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Background and Aims: Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America., Methods: The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21-day all-cause mortality or requirement for liver transplantation (death/LT)., Results: Patients with hypochloremia (<98 mEq/L) had a significantly higher 21-day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant-free cumulative survival in the hypochloremic group than in the normo- or hyper-chloremic groups (log-rank, χ 2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21-day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969-0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13-0.25) but underestimated the probability of transplant-free survival in 34% of patients (NRI = -0.34, 95% CI: -0.39 to -0.28)., Conclusions: Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG-Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are fatal adverse skin reactions characterized by high fever, epidermal detachment, and mucositis. It is well known that SJS/TEN occasionally affects various organs, leading to permanent damage and death in some patients. Although acute liver dysfunction is a relatively common complication of SJS/TEN, severe acute liver dysfunction requiring liver transplantation is rare. We present the case of a 14-year-old girl with SJS complicated by severe and rapidly progressive liver dysfunction, specifically, acute liver failure (ALF) requiring liver transplantation. A lymphocyte transformation test showed positive results for acetaminophen and cefdinir. Furthermore, human leukocyte antigen (HLA) genotyping revealed the presence of the HLA-A*02:06 genotype, which is reported to be strongly associated with acetaminophen-related SJS/TEN with severe ocular complications. These results suggested that our patient may have presented with acetaminophen-induced SJS complicated by ALF, but no ocular complications. This is the first report of a pediatric patient with SJS who required liver transplantation. In rare instances, severe liver dysfunction requiring liver transplantation should be considered as a possible complication of SJS/TEN., (© 2021 Japanese Dermatological Association.)

Background & Aims: Acute liver failure patients who meet poor prognostic criteria have high early mortality without emergency liver transplantation. A recent study however, reported that patients that survive spontaneously have a poorer outcome compared with patients undergoing transplantation. In this single centre study, we aimed to confirm or refute this observation., Methods: Early survivors (acute liver failure patients who survived 90 days after the ICU admission) were assessed for long-term outcomes in four distinctive cohorts, incorporating aetiology (Acetaminophen overdose or non-Acetaminophen overdose), and management strategy (conservative or liver transplantation). Chi Squared or Fisher test were used to compare outcomes among the four cohorts (P < 0.05) and Kaplan-Meier curve (Log Rank test) to represent cumulative survival., Results: Two hundred consecutive acute liver failure patients between 1990 and 2014 were included; mean age 38.3, ±12.8, male 70, 35%. 124/200 (62%) early survivors were identified; 13/124 (10.5%) acetaminophen patients underwent transplantation and 48/124 (38.7%) survived spontaneously; 36/124 (29.0%) non-acetaminophen underwent transplantation and 27/124 (21.8%) survived spontaneously. A total of 11/124 (8.9%) died subsequently (median survival 5.3± IQR 9.1), three spontaneous survivors and eight transplanted patients (P = 0.025); of the eight transplanted patients, six died of transplant related complications and two of suicide., Conclusion: The results of this study suggest that although liver transplantation is a life-saving procedure for acute liver failure patients, they have a worse long-term outcome compared with spontaneous survivors. Novel therapies to increase the percentage of spontaneous survivors are urgently needed., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4., Methods: Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors., Results: We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA., Conclusion: Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: We previously found that hepatic stellate cell activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure. Nitric oxide has shown to induce hepatic stellate cell apoptosis. Whether and how nitric oxide is involved in acute liver failure and autophagy remains unclear., Methods: Acute liver failure patients were recruited to investigate the correlation between plasma nitric oxide levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from acute liver failure patients who had undergone liver transplantation. The expression of nitric oxide synthases and hepatic stellate cell activation (alpha-SMA), and autophagic activity (LC3) were investigated by immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot analysis, confocal microscopy, and flow cytometry in hepatic stellate cells treated with nitric oxide donors., Results: Plasma nitric oxide level was significantly increased in patients with acute liver failure compared to those with cirrhosis (53.60±19.74 μM vs 19.40±9.03 μM, Z=-7.384, P<.001) and positively correlated with MELD-Na score (r=.539, P<.001), implicating nitric oxide in acute liver failure. At least some Nitric oxide was produced by overexpression of inducible nitric oxide synthases and endothelial nitric oxide synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo observation revealed that autophagy was inhibited in hepatic stellate cells based on decreased LC3 immunostaining, and in vitro experiments demonstrated that Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic stellate cell apoptosis, which was rescued by an autophagy inducer., Conclusions: Increased nitric oxide synthases/ nitric oxide promotes apoptosis through autophagy inhibition in hepatic stellate cells during acute liver failure, providing a novel strategy for the treatment of patients with acute liver failure., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: The outcome of paediatric acute liver failure largely depends on age and aetiology. The aim of this work was to study the aetiological spectrum and outcome of the paediatric acute liver failure cases., Methods: This prospective observational study included all children (<18 years age) fulfilling paediatric acute liver failure study group definition. Aetiological evaluation was done and predictive factors for poor outcome (death or liver transplantation) were analysed., Results: There were 109 children in total. The commonest aetiology was viral infections (50, 45.8%) followed by metabolic liver diseases (14, 13.2%) and drug-induced liver injury (12, 11%). Viral, indeterminate and drug-induced liver injury group were older in age, had higher international normalized ratio and alanine transaminases in comparison with those with metabolic liver diseases and other aetiologies (P<.05). At 90 days from presentation, 52 (47.7%) children survived with native liver. On multivariate analysis, jaundice to encephalopathy interval >7 days (adjusted OR: 9.16, 95% CI: 1.55-53) and higher paediatric/model for end-stage liver disease scores at 72 hours (adjusted OR: 1.2, 95% CI: 1.08-1.32) were associated with poor outcome., Conclusion: Viral infections, indeterminate and drug-induced liver injury-related paediatric acute liver failure usually present in older children with higher international normalized ratio and alanine transaminases. Jaundice to encephalopathy interval >7 days and paediatric/model for end stage liver disease score >24 at 72 hours are associated with poor outcome., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Serum ferritin and transferrin have been identified as prognostic markers in patients with chronic diseases. In this study, we investigated if these parameters can predict outcome in patients with acute liver failure., Methods: A total of 102 consecutive patients with acute liver failure were retrospectively analysed. The patients were grouped by outcome: spontaneous recovery vs liver transplantation and/or death or survival vs death. Routine laboratory parameters, transferrin and ferritin concentrations in serum, and anthropomorphic data collected on admission were analysed., Results: Non-spontaneously recovering patients had higher ferritin (12 252±25 791 vs 4434.4±9027.2 μg/L; P<.05) and lower transferrin levels (140.4±66.7 vs 206.9±65.8 mg/dL; P<.05) than spontaneously recovering patients. Similarly non-survivors exhibited higher serum ferritin and lower transferrin than non-transplanted survivors. Patients with severe hepatic inflammation (A3) had higher ferritin levels compared to patients with mild-moderate inflammation (A1-2) (5280±5094 vs 2361±2737 μg/L; P=.025). ROC analysis of single parameters was performed in non-transplanted patients, resulting in an area under the curve, sensitivity and specificity of 0.812%, 83.3%, and 77.1% for age, 0.871%, 84.1% and 75% for transferrin and 0.802%, 91.7% and 62.9% for ferritin. A model incorporating age, MELD and transferrin had the best predictive value with an area under the curve of 0.947, a sensitivity of 100% and corresponding specificity of 77.8%., Conclusions: High ferritin and low transferrin levels are associated with worse outcome in patients with acute liver failure. A model incorporating age, MELD score and transferrin outperformed MELD score for 90-day overall survival of non-transplanted patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Patients with acute liver failure have high rates of infections, likely from defects in immune function. Whether infections are independently associated with poor outcomes is unclear. We hypothesized that patients with acute liver injury who developed infections were at increased risk of adverse outcomes., Methods: We conducted a retrospective analysis of 150 critically ill adult patients admitted with acute liver dysfunction at a single academic institution between 2005 and 2011. We excluded patients with immunocompromised states, patients with chronic liver disease and patients who died or were discharged within 48 h of admission. Our primary endpoint was a 30-day event-free survival, with events defined as either death or liver transplantation. Our secondary endpoint was length of stay. Univariate and multivariate analyses were performed to determine associations between presence of infection and our primary and secondary endpoints., Results: Of our cohort of 150 patients, 62 (41%) were infected and 88 (59%) were not infected. Of the infected patients, 45% died or underwent transplantation, compared to 22% for the non-infected patients (P = 0.003). Univariate and multivariate analyses demonstrated that infections in patients with acute liver dysfunction were an independent predictor of poor outcome (i.e. death or transplantation). In addition, specific types of infection, including pneumonia, independently led to a 48% increase in length of stay (P = 0.002)., Conclusions: Infections in patients with acute liver dysfunction are associated with increased risk of death or transplant and increased hospital length of stay., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: The long-term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. The aim of this study was to provide an overview of the 2-year clinical outcomes among initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrolment in the Acute Liver Failure Study Group (ALFSG)., Methods: Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed., Results: Two-year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous survivors (SS) (89.5%) and 200 non-APAP SS (75.5%) (P < 0.0001). The causes of death were similar in the three groups but the time to death was significantly longer in the LT recipients (P < 0.0001). Independent predictors of 2-year mortality in the APAP group were a high serum phosphate level and patient age (c-statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non-APAP group (c-statistic = 0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c-statistic = 0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level (P < 0.05)., Conclusions: Two-year outcomes in initial survivors of ALF are generally good but non-APAP patients have a significantly lower survival which may relate to pre-existing medical comorbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow-up from ongoing psychiatric and substance abuse issues., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The host response to cell death underpins the immune activation that follows acute liver injury, and measurement of circulating cell death markers could therefore aid prognostication following paracetamol overdose. Nucleosomes, formed during apoptosis, can complex with high-mobility group box 1 (HMGB1) protein and may play a pathogenic role in liver injury., Aims: To explore the levels and prognostic significance of nucleosomes, HMGB1, and other cell death markers following acute liver injury., Methods: Levels of plasma nucleosomes, HMGB1, caspase-cleaved cytokeratin-18 (M30) and total cytokeratin-18 (M65) were measured by immunoassay, in a cohort of 33 patients with paracetamol- and non-paracetamol-induced acute liver injury., Results: Admission nucleosome levels in paracetamol overdose patients were significantly higher than in chronic liver disease and healthy control subjects, but were similar in paracetamol and non-paracetamol patients (P=0.11). Nucleosome levels were not associated with death or requirement for liver transplantation, fulfillment of poor prognostic criteria or organ failure in paracetamol patients. Nucleosome levels correlated with levels of HMGB1 (r=0.500, P=0.009), alanine aminotransferase (r=0.410, P=0.038) and M65 (r=0.709, P<0.001), but not with M30 (r=0.309, P=0.124). None of the cell death markers analysed improved prognostication in paracetamol patients beyond the King's College criteria., Conclusions: Plasma nucleosomes are significantly elevated following acute liver injury. Neither apoptotic nor necrotic cell death markers accurately predict survival following paracetamol-induced hepatotoxicity, suggesting that the extent and type of cell death play a limited role in determining outcome., (© 2011 John Wiley & Sons A/S.)

Aims: Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported., Methods: Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit., Results: Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P < 0.001). The King's College poor prognostic criteria had reduced sensitivity in unintentional overdoses (77.8%, 95% confidence intervals (CI) 62.9, 88.8) compared with intentional overdoses (89.9%, 95% CI 83.4, 94.5). Unintentional overdose was independently predictive of death or liver transplantation on multivariate analysis (odds ratio 1.91 (95% CI 1.07, 3.43), P = 0.032)., Conclusions: Unintentional paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

This manuscript describes a 28-year-old patient with a history of Graves' disease who was transferred to Tulane University Hospital with fulminant hepatic failure. He reported associated nausea, vomiting, anorexia, as well as jaundice and abdominal discomfort for a period of 3 weeks prior to his admission. His thyroid function tests on admission were TSH, 0.013 μU/mL; T3, 94.9 μU/mL; T4, 9.37 μU/mL; Free T4, >6 μU/mL. His liver function tests were characteristic of hepatic failure. The patient underwent an emergent liver transplant. His surgery was complicated by heart failure and acute respiratory distress syndrome. Given the patients clinical presentation and laboratory results, a diagnosis of thyroid storm was made and a decision was made to proceed with an emergent thyroidectomy. The posttransplant multiorgan dysfunction was rapidly reversed by prompt thyroidectomy and decisive management. The patient was discharged from the hospital with normal thyroid and liver function tests.

Herpes simplex virus hepatitis is a rare but potentially fatal condition that usually affects the immunocompromised, including pregnant women. This case report details the course of fulminant hepatic failure in a woman at 31 weeks gestation resulting in emergent delivery of the fetus and liver transplant in the mother., (© 2010 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2010 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure (ALF) in the UK. Patients often consume the drug with suicidal intent or with a background of substance dependence., Aims and Methods: We compared the severity of pretransplant illness, psychiatric co-morbidity, medical and psychosocial outcomes of all patients who had undergone liver transplantation (LT) emergently between 1999-2004 for acetaminophen-induced ALF (n=36) with age- and sex-matched patients undergoing emergent LT for non-acetaminophen-induced ALF (n=35) and elective LT for chronic liver disease (CLD, n=34)., Results: Acetaminophen-induced ALF patients undergoing LT had a greater severity of pre-LT illness reflected by higher Acute Physiology and Chronic Health Evaluation II scores and requirement for organ support compared with the other two groups. Twenty (56%) acetaminophen-induced ALF patients had a formal psychiatric diagnosis before LT (non-acetaminophen-induced ALF=0/35, CLD=2/34; P<0.01 for all) and nine (25%) had a previous suicide attempt. During follow-up (median 5 years), there were no significant differences in rejection (acute and chronic), graft failure or survival between the groups (acetaminophen-induced ALF 1 year 87%, 5 years 75%; non-acetaminophen-induced ALF 88%, 78%; CLD 93%, 82%: P>0.6 log rank). Two acetaminophen-induced ALF patients reattempted suicide post-LT (one died 8 years post-LT)., Conclusions: Despite a high prevalence of psychiatric disturbance, outcomes for patients transplanted emergently for acetaminophen-induced ALF were comparable to those transplanted for non-acetaminophen-induced ALF and electively for CLD. Multidisciplinary approaches with long-term psychiatric follow-up may contribute to low post-transplant suicide rates seen and low rates of graft loss because of non-compliance.

Introduction: Liver transplantation (LT) in cirrhotics is characterized by severe coagulopathy, associated with a well documented heparin-like effect (HLE) seen by thromboelastography (TEG) after reperfusion. The amount of HLE present in patients with acute liver failure (ALF) and its role in their bleeding tendency before LT has not been investigated., Aim: To investigate the presence and extent of HLE in patients with ALF undergoing LT and to compare the extent of HLE in this group with a group of cirrhotics undergoing LT., Material and Methods: Ten consecutive ALF and 10 cirrhotic patients undergoing LT were included. TEG (with and without heparinase I), surrogate total thrombin generation (TTG) derived by TEG and haemodynamic variables were recorded for every stage of the LT. HLE was defined as a correction of r+k times on TEG of more than 50% by the addition of heparinase I., Results: Before incision, patients with ALF showed a significantly greater HLE compared with patients with cirrhosis (r+k time: 66 min corrected to 29 vs 45 min corrected to 32 min, P=0.001). After reperfusion, all the patients showed extensive HLE, without any difference between the two groups. Despite the greater HLE, patients with ALF showed similar TTG compared with the cirrhotic group. By the end of the operation, the extent of the HLE was greatly reduced in both the groups., Conclusions: Before transplantation, patients with ALF have a greater HLE than patients with liver cirrhosis. However, this did not affect the thrombin generation calculated by TEG and resolved after transplantation.

Background/aims: Although eosinophils are considered to play an important role in the pathogenesis of various parasitic, allergic and autoimmune digestive diseases, their role in fulminant hepatic failure (FHF) is unknown. Our contribution was to identify and quantify eosinophils and cytokine levels [interleukin (IL)-6, IL-5 and macrophage inflammatory protein (MIP)-1alpha] in liver parenchyma and peripheral blood from FHF patients at pre- and post-transplantation steps., Methods: Histochemical methods were used to identify/quantify eosinophils in liver samples. Liver and plasma cytokine levels were quantified using immunofluorescence methods., Results: Fulminant hepatic failure patients showed a high number of intrahepatic eosinophils concomitant with an increased expression of IL-6, besides the IL-6-positive eosinophils associated with the lack of IL-5. Also, an increased number of eosinophils and soluble IL-6 and MIP-1alpha with a low expression of IL-5 in peripheral blood at the pretransplantation step was observed., Conclusions: The increased number of intrahepatic eosinophils, besides the high production of IL-6, may be involved in liver dysfunction. In addition, the low presence of IL-5 in liver and peripheral blood may represent a particular pattern of eosinophil behaviour in human liver failure, which may also involve MIP-1alpha. Further ex vivo studies are necessary to evaluate the specific role of eosinophils in FHF.

Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.

Background: Severe liver dysfunction occurring during pregnancy is an unusual but dramatic event that poses special technical and ethical issues because it involves two lives., Methods and Results: We report the case of a 35-year-old woman with cryptogenic fulminant hepatic failure who underwent successful orthotopic liver transplantation at 22 weeks of pregnancy. After a relatively uneventful post-operative course she delivered a normal offspring at the 27th week of gestation. There were no obstetrical complications and neonatal outcome was excellent. After a year of follow-up, the patient is doing well,and the newborn has exhibited normal psychomotor and weight/height development., Conclusion: This case illustrates the challenge of treating fulminant hepatic failure during pregnancy and demonstrates that liver transplantation is a feasible therapeutic option for treatment of patients with this condition, allowing successful completion of pregnancy.

Background: We report on our experiences with orthotopic liver transplantation (OLT) in HIV-infected patients. Between July 1998 and October 2001, five HIV-infected patients underwent OLT because of virus-induced liver cirrhosis. One patient suffered from hepatitis B virus (HBV)-, three patients from hepatitis C virus (HCV)- and one patient from HCV/HBV/HDV-related cirrhosis (HDV, hepatitis D virus). The mean duration of HIV infection was 15 years. Patients were prospectively followed up with a mean duration of 25.6 months., Results: Three patients died 3, 10 and 31 months after OLT, respectively, due to graft failure. The causes of graft failure were: recurrent thrombosis of the hepatic artery, HCV-associated cholestatic hepatitis and chemotherapy-induced liver damage due to Hodgkin's disease, which was diagnosed 17 months after OLT, in addition to chronic HCV disease. The two survivors show a stable liver function and non-progredient HIV infection under antiretroviral therapy 61 and 23 months after OLT, respectively., Conclusions: A medium- or even long-term survival after OLT can be achieved in HIV-infected patients without progression of HIV disease under antiretroviral therapy. However, in our study three out of five patients died due to graft failure. Therefore, prognostic criteria have to be defined for the selection of HIV-infected patients, who may benefit from OLT.

Background: Mechanical hyperventilation is an established treatment to reduce brain edema and intracranial pressure in patients with encephalopathia caused by acute liver failure. Hyperventilation and ensuing hypocarbia may also affect central and systemic circulation and thereby influence graft performance in patients following orthotopic liver transplantation (OLT)., Methods: We measured the effects of normocapnia and hypocapnia on systemic hemodynamics, gastric tonometry, as a marker of splanchnic oxygenation, and the indocyanine green kinetic, as a global marker of graft function, in humans post OLT., Results: Hyperventilation was performed to a PaCO2 of 4.2 +/- 0.4 kPa (31 +/- 3.4 mm Hg) for about 1 h in 14 liver transplant recipients. Systemic hemodynamics as well as indices of splanchnic oxygenation and indocyanine green kinetics remained statistically unchanged., Conclusion: We did not observe any statistically significant circulatory effects or changes in indocyanine green kinetics in liver transplant recipients in the immediate OLT postoperative period caused by short-term mechanical hyperventilation.

To simplify liver support using an ex vivo perfused liver, an isolated pig liver was perfused with arterial blood from the recipient pig while monitoring the metabolic capacity of the ex vivo perfused liver. It was possible to perfuse the isolated liver for more than 24 h using arterial blood from a pig with ischemic liver failure. The viability of the isolated liver during support from the liver failure pig was well maintained as evidenced by the high adenylate energy charge (0.815) and a constant ketone body ratio (KBR) of over 1.0 sampled from the hepatic vein. Oxygen consumption (mean, 29.0 microl/min/g of liver) and bile production (mean, 24.2 microl/h/g of liver) were significantly higher in the isolated liver connected to the liver failure pig than in the organ connected to the pig without liver failure (15.5 microl/min/g and 7.3 microl/h/g, respectively). These findings suggest that this liver support system has sufficient metabolic capacity to support a failed liver. Further studies may provide the experimental basis necessary for the clinical application of this device in treatment of patients with acute liver failure.

Acute liver failure (ALF) is a relatively uncommon but dramatic clinical syndrome with high mortality rates, in which a previously normal liver fails within days or weeks. Paracetamol overdose remains the major cause of ALF in the UK, while viral hepatitis is the commonest cause world-wide. Cerebral oedema is the leading cause of death in patients with ALF. Despite advances in intensive care and the development of new treatment modalities, ALF remains a condition of high mortality best managed in specialist centres. Orthotopic liver transplantation is the only new treatment modality that has made a significant impact in improving outcome. Bioartificial liver support systems and hepatocyte transplantation are new promising treatment options that may change the management of ALF in the future.