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Many drugs are known to potentially cause liver injury; however, only a few reports investigate the association between levofloxacin and acute liver failure (ALF).  The case describes a 65-year-old man who was admitted with primary diagnoses of cerebrovascular accident (CVA) and acute coronary syndrome (ACS) who developed an upper respiratory tract infection for which he was started on levofloxacin. Following its administration, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased more than 100-fold above the upper limit of normal. Over the next 24 hours, AST peaked at 9334 U/L, ALT at 4525 U/L, prothrombin time to 24.6 seconds, international normalized ratio (INR) to 2.22, and serum ammonia to 157 µmol/L. The patient developed signs and symptoms of decompensated liver disease, namely hepatic encephalopathy (HE). Levofloxacin was discontinued immediately, and evidence-based treatment per society guidelines from The American Association for the Study of Liver Diseases consisting of IV n-acetylcysteine as well as lactulose and rifaximin was initiated. Such medical management resulted in clinical resolution of his ALF, but he had a poor overall prognosis and eventually succumbed to critical illness.

Fulminant liver failure is usually characterized as severe acute liver injury with encephalopathy and synthetic dysfunction (international normalized ratio [INR] ≥1.5) in a patient without cirrhosis or previous liver disease. Management of patients with acute liver failure includes ensuring that the patient is cared for appropriately, monitoring for worsening liver failure, managing complications, and providing nutritional support. Patients with acute liver failure should be treated at a liver transplant center whenever possible. Serial laboratory tests are used to monitor the course of a patient's liver failure and to monitor for complications. It is necessary to monitor the level of aminotransferases and bilirubin in serum daily. More frequent monitoring (three to four times a day) of blood coagulation parameters, complete blood count, metabolic panels, and arterial blood gases should be performed. For some causes of acute liver failure, such as acetaminophen intoxication, treatment directed at the underlying cause may prevent the need for liver transplantation and reduce mortality. Lactulose has not been shown to improve overall outcomes, and it can lead to intestinal distention, which can lead to technical difficulties during liver transplantation. Early in acute liver failure, signs and symptoms of cerebral edema may be absent or difficult to detect. Complications of cerebral edema include increased intracranial pressure and herniation of the brain stem. General measures to prevent increased intracranial pressure include minimizing stimulation, maintaining an appropriate fluid balance, and elevating the head of the patient's bed. For patients at high risk of developing cerebral edema, we also offer hypertonic saline prophylaxis (3%) with a target serum sodium level of 145 to 155 mEq/L (level 2C). High-risk patients include patients with grade IV encephalopathy, high ammonia levels (>150 µmol/L), or acute renal failure, and patients requiring vasopressor support. Approximately 40 % of patients with acute liver failure recover spontaneously with supportive care. Predictive models have been developed to help identify patients who are unlikely to recover spontaneously, as the decision to undergo liver transplant depends in part on the likelihood of spontaneous recovery of the liver. However, among those who receive a transplant, the one-year survival rate exceeds 80 %, making this treatment the treatment of choice in this difficult patient population.

In the era of antiretroviral therapy (ART), Hodgkin Lymphoma (HL) is a common non-AIDS-defining cancer with increasing incidence in people with human immunodeficiency virus (PWH). Through review of these cases, we identify clinical patterns such as declining CD4 count despite ART, hyperbilirubinemia and recurrent fever, which preceded diagnosis. Identifying these important signs and symptoms may lead to earlier diagnosis and initiation of therapy. Fulminant hepatic failure limits the ability to give standard of care chemotherapy, likely jeopardizing outcomes in this patient population. Alternative bridging therapies should be considered until hepatic function improves. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios. [ABSTRACT FROM AUTHOR]

The introduction of new stimulants seems not to hamper the still widespread consumption of MDMA (3,4-methylenedioxymethamphetamine) among young people, especially in determined nightlife settings. Herein, we present two different MDMA-related deaths, providing pathological, histopathological and toxicological data integration. A hypothesis for the mechanisms of the deaths is also discussed. Case 1: an insulin-dependent 16-year-old girl died in a discotheque after the ingestion of MDMA. Before dying she presented seizure, bruxism, trismus, sweating and reduced consciousness. Biochemistry showed hyperglycaemia and hyponatraemia. Toxicological analyses revealed blood MDMA concentration of 1750 ng/mL. Autopsy, accompanied by histological examination, identified cerebral oedema due to hypotonic hyponatraemia as cause of death. Case 2: a 16-year-old girl collapsed during dancing at a rave party. She died 15 hours later in hospital. Autopsy and histology revealed epicardial haemorrhage, hepatitis and disseminated intravascular coagulation. Toxicological analyses revealed blood MDMA concentration of 3700 ng/ml. Cause of death was identified as fulminant liver failure. Since death is not strictly correlated with MDMA blood concentration, to better understand the aetiology of the death after MDMA consumption an integrated and multidisciplinary approach is strongly recommended. [ABSTRACT FROM AUTHOR]

Acute liver failure is a rare but important clinical syndrome, with a high mortality rate. Prompt recognition, appropriate management and early referral to a liver transplant centre can lead to good outcomes in these critically unwell patients. This article gives an overview of the key clinical challenges and optimal management of patients with acute liver failure. Acute liver failure is defined and a comprehensive list of aetiologies and suggested investigations is provided. The clinical challenges of sepsis, renal impairment, coagulopathy, hypoglycaemia, haemodynamic instability and cerebral oedema are discussed. Quadruple H therapy, a combination of therapies aimed to reduce cerebral oedema in acute liver failure, is described. A systemic guide to managing patients with acute liver failure is provided, as are indications for referral to a liver transplant centre. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure (ALF) may be the first and most dramatic presentation of Wilson's disease (WD). ALF due to WD (WD-ALF) is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation. There is no firm recommendation on specific and supportive medical treatment for this condition., Aim: To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver., Methods: A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023., Results: During the study period, 16 children (9 males) received a diagnosis of WD and 2 of them presented with ALF. The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids, and survived without liver transplant. The second, exclusively treated with supportive therapy, needed a hepatotransplant to overcome ALF., Conclusion: Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition, which is currently only treated with liver transplantation., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: In India, infectious Hepatitis is one of the major health care burdens, with viral hepatitis being the most common culprit, followed by dengue, typhoid, and malarial hepatitis. Fulminant hepatitis manifests as a sudden abnormality in liver function enzymes in a child with no prior hepatic pathology. Aims and Objects: This study was aimed at identifying the various etiological factors and correlating clinical features of viral hepatitis, and fulminant liver failure. Materials and Methods: This observational study was conducted in the paediatrics in-patient department of S.P. Medical College & P.B.M. Associated Group of Hospitals, Bikaner (Rajasthan) over a period of one year. A total of 125 children with a clinical and lab-confirmed diagnosis of acute infective hepatitis were included. Data including clinical signs, symptoms, and laboratory parameters were obtained and analyzed. Results: Most commonly affected age group was between 5-10 years with the mean age being 7.1±4.6 years. The most common etiology was hepatitis A (n=39), followed by hepatitis E (n=24) and mixed hepatitis A virus (HAV)/hepatitis E virus (HAE) infection (n=20). Other causative organisms were dengue virus (n=16), typhoid (n=13), malaria (n=9), and hepatitis B. The most common clinical symptoms were fever, jaundice, loss of appetite, and vomiting/nausea. There were some clinical features seen more commonly in case of infection with certain organisms. High frequency of diarrhoea, arthralgia, and thrombocytopenia was seen with HAV. Neurological, renal complications and high mortality were associated with HEV or HAV/HEV co-infection. While retroorbital pain and purpuric rash were exclusive with dengue, malarial hepatitis was strongly associated with pallor and altered sensorium. Conclusion: Acute infective hepatitis is most commonly caused by HAV and HEV in Western Rajasthan. It is imperative to educate the masses regarding the prevention of common infections transmissible by infected drinking water, poor hand hygiene, improper waste disposal, and open defecation.

Introduction: In India, infectious Hepatitis is one of the major health care burdens, with viral hepatitis being the most common culprit, followed by dengue, typhoid, and malarial hepatitis. Fulminant hepatitis manifests as a sudden abnormality in liver function enzymes in a child with no prior hepatic pathology. Aims and Objects: This study was aimed at identifying the various etiological factors and correlating clinical features of viral hepatitis, and fulminant liver failure. Materials and Methods: This observational study was conducted in the paediatrics in-patient department of S.P. Medical College & P.B.M. Associated Group of Hospitals, Bikaner (Rajasthan) over a period of one year. A total of 125 children with a clinical and lab-confirmed diagnosis of acute infective hepatitis were included. Data including clinical signs, symptoms, and laboratory parameters were obtained and analyzed. Results: Most commonly affected age group was between 5-10 years with the mean age being 7.1±4.6 years. The most common etiology was hepatitis A (n=39), followed by hepatitis E (n=24) and mixed hepatitis A virus (HAV)/hepatitis E virus (HAE) infection (n=20). Other causative organisms were dengue virus (n=16), typhoid (n=13), malaria (n=9), and hepatitis B. The most common clinical symptoms were fever, jaundice, loss of appetite, and vomiting/nausea. There were some clinical features seen more commonly in case of infection with certain organisms. High frequency of diarrhoea, arthralgia, and thrombocytopenia was seen with HAV. Neurological, renal complications and high mortality were associated with HEV or HAV/HEV coinfection. While retroorbital pain and purpuric rash were exclusive with dengue, malarial hepatitis was strongly associated with pallor and altered sensorium. Conclusion: Acute infective hepatitis is most commonly caused by HAV and HEV in Western Rajasthan. It is imperative to educate the masses regarding the prevention of common infections transmissible by infected drinking water, poor hand hygiene, improper waste disposal, and open defecation. [ABSTRACT FROM AUTHOR]

Abstract Background Fulminant liver failure (FHF) is a serious clinical problem and liver transplantation is the major intervention. But the overall survival rate of FHF is low owing to the donated organ shortage. Apolipoprotein A-V (ApoA5) is a regulator of triglyceride metabolism and has been reported to act as a predictor for remnant liver growth after preoperative portal vein embolization and liver surgery. This study aimed to investigate the therapeutic effect of ApoA5 on lipopolysaccharide/d-galactosamine (LPS/d-GalN)—induced fulminant liver failure in mice. Methods FHF mouse model was established using LPS/d-GalN and ApoA5 plasmid was injected by tail vein prior to LPS/d-GalN treatment. The expressions of ApoA5, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B p65 (NF-κBp65) were assessed by real-time PCR and western blotting. Serum alanine aminotransferase (ALT) and tumor necrosis factor-α (TNF-α) levels were measured using automatic biochemical analyzer. Histological assessment and immunohistochemical (IHC) staining were conducted. Survival rate after LPS/d-GalN administration was also determined with Kaplan–Meier curve. Meanwhile, the expression of ApoA5 in injured huh7 cells was tested. Cell apoptosis analysis was performed after huh7 cells were transfected with ApoA5 plasmid and stimulated with LPS. Results The expressions of ApoA5 decreased both in injured huh7 cells and FHF mice. ApoA5 overexpression reduced cell death rate using flow cytometry. ApoA5 not only decreased the serum ALT and TNF-α levels but also attenuated hepatic damage in hematoxylin–eosin (HE)-stained liver section. The protein expressions of TLR4, MyD88 and NF-κBp65 were inhibited when ApoA5 overexpressed. But the inhibitory effect would weaken with the increasing concentration of LPS in spite of ApoA5 overexpression. Besides, ApoA5 improved liver injury in a dose-dependent manner and the survival rate in FHF mice increased with increasing concentration of ApoA5. Conclusion ApoA5 had a protective effect against LPS/d-GalN-induced fulminant liver failure in mice within a certain range by inhibiting TLR4-mediated NF-κB pathway.

Abstract Background Dengue has global importance as a dreaded arboviral infection. It has 4 serotypes of epidemiological imporatnce. The classification denotes two clinical spectrums- dengue fever (DF) and dengue haemorragic fever (DHF). Most cases are stereotype and amenable to fluid resuscitation. However, unusual manifestations cause fatalities and often overlooked. This study describes 10 such dengue cases to fill the knowledge gaps. Case presentation All 10 patients presented to the Teaching Hospital, Peradeniya, Sri Lanka during mid-year epidemic of dengue in 2016. The mean age is 27 years (range 12-51 years) comprising 6 females and 4 males. The group had 7 DHF, 3 DF and 2 primary dengue infections who predominantly had severe bleeding into gut. Other potentially life threatening problems were acute severe hepatitis, severe septic shock, myocarditis, erratic rapid plasma leak, intracranial bleeding, diarrhoea and decompenstaed dengue shock due to 3rd space fluid leak. Blood transfusions and other empirical therapeutic methods were used apart from meticulous fluid management to suit issues of each patient. Bedside ultrasound scanning helped early detection of critical phase. All recovered fully. Conclusions Dengue is an extremely challenging infection to treat in the globe today. Above unusual presentation and complications could be fatal, if not detected early where therapeutic window period is very short. Clinicians need awareness of these problems which are not uncommon, but underreported and often overlooked. The clinical management of each patient was described for the purpose sharing the experiences.

Background and Aims: Traditional laboratory markers are insensitive in distinguishing between patients with acute liver failure (ALF) who will require urgent liver transplantation (LT) from those who will recover spontaneously, particularly within 24 h of presentation. Coagulation factor-V (FV) may improve the accuracy of outcome prediction in ALF due to its predominant synthesis in the liver and short half-life in plasma. Methods: Patients enrolled in the ALF Study Group Registry from a single site had FV determined within 24 h of presentation (Derivation-Cohort). Area under the receiver operating characteristic curves (AUROC) dichotomized by ALF etiology [acetaminophen (APAP) or non-APAP] were constructed to evaluate the diagnostic performance of FV for transplant-free-survival (TFS). Multivariate logistic regression modeling was performed using FV and other clinical variables to predict TFS. Accuracy of FV and multivariable model were performed in a Validation-Cohort from a different site. Results: 90-patients (56% with APAP) were included in the Derivation-Cohort. Median FV was significantly higher in TFS versus those who died/LT (31% vs. 15%, respectively; p = 0.001). When dichotomized by etiology, AUROC for FV was 0.77 for APAP (cutoff, sensitivity, specificity 10.5%, 79%, 69%, respectively) and 0.77 for non-APAP (22%, 85%, 67%, respectively). When the optimal cutoffs for FV in the Derivation-Cohort were applied to the Validation-Cohort (N = 51; 59% with APAP), AUROC for FV was 0.75 for APAP (sensitivity/specificity 81/44) and 0.95 for non-APAP (sensitivity/specificity 90/73). In multivariate analyses, AUROC for FV model was 0.86 in the Derivation-Cohort and 0.90 in the Validation-Cohort. Conclusion: Admission FV may improve selection of patients who are likely to improve without LT. [ABSTRACT FROM AUTHOR]

We aimed to share our case who developed liver failure due to covid-19, which is more severe than we have ever encountered. A 67-year-old male patient was brought to our hospital by ambulance with complaints of weakness and eating and drinking disorder. In the first examination, the patient was conscious, oriented and cooperative. The liver and kidney function tests and whole blood parameters of the patient at the first admission were within normal limits. The patient was admitted to the intensive care unit because of comorbidities and oxygen support may be required. It was found that the patient's liver function tests were found to be elevated in the examinations on the first intensive care unit day. Transplantation and Plasmapheresis could not be performed due to the patient's general condition. In the follow-up, orotracheal intubation was performed for the patient whose general condition deteriorated, blood pressure decreasing and positive inotropic therapy was initiated on the second ICU day. The patient whose general condition deteriorated could not be saved despite all interventions. Although our knowledge about SARS-CoV-2 is not sufficient yet, we think that it should be kept in mind that it may also cause fulminant liver failure. [ABSTRACT FROM AUTHOR]

Introduction. Congenital syphilis is a well-known infectious disease caused by the passing of Treponema pallidum from the infected mother to the fetus. In most cases, it leads to fetal death. Still, in the survivors, it can manifest clinically as early congenital syphilis in the first two years of life or late congenital syphilis after ward. Current epidemiological data suggest that the incidence is very low in developed countries due to screening. Case report. We report the case of a 2-month-old male infant who presented with a sepsis-like picture, generalized edema, and hepatosplenomegaly. He had elevated inflammatory markers (C-reactive protein and procalcitonin), acute kidney injury, and fulminant liver failure. The radiographic exam revealed periostitis of the long bones. The brain magnetic resonance imaging (MRI) revealed encephalitis, ventriculomegaly and cerebral atrophy, suggesting neurosyphilis. The diagnosis of congenital syphilis was confirmed by the positive Venereal Disease Research Laboratory (VDRL) test. We initiated the treatment with penicillin, then we associated ceftriaxone for neurological involvement. He also needed blood transfusions due to severe anemia and thrombocytopenia, diuretics, and hydrocortisone treatment. Conclusions. There are cases when screening methods are omitted, therefore congenital syphilis should always be considered in the differential diagnosis of sepsis in young infants. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchange (TPE) has been utilized in various liver disorders. There is limited data on the efficacy of TPE in patients with acute liver failure (ALF). Methods: Study group consisted of patients who underwent TPE for ALF due to yellow phosphorous poisoning (YPP) between 2015 and 2019. Demographic data and biochemical parameters were recorded before and after TPE. Overall survival and transplant-free survival (based on King's College Hospital Criteria [KCHC]) were analyzed. Results: Forty-three patients underwent TPE for ALF due to YPP. Most of them were young males. Overall survival was 34 (79.06%). In our study population, 20 patients fulfilled KCHC (Group A) and 23 did not fulfill KCHC (Group B). Both the groups showed significant improvement in alanine aminotransferase, aspartate aminotransferase, and international normalized ratio (INR) after TPE (p < 0.05). In Group B, there was significant improvement in ammonia after TPE (p < 0.05) and all 23 patients (100%) survived after TPE. In Group A, 4 underwent liver transplantation (LT), 7 survived without LT, and the remaining 9 died without LT. Mean survival after completing TPE was 41.2 ± 44.5 days in Group A and 90 days in Group B. This difference was statistically significant (p = 0.001). There was statistically significant difference in post-TPE values of INR (p = 0.012) and ammonia (p = 0.011) between non-survivors and survivors. Adverse events such as hypotension (11.62%) and minor allergic reaction (4.65%) were managed conservatively. Conclusion: TPE is an effective procedure in ALF due to YPP, not fulfilling KCHC for LT. In KCHC fulfilled group, though it shows LT-free survival benefit, there is requirement of prospective, large volume, multi-center study to assess its efficacy. [ABSTRACT FROM AUTHOR]

Background and Aim: Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague. Methods: We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three‐dimensional reconstruction of serial sections were applied. Results: Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed α‐fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re‐establish the hepatic lobules. Conclusions: Regeneration of human livers following massive hepatic necrosis can occur in two ways—either through proliferation of α‐fetoprotein‐positive acinary‐arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications. [ABSTRACT FROM AUTHOR]

Abstract Background The pathogenesis of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is not well understood. The aim of this study was to investigate whether there is an association between HBV polymerase (P)/overlapping surface (S) gene and basal core promoter (BCP)/precore (PC) variants and development of ACLF in CHB. Methods Two CHB patient cohorts were compared: (i) ACLF (N = 12) (11/12 M, median age 52 yrs., 5/9 genotype C, 6/12 HBeAg+), (ii) 27 treatment native CHB carriers (15/27 M, median age 44 yrs., 9 genotype B, 10 genotype C, 1 genotype A, 5 genotype D, 2 genotype E). Clonal sequencing of PCR-amplified HBV P/S and BCP/PC gene fragments was done and HBV diversity, frequency of immune escape (IE) and drug resistance (DR) mutations and mutations in BCP/PC gene (G1896A and A1762T/G1764A), were compared between each group. Results Our data showed the incidence of IE and clusters of mutations in the HBV S region was significantly greater in ACLF patients vs. treatment naïve CHB patients (p

Wilson’s disease is a rare congenital disease caused by deficiency of the copper-transporting P-type ATPase-B enzyme. The course of disease varies widely from the latent form to the acute liver failure which is observed in 5% of Wilson’s disease cases. This clinical case represents experience of liver transplantation as the only curative treatment for patients with fulminant form of Wilson’s disease demonstrating excellent postoperative results. Living donor liver transplantation allows performing the operation in the shortest possible time which is necessary in acute liver failure. The plasmapheresis with plasma exchange AB (IV) allows preparing the patient for transplantation with incompatible blood group.

Background: Work from our laboratory has shown that the ethanol-induced increase in apoptotic hepatocellular death is closely related to the impairment in the ability of the asialoglycoprotein receptor (ASGP-R) to remove neighboring apoptotic cells. In this study, we assessed the role of ASGP-R in fulminant liver failure and investigated whether prior treatment with betaine (a naturally occurring tertiary amine) is protective. Methods: Lipopolysaccharide (LPS; 50 μg/kg BW) and galactosamine (GalN; 350 mg/kg BW) were injected together to wild-type and ASGP-R-deficient mice that were treated for two weeks prior with or without 2% betaine in drinking water. The mice were sacrificed 1.5, 3, or 4.5 h post-injection, and tissue samples were collected. Results: LPS/GalN injection generate distinct molecular processes, which includes increased production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thus causing apoptosis as evident by increased caspase-3 activity. ASGP-R deficient animals showed increased liver caspase activities, serum TNF-α and IL-6 levels, as well as more pronounced liver damage compared with the wild-type control animals after intraperitoneal injection of LPS/GalN. In addition, prior administration of betaine was found to significantly attenuate the LPS/GalN-induced increases in liver injury parameters. Conclusion: Our work underscores the importance of normal functioning of ASGP-R in preventing severe liver damage and signifies a therapeutic role of betaine in prevention of liver injuries from toxin-induced fulminant liver failure.

Objective: To evaluate the effects of molecular adsorbent recirculating system (MARS) and therapeutic plasma exchange (TPE) on patients with amanita phalloides- induced fulminant liver failure.Material and Methods: We retrospectively analyzed nine cases of amanita phalloides poisoning where MARS and/or TPE was applied.Results: The survival rate for the nine patients in this study was 66.7%. Patients who received both MARS and TPE therapies experienced higher survival rates than those who received MARS or TPE alone (100% vs 0%, 50%). A single session of TPE produced greater improvements in ALT (-58.6% vs -12.5%), AST (-44.2% vs -26.9%), total bilirubin (-44.4% vs -12.5%), and PT (-51.2% vs -4.89%) compared to a single session of MARS (all p

Acute liver failure (ALF) is a life-threatening condition with many possible causes. In developed countries, common causes include paracetamol overdose, toxin exposure (e.g. mushrooms) and idiosyncratic drug reactions. Viral hepatitis is much more common in developing countries, although must be considered in any location. The clinical syndrome of ALF is remarkably independent of the cause and comprises the following key features: jaundice, encephalopathy with cerebral oedema, coagulopathy, vasodilatory state, renal dysfunction, hypoglycaemia and immune dysfunction. Management of the patient with severe ALF is threefold in aim: (i) prevent further liver damage by treating the underlying cause of ALF where possible; (ii) prevent and treat complications of ALF (e.g. cerebral oedema, shock and infection); and (iii) early referral to specialist centre for consideration of liver transplantation. Despite modern intensive care practices, the mortality of severe ALF remains high. Optimal supportive care aims to extend the period available to source an organ for transplantation and/or to allow full recovery. This article provides a practical approach to the diagnosis and management of critically ill patients with ALF. [ABSTRACT FROM AUTHOR]

Introduction. Drug-induced liver injury (DILI) remains a major problem for drug development and represents a challenging diagnosis for clinicians. The absence of specific biomarkers for diagnosing DILI precludes the availability of reliable data on the epidemiology of the disease. In this study we aimed to describe the features of idiosyncratic hepatotoxicity reports in Latin American countries.Material and methods. A literature search was performed using the online version of MEDLINE, EMBASE, Scopus, Google Scholar and specific data bases from Latin America (LA) (Scielo, Lilacs) to identify any case report or case series of published DILI from 1996 to 2012. From 1996 to 2012, a total of 176 patients with DILI were published in LA, involving 53 suspicious drugs. The median age in the adult population of these patients was 55 years (17-82) with prevalence of women (67%). Among main therapeutic classes, the rank order was led by non-steroidal anti-inflammatory (61 cases) and systemic antibacterial drugs (37 cases). Nimesulide was the individual drug responsible for the highest number of cases (53), followed by cyproterone acetate (18), nitrofurantoin (17), antituberculous drugs (13) and flutamide (12). Thirty two percent of published cases evolved to acute liver failure (ALF), and half of the subjects required liver transplantation or eventually died.Conclusions. This study represents the first structured attempt to assess the spectrum of DILI profile in LA. The establishment of a Latin American registry to collect prospective DILI cases using a standardized protocol will advance our knowledge about idiosyncratic DILI in this region.

No abstract available. Article truncated at 150 words. The fellows performed an excellent follow-up to our last journal club in which we reviewed the above article. This cohort consisted of 140 patients who underwent ICP monitoring for grade III/VI encephalopathy, and 489 non-monitored controls. Only 87/140 (62%) of monitored patients had sufficient available data for analysis, 51% of whom had demonstrable intracranial hypertension (ICH) that was associated with nearly a doubling of mortality (43 vs.23% p=0.05). Monitoring and control groups were dissimilar. Monitored patients were statistically more likely to require mechanical ventilation, vasopressors and dialysis, and ultimately more than twice as likely to undergo liver transplant. Reasonably, monitored patients also received more treatments aimed at reducing ICH including osmotic therapy and hypothermia, although no treatment protocol was stipulated. Fatal hemorrhagic complications of ICP monitoring occurred in 3 of 56 patients for whom this outcome could be determined. Overall, 21-day mortality was similar in monitored and control patients: 33% ...

Background There is no standard therapy for acute liver failure. Hepatocyte transplantation has been proposed for temporary liver function support, while the injured liver regenerates or while waiting for transplantation. We have previously shown such efficacy for microencapsulated porcine hepatocytes in mice with fulminant liver failure. We aimed to establish a large animal model for fulminant liver failure to assess the efficacy of microencapsulated porcine hepatocytes in temporary liver function support. Methods The model was developed in baboons; for testing microencapsulated hepatocytes, the best condition was 75% hepatectomy and 60 min warm ischemia time. Fulminant liver failure was characterized by steep increases in liver biochemical parameters, severe steatosis, and massive hepatocyte necrosis during the first 10 days. Hepatocytes from miniature swine were microencapsulated in alginate-poly- l-lysine microspheres, and transplanted intraperitoneally immediately after hepatectomy and warm ischemia (80-120 mL packed hepatocytes in 200-350 mL microspheres, about 30%-50% of the baboon's native liver volume). Results In the control group, three of five animals were sacrificed after 6-10 days because of fulminant liver failure, and two of five animals recovered normal liver function and survived until elective euthanasia (28 days). In the treatment group of four animals, one animal developed liver failure but survived to 21 days, and three animals recovered completely with normal liver function. Conclusions The results indicate that microencapsulated porcine hepatocytes provide temporary liver function support in baboons with fulminant liver failure. These data support development of this cell therapy product toward clinical trials in patients with acute liver failure. [ABSTRACT FROM AUTHOR]

Background. Acute liver failure (ALF) is a rare but potentially life-threatening condition and liver transplantation (LTX) remains frequently the only effective therapy. Nevertheless, some patients recover without LTX but the individual indication for or against LTX remains difficult.Aim. To evaluate maximal liver function capacity (LiMAx) for predicting the prognosis of ALF.Material and methods. Clinic data of 12 patients was retrospectively analyzed to compare the different liver function test results with the patients’ clinical outcome. Patients were assessed by the LiMAx test, a non-invasive breath test determining cytochrome P450 1A2 capacity using intravenous 13C-methacetin. Statistical analysis compared patients with spontaneous recovery versus non-recovery (LTX or death).Results. Twelve patients (6 male, 6 female; 49 [11–72] years) with viral hepatitis (n = 2), toxic liver injury (n = 3), or cryptogenic liver failure (n = 7) were analyzed. Seven patients fully recovered from ALF and were discharged without LTX. Three patients died and two underwent LTX. The King’s College Criteria (KCC) was fulfilled in only one out of five patients without recovery. The LiMAx was 19 ± 19 (16–62) for non-recovery vs. 94 ± 119 (39–378) μg/kg/h for recovery (P = 0.018). In contrast, all biochemical parameters [bilirubin (P = 0.106), creatinine (P = 0.343), AST (P = 0.53), ALT (P = 0.876) and INR (P = 0.876) were statistically indistinct. Also the Model for End-Stage Liver Disease (MELD) score did not show a difference [35 ± 4.3 (29–40) vs. 30 ± 11.5 (6–40); P = 0.27].Conclusions. Maximal liver function capacity determined by LiMAx test is severely impaired in patients with ALF. The LiMAx test might be effective in predicting the individual prognosis and the need for LTX in ALF.

Introduction. There is significant geographic variation in the etiology and prognosis of acute liver failure (ALF). Since, little information is available for Latin America. We analyzed ALF mortality trends in Mexico.Material and methods. The rates of mortality attributable to ALF were obtained for 1998 to 2009 from the National System of Health Information in Mexico and analyzed according to date, etiology, sex, age and geographic characteristics through graphical assessment and joinpoint regression.Results. From 1998 to 2009, 2,193 ALF-related deaths were reported. A threefold increase in ALF mortality was observed during the period from 1998 to 2009 (the global mortality rate increased from 13.1 to 40.2 deaths per 10,000,000 inhabitants). The most significant increase was observed for viral etiologies after 2006, affecting people 45 years old and over.Conclusion. ALF-related deaths have increased since 2006. Although we cannot speculate on the specific causes of this increase, it may reflect improvements in the access of vulnerable populations to health care.

Acute liver failure is a rare but often catastrophic illness affecting the liver and multiple organ systems. Patients with acute liver failure require a multidisciplinary approach for adequate management. With improved critical care and the availability of liver transplantation, survival has significantly improved. Hepatic encephalopathy, cerebral edema and infections are the most common complications of acute liver failure. The evaluation requires a diligent search for a specific etiology of the liver failure, since certain causes may respond well to specific pharmacological therapies. Acetaminophen and non-acetaminophen drug-induced hepatotoxicity account for more than 50% of cases of acute liver failure. Assessment of prognosis frequently (at least on a daily basis) by using various prognostic tools, allows the treating team to decide whether or not to proceed with urgent liver transplantation. Artificial liver support devices are still in evaluation and not ready for use in clinical practice. While it is determined whether or not there is sufficient hepatic regeneration, the care of the patient with acute liver failure revolves around managing the dysfunction of multiple extra hepatic systems.