Case Of Acute Hepatic Failure Research Articles

Two sides to every story: Reappraising the early history of liver transplantation at Addenbrooke's Hospital, Cambridge.

Over the course of the past six decades, liver transplantation has evolved to become the treatment of choice for chronic end-stage liver disease and some cases of acute hepatic failure. Currently, more than 34,000 liver transplants are conducted worldwide per annum, and overall one year survival rates exceed 90%. However, the early years of human liver transplantation were beset by failure. Eyewitness reports from this period make for tragic, yet compelling reading. Volume 12 of The History of Anaesthesia Society Proceedings contains one such account, written by Dr Elizabeth Gibbs. This outlined the experience of single-handedly anaesthetising the recipient of the first liver transplant to be undertaken at Addenbrooke's Hospital, Cambridge, UK, in June 1967. Despite the best efforts of the team, the patient died from uncontrollable haemorrhage 19 hours after the start of the procedure. While this tragic outcome might have been expected in the early days of liver transplantation, Gibbs included an unsettling postscript in her paper. This stated that all of the patient's records had apparently been 'lost', and the date of the first Cambridge liver transplant was publicly reported as 2 May 1968, some 11 months after the events described. This article outlines the results of research aimed at critically appraising this postscript. In doing so a number of unexpected discoveries were made. These highlight some important lessons for medical historians and demonstrate that if you look hard enough, there really are two sides to every story.

Suspected Adenovirus Causing an Emerging HEPATITIS among Children below 10 Years: A Review.

In October 2021, a case of acute hepatic failure without any known cause was identified in the United States of America. Upon further investigation, other children aged 1–6 years were reported to have the same liver failure, and some of them were positive for adenovirus 41 type F. On 21 April 2022, the Centers for Disease Control and Prevention (CDC) released an alert after 74 cases were identified in United Kingdom (UK) between 5 and 8 April in children below 10 years of age, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients’ liver enzymes were remarkably increased. A total of 650 cases had been reported from 33 countries as of 27 May 2022, among which 222 cases were reported in the UK alone. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.

A case of acute hepatic failure with hepatic coma caused by regular doses of acetaminophen

A case of acute hepatic failure with hepatic coma caused by regular doses of acetaminophen

Hepatotoxicity Profile of Single Agent As2O3 in the Management of Newly Diagnosed Cases of Acute Promyelocytic Leukemia: Impact on Outcome and Correlation with Genetic Polymorphisms.

As2O3 is an effective therapeutic agent in the management of acute promyelocytic leukemia (APL). Concerns have been raised about its potential cardiac and hepatotoxicity. We retrospectively analyzed the hepatotoxicity profile in newly diagnosed patients treated at our center, its impact on survival and also studied the effect of genetic polymorphisms on its incidence. Polymorphisms that were studied included some members of the GST family of genes (GSTM1, GSTT1and GSTA1) and that of the MTHFR gene (MTHFR C677T and MTHFR A1289C), these could potentially have a role in the bio-transformation of As2O3 and in handling reactive oxygen species generated by it.Between January 1998 and April 2005, 83 newly diagnosed patients with APL were treated with a regimen of single agent As2O3 in induction, consolidation and maintenance at doses of 10 mg/day for adults and 0.15mg/kg/day for the pediatric population. [Display omitted] There were 7 early deaths (6 IC bleeds, 1 sepsis), these patients were not evaluable for toxicity. Liver function tests (LFT) were done weekly in induction, once in 2 weeks in consolidation, prior to every course of maintenance and at three monthly intervals on follow up.Of the 76 evaluable patients in 46 (60.5%) there was no evidence of hepatotoxicity, grade 1, 2, 3 and 4 toxicity (NCI-CTC v2.0) was seen in 14(18.4%), 8(10.5%), 4(5.3%) and 4(5.3%) patients respectively. Of the 4 patients with grade 4 toxicity; in 3 there was documented acute hepatitis B infection. Onset of hepatotoxicity occurred in induction in 19 (63.3%), during consolidation in 3 (9.9%), during maintenance in 6 (20%) and following completion of therapy in 2 (6.6%). Of the 30 (39.5%) patients who developed hepatotoxicity in the majority the prominent abnormality was transaminitis (29 – 96.6%), it was transient (<4 weeks duration) in 20 (66.7%) and resolved on continuing As2O3 in 20 (66.7%). For all patients with grade 3 – 4 toxicity As2O3 was withheld till the LFT had normalized. One patient with grade 2 toxicity died on day 42 secondary to uncontrolled sepsis. Two patients have persisting LFT abnormality post completion of therapy (one each grade 1 and grade 2). There were no cases of acute hepatic failure or mortality attributable to hepatic toxicity.There was a significant association of hepatotoxicity with the MTHFR A1298C polymorphism (p=0.033). There was no statistical correlation of hepatotoxicity and null phenotype of GSTT1 or GSTM1 or with polymorphisms of GSTA1and MTHFR C677T. Occurrence of hepatotoxicity had no impact on OS in this group of patients (Log rank test p=0.666). In patients who developed hepatotoxicity EFS was superior to those that did not (97% vs 73%) though this did not reach statistical significance (p=0.116).Conclusion: The hepatotoxicity profile of single agent As2O3 as used in this regimen in the treatment of newly diagnosed cases of APL is mild and transient in the majority of patients. Its occurrence correlates with presence of the MTHFR A1298C polymorphism and it does not have an adverse impact on EFS or OS.

A case of acute hepatic failure induced by severe heatstroke.

A case of acute hepatic failure induced by severe heatstroke.

Cetrimide-Chlorhexidine-Induced acute hepatic failure

Hydatid cystsarefrequently found in the liver and may be asymptomatic until growth occurs. Scolicidal agents, such as cetrimide-chlorhexidine, have been used safely in hydatid cyst surgery for many years. Here we presenta case of acute hepatic failure after the usage of the cetrimide-chlorhexidine solution during hepatic hydatid cyst surgery. To the best of our knowledge, this is the first such report in the literature.

2255 Acute on Chronic Hepatic Failure From Primary Amyloidosis (AL): A Fatal Complication

INTRODUCTION: Hepatic involvement in primary amyloidosis (AL) is common but rarely causes severe cholestasis. We are here reporting a case of acute on chronic hepatic failure from amyloidosis leading to a severe decline in patient’s clinical status and fatality. CASE DESCRIPTION/METHODS: 44 years old man was initially seen for persistent cough and recurrent right-sided pleural effusion. Thoracentesis showed exudative effusion. A right VATS with decortication was done. Pathology showed extensive caseating granulomas and tissue cultures came back positive for MTB. Initial labs showed elevated LFT’s with a cholestatic pattern. The patient was started on levofloxacin, rifabutin and ethambutol due to less hepatotoxic profile. During hospitalization, patient LFTs kept on worsening. Medications were stopped and a liver biopsy was done. There was significant involvement of the liver by amyloidosis (AL). Patient further workup included a bone marrow biopsy which revealed 30-40% cellularity, 5-10% plasma cells, amyloidosis AL (Kappra type) consistent with multiple myeloma. Oncology team recommended chemotherapy with CyborD (Bortezomib, dexamethasone and cyclophosphamide) for multiple myeloma. In spite of chemotherapy patient hepatic, renal and cardiac functions were worsening. Patient developed abdominal pain, moderate ascites and hypotension with elevated INR and bilirubin of 30. He was ultimately transferred to ICU where he developed cardiac arrest and could not survive. DISCUSSION: Primary amyloidosis (AL) is the most common form of systemic amyloidosis with mean age of diagnosis 65 years and less than 10% of patients being 50 years of age. As compared to myeloproliferative disease, leukemias and lymphomas, hepatic involvement is less common in multiple myeloma (32%). Amyloid deposits may be seen in the liver with hepatomegaly and normal to mild elevation of hepatic enzymes but serious manifestations such as hepatic failure and portal hypertension are rare. Previously in literature very few cases of acute hepatic failure from AL amyloidosis have been reported. Diagnosis is made by biopsy of the involved site showing amyloid deposits. There has been reported limited success for liver transplantation as the disease progression is unchanged in the presence of plasma cell dyscrasias. In the literature combined approach with autologous stem cell transplant and liver transplant have been suggested but the prognosis still remains poor.

2227 Herpes Simplex Virus - 1 Related Acute Fulminant Liver Failure Successfully Treated With Medical Therapy

INTRODUCTION: Herpes simplex virus (HSV 1&amp;2) is an uncommon cause of asymptomatic hepatitis and acute liver failure. Fatal disease often occurs in immunocompromised adults but is a rare event in immunocompetent patients. Early suspicion of infection is imperative as late diagnosis and treatment carries poor prognosis and high mortality. We describe a case of acute hepatic failure from HSV-1 virus in an immunocompetent adult successfully treated with medical therapy without need for liver transplantation. CASE DESCRIPTION/METHODS: A 55-year-old diabetic male with recent hospitalization for necrotizing fasciitis of the groin (discharged on amoxicillin/clavulanate 5 days ago) presented to the hospital with fever, vomiting, abdominal pain and was found to have severe elevation in liver enzymes. Patient denied prior history of liver disease. Physical exam was notable for fever: 102 degree F, tachycardia, multiple small circular lesions on the oral mucosa and tender hepatomegaly. Liver tests at baseline were normal and on admission showed: AST 1317 U/L (normal:&lt; 32 U/L), ALT 966 U/L (normal:&lt; 36 U/L), total bilirubin 0.4mg/dL (normal:0.2-1.2 mg/dL), alkaline phosphatase 86 U/L (normal:45-117 U/L) and INR 1.7 (normal:0.8-1.2). Urine drug screen was negative of acetaminophen. Imaging excluded hepatic venous thrombosis. Laboratory tests for viral and autoimmune hepatitis, wilson’s disease were negative. Patient was empirically started on IV acyclovir given concern for herpes hepatitis based on oral exam. Diagnosis was confirmed with a positive blood and oral swab HSV DNA PCR and a liver biopsy (Figures 1 and 2) showing herpes simplex viral inclusions. Due to progressive worsening of liver tests and patient’s condition while on treatment, intravenous immunoglobulin (IVIG) therapy was added eventually leading to clinical and laboratory signs of improvement (Table 1). He was discharged on an oral course of valganciclovir and continues to do well on follow up visit. DISCUSSION: Fulminant liver failure from herpes virus has been infrequently reported in immunocompetent adults and usually represents disseminated infection. It is a potentially treatable condition that requires high degree of diagnostic suspicion as presenting symptoms can be non-specific. Early empiric treatment with acyclovir while awaiting HSV PCR or liver biopsy has been shown to improve outcomes and decrease need for liver transplantation. We herein describe a novel approach to treat HSV hepatic failure with combination therapy of acyclovir and IVIG.

N,N-dimethylformamide-induced acute hepatic failure: A case report and literature review.

N,N-dimethylformamide (DMF) is a major solvent predominantly used in the chemical industry. The main toxic effects following exposure to DMF are gastric irritation, skin eruption and hepatotoxicity. However, hepatic failure induced by DMF is rare. In this report, we present a case of acute hepatic failure following exposure to a toxic dose of DMF via respiratory tract inhalation and skin absorption with detailed abdominal computed tomography scan, sequential laboratory data and polymorphisms. The patient recovered satisfactorily following artificial liver support therapy and pharmacological agents to protect the liver in addition to plasma, blood platelet and albumin transfusions. In view of the high mortality rate and rare occurrence rate of acute hepatic failure, the clinical characteristics, polymorphisms and therapeutic strategy of DMF poisoning are discussed.

Fulminant hepatitis E in a pregnant woman

Hepatitis E is an inflammatory liver disease caused by hepatitis E virus (HEV) infection, which is endemic in China, India, Nepal, and in several Asian and African countries, where the prevalence can be as high as 50%. In non-endemic countries, an increasing number of non-travel associated HEV has been reported in recent years, particularly in Europe.The authors describe the clinical case of a puerperal 24-year-old woman from Pakistan admitted to our Tertiary Care Medical Center with acute hepatic failure developed during the third trimester of her pregnancy. She was icteric with grade III encephalopathy and hypothermia. Laboratory values showed significant AST, ALT and LDH elevations of twelve times the upper normal limit, and total bilirubin was significantly elevated (41.20mg/dL). Prothrombin time was prolonged (4s) and factor V activity was diminished (15.1%). Extracorporeal albumin dialysis was initiated, but clinical deterioration occurred within 48h, so she underwent OLT at day 4 post-admission.Severe forms of HEV are known to be more pronounced in pregnant women. Even though most of the described cases of acute hepatic failure associated to HEV during pregnancy had a favorable clinical course, some cases of fulminant liver failure and death are described. It is unknown whether liver transplant outcomes in this setting are different from other causes of acute liver failure. To our knowledge, this is the first case report in Portugal from a pregnant woman who developed hepatic failure due to fulminant hepatitis E that underwent successful liver transplantation.

Combination Therapy Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Associated with Hepatic Failure

A single pill daily fixed dose combination of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) provides a potent and convenient treatment option for HIV/AIDS. The components have been shown to be well tolerated and are effective in randomized controlled trials. A literature search revealed no case of hepatic failure reported with this drug combination. We here in describe the 1st case of acute hepatic failure developing after 3 months of treatment with EFV/FTC/TDF in a 41 year old African American male without pre-existing liver disease or risk factors. Keywords: Drug induced hepatic failure, AIDS combination therapy, antiretroviral, NNRTI, Emtricitabine, hepatic failure, hepatotoxicity, gonococcal, syphilis, genital herpes

Combination Therapy Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Associated with Hepatic Failure

A single pill daily fixed dose combination of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) provides a potent and convenient treatment option for HIV/AIDS. The components have been shown to be well tolerated and are effective in randomized controlled trials. A literature search revealed no case of hepatic failure reported with this drug combination. We here in describe the 1st case of acute hepatic failure developing after 3 months of treatment with EFV/FTC/TDF in a 41 year old African American male without pre-existing liver disease or risk factors.

Acute Liver Failure Secondary to Metastatic Breast Cancer

Introduction: 40-60% of patients with breast cancer have liver metastasis at time of death. Most liver metastases are asymptomatic. However, rarely, patients can have disseminated intra-sinusoidal metastatic liver disease (DISML) leading to acute liver failure and death. Case Report: A 57-year-old female presented to University of Arizona Medical Center with altered mental status. Her past medical history was significant for a history of infiltrative ductal breast carcinoma for which she had bilateral mastectomies, chemotherapy and right breast radiotherapy 4 months prior to admission. Two weeks before the admission, she was seen in an emergency department for abdominal pain and was noted to have aspartate aminotransferase (AST) level of 280 IU/dL, alanine aminotransferase (ALT) level of 162 IU/dL and total bilirubin of 0.8 mg/dL. Physical examination on admission revealed a comatose patient with jaundice and ascites. Laboratory studies showed serum creatinine of 2.5 mg/dL, ALT of 363 IU/dL, AST of 1249 IU/dL, GGT of 665 IU/dL, alkaline phosphatase of 756 IU/dL and total bilirubin was 17.6 mg/dL. The patient was noted to have platelets of 65 K/μL and INR was 2.7. Serologies for hepatitis A, B and C were negative with acetaminophen level was less than 3 ug/mL. Doppler ultrasound revealed hepatomegaly and no evidence of thrombus in the hepatic or portal veins. MRI showed hepatic steatosis and a normal spleen and pancreas. The patient's condition deteriorated with worsening encephalopathy, coagulopathy, sepsis and hepatorenal syndrome resulting in death 4 days following admission. At autopsy, there were widespread nodular metastases in the liver. Microscopic examination showed malignant cells plugging the hepatic sinusoids and small vascular spaces with infiltration of adjacent hepatic parenchyma. There were no peritoneal metastases. Conclusions: Liver is the most common site for metastasis from a variety of tumors, however, only 0.1% of all cases of acute hepatic failure are attributed to malignancies. Given no obvious mass lesions, the lack of radiologic evidence of widespread metastasis, as in our case, makes this a diagnostic challenge. More commonly, patients with cancer may present with hepatic failure due to drugs or infections such as herpes simplex. Nonetheless, DISML should be added to this list of causes of acute hepatic failure in patients with a history of cancer.

Fulminant hepatitis A infection in second trimester of pregnancy requiring living‐donor liver transplantation

We present an 18-year-old pregnant woman who was referred to our emergency clinic as a case of acute hepatic failure and hepatic encephalopathy. Laboratory tests showed abnormal liver function tests and serological workup was consistent with acute hepatitis A infection. Ultrasonography revealed a single live fetus with fetal biometry compatible with 18 gestational weeks. The patient underwent a highly urgent liver transplantation using a right lobe graft from her husband. Histological examination of the explanted liver showed acute, lymphocyte-rich, diffuse necrotizing hepatitis, consistent with acute necrotizing hepatitis A. After the operation her allograft function gradually recovered. Her follow-up obstetrics ultrasound revealed a male fetus with severely decreased amniotic fluid. The patient was informed about the poor prognosis of her pregnancy and the pregnancy was terminated by vaginal misoprostol induction. She has maintained a good general condition and liver function for 4 months postoperatively, up to the present time.

Acute hepatic failure as a leading manifestation in exertional heat stroke.

Background. Acute hepatic failure (AHF) is uncommon as a leading symptom in patients with exertional heat stroke (EHS). Which stage to perform the liver transplantation for severe hepatic failure in EHS is still obscure at clinical setting. The conservative management has been reported to be successful in treating heat-stroke-associated AHF even in the presence of accepted criteria for emergency liver transplantation. Case Presentation. Here, we reported a 35-year-old male who presented with very high transaminases, hyperbilirubinemia, significant prolongation of the prothrombin time, and coma. No other causes for AHF could be identified but physical exhaustion and hyperthermia. Although the current patient fulfilled London criteria for emergency liver transplantation, he spontaneously recovered under conservative treatment including intravenous fluids, cooling, diuretics as mannitol, and hepatocyte growth-promoting factors. Conclusions. Meticulous supportive management could be justified in some selected cases of AHF due to EHS.

Multiple Organ Failure Caused by Non-exertional Heat Stroke After Bathing in a Hot Spring

Heat stroke is a life-threatening illness, and the disease spectrum can include the involvement of multiple organs to varying degrees. Rhabdomyolysis with renal function impairment is frequently noted in this disease. However, acute hepatic failure has been rarely reported in non-exertional heat stroke. We report a case of acute hepatic failure combined with disseminated intravascular coagulopathy, acute renal failure, and neurological deficit caused by heat stroke after bathing in a hot spring. Molecular adsorbent recirculating system (MARS) treatment was performed daily on days 10-12 of admission. As a result of progressive azotemia, hemodialysis was performed. Unfortunately, after a long course of intensive care, the patient died from septic shock and multiple organ failure. According to available evidence, MARS and hemodialysis are beneficial in treating exertional heat stroke. However, a limited number of studies have treated non-exertional heat-stroke-related acute hepatic failure. Early cooling to reduce the overwhelming heat-stress-related cytokine storm, and advanced MARS to eliminate circulating toxin might have a role in treating this rare but fatal illness.

Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.

Prevalence of dengue infection in north Indian children with acute hepatic failure

Hepatic manifestations of dengue viral infection are well known and cases of acute hepatic failure (AHF) with evidence of dengue infection are reported.Objectives: To study the role of dengue infection in AHF presenting to hospital.Methods: Setting: Pediatric wards of a teaching hospital in northern India. Subjects: Consecutive children hospitalized with AHF over a 3 month period in 2006. Clinical and laboratory details of subjects were charted. ELISA tests for dengue IgM were done in all patients using commercial kits. Real time PCR assays for dengue genome were done in randomly chosen subjects from those testing positive and negative for IgM. A PCR positive case was considered as definite dengue infection, while those who were only IgM positive were considered as ‘probable’ dengue.Results: Between July and September 2006, 27 patients were enrolled. Thirteen were unequivocally positive for dengue IgM. A random sample of 7 IgM positive and 3 IgM negative patients was tested by PCR, of which 4 IgM positive and one IgM negative patients were PCR positive. Prevalence of definite dengue infection in AHF was therefore 5/27 or 18.5%. No significant differences were observed in clinical and laboratory features of dengue and nondengue aHF.Conclusions: Dengue infection should be considered in the etiology of AHF in this part of the world. Clinico-laboratory differentiating features of dengue AHF should be studied in a larger sample of patients.

Benefit-Risk Assessment of Telithromycin in the Treatment of Community-Acquired Pneumonia

The purpose of this review is to assess the benefits and risks associated with the use of the ketolide antibacterial telithromycin, currently licensed for the treatment of adults with mild to moderate community-acquired pneumonia (CAP). Telithromycin is active against both the major (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) and atypical/intracellular (Chlamydophila pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) CAP pathogens. It is associated with a low potential to select for resistance and has maintained its in vitro activity against isolates of respiratory pathogens in countries where it has been in clinical use for several years. In randomized clinical trials, telithromycin has demonstrated efficacy comparable to the established antibacterial classes (macrolides, fluoroquinolones and beta-lactams) in the treatment of CAP.The safety profile of telithromycin is broadly similar to that of other antibacterials used to treat CAP. The most common adverse events are gastrointestinal adverse effects and headache; these are generally mild to moderate in severity and reversible. Telithromycin appears to be well tolerated by adult patients in all age groups, including those with co-morbid conditions. In common with other antibacterials, telithromycin has the potential to affect the corrected QT interval; the concomitant use of cisapride or pimozide with telithromycin is contraindicated, while telithromycin should be avoided in patients receiving Class IA or Class III antiarrhythmic drugs. Visual disturbances (usually transient) have occurred in a small proportion of patients treated with telithromycin; it is recommended that activities such as driving are minimized during treatment. Telithromycin is contraindicated in patients with myasthenia gravis. Hepatic dysfunction may occur in some patients taking telithromycin; rare cases of acute hepatic failure and severe liver injury, including deaths, have been reported. As telithromycin is an inhibitor of the cytochrome P450 (CYP) 3A4 system, coadministration of telithromycin with drugs metabolized by this pathway may require dose adjustments (e.g. with benzodiazepines) or a temporary hiatus in the use of the coadministered drug (e.g. HMG-CoA reductase inhibitors) metabolized by CYP3A4. Telithromycin may potentiate the effects of oral anticoagulants; careful monitoring is recommended in patients receiving telithromycin and oral anticoagulants simultaneously.Although serious and sometimes fatal events have occurred in patients receiving telithromycin therapy, current data indicate that telithromycin offers an acceptable benefit risk ratio in the treatment of mild to moderate CAP.

Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?

While cardiopulmonary symptoms are common in patients undergoing classical or, due to physical exercise, exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio (INR). No other causes for liver failure could be identified but physical exhaustion and hyperthermia.