement solution in a critically ill Covid‐19 patient with cytokine release syndrome. This could constitute a major benefit in terms of security compared to long‐lasting immunosuppressive monoclonal antibodies, or to therapeutic plasma exchange with plasma as replacement fluid. Hence, we think that a further evaluation of risk‐benefit balance of this therapy in severe cases of Covid‐19 should rapidly be undertaken.     

How atypical can Atypical Hemolytic Uremic Syndrome be?

A 24‐year‐old man with diarrhea found to have acute renal failure with microangiopathic hemolytic anemia (MAHA). A diagnosis of hemolytic uraemic syndrome (HUS) was made. He was initiated on plasma exchange and hemodialysis. On day 6, he was started on eculizumab. His renal functions progressively improved. His main complication during eculizumab therapy was hypertension‐related posterior reversible encephalopathy syndrome.     

肝功能衰竭肝性脑病大鼠5-羟色胺和去甲肾上腺素的变化

目的研究5-羟色胺(5-HT)及去甲肾上腺素(NA)在大鼠急性肝功能衰竭(ALF)和慢性肝功能衰竭(CLF)肝性脑病时的变化。方法将110只SD大鼠随机分为正常对照组(20只)、ALF组(45只)及CLF组(45只)。ALF模型按500mg/kg硫代乙酰胺(TAA)间隔24h两次灌胃;CLF模型按质量分数为0.03%的TAA作为饮用水灌饲10周,并根据每周体重的变化增减50%的TAA含量。造模成功后从眼底静脉丛取血,检测5-HT、NA、血氨和肝功能指标;处死动物,取肝、脑组织,光镜下观察组织病理学变化。结果ALF组和CLF组均出现不同程度的肝功能损害表现,血中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、白蛋白(ALB)、白蛋白/球蛋白(A/G)、血氨均有明显变化(P<0.05或P<0.01);肝脏及脑组织病理学符合ALF和CLF肝性脑病表现。ALF组和CLF组5-HT(16.06±1.08)μmol/L和(15.32±1.48)μmol/L均较正常对照组(2.75±0.26)μmol/L显著升高(P均<0.01),CLF组NA值下降(94.0±2.13)pmol/L比(121.2±14.8)pmol/L,P<0.05。结论5-HT在大鼠ALF和CLF所致肝性脑病时明显升高;NA在大鼠CLF所致肝性脑病时明显下降。     

Blood exchange transfusion in viral hepatitis in a small infant: a case report

We report a case of blood exchange transfusion to treat acute liver failure following hepatitis B infection at the Infectious Disease Department of Children's Hospital No.2 in Ho Chi Minh City, Vietnam. A 3.5-month old baby boy was admitted to the hospital with a presentation of progressively worsening jaundice for the past one month. The patient was diagnosed with hepatitis B infection with a positive HBV DNA quantitative assay. Plasma exchange was indicated in view of progressive liver failure and gradually increasing hepatic coma. However, it was impossible to perform plasmapheresis in this case because the patient was small (in terms of age and weight) and there was no suitable plasma exchange filter. Accordingly, the patient was treated with 3 times of blood exchange transfusion in combination with an antiviral drug, lamivudine. After each blood exchange transfusion, the biochemical values (bilirubin, liver enzymes, and coagulation profile) gradually improved and he was discharged after 1 month of treatment. Blood exchange transfusion is an effective procedure for managing acute liver failure, where plasma exchange is not possible while waiting for the recovery of liver functions or liver transplantation.     

非生物型人工肝治疗儿童急性肝衰竭的疗效分析

目的:探讨非生物型人工肝治疗儿童急性肝衰竭(acute liver failure,ALF)的疗效。方法:回顾分析2008年8月—2013年7月复旦大学附属儿科医院收治的47例儿童ALF患者的临床资料,其中17例患者采用常规内科综合治疗(对照组),30例患者在常规内科综合治疗基础上采用非生物型人工肝治疗(研究组),分析ALF患儿的年龄分布特征及病因情况,比较研究组患儿治疗前后主要生化指标、凝血功能指标的变化以及2组患儿病死率。结果:47例ALF患儿中≤1岁患儿23例、1~3岁10例、≥3岁14例;34.0%患儿病因不明。与治疗前比较,研究组患儿治疗后血清总胆红素(total bilirubin,TBIL)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)均降低(P0.05),国际化标准比值(international normalized ratio,INR)、凝血酶原活度(prothrombin time activity,PTA)、白蛋白(albumin,ALB)均升高(P0.05)。研究组病死率低于对照组,但差异无统计学意义。结论:非生物型人工肝治疗儿童ALF是有效的,可改善患儿的生化指标、凝血功能及预后。     

Acute liver failure with thrombotic microangiopathy due to sodium valproate toxicity: A case report

BACKGROUNDSodium valproate is widely used in the treatment of epilepsy in clinical practice. Most adverse reactions to sodium valproate are mild and reversible, while serious idiosyncratic side effects are becoming apparent, particularly hepatotoxicity. Herein, we report a case of fatal acute liver failure (ALF) with thrombotic microangiopathy (TMA) caused by treatment with sodium valproate in a patient following surgery for meningioma.CASE SUMMARYA 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue, severe jaundice accompanied by oliguria, soy sauce-colored urine, and ecchymosis. His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level, severe liver and kidney dysfunction, and disturbance of the coagulation system. He was diagnosed with drug-induced liver failure combined with TMA. After plasma exchange combined with hemoperfusion, pulse therapy with high-dose methylprednisolone, and blood transfusion, his liver function deteriorated, and finally, he died.CONCLUSIONALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.     

Brain edema in acute liver failure

Acute liver failure (ALF) is a syndrome of rapidly deteriorating liver function that manifests as coagulopathy and encephalopathy in a previously healthy individual. This article analyzes the repercussions of ALF on the brain through a discussion of special features of this syndrome, important for the interpretation of neurologic findings. Of particular interest within the context of ALF are hepatic encephalopathy and the pathogenesis of brain edema in acute liver failure as well as its clinical and therapeutic aspects.     

儿童急性肝衰竭的诊疗进展

急性肝衰竭（acute liver failure,ALF）是一种严重的累及多个系统的临床综合征,在短时间内出现严重的肝功能损伤,并有脑水肿、肝性脑病、多器官衰竭等并发症的出现,病死率极高。ALF在儿童中的确切发生率还不清楚,在需要肝移植的儿童患者中,ALF的患者占10％～15％。对儿童ALF的诊断和治疗,缺乏大规模、多中心的临床研究。目前儿童ALF的诊疗方案,主要来源于成人ALF的经验。但是,儿童ALF的病因、临床特点、发病机制等都有别于成人ALF,因此有必要对儿童ALF进行专门的探讨。本文就儿童ALF的诊疗进展作一综述。     

探讨人工肝支持治疗对判断重型肝炎患者预后的临床意义

目的 观察161例经人工肝治疗的重症肝炎患者的转归,探讨人工肝治疗对判断患者预后的临床意义。方法 161例重症肝炎肝功能衰竭患者各行血浆置换(plasma exchange,PE)、胆红素特异性吸附(bilirubin specific adsorption,BSA)、活性炭灌流(hemoperfusion,HP)、分子吸附循环系统(molecular adsorbent recy—cling system,MARS)、组合型生物人工肝(hybrid bioartificial liver,HBL)、人工肝治疗,平均治疗2.7次。于治疗前、治疗中、治疗后分4个不同时段取血分别测肝功能、血氨、凝血酶原活动度及血清内毒素水乎,并观察临床症状及体征变化。结果 20例治疗前伴肝性脑病患者昏迷程度减轻。与治疗前比较,患者血清总胆红素及内毒素水平明显降低(P<0.01),凝血酶原活动度及胆碱脂酶显著升高(P<0.O1和P<0.05)。92例患者痊愈,33例成功的实施肝移植,其余36例分别死于严重感染者、消化道大出血和肝肾综合征,存活率为77.64％。结论 人工肝可能作为治疗重型肝炎肝衰竭的有效方法之一,并作为判断患者能否自然恢复或必须进行肝移植的主要指标。     

Emergency ABO‐incompatible liver transplant secondary to fulminant hepatic failure: Outcome,role of TPE and review of the literature

The increasing demand for solid organ transplants has brought to light the need to utilize organs in critical situations despite ABO‐incompatibility. However, these transplantations are complicated by pre‐existing ABO antibodies which may be potentially dangerous and makes the transplantation prone to failure due to rejection with resulting necrosis or intrahepatic biliary complications. We report the clinical outcome of an emergency ABO‐incompatible liver transplant (due to fulminant hepatic failure with sudden and rapidly deteriorating mental status) using a modified therapeutic plasma exchange (TPE) protocol. The recipient was O‐positive with an initial anti‐B titer of 64 and the cadaveric organ was from a B‐positive donor. The patient underwent initial TPE during the peri‐operative period, followed by a series of postoperative daily TPE, and later a third series of TPE for presumptive antibody‐mediated rejection. The latter two were performed in conjunction with the use of IVIg and rituximab. The recipient's anti‐B titer was reduced and maintained at 8 or less 8 months post‐op. However, an elevation of transaminases 3 months post‐transplant triggered a biopsy which was consistent with cellular rejection and with weak C4d positive staining suggestive of antibody mediated rejection. Additional plasma exchange procedures were performed. The patient improved rapidly after modification of her immunosuppression regimen and treatment with plasma exchange. This case illustrates that prompt and aggressive plasma exchange, in conjunction with immunosuppression, is a viable approach to prevent and treat antibody mediated transplant rejection in emergency ABO‐incompatible liver transplant. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.     

混合型生物人工肝治疗急性肝衰竭动物的实验研究

目的评估混合型生物人工肝对急性肝衰竭动物的治疗效果。方法混合型生物人工肝由血浆置换、血液滤过和猪肝细胞型生物人工肝构成。6只中国实验小型猪采用D-氨基半乳糖静脉注射建立急性肝衰竭动物模型,在给药48h后给予混合型生物人工肝治疗,先进行血浆置换联合血液滤过,再经过猪肝细胞型生物人工肝处理。观察比较实验动物治疗前后的临床表现及各相关指标的变化;并比较血浆置换联合血液滤过后猪肝细胞型生物人工肝处理后血液中相应指标的变化。结果本组实验动物在混合型生物人工肝治疗过程中生命体征平稳,未发生严重不良反应。与治疗前相比,治疗后实验动物血液中总胆红素、氨、丙氨酸转移酶、内毒素、肌酐明显减少(P0.01),纤维蛋白原、凝血酶原活动度和甲胎蛋白明显增加(P0.01);与血浆置换联合血液滤过比较,猪肝细胞型生物人工肝治疗后血液中纤维蛋白原、凝血酶原活动度有所增加(P0.05),血氨、总胆红素明显降低(P0.01)。结论应用混合型生物人工肝治疗急性肝衰竭安全、有效。混合型生物人工肝较非生物型人工肝(血浆置换+血液滤过)效果好。     

Serial changes of liver stiffness measured by acoustic radiation force impulse imaging in acute liver failure: a case report

Acoustic radiation force impulse (ARFI) imaging is a new technology used to determine liver elasticity. We report the case of a patient that survived hyperacute-type acute liver failure (ALF) and who showed a dramatic change in the value of shear wave velocity (SWV) measured by ARFI, which corresponded with the severity of her liver damage. The value of SWV increased significantly up to 3.6 ± 0.3 m/s during the encephalopathy phase and then decreased along with the recovery of liver function, the blood flow of the right portal vein, and the liver volume. These findings suggest the value of SWV in ALF as a reliable marker of liver tissue damage. Further investigations of the pathophysiological significance of SWV in ALF are warranted.     

Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats

In acute liver failure (ALF), a poorly controlled innate immune response causes massive hepatic destruction, which elicits a systemic inflammatory response, progressive multiple organ failure and ultimate sudden death. Although the liver has inherent tissue‐repairing activities, its regeneration during ALF fails, and orthotopic liver transplantation is the only curative approach. Here we show that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED‐derived serum‐free conditioned medium (SHED–CM) into the d ‐galactosamine‐induced rat model of ALF markedly improved the condition of the injured liver and the animals’ survival rate. The engraftment of infused SHEDs was very low, and both SHEDs and SHED–CM exerted similar levels of therapeutic effect, suggesting that the SHEDs reversed ALF by paracrine mechanisms. Importantly, SHED–CM attenuated the ALF‐induced pro‐inflammatory response and generated an anti‐inflammatory/tissue‐regenerating environment, which was accompanied by the induction of anti‐inflammatory M2‐like hepatic macrophages. Secretome analysis by cytokine antibody array revealed that the SHED–CM contained multiple tissue‐regenerating factors with known roles in anti‐apoptosis/hepatocyte protection, angiogenesis, macrophage differentiation and the proliferation/differentiation of liver progenitor cells. Taken together, our findings suggest that SHEDs produce factors that provide multifaceted therapeutic benefits for AFL. Copyright © 2015 John Wiley & Sons, Ltd.     

Role of Contrast‐Enhanced Ultrasonography in Primary Hepatic Lymphoma

Objective. Ultrasonography is the first examination performed for screening of hepatocellular carcinoma (HCC); contrast‐enhanced ultrasonography (CEUS) can help discriminate between HCC and other lesions. Primary hepatic lymphoma (PHL), even if rare, should be considered in the differential diagnosis of focal liver lesions (FLLs). Few data are available in the literature about the role of CEUS in the diagnosis of PHL; we tried to determine whether CEUS could have a role in this setting. Methods. we describe 2 cases of primary non‐Hodgkin lymphoma of the liver associated with hepatitis B virus (HBV) infection. The first patient was a 62‐year‐old man who was an HBV‐inactive carrier, and the second was a 58‐year‐old man with type 2 diabetes and chronic HBV hepatitis. Results. in both cases, ultrasonography showed a hypoechoic liver lesion (4 and 3 cm, respectively) with irregular margins in segment 4 of the liver. On CEUS, these lesions were inhomogeneously hyperenhanced in the arterial phase and hypoenhanced in the portal and late phases. Contrast‐enhanced computed tomography (CT) in both patients showed slight hyperenhancement in the arterial phase and hypoenhancement in the remaining phases. Needle biopsy showed marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue type in both patients. Conclusions. Contrast‐enhanced ultrasonography and CT did not help us differentiate PHL from HCC; in fact, in both cases we saw the characteristic findings of primary HCC. Primary hepatic lymphoma is a rare condition, but it should always be considered in the differential diagnosis of FLLs. We stress the important role of liver biopsy when imaging indicates HCC in patients without underlying cirrhosis.     

Successful rescue of acute liver failure and hemophagocytic lymphohistiocytosis following varicella infection: A case report and review of literature

Herein we report a case of acute liver failure (ALF) and hemophagocytic lymphohistiocytosis (HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient’s condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction (PCR) amplifications of varicella-zoster virus (VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient’s symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.     

Plasma and red cell exchange transfusions for erythropoietic protoporphyria: A case report and review of the literature

Erythropoietic protoporphyria (EPP) is a rare and usually autosomal dominant disorder characterized by ferrochelatase deficiency and accumulation of protoporphyrin in red blood cells (RBCs), skin, and liver. A small minority of patients develop severe liver dysfunction for which optimum treatment is lacking. Therapeutic plasma exchange (TPE) and RBC exchange (RCE) have been anecdotally reported to benefit patients with EPP and liver failure. A 50‐year‐old female with EPP developed severe liver dysfunction after knee replacement surgery and high‐dose acetaminophen use. Liver biopsy showed cholestatic liver injury without fibrosis. A total of 20 TPE procedures, six RCE procedures, and then 14 more TPE procedures were performed as adjunctive therapy with the purpose of preventing progression to end‐stage liver failure. After initial TPE, the plasma and RBC protoporphyrin levels decreased from 834.9 to 180.4 μg/dL (normal, ≤1 μg/dL), and from 3,905 to 2,879 μg/dL (normal, ≤80 μg/dL), respectively, without liver function improvement. RCE decreased RBC protoporphyrin levels from 2,879 to 1,225 μg/dL but plasma protoporphyrin increased from 180.4 to 1,044.1 μg/dL, and liver function failed to improve. Additional TPE again stabilized plasma protoporphyrin and improved RBC protoporphyrin levels but the patient ultimately died owing to end‐stage liver disease complications. This case illustrates that TPE and RCE may improve the plasma and RBC biochemical markers of EPP activity but liver function abnormalities may persist and patients may still progress to liver failure either because of irreversible liver injury or independent pathobiological factors unrelated to EPP‐induced hepatotoxicity. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.     

Heterogeneous presentation of caspr2 antibody‐associated peripheral neuropathy – A case series

Contactin‐associated protein 2–like (caspr2) antibodies have been discovered recently. Since then a multitude of patients with caspr2 antibodies presenting with different neurological symptoms have been reported. Here, we describe three patients with caspr2 antibodies with different types of pain/no pain in combination with peripheral neuropathy. The first patient, a 33‐year‐old woman, presented with erythromelalgia‐like pain and autonomic symptoms; the second patient, a 58‐year‐old man, with paresthesia and pain while walking together with signs of peripheral motor neuron hyperexcitability in combination with optic neuritis, and the third patient, a 74‐year‐old man, without any pain but with polyneuropathy and encephalopathy. These cases illustrate the spectrum of symptoms in anti‐caspr2 diseases. The pain in such cases can be treated causally.