Incidence Of Acute Liver Failure Research Articles

A305 ANONYMOUS LIVING LIVER DONATION IMPROVES ACCESS FOR MEDICALLY UNDERSERVED CHILDREN IN NEED OF LIVER TRANSPLANTATION

Abstract Background Since our first pediatric anonymous non-directed live donor liver transplant (A-LDLT) performed in April 2005, 62 children have undergone live donor liver transplant (LDLT) with an anonymous non-directed graft. Anon-LDLT organs being allocated as per our deceased donor liver transplant (DDLT) wait list. Aims To evaluate clinical outcomes, recipient characteristics and social determinants of health of pediatric recipients of A-LDLT in comparison to those who received a directed LDLT (Dir-LDLT) and DDLT. Methods Retrospective analysis of all recipients of LDLT performed between January 2005 and March 2023. Demographic and clinical data included age, sex, race, ethnicity, single-parent households, primary diagnosis, recipient blood type, time on waiting list, post-LT intensive care unit (ICU) length of stay (LOS), time to extubation, and post-transplant comorbidities were assessed as covariates. A comparative analysis was conducted between children receiving A-LDLT, Dir-LDLT versus DDLT. Results A total of 422 (50% male, 57% white, 23% Asian, 7% Black, 5% indigenous) childrenunderwent LT during the study period. Biliary atresia (40%) and metabolic diseases (19%) were the commonest primary indications. A-LDLT was done in 62 children (15%) with no directed donor options. Dir-LDLT was in 174 children (41%). Of 186 DDLTs (44%), 25% were split grafts, 26% reduced, and 49% whole liver grafts. In A-LDLT recipients, the primary diseases were more frequently characterized by metabolic disorders (31%), while the incidence of acute liver failure was notably lower (0%). Recipients of Anon-LDLT were more often Indigenous recipients in comparison to Dir-LDLT or DDLT recipients (p=0.044). Anon-LDLT recipients were more frequently living in single parent households (18% vs 3% vs 10%, pampersand:003C0.001) and to require interpreter assistance (11% vs 3% vs 0.5%, pampersand:003C0.001) (Table), compared to children who received Dir-LDLT or DDLT. Median time on the wait list was longer for Anon-LDLT (92 days) compared to Dir-LDLT (62 days) and DDLT (72 days) recipients (p=0.004). Post-LT ICU LOS, time to extubation, other post-LT complications or patient prognosis were better in the A-LDLT and Dir-LDLT recipients than DDLT recipients. Conclusions This retrospective analysis of 422 children undergoing LT at a single institution confirms excellent patient and graft survival for A-LDLT recipients. Patients from Indigenous communities, single parent and households where English is a second language, are more frequently the beneficiaries of Anon-LDLT grafts. Anon-LDLT, as utilized in this single center analysis, benefits medically underserved pediatric patients who otherwise have limited access to the advantages of LT. Funding Agencies None

Epidemiological changes in the incidence of acute liver failure at a hospital in Mexico City

Epidemiological changes in the incidence of acute liver failure at a hospital in Mexico City

High Incidence of Acute Liver Failure among Patients in Egypt Coinfected with Hepatitis A and Hepatitis E Viruses.

Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are transmitted through the fecal-oral route. HAV outbreaks and one HEV outbreak have been reported in Egypt. However, the impact of HAV-HEV co-infection is not known. In this study, we assessed HEV markers in acute HAV-infected patients (n = 57) enrolled in Assiut University hospitals. We found that 36.8% of HAV-infected patients were also positive for HEV markers (anti-HEV IgM and HEV RNA), while 63.2% of the patients were HAV mono-infected. Demographic and clinical criteria were comparable in both HAV mono-infected patients and HAV-HEV co-infected patients. Although liver enzymes were not significantly different between the two groups, liver transaminases were higher in the co-infected patients. Six patients developed acute liver failure (ALF); five of them were HAV-HEV-co-infected patients. The relative risk of ALF development was 8.5 times higher in HAV-HEV co-infection compared to mono-infection. Three cases of ALF caused by HAV-HEV co-infection were reported in children (below 18 years) and two cases were reported in adults. All patients developed jaundice, coagulopathy, and encephalopathy; all were living in rural communities. In conclusion: HAV-HEV co-infection can be complicated by ALF. The risk of ALF development in HAV-infected patients is higher when coinfection with HEV is present.

Acute liver failure due to herpes simplex viral hepatitis diagnosed by skin lesions and blood tests: a case report

BackgroundThe incidence of acute liver failure from herpes simplex virus is rare.Case presentationA 71-year-old Japanese man was diagnosed with acute liver failure and was transferred to our hospital. Steroid therapy, plasma exchange, and hemodiafiltration were started for liver failure, and antimicrobial therapy was initiated for pneumonia. Staphylococcus epidermidis was detected in blood culture. Skin rash appeared; a positive anti-herpes simplex virus result led to the diagnosis of acute liver failure from herpes simplex virus. Hence, acyclovir was started. After blood tests improved, treatments for acute liver failure were discontinued. Antimicrobial therapy was continued; however, he died. In this case, persistent bacteremia and drug-induced liver damage due to acyclovir may have contributed to his death.ConclusionsAcute liver failure can lead to complications and death. Thus, careful observation is crucial, even if the patient has shown some improvements.

Clinical outcomes of coronavirus disease 2019 in liver transplant recipients.

BACKGROUNDLiver transplant patients are at higher risk of infection due to immunosuppression. Whether liver transplant recipients are also more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and will have worse outcomes than the general population if they develop coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 is a topic of ongoing studies, including ours. AIMTo assess the clinical outcomes of COVID-19 in liver transplant recipients.METHODSThis was a case-control study, with a database search performed (at the study site) from March 1, 2020 through February 28, 2021. Patients 18 years or older who tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) were included in the study. Patients with infection other than pneumonia at the time of admission were excluded. After selection, patients who had been the recipient of liver transplant were considered cases and those without as controls. After being matched by age, sex, and obesity, two controls were randomly selected for each case. Death and hospitalization due to COVID-19 infection were the primary outcomes. Secondary outcomes were pertinent only to patients who were hospitalized, and they included duration of hospital stay, need for supplemental oxygen, presence of at least one type of end-organ damage, effects on liver enzymes, incidence of acute liver failure, effect on d-dimer levels, and incidence of venous thromboembolism (VTE). Chi-square or Fisher’s exact test was used to compare all primary and secondary outcomes with the exception of duration of hospital stay and d-dimer levels, which were compared using the Wilcoxon signed-rank test. Alpha criterion was set at 0.05. Logistic regression was performed for each primary outcome (as the dependent variable). Statistical analyses were performed using R software.RESULTSOf the 470 Liver transplant recipients who were tested for COVID-19 via the PCR test, 39 patients tested positive (8.3%). There was no significant difference between cases and controls regarding death [odds ratio (OR): 2.04, 95% confidence interval (CI): 0.14–29.17; P = 0.60] and hospitalization rates (OR: 1.38, 95%CI: 0.59–3.24; P = 0.46). There also was no significant difference between cases and controls with respect to all secondary outcomes. Among all patients who had elevated liver enzymes, their levels were either normalized, improving, or remained stable at the time of discharge. No patient developed acute liver failure. Of the 31 hospitalized patients, 27 received a prophylactic anticoagulation dose and no patient developed VTE in either group. Among cases who were hospitalized, immunosuppression was decreased in 5 patients and there was no change in immunosuppression among the remaining 7 patients. One patient died in each of these two subgroups. Logistic regression analysis was done, but all of the models had poor model predictions as well as insignificant predictors (independent variables). Therefore, they could not be used for either prediction or inference.CONCLUSIONClinical outcomes of COVID-19 in liver transplant recipients are not different than those without transplantation. COVID-19 should not impact timely health care access and immunosuppression continuation among these patients.

Dengue hemorrhagic fever and the liver.

Dengue hemorrhagic fever (DHF) is one of the most rapidly emerging infections of tropical and subtropical regions worldwide. It affects more rural and urban areas due to many factors, including climate change. Although most people with dengue viral infection are asymptomatic, approximately 25% experience a self-limited febrile illness with mild to moderate biochemical abnormalities. Severe dengue diseases develop in a small proportion of these patients, and the common organ involvement is the liver. The hepatocellular injury was found in 60%-90% of DHF patients manifested as hepatomegaly, jaundice, elevated aminotransferase enzymes, and critical condition as an acute liver failure (ALF). Even the incidence of ALF in DHF is very low (0.31%-1.1%), but it is associated with a relatively high mortality rate (20%-68.3%). The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis, immune-mediated hepatocyte injury induced hepatitis, and cytokine storm. Hepatic hypoperfusion is another contributing factor in dengue shock syndrome. The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.

Acute Liver Failure: Indian Perspective.

Acute Liver Failure: Indian Perspective.

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients.

Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. In the derivation cohort (n=3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR=1.014, 95% CI: 1.005-1.023), baseline ALT (HR=1.014, 95% CI: 1.003-1.024), haemoglobin (HR=1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR=1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n=1497) of which 85 (5.7%) developed ATDILI. Age (HR=1.029, 95% CI: 1.003-1.056), baseline AST (HR=1.036, 95% CI: 1.010-1.062), previous TB treatment (HR=3.894, 95% CI: 1.304-11.625) and active drinking (HR=3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. Elevation of ALT of ≥3×ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.

Acute liver failure in newborns.

Acute liver failure is a condition that is defined as a sudden, complete, or nearly complete loss of liver functions without any previous liver disease, usually accompanied by encephalopathy, which can be reversible, but with a mortality rate of 55-70%. Acute liver failure newborns is an acute liver failure in the first 28 days of life. The Pediatric Acute Liver Failure Working Group identified the presence of coagulopathy as the main finding for the identification of acute liver failure in childhood following vitamin K administration. Although the incidence of acute liver failure is reported to be 17/100 000 in all ages, its incidence is not known exactly in newborn and childhood. The most common cause of acute liver failure in the newborn period is the gestational alloimmune liver disease that was previously known as neonatal hemochromatosis. This is followed by viral infections, metabolic diseases, hemophagocytic lymphohistiocytosis, and other rare causes. In the neonatal period, acute liver failure is a rare condition with a high mortality rate. For this reason, the vital signs of the patients should be closely monitored and supportive treatments should be planned according to the follow-up and the etiology of the disease should be clarified urgently. In this process, acyclovir treatment until herpes simplex virus infection is excluded and lactose-free feeding until galactosemia is excluded are recommended as life-saving treatments. In the literature, since there is a limited number of studies related to neonatal acute liver failure, prospective studies investigating the factors affecting treatment and prognosis are needed.

Hypothermia Advocates Functional Mitochondria and Alleviates Oxidative Stress to Combat Acetaminophen-Induced Hepatotoxicity.

For years, moderate hypothermia (32 °C) has been proposed as an unorthodox therapy for liver injuries, with proven hepatoprotective potential. Yet, limited mechanistic understanding has largely denied its acceptance over conventional pharmaceuticals for hepatoprotection. Today, facing a high prevalence of acetaminophen-induced liver injury (AILI) which accounts for the highest incidence of acute liver failure, hypothermia was evaluated as a potential therapy to combat AILI. For which, transforming growth factor-α transgenic mouse hepatocytes (TAMH) were subjected to concomitant 5 mM acetaminophen toxicity and moderate hypothermic conditioning for 24 h. Thereafter, its impact on mitophagy, mitochondrial biogenesis, glutathione homeostasis and c-Jun N-terminal kinase (JNK) signaling pathways were investigated. In the presence of AILI, hypothermia displayed simultaneous mitophagy and mitochondrial biogenesis to conserve functional mitochondria. Furthermore, antioxidant response was apparent with higher glutathione recycling and repressed JNK activation. These effects were, however, unremarkable with hypothermia alone without liver injury. This may suggest an adaptive response of hypothermia only to the injured sites, rendering it favorable as a potential targeted therapy. In fact, its cytoprotective effects were displayed in other DILI of similar pathology as acetaminophen i.e., valproate- and diclofenac-induced liver injury and this further corroborates the mechanistic findings of hypothermic actions on AILI.

Moderate Hypothermia Effectively Alleviates Acetaminophen-Induced Liver Injury With Prolonged Action Beyond Cooling.

Acetaminophen (APAP) overdose accounts for the highest incidence of acute liver failure, despite the availability of an antidote i.e. N-acetylcysteine. This calls for alternative strategies to manage APAP-induced liver injury (AILI). Therapeutic hypothermia has been explored in past studies for hepatoprotection, but these phenomenal reports lack clarification of its optimal window for application, and mechanistic effects in specific AILI. Hence, we conducted an in vitro study with transforming growth factor-α transgenic mouse hepatocytes cell line, TAMH, and human liver hepatocytes cell line, L-02, where cells were conditioned with deep (25°C) or moderate (32°C) hypothermia before, during or after APAP toxicity. Cell viability was evaluated as a hallmark of cytoprotection, along with cell death. Simultaneously, cold shock proteins (CSPs) and heat shock proteins expressions were monitored; key liver functions including drug-metabolizing ability and hepatic clearance were also investigated. Herein, we demonstrated significant hepatoprotection with 24-hour moderate hypothermic conditioning during AILI and this effect sustained for at least 24 hours of rewarming. Such liver preservation was associated with a CSP—RNA-binding motif protein 3 (RBM3) as its knockdown promptly abolished the cytoprotective effects of hypothermia. With mild and reversible liver perturbations, hypothermic therapy appears promising and its RBM3 involvement deserves future exploration.

Soft tissue calcifications secondary to Hymenoptera stings: a potential prognostic CT imaging sign in pediatric patients

Context: Soft tissue calcifications (STCs) were incidentally found in some of the Hymenoptera-stung (HS) children when they underwent computed tomography (CT) scans for evaluating complications of vital organs. Afterwards, a predilection of STCs to the children with severe complications was clinically noticed. A hypothesis was then developed that STCs secondary to HS may correlate with poor outcomes.Objective: This study aims to firstly characterize the CT findings of STCs in HS children and to confirm our hypothesis that the occurrence of STCs may act as an indicator of poor outcomes in HS children.Materials and methods: Children who received CT scanning after Hymenoptera sting from January 2011 to October 2016 in our hospital were analyzed retrospectively. Shape, location, and distribution of the STCs were described according to the CT findings. Then the enrolled cases were classified into Soft Tissue Calcification Group (STCG) and non-Soft tissue Calcification Group (non-STCG) to conduct prognostic comparisons of Sequential Organ Failure Assessment (SOFA) scores, incidence of main complications (acute liver failure (ALF), acute kidney injury stage III (AKI-III) and multiple organ failure (MOF)), length of hospital days, and in-hospital death, respectively. Pearson correlation was also utilized between the cumulative volume of STCs and the SOFA score.Results: Sixteen cases were enrolled, and STCs’ incidence was 56.25% (9/16). Two STCG cases had diffuse nodular calcifications in their swollen subcutaneous tissue, and another seven had symmetrically stripy or patchy calcifications within or along local muscles. The SOFA scores during the first 3 days were all higher in STCG, and rose to the greatest difference at the third day (9.78 ± 2.17 vs. 2.29 ± 2.06, t = 7.009, p < .001); the incidence of ALF, AKI-III and MOF were significantly higher in STCG (66.67% vs. 0, p = .011), (77.78% vs. 0, p = .003) and (77.78% vs. 14.29%, p = .041); and children in STCG were treated with longer hospital durations (26.33 ± 8.41 days vs. 12.29 ± 7.36 days, t = 3.493, p = .004). One child in STCG died of cardiopulmonary failure, and no deaths occurred in non-STCG. No significant correlations presented between STCs cumulative volumes and SOFA score (rDay1 = 0.096, p = .806; rDay2 = 0.067, p = .863; rDay3 = 0.024, p = .950).Conclusion: Soft tissue calcifications detected on CT imaging following multiple Hymenoptera stings in pediatric patients may be a potential prognostic indicator of more severe complications and poorer outcomes.

Hepatectomy for spontaneous rupture of hepatocellular carcinoma without portal triad clamping

Hepatectomy without portal triad clamping may decrease the incidence of liver injury; however, the effects of hepatectomy without portal triad clamping in the treatment of spontaneous rupture of hepatocellular carcinoma (SRHCC) remain unclear. The aims of the present study were to evaluate the therapeutic value of hepatectomy without portal triad clamping in the treatment of patients with SRHCC. The present study retrospectively reviewed patients with SRHCC who received hepatectomy without portal triad clamping (non-clamping group) and the therapeutic efficacy was compared with that of 20 patients with SRHCC undergoing the same surgery in the presence of portal triad clamping (clamping group). Following hepatectomy, the non-clamping group exhibited a significantly lower incidence of acute liver failure compared with the clamping group (P<0.05). No significant differences in operative time, intra-operative blood loss, disease-free or overall survival times between the two groups were identified (all P>0.05). At 1 week and 2 weeks after surgery, the non-clamping group exhibited significantly lower alanine aminotransferase, aspartate aminotransferase and total bilirubin serum levels compared with the clamping group (all P<0.05). Hepatectomy without portal triad clamping may decrease the incidence of liver injury and liver failure in patients with SRHCC, suggesting that it may be a safe and effective therapeutic strategy.

Incidence and Clinical Outcome of Acute Liver Failure Caused by Dengue in a Hospital for Tropical Diseases, Thailand.

Acute liver failure is an atypical manifestation of dengue with a high mortality. We performed a retrospective cohort study at the Hospital for Tropical Diseases, Bangkok, Thailand. In total, 1,926 patients with serologically confirmed dengue were enrolled in the study from 2011 to 2015. Of these, six patients presented with acute liver failure, four died, and two survived. The incidence of dengue-associated acute liver failure was 0.31%. Dengue-associated acute liver failure was most common among young adults (median age, 29 years). The median duration from onset of fever to development of acute liver failure was 7.5 days. Patients with the severe stage of dengue had a higher risk of developing acute liver failure (P < 0.001). The baseline risk factors associated with the development of acute liver failure were an age of ≤ 40 years (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, P < 0.05), a > 10% ratio of atypical lymphocytes (OR = 2.3, 95% CI = 1.8-3.0, P < 0.001), and a platelet count of < 50,000 mm3 (OR = 2.8, 95% CI = 2.2-3.6, P < 0.001). The incidence of acute liver failure in patients with dengue was quite low, but its impact on morbidity, mortality, and poor clinical outcomes was significant. In summary, this study indicates that various baseline risk factors are associated with acute liver failure in patients with dengue.

Incidence, Management, and Outcomes of Acute Liver Failure Secondary to Thyroid Storm in the United States

Introduction: Thyroid storm (TS) accounts for approximately 1-2% of admissions for thyrotoxicosis. In these patients liver dysfunction can result from hepatic congestion, hypoperfusion, or direct effect from the hyperthyroidism. While the pathophysiology for this has been described in small case series, the epidemiology and outcomes of acute liver failure (ALF) is described only in small case series and large nationally representative data is lacking. Methods: We queried the National Inpatient Sample database for patients with the discharge diagnosis of thyroid storm from 2003 to 2011. Results: We identified a total of 42,765 patients with a discharge diagnosis of TS. The overall incidence of ALF was 1.3% with a rise in incidence from 0.3% in 2003 to 3.7% in 2011. This increase was independent of sex, race and a dichotomized age of 65 years. Patients with ALF were more likely to be younger (p=0.001), men (p < 0.001), alcoholic (p=0.002) and have pre-existing iron deficiency anemia, congestive heart failure, coagulopathy, chronic liver disease, electrolyte disturbances, psychoses and renal failure (p < 0.001 for all). 8.1% of patients with ALF developed hepatic encephalopathy and mortality was high at 34.5%. However, mortality has decreased from 46.9% in 2003 to 27.4% in 2011 (p=0.005). 8.1% of patients received liver transplantation during their hospital stay and mean duration of hospitalization was 17.4 ±18.7 days Conclusion: While incidence of ALF is increasing, mortality from this condition has reduced significantly from 2003 to 2011.Figure 1

Hepatitis B virus and its sexually transmitted infection - an update.

Epidemiology: incidence and prevalence: About 5% of the world’s population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of chronic HBV infection in human immunodeficiency virus (HIV)-infected individuals is 5%-15%; HIV/HBV coinfected individuals have a higher level of HBV replication, with higher rates of chronicity, reactivation, occult infection, and HCC than individuals with HBV only. The prevalence of HBV genotype A is significantly higher among men who have sex with men (MSM), compared with the rest of the population. Molecular mechanisms of infection, pathology, and symptomatology: HBV replication begins with entry into the hepatocyte. Sodium taurocholate cotransporting polypeptide was identified in 2012 as the entry receptor of HBV. Although chronic hepatitis B develops slowly, HIV/HBV coinfected individuals show more rapid progression to cirrhosis and HCC. Transmission and protection: The most common sources of HBV infection are body fluids. Hepatitis B (HB) vaccination is recommended for all children and adolescents, and all unvaccinated adults at risk for HBV infection (sexually active individuals such as MSM, individuals with occupational risk, and immunosuppressed individuals). Although HB vaccination can prevent clinical infections (hepatitis), it cannot prevent 100% of subclinical infections. Treatment and curability: The goal of treatment is reducing the risk of complications (cirrhosis and HCC). Pegylated interferon alfa and nucleos(t)ide analogues (NAs) are the current treatments for chronic HBV infection. NAs have improved the outcomes of patients with cirrhosis and HCC, and decreased the incidence of acute liver failure.

RE: Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol‐induced hepatotoxicity

This article has had a strong following in the German pharmaceutical, medical and life style media, which aroused my interest in this publication. Unfortunately, the authors failed to mention their previous evaluation of the same data set published in Br J Clin Pharmacol in the spring of 2011 [1]. In this paper the investigated categories were intentional overdose, unintentional overdose and intention unknown. These criteria are very similar to those in the recent publication, namely single time point, staggered overdose pattern and not attributable. When comparing the numbers given in the abstract it becomes obvious that unintentional together with intention unknown correspond to the category staggered overdose pattern and that intentional corresponds to single time point together with not attributable (Table 1). Also, when comparing the percentage numbers given in Table 1 of both papers which show admission clinical and laboratory data it is clear that there is an almost complete overlap of the categories used and the recent paper is nearly a duplication of the former with few additional data. Nevertheless the recent article has had a much stronger following in the German pharmaceutical, medical and even life style media than the previous with some peculiarities [2–6]. I find it a problem that the term ‘staggered overdose’ is commonly referred to as ‘slightly elevated dosing’, (in German: ‘geringfügig erhöhte Dosis’). This is made worse by omitting information regarding the highly selective nature of the patient group (admitted to SLTU because of severe liver injury) and also the omission of information as to the low incidence in the total population. For the Scottish population the annual incidence of acute liver failure due to paracetamol overdose is 0.43 cases per 100 000 per year , irrespective ofparacetamol dosing regimen in the years 1992 to 2009 [7]. Journalists readily latch onto the phrase ‘despite lower total ingested paracetamol dose’ in the abstract and ignore the context: low compared with single time overdose. This is further compounded, albeit inadvertently, through the loose definitions of ‘potentially toxic amount’ and ‘staggered overdose’ together with the unclear definition of a ‘supratherapeutic’ dose. These definitions would include ‘slightly elevated dosing’ but since most patients have taken excessively high doses there are no data that really support the fact that a considerable number of patients have had only slightly elevated dosing. The authors should be aware that they could be interviewed and cited due to the misleading nature of their articles which could possibly compromise their reputations as scientists [8]. The author has obtained consulting fees from a paracetamol selling company.

Comparison of the Clinical Features of Hepatitis A between HBsAg-Positive and HBsAg-Negative Patients

Background/AimsThe notion that acute hepatitis A superimposed on chronic hepatitis B infection leads to a worse outcome than acute hepatitis A alone remains controversial. The aim of this study was to determine the influence of the presence of hepatitis B surface antigen (HBsAg) on the severity of acute hepatitis A.MethodsWe retrospectively analyzed 449 patients hospitalized for acute hepatitis A from January 2000 to February 2010 and compared clinical outcomes based on the presence of HBsAg.ResultsOf the 449 patients, 30 patients were in the HBsAg-positive group and 419 in the HBsAg-negative group. The HBsAg-positive group was older than the HBsAg-negative group (36.1±8.3 vs 31.8±8.5 years, p=0.004); however, other baseline characteristics were similar between the 2 groups. Mean peak values of prothrombin time, serum total bilirubin, and serum creatinine at admission were significantly higher in the HBsAg-positive group. When comparing clinical outcomes between the 2 groups, gastrointestinal bleeding, acute renal failure, and acute liver failure were more frequently observed in the HBsAg-positive group. In particular, the incidence of acute liver failure was approximately 9-fold higher in the HBsAg-positive group than in the HBsAg-negative group (23.3% vs 3.3%; odds ratio [OR], 8.80; p<0.001). Multivariate analysis showed that HBsAg (OR, 7.43; 95% confidence interval [CI], 2.56 to 21.57) and age (OR, 1.07; 95% CI, 1.02 to 1.13) were independent risk factors for the occurrence of acute liver failure.ConclusionsIn patients with chronic hepatitis B infection, acute hepatitis A is associated with more severe clinical outcomes, including acute liver failure, compared with patients with acute hepatitis A alone.

Sistemas de soporte hepático extracorpóreo

Background. Extracorporeal liver support systems (ELS) have emerged as an alternative to liver transplant (LT), given the growing incidence of acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and the limited organ supply. Objective. Review of literature about Extracorporeal Liver Support Systems. Methodology. A literature search was conducted on the main medical databases including MEDLINE, SciELO and EMBASE for papers published between July 1990 and November 2010 looking at technologies associated with liver support systems, their technical specifications, their use, and evidence regarding their effectiveness in patients with some forms of liver failure requiring support. Results. These systems may be divided into artificial (hemofiltration, MARS) and bioartificial (such as the Hepatassist™). They work by replacing detoxification processes associated specifically with bilirubins, aromatic aminoacids, and inflammatory agents, and the elimination of breakdown products of coagulation. Recent advances in bioengineering and biogenetics have brought these technologies closer to the ideal, enabling their use in humans with a relative degree of success. ELS systems, most of them still under development, are designed not only to act as a bridge for LT but may also become the cornerstone of treatment in specific cases while the ALF resolves.

Phenotypic and Genetic Characterization of a Cohort of Pediatric Wilson Disease Patients

BackgroundIn Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited. The aim of this study is to highlight the clinical, laboratory and genetic characteristics of this disease in our pediatric population as well as to report our experience with both treatment options and outcome.MethodsThe study included 77 patients from 50 unrelated families (62 were followed up for a mean period of 58.9 ± 6.4 months and 27 were asymptomatic siblings). Data were collected retrospectively by record analysis and patient interviews. Diagnosis was confirmed by sequencing of the ATP7B gene in 64 patientsResultsOur patients had unique characteristics compared to other populations. They had a younger age of onset (median: 10 years), higher prevalence of Kayser-Fleischer rings (97.6% in the symptomatic patients), low ceruloplasmin (93.5%), high rate of parental consanguinity (78.9%) as well as a more severe course. 71.42% of those on long term D-penicillamine improved or were stable during the follow up with severe side effects occurring in only 11.5%. Preemptive treatment with zinc monotherapy was an effective non-toxic alternative to D-penicillamine. Homozygous mutations were found in 85.7%, yet limited by the large number of mutations detected, it was difficult to find genotype-phenotype correlations. Missense mutations were the most common while protein-truncating mutations resulted in a more severe course with higher incidence of acute liver failure and neurological symptoms.ConclusionsEgyptian children with Wilson disease present with early Kayser-Fleischer rings and early onset of liver and neurological disease. The mutational spectrum identified differs from that observed in other countries. The high rate of homozygous mutations (reflecting the high rate of consanguinity) may potentially offer further insights on genotype-phenotype correlation