Liver Transplantation for Acute Liver Failure Due to Yellow Phosphorus Poisoning - A Comprehensive Review.

Yellow phosphorus or metal phosphide (YP-MP) rodenticide poisoning has been a known cause of acute liver failure (ALF) in many countries of Asia and North and South America over the last decade. It is a highly toxic compound and is a well-known cause of intentional or accidental poisoning in both adults and children. In lower doses, it causes gastrointestinal symptoms and mild hepatic injury, and patients may spontaneously recover. In higher doses, hepatic necrosis and fatty infiltration may cause significant injury and may even lead to ALF, characterized by hepatic encephalopathy, coagulopathy, and lactic acidosis. Cardiotoxicity, rhabdomyolysis, and neutropenia are other well-documented complications. If untreated, it may lead to multi-organ dysfunction and death. Plasmapheresis and continuous renal replacement therapy (CRRT) have been used with limited success in patients who do not recover spontaneously. However, patients who develop ALF often need liver transplantation (LT). Liver transplantation has been successfully performed in ALF due to YP-MP poisoning in several countries, with good results in both adult and pediatric patients. Separate criteria for LT are important to ensure early and rapid listing of critical patients on the waiting list. The success rates of LT for ALF due to YP-MP rodenticide poisoning are very promising, provided there are no contra-indications to transplant. Plasma exchange, CRRT, or cytosorb can be used as a bridge to transplant in selected patients. In the long term, only with an increase in public awareness and sale restrictions can we prevent the intentional and accidental poisoning caused by this easily available, highly toxic compound.

Re-evaluation of King Wilson Index in Children With Acutely Decompensated Hepatic Wilson Disease.

OBJECTIVES: Liver transplantation (LT) in Wilson disease (WD) is a life-saving option for patients presenting with liver failure and encephalopathy. Patients without encephalopathy can avoid LT and treated successfully with chelation therapy. It is essential to predict the risk of fatal outcomes where LT is required. We aim to critically analyse the validity of the WD Index prospectively from a cohort of WD patients managed at our institution. METHODS: WD Index and other clinical data from 2005 to 2018, recorded prospectively as part of clinical management, were analysed. RESULTS: Over 13-year period, 52 children with WD (29 boys) with median age at diagnosis of 11.69 (range 3.92-17.26) years were studied. Of these, 17 were diagnosed as part of family screening, 17 presented with abnormal liver enzyme, and 18 with acute hepatic decompensation (AHD) as per PALF definition. Patients presented with abnormal liver enzyme and in the pre-symptomatic group had WD Index <11, and none of them required LT. WD Index is still a good predictor for LT in WD patients with AHD, providing a sensitivity of 80%, specificity of 100%, positive-predictive, and negative-predictive value of 100% and 80%, respectively. Patients presented with an index of 8-10 also required LT at median duration of 58 days (IQR 48-135 days). CONCLUSIONS: WD patients presenting with AHD who had an index of ≥11 do require LT. Children with a WD Index of 8 to 10 within the first 2 months of admission require close monitoring as LT may become necessary.

Evaluation of drug-induced liver injury as etiology for acute liver failure in Brazil.

INTRODUCTION AND OBJECTIVES: Little is known about the etiology of acute liver failure (ALF) in Latin America. The objective of this paper is to investigate the main etiologies of ALF in Brazil, including Drug Induced Liver Injury (DILI) using stringent causality criteria. PATIENTS OR MATERIAL AND METHODS: All the cases of individuals who underwent liver transplantation (LT) in 12 centers in Brazil for ALF were reviewed. When DILI was stated as the cause of ALF, causality criteria were applied on site by the main investigator in order to rule out other etiologies. RESULTS: 325 individuals had ALF mainly for unknown reasons (34%), DILI (27%) and AIH (18%). Reassessment of the 89 cases of DILI, using stringent causality criteria, revealed that in only 42 subjects could DILI be confirmed as the cause of ALF. Acetaminophen (APAP) toxicity (n = 3) or DILI due to herbal and dietary supplements (HDS) (n = 2) were not commonly observed. CONCLUSIONS: Undetermined etiology and DILI are the main causes of ALF in Brazil. However, APAP toxicity and DILI due to HDS are mostly uncommon.

Critical care management in patients with acute liver failure.

Acute liver failure (ALF) is defined as severe hepatic dysfunction (marked transaminases elevation, detoxification disorder (jaundice and coagulopathy with international normal ratio (INR) > 1.5), the presence of hepatic encephalopathy, and exclusion of underlying chronic liver disease, and a secondary cause like sepsis or cardiogenic shock. Reasons for ALF include paracetamol and warfarin toxicity, autoimmune and viral (mainly hepatitis B and E) hepatitis, and herbal and dietary supplements. Even in terms of meticulous and careful review of the patient, around 20-30% of the reasons remains unknown. In order of its rarity, a randomized controlled trial could hardly be done. However, because of improved ICU treatment, the mortality, even in the advanced stage of ALF decreased. However, in 5-10% of the cases an emergency transplantation is required. This justifies the treatment of this patient cohort in institutions that can provide this kind of treatment.

Acute Liver Failure Caused by Use of Fat Burner: A Case Report.

Acute liver failure is a rare condition consisting of abrupt and extensive hepatocyte injury, leading to significant liver dysfunction associated with a high mortality. Liver transplantation is the most effective treatment in severe cases. The most common cause of acute liver failure in Western countries is drug-induced liver injury caused by prescription drugs and herbal and dietary supplements. Thermogenics, or fat burners, are a category of dietary supplements that claim to increase the resting metabolic rate, leading to weight loss. There are previous reports of acute liver failure associated with specific thermogenic formulations. We report the case of a 36-year-old male patient who developed jaundice 7 days after he started taking a thermogenic dietary supplement (Thermo Gun), with progressive deterioration of hepatic function and development of hepatic encephalopathy 19 days after the beginning of the symptoms. He had a Model for End-Stage Liver Disease score of 38 and fulfilled 4 of the King's College Criteria for poor prognosis in patients with acute liver failure. He underwent liver transplantation, receiving a graft from a cadaveric donor, and is alive with good liver graft function 2 years after the transplant. No possible causes for acute liver injury were identified other than the use of the supplement, which contained N-acetyl-L-tyrosine; 1,3,7-trimenthylxanthine; white willow; and 1-hydroxypholedrine. We found no previous reports in the literature of acute liver failure associated with those particular substances. This manuscript is compliant with the Helsinki Congress and the Istanbul Declaration.

Acute Liver Failure due to Wilson Disease: Eight Years of the National Liver Transplant Program in Uruguay.

INTRODUCTION AND AIM: Wilson's disease (WD) is an uncommon cause of acute liver failure (ALF). Our aim was to describe clinical features, diagnostic findings, treatments, and outcomes of patients with ALF due to WD. MATERIAL AND METHODS: Retrospective medical record reviews of all patients with ALF due to WD in eight years in Uruguay. RESULTS: WD was the cause of six (15%) of thirty-nine ALF cases. All patients were females, with a mean age of 18 years. Four patients presented with hyperacute liver failure and two with acute failure. Jaundice was the main complaint of all patients. Mean total bilirubin (TB), alkaline phosphatase (AP), AST, and ALT were 27.5 mg/dL, 45.5 lU/l, 156 IU/L, and 51 IU/L, respectively. Ceruloplasmin levels were low in four patients, urinary cooper was high in four, and two had Kayser-Fleischer rings. All patients had Coombs-negative hemolytic anemia, acute kidney injury, histochemical identifiable copper, and advanced fibrosis on liver histology. The average MELD score was 36. All patients were treated with d-penicillamine and listed for urgent liver transplantation (LT). Prometheus® was performed in one patient. Three patients died: two without LT and one after LT. Three patients survived: one without LT (New Wilson Index<11) and two with LT. The referral time to the program and the total time (referral plus waiting list time) were longer for non-survivors than for survivors (14 vs. 3 days and 23 vs. 8 respectively). CONCLUSION: All cases had typical clinical, analytical and histopathology characteristics. Early referral was determinant of prognosis.

Acute Liver Failure Induced by Carthamus tinctorius Oil: Case Reports and Literature Review.

BACKGROUND: Acute liver failure (ALF) is a clinical syndrome that results from the abrupt loss of liver function in a patient without previous liver disease. The most frequent causes are viral hepatitis, drug induced, and autoimmune disease, but in 20% of cases no cause is identified. Carthamus tinctorius (safflower) oil is used as a dietary supplement for weight loss and antioxidant. There are 4 cases described in the literature of ALF induced by the use of this substance. The objective of this study was to report 3 cases of ALF treated at the Clinical Hospital of the State University of Campinas that suggest the use of C tinctorius oil as a probable etiologic factor. CASE REPORTS: The 3 patients had a diagnosis of ALF according to the King's College criteria. All had a history of ingestion of this oil for weight loss. During etiologic evaluation, viral hepatitis, autoimmune diseases, or any other drug cause were excluded, thus pointing to C tinctorius oil as the triggering factor. All 3 patients underwent liver transplantation: 2 had good postoperative evolution, and 1 died 12 days after the procedure. CONCLUSIONS: Two cases are described in which the hepatic insufficiency induced by C tinctorius oil was successfully treated through liver transplantation. This highlights the risk of misuse of this substance for weight loss.

Flupirtine drug-induced liver injury in a patient developing acute liver failure.

A patient is admitted with complaints of recent onset nausea, discomfort, jaundice and blood tests that reveal severe hepatitis. At the time, she had been taking medication with Hypericum perforatum (St John's wort) for 6 months, and 6 weeks before this event, she took flupirtine maleate. A few days after being admitted, she developed encephalopathy progressing to acute liver failure (ALF) requiring unsuccessful liver transplantation. The patient was ultimately diagnosed with drug-induced liver injury (DILI). In this context, while H. perforatum could interfere with other medication or trigger DILI itself, flupirtine appears to have triggered the DILI, given its liver toxicity capacity. DILI is one of the major ALF causes and can jeopardise patient's life. Accordingly, all efforts to reduce medication potentially hazardous to the liver are recommended.

Marked Decrease in Urgent Listing for Liver Transplantation Over Time: Evolution of Characteristics and Outcomes of Status-1 Liver Transplantation.

BACKGROUND: Approximately 5% of liver transplants annually are performed urgently with "status-1" designation. This study aims to determine if the demand, characteristics, and outcome for status-1 liver transplantation has changed over time. METHODS: We used the Scientific Registry of Transplant Patients (2003-2015) to characterize 2352 adult patients who underwent 2408 status-1 liver transplants and compared them between Era1 (2003-6/2009) and Era2 (7/2009-2015). RESULTS: Overall, there were fewer liver transplants performed with the status-1 designation in Era2 than Era1 (1099 vs 1309). Although the number of urgent liver transplants was relatively constant with successive years, the proportion transplanted with status-1 designation decreased markedly over time. Era2 patients were older (43.2 years vs 41.7 years, P = 0.01) and less likely be ABO-incompatible (1.1% vs 2.4%, P = 0.01) or retransplant (77 vs 124, P = 0.03). In terms of disease etiology, the largest group was "acute liver failure (ALF), nonspecified" (43.4%). There was no difference in proportion with drug-induced liver injury (DILI), but the subset of herbal/dietary supplements increased in Era2 (1.3% vs 0.46%, P = 0.04). Survival was increased in Era2 in the overall cohort and for patients with autoimmune disease (P < 0.05), despite longer waiting times for this etiology (186 days vs 149 days). DILI or nonspecified ALF had shorter waiting times, and 90% were transplanted within 7 days. CONCLUSIONS: Liver transplantation for the most urgent indications (status-1) is decreasing while survival remains excellent. Fewer incidences of ALF are classified as indeterminate, mostly as a result of increasing awareness of autoimmune hepatitis and DILI as causes of the syndrome.

Liver transplantation for non-exertional heat stroke-related acute liver failure.

Heat stroke is a life-threatening condition characterised by hyperthermia leading to multiple organ dysfunction. Acute liver failure is a rare and potentially fatal consequence of heat stroke. Management of heat stroke is mainly supportive but liver transplantation can be considered as the treatment of acute liver failure in heat stroke. However, literature on liver transplantation as a treatment for acute liver failure in heat stroke is scarce. Until now, no cases of liver transplantation for acute liver failure in non-exertional heat stroke have been reported. Here, we present the first case report of a successful liver transplantation in a patient with acute liver failure caused by non-exertional heat stroke after a sauna visit.

Liver transplantation is associated with good clinical outcome in patients with active tuberculosis and acute liver failure due to anti-tubercular treatment.

BACKGROUND: Active tuberculosis (TB) is commonly considered a contraindication for liver transplantation (LT). However, in patients with TB who develop acute liver failure (ALF) due to toxicity induced by anti-tubercular treatment (ATT), LT could be the only opportunity for treatment. The aim of this study was to evaluate the feasibility of LT in this scenario. METHODS: We described 2 cases and comprehensively reviewed the literature finding 26 cases of LT performed in patients having a concomitant active TB and liver failure secondary to ATT toxicity. RESULTS: TB was classified as pulmonary in 18/26 (69%), nodal in 3/26 (11%) TB cases, while the remaining 5/26 cases included disseminated, pleural, renal, ovarian, and vertebral TB localization (1 case each). ATT following LT consisted mainly of isoniazid or rifampin (RIF)-sparing regimens and included primarily fluoroquinolones and ethambutol. Rejection episodes and liver toxicity were reported in 19% and 8% of patients respectively. Graft rejection was more frequent among patients treated with RIF-containing regimens (P<.001). Mortality rate was 15% after a median follow up of 12 months. In only one case was death attributed to uncontrolled TB infection. CONCLUSION: Our findings suggest that LT is an effective therapeutic option for patients with active TB developing ALF following ATT and should be considered for patients failing medical treatment.

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case Series.

BACKGROUND/AIM: Herbal and dietary supplement (HDS) hepatotoxicity is increasingly being reported in the USA. This case series describes the presenting clinical features and outcomes of seven patients with liver injury attributed to OxyELITE Pro enrolled in the Drug-Induced Liver Injury Network (DILIN) study. METHODS: The 6-month outcomes of patients with hepatotoxicity attributed to OxyELITE Pro enrolled in the DILIN prospective registry between 2004 and 2015 are presented. RESULTS: Six of the seven patients (86 %) presented in 2013 with symptoms of hepatitis and acute hepatocellular injury. The median duration of OxyELITE Pro use was 18 weeks (range 5-102 weeks). Median age was 36 years (range 28-62), 86 % were female, and 43 % were Asian. One patient had rash, none had eosinophilia, and three had antinuclear antibody reactivity. The median peak ALT was 2242 U/L, alkaline phosphatase 284 U/L and bilirubin 15.0 mg/dL. Six patients (86 %) were hospitalized, three developed acute liver failure and two underwent liver transplantation. DILIN causality scores for OxyELITE Pro were definite in 1, highly likely in 3, probable in 2, and possible in 1. Four of the five patients without liver transplant recovered completely within 6 months, while one patient had mild residual ALT elevations. CONCLUSIONS: Seven cases of severe acute hepatocellular injury attributed to OxyELITE Pro are reported. These results reinforce the need to assess for HDS supplement use in patients presenting with unexplained acute hepatitis and point to the need for additional regulatory oversight of HDS products.

The changing face of liver transplantation for acute liver failure: Assessment of current status and implications for future practice.

The etiology and outcomes of acute liver failure (ALF) have changed since the definition of this disease entity in the 1970s. In particular, the role of emergency liver transplantation has evolved over time, with the development of prognostic scoring systems to facilitate listing of appropriate patients, and a better understanding of transplant benefit in patients with ALF. This review examines the changing etiology of ALF, transplant benefit, outcomes following transplantation, and future alternatives to emergency liver transplantation in this devastating condition.

Direct intrahepatic portocaval shunt for treatment of portal thrombosis and Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) refers to hepatic venous outflow obstruction that in severe cases can lead to acute liver failure prompting consideration of revascularization or transplantation. Here, a 22 year old female with angiographically proven BCS secondary to JAK2/V617F positive Polycythemia vera on therapeutic warfarin presented with acute liver failure (ALF). Imaging revealed a new, near complete thrombotic occlusion of the main portal vein with extension into the superior mesenteric vein. An emergent direct intrahepatic portocaval shunt (DIPS) was created and liver function promptly normalized. She has been maintained on rivaroxaban since that time. Serial assessment over 1 year demonstrated continued shunt patency and improved flow in the mesenteric vasculature on ultrasound as well as normal liver function. DIPS is a viable alternative in the treatment of ALF from BCS when standard recanalization is not feasible. Improved blood flow may also improve portal/mesenteric clot burden. While further investigation is needed, new targeted anticoagulants may be viable as a long term anticoagulation strategy.

Acute liver failure associated with Garcinia cambogia use.

Millions of Americans regularly use herbal supplements, but many are unaware of the potential hidden dangers. Numerous supplements have been associated with hepatotoxicity and, indeed dietary/herbal supplements represent an increasingly common source of acute liver injury. We report a case of acute liver failure requiring liver transplantation associated with the use of Garcinia cambogia, a supplement widely promoted for weight loss. When patients present with acute hepatitis or liver failure from an unknown etiology, a careful history of supplement use should be performed.