Cause Of Hepatic Failure Research Articles

Electroacupuncture Promotes Liver Regeneration by Activating DMV Acetylcholinergic Neurons-Vagus-Macrophage Axis in 70% Partial Hepatectomy of Mice.

Lack of liver regenerative capacity is the primary cause of hepatic failure and even mortality in patients undergoing hepatectomy, with no effective intervention strategies currently available. Therefore, identifying efficacious interventions to enhance liver regeneration is pivotal for optimizing clinical outcomes. Recent studies have demonstrated that vagotomy exerts an inhibitory effect on liver regeneration following partial hepatectomy, thereby substantiating the pivotal role played by the vagus nerve in the process of liver regeneration. In recent years, electroacupuncture (EA) has emerged as a non-invasive technique for stimulating the vagus nerve. However, EA on hepatic regeneration remains uncertain. In this study, a 70% partial hepatectomy (PH) mouse model is utilized to investigate the effects of EA on acute liver regeneration and elucidate its underlying molecular mechanisms. It is observed that EA at ST36 acutely activated cholinergic neurons in the dorsal motor nucleus of the vagus nerve (DMV), resulting in increased release of acetylcholine from hepatic vagal nerve endings and subsequent activation of IL-6 signaling in liver macrophages. Ultimately, these events promoted hepatocyte proliferation and facilitated liver regeneration. These findings provide insights into the fundamental brain-liver axis mechanism through which EA promotes liver regeneration, offering a novel therapeutic approach for post-hepatectomy liver regeneration disorders.

Farnesoid X receptor in chronic liver diseases: an immunohistochemical study

ABSTRACT Chronic hepatitis C virus (HCV) related liver diseases are still an ongoing cause of hepatic failure despite the effective role of direct-acting anti-viral agents. Farnesoid X receptor (FXR) agonists have a potential therapeutic effect on the management of chronic liver diseases (CLD). However, data regarding FXR protein expression in human CLDs are limited and conflicting. We aimed to assess the immunohistochemical expression of FXR in HCV-related chronic hepatitis and cirrhosis in comparison with metabolic-associated fatty liver disease (MAFLD) and normal liver tissue. The expression of FXR was low both in hepatocytes and bile ducts of HCV-related chronic hepatitis and cirrhosis (p = .001, respectively). In addition, a significantly low expression of FXR was observed in HCV-related hepatitis and cirrhosis groups compared to MAFLD in hepatocytes (p < .001, for both) and bile ducts (p = .004 and p = .018). FXR expression in HCV-related cirrhosis was significantly associated with compensated liver function (p = .032) and low inflammatory activity (p = .022). FXR expression decreases in HCV-related CLDs. There was some evidence that FXR expression could protect against post-hepatitis cirrhosis.

Natural Product 2-Oxokolavenol Is a Novel FXR Agonist.

Acetaminophen (APAP) toxicity is a common cause of hepatic failure, and the development of effective therapy is still urgently needed. Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, has been identified as a master gene for regulating enterohepatic metabolic homeostasis and has proven to be a promising drug target for various liver diseases. Through high-throughput chemical screening, the natural product 2-oxokolavenol was identified as a novel and selective FXR agonist. Further investigations revealed that 2-oxokolavenol exerts therapeutic efficacy against APAP-induced hepatocyte damage in an FXR-dependent manner. Mechanistically, 2-oxokolavenol forms two hydrogen bonds with M265 and Y369 of human FXR to compatibly fit into the ligand binding pocket of FXR, which potently leads to the recruitment of multiple co-regulators and selectively induces the transcriptional activity of FXR. Our findings thus not only reveal the direct target of natural product 2-oxokolavenol, but also provide a promising hit compound for the design of new FXR modulators with potential clinical value.

P-46 EPIDEMIOLOGICAL PROFILE AND CLINICAL OUTCOMES OF PATIENTS INTOXICATED WITH ACETAMINOPHEN FOR SUICIDAL PURPOSES AT HOSPITAL SAN VICENTE FUNDACIÓN RIONEGRO: A CASE SERIES

Acetaminophen is the most widely used analgesic in the world and its overdose is a major cause of hepatic failure in developed countries. This study aims to describe patients with overdose intake of acetaminophen between 2019 and 2020 at a reference center for liver transplantation in Rionegro-Colombia. Case-series study derived from a secondary analysis of the clinical records between January 1st of 2019 to December 31st of 2020. Inclusion criteria were individuals with voluntary acute ingestion of toxic doses of acetaminophen (>4 g/day). 63 cases, 68% women, 67% <18-year-old, and 54% students. 60% had a personal history of psychiatric illness and 35% reported at least one previous suicide attempt. The median dose of acetaminophen was 15g (IQR:11.5g; Max:50g), 46% referred to co-ingestion with other substances and 13% were under the effect of any psychoactive substance. 57% had a clear intention of suicide. 81% vomited before the arrival to the emergency room, 22% received decontamination intervention with gastric lavage or activated charcoal, and 10% did not receive any dose of N-Acetylcysteine. 15 individuals developed an acute liver injury, 9 with severity criteria, and 1 developed acute kidney injury. The population was predominantly young, the personal history of psychiatric disease was highly prevalent, and most of the cases referred to a vital event that explains the impulsive behavior in acetaminophen consumption. No one developed criteria for liver transplantation and this could be explained by the young age of the individuals, the episodes of early vomiting, and the absence of chronic liver disease or hepatotoxic substance consumption.

A pilot study of the value of a stool color card as a diagnostic tool for extrahepatic biliary atresia at a single tertiary referral center in a low/middle income country

Background and study aimsBiliary atresia (BA) is a major cause of hepatic failure and consequent liver transplantation in pediatrics. If BA is not diagnosed early and the proper surgical intervention is not performed before the age of 3 months, the survival of the affected infant is significantly reduced. In 1994, a stool color card (SCC) for early detection of BA was developed and used in Japan, a country where the parents’ socioeconomic and education levels are high. We aimed to assess the value of using the SCC as a screening tool for early diagnosis of BA at a tertiary referral center in Egypt (a low/middle-income country). Patients and methodsThis prospective study enrolled 108 infants (56 females) aged 1 day to 4 months who presented with cholestasis to the Hepatology Unit of Cairo University Children's Hospital from January 2018 to August 2019. In most of our patients, the mothers were the main caregivers and the parents’ socioeconomic and education levels were generally modest or low. We utilized the SCC courtesy of the Perinatal Services BC (Vancouver, Canada) with an Arabic translation. This SCC contains nine colored stool photos: the first six are ranked as abnormal colors and the last three are ranked as normal. ResultsWe found that almost all referring physicians were unfamiliar with or unaware of the SCC concept. Twenty-six of our babies' mothers were illiterate and 36 had not completed their primary school education. In spite of this low education level, 43 mothers of babies who were finally confirmed to have BA correctly matched a stool color of BA on the SCC with their babies' stools, and 56 mothers of babies who were finally confirmed not to have BA correctly matched a stool color not of BA with their babies' stools. Only nine mothers made a wrong match. Therefore, the overall “lay” mothers' sensitivity and specificity in diagnosis of BA using the SCC were 93.48% (95% confidence interval [CI] 82.1%–98.63%) and 90.32% (95% CI 80.12%–96.37%), respectively. ConclusionTo the best of our knowledge, this is the first study reporting the use of the SCC (with an Arabic translation) in a low/middle-income country. Despite the referring physicians' unfamiliarity with the SCC and the mothers’ relatively low education level at our center; SCC proved to be a simple, efficient, highly sensitive, specific, and applicable method for early diagnosis of BA. Therefore, SCC screening might increase motherś (as well as physicianś) awareness of BA, and we recommend that it be more publicized and used as a mass neonatal screening tool in low/middle-income countries such as Egypt.

Hepatic Failure in a Young Woman Following Ingestion of Tribulus Terrestris

Background: Plants have been used for the treatment of a wide range of conditions since ancient times but some have side effects and toxic effects that limit their use. Tribulus terrestris is traditionally used for lowering blood pressure, inhibiting kidney stone formation and inducing weight loss. In this case study, we present an Iranian woman who suffered from liver failure after using this plant. Case presentation: A 31-year-old Iranian woman was admitted to Emam-Reza hospital due to epigastric pain radiating to back and shoulders, and weakness, Malas,neusia and icterus. Upon admission,, her vital signs were normal. She had been consuming Tribulus terrestris as an herbal tea , several times a day for 2-3 months, in order to lose weight. Upon physical examination, the patient had generalized icterus and laboratory tests showed elevated transaminases, PT, and INR. Various causes of hepatic failure, such as viral hepatitis and autoimmune hepatitis, were ruled out and the only probable diagnosis was toxin-induced liver failure. Conclusion: Herbal plants may have some beneficial medical effects but they can also cause toxicity. Consistent use and high dose of Tribulus terrestris may cause hepatic failure and death.

Protective effects of 2-methoxycinnamaldehyde an active ingredients of Cinnamomum cassia on warm hepatic ischemia reperfusion injury in rat model.

Objective(s):Hepatic ischemia/reperfusion injury (IRI) is one of the major causes of hepatic failure during liver transplantation, trauma, and infections. The present study investigated the protective effect of intra-portal administration of 2-methoxycinnamaldehyde (2-MCA) on hepatic IRI in rats. Materials and Methods:Twenty-four rats were equally divided into four groups; 1) sham group, (no IRI or transfusion), 2) Hepatic IRI (60 min ischemia + 120 min reperfusion, 3) Hepatic IRI+ NS (IRI + normal saline), 4) Hepatic IRI+2-MCA, (IRI + 2-MCA). In groups 3 and 4, 1 ml/kg normal saline and 2-MCA were administered slowly into the vein of the left lateral and median lobes of the liver 10 min before induction of hepatic reperfusion (upper the site of clumping), respectively. The harvest time points were at 2 hours post-reperfusion in all groups. Results:Histologically, cell death, degenerative changes, sinusoidal dilatation, congestion, hemorrhage, and infiltration of inflammatory cells were observed in IRI group, while these pathological changes were attenuated in the 2-MCA administrated group. The level of alanine transaminase, aspartate transaminase, tumor necrosis factor- α and interleukin-6 in serum and hepatic malondialdehyde were significantly increased by IRI, and 2-MCA administration reduced all these markers. In addition, caspase-3 and nuclear factor κB (NF-κB) expression were investigated immunohistochemically. Administration of 2-MCA considerably decreased caspase-3 positive cells and NF-κB activity in comparison with IRI group. Conclusion:As a conclusion, in situ administration of 2-MCA protects against hepatic IRI via anti-inflammatory, and anti-apoptotic properties.

MRI-based preclinical discovery of DILI: A lesson from paracetamol-induced hepatotoxicity

Worldwide, drug-induced liver injury (DILI) is a major cause of hepatic failure. It is also the leading cause of withdrawal, cautionary labeling, and restricted usage of licensed drugs; therefore, European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) warn that the existing methods of assessing DILI are insufficient and that some of the translational biomarkers of hepatotoxicity must be relooked. Magnetic resonance imaging (MRI) seems to be a proper tool in elucidating the effects of DILI in both preclinical and clinical studies, providing excellent visualization of the morphology of the liver parenchyma. Therefore, herein, we propose preclinical MRI assessment of liver injury in experimental paracetamol-treated rats. Quantitative MRI clearly provides evidence of adverse effects in the liver tissue caused by a single overdose of paracetamol (1 g kg−1 and 1.5 g kg−1 b.w.). The results of the MRI were confirmed by the histopathological examination (H&E) of the rat liver specimen, however the adverse effects were not disclosed due to standard aminotransferase assays (ALT/AST) in rat blood serum. The results of our analysis demonstrate the successful application of MRI in the examination of paracetamol-induced hepatotoxicity in rats; it has a potential to serve as the early diagnostic tool for the prediction of DILI in preclinical evaluation.

The Protective Effect of Humanin Derivative AGA(C8R)-HNG17 Against Acetaminophen-Induced Liver Injury in Mice

Until recently, necrotic cells death was considered an uncontrolled process. However, evidence was recently presented that necrosis is a regulated process associated with many clinical conditions. Humanin and its derivatives are peptides known for their anti-apoptotic activity against Alzheimer’s disease. Recently, the humanin-derivative AGA(C8R)-HNG17 (PAGASRLLLLTGEIDLP) was found to have protective effect against necrosis in traumatic brain injury model in mice. We have demonstrated now the protective effect of AGA(C8R)-HNG17 against necrosis in a dose dependent manner in HepG2 cells in vitro, where necrosis was induced in a glucose-free medium by chemohypoxia. Moreover, it was further demonstrated in a model of acetaminophen-induced liver injury in C57BL/6J male mice, in vivo. Intraperitoneal administration of the peptide at 10 and 30 mg/kg significantly prevented the increase in two plasma markers for necrosis, alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1). Mitochondrial dysfunction is known to be the main cause of hepatic failure. Hence, the protection from liver injury by AGA(C8R)-HNG17, which we have recently found to target the mitochondria, may be mediated by mitochondrial regulation. Currently, there is no effective treatment for liver diseases, in which necrosis is involved. These findings may provide a new anti-necrotic strategy against APAP-induced liver injury and other liver diseases associated with necrosis using AGA(C8R)-HNG17 as a therapeutic agent.

Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.

Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure. Cellular oxidative stress, DNA damage and cell proliferation events were investigated by mitochondrial membrane potential assays, flow cytometry, fluorescence staining, comet assays and spotted arrays for protein expression after acetaminophen exposures. In experimental groups with acetaminophen toxicity, impaired mitochondrial viability and substantial DNA damage were observed with rapid loss of cells in S and G2/M and cell cycle restrictions or even exit in the remainder. This resulted from altered expression of the DNA damage regulator, ATM and downstream transducers, which imposed G1/S checkpoint arrest, delayed entry into S and restricted G2 transit. Tissues from people with acute liver failure confirmed hepatic DNA damage and cell cycle-related lesions, including restrictions of hepatocytes in aneuploid states. Remarkably, treatment of cells with a cytoprotective cytokine reversed acetaminophen-induced restrictions to restore cycling. Cell cycle lesions following mitochondrial and DNA damage led to failure of hepatic regeneration in acetaminophen toxicity but their reversibility offers molecular targets for treating acute liver failure.

INDIAN CHILDHOOD CIRRHOSIS: CASE REPORT AND PEDIATRIC DIAGNOSTIC CHALLENGES

Introduction: Indian childhood cirrhosis is a chronic liver disease usually seen in paediatric age group and is unique to the Indian subcontinent. The definitive causative factor for the disease is not found till now but excess copper ingestion has been associated with it.Case presentation: An Indian origin one and half year old premorbidly normal male child presented with history of gradual distension of abdomen for 6 months and jaundice, generalized body swelling, high colour urine for 20 days. There was no history of any bleeding or feature suggestive of hepatic encephalopathy. On physical examination child was icteric, pale and had anasarca, massive hepatosplenomegaly and ascites. The child was evaluated for various causes of hepatic failure in pediatric age group including infective, metabolic and autoimmune etiologies. Unfortunately the child succumbed to the illness. The post-mortem liver biopsy and copper estimation cleared the air, revealing Indian childhood cirrhosis as the underlying etiology.Conclusion: Though Indian childhood cirrhosis is a rare entity and reported less frequently in literature, the treating pediatrician should keep this as a differential in case of pediatric hepatic failure. The liver biopsy and hepatic copper estimation are the gold standard diagnostic tests for diagnosing Indian Childhood cirrhosis.

Transarterial chemoembolization aggravated peritumoral fibrosis via hypoxia-inducible factor-1α dependent pathway in hepatocellular carcinoma.

It was commonly accepted that chemotherapeutic cytotoxicity was the main cause for hepatic failure in hepatocellular carcinoma patients after repeated transarterial chemoembolization (TACE). However, the effect of embolization-induced hypoxia on liver cirrhosis has rarely been concerned. Serum levels of alanine aminotransferase, aspartate aminotransferase, and albumin were used to detect liver injury. Hepatic artery ligation was performed in carbon tetrachloride-induced rat hepatic fibrosis model to mimic the effect of hepatic hypoxia on liver fibrosis after TACE. Sirius Red staining and immunohistochemical analysis of alpha-smooth muscle actin (α-SMA) were used to detect the activation of hepatic stellate cells. Moreover, the expression of hypoxia and fibrosis-related molecules were analyzed at protein and/or mRNA level. Patients showed a significant increase in alanine aminotransferase and aspartate aminotransferase (P = 0.006), accompanied by a decrease in albumin (P = 0.005) after repeated TACE. Hepatic artery ligation significantly promoted carbon tetrachloride-induced rat liver fibrosis progression as indicated by Sirius Red and α-SMA staining, as well as increased expression of hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF). Conditioned media of hypoxia-treated L02 cells induced the expression of Collagen I and α-SMA in LX-2 cells, which was inhibited by HIF-1α small interfering RNA. Finally, HIF-1α inhibitor LW6 attenuated the hypoxia-induced fibrosis progression in vivo. Our data demonstrate that TACE-induced hepatic hypoxia aggravates the fibrosis progression in peritumoral liver tissue, thus leads to the deterioration of liver function. Intervention of HIF-1α might be a valuable strategy to optimize the efficacy and reduce the complication of TACE.

A switch in the source of ATP production and a loss in capacity to perform glycolysis are hallmarks of hepatocyte failure in advance liver disease

The cause of hepatic failure in the terminal stages of chronic injury is unknown. Cellular metabolic adaptations in response to the microenvironment have been implicated in cellular breakdown. To address the role of energy metabolism in this process we studied mitochondrial number, respiration, and functional reserve, as well as cellular adenosine-5'-triphosphate (ATP) production, glycolytic flux, and expression of glycolysis related genes in isolated hepatocytes from early and terminal stages of cirrhosis using a model that produces hepatic failure from irreversible cirrhosis in rats. To study the clinical relevance of energy metabolism in terminal stages of chronic liver failure, we analyzed glycolysis and energy metabolism related gene expression in liver tissue from patients at different stages of chronic liver failure according to Child-Pugh classification. Additionally, to determine whether the expression of these genes in early-stage cirrhosis (Child-Pugh Class A) is related to patient outcome, we performed network analysis of publicly available microarray data obtained from biopsies of 216 patients with hepatitis C-related Child-Pugh A cirrhosis who were prospectively followed up for a median of 10years. In the early phase of cirrhosis, mitochondrial function and ATP generation are maintained by increasing energy production from glycolytic flux as production from oxidative phosphorylation falls. At the terminal stage of hepatic injury, mitochondria respiration and ATP production are significantly compromised, as the hepatocytes are unable to sustain the increased demand for high levels of ATP generation from glycolysis. This impairment corresponds to a decrease in glucose-6-phosphatase catalytic subunit and phosphoglucomutase 1. Similar decreased gene expression was observed in liver tissue from patients at different stages of chronic liver injury. Further, unbiased network analysis of microarray data revealed that expression of these genes was down regulated in the group of patients with poor outcome. An adaptive metabolic shift, from generating energy predominantly from oxidative phosphorylation to glycolysis, allows maintenance of energy homeostasis during early stages of liver injury, but leads to hepatocyte dysfunction during terminal stages of chronic liver disease because hepatocytes are unable to sustain high levels of energy production from glycolysis.

Screening for Hepatitis C Is Inconsistently Prompted by Guidelines

Purpose: Chronic hepatitis C (HCV) is one of the most common causes of hepatic failure and death in the United States. It is estimated that 4.5 million are infected in this nation. However, the prevalence of chronic HCV may be underestimated. It is recommended that adults born between 1945 and 1965 be screened for HCV to aid in decreasing the morbidity and mortality related to this infection. This study evaluated the rate and reason of HCV testing in patients receiving preventative care. Methods: A retrospective medical record review was performed using a multispecialty electronic health record. Consecutive patients born 1945-1965 referred to an academic gastroenterology practice for colorectal cancer screening were included. There were no exclusion criteria. Patient age, gender, performance of HCV, antibody, and reason for HCV testing were obtained. A database maintaining patient confidentiality was created. Statistical analysis was performed using Fisher's exact test, with significance set at p<0.05. The study was approved by the university IRB. Results: Four hundred fifty-five medical records were reviewed. There were 174 men and 271women, with mean age of 57.7 years (95% confidence interval 57.2-58.2). 102 of 455 (22.4%) patients were tested for HCV. 51 (50%) patients were screened for HCV based upon birth cohort. 51 (50%) patients had other documented reasons that prompted HCV testing, including abnormal liver enzymes (14), report of a history of hepatitis C (13), rheumatologic disorder (4), chronic kidney disease (3), HIV (2), hepatitis B (2), pre-operative evaluation (1), parent with hepatocellular carcinoma (1), fatigue (1), hyperlipidemia (1), and miscellaneous factors (10). 11 patients had a positive HCV antibody. None of the patients screened based upon their birth cohort were HCV positive. The 11 HCV-positive patients had reported a history of HCV. None of the other reasons prompting HCV testing resulted in a positive HCV antibody. There was a significant difference (p<0.0001) in the rate of positive HCV antibody in patients screened based upon birth cohort and those reporting a history of HCV. Conclusion: This study revealed that patients undergoing preventative care, who were referred for screening colonoscopies, had been infrequently tested for HCV. Despite published guidelines, only half of the HCV tested patients were screened based upon their birth cohort. None of the patients screened based upon their age had a positive HCV antibody. All of the individuals who were positive for HCV had reported a history of HCV infection. This study suggests efforts should be made to improve ageappropriate HCV screening. Gastroenterologists can assist in HCV screening by testing patients referred for colonoscopies.

Biliary cirrhosis caused by Campula spp. in a dolphin and four porpoises

Biliary cirrhosis produced by Campula spp. is described in 1 striped dolphin Stenella coeruleoalba and 4 harbour porpoises Phocoena phocoena. The hepatic lesions consisted of severe proliferation of fibrous connective tissue with loss of the lobular pattern, nodular regeneration of the hepatic tissue, bile duct hyperplasia and severe inflammatory infiltrate composed of eosinophils, macrophages, lymphocytes and plasma cells. These lesions were associated with severe infestation by Campula spp. Although inflammatory and degenerative hepatic lesions are frequently found in stranded dolphins, biliary cirrhosis has not been previously reported in cetaceans. Massive infestation by these parasites should be included as a cause of hepatic failure resulting in stranding of marine mammals.

Risk Factors of Mortality in Children with Hepatic Encephalopathy

Background: Hepatic encephalopathy is a serious but potentially reversible complication in children with liver disease. The aim of this study is to evaluate the risk factors of mortality in children with hepatic encephalopathy. Method: Totally 42 patients including 22 boys and 20 girls with clinical diagnosis of hepatic encephalopathy who admitted to Pediatric Intensive Care Unit at Nemazee Hospital affiliated to Shiraz University of Medical Sciences, during 5 years period were enrolled in this study. Demographic features, cause of hepatic failure, grade of hepatic encephalopathy, predisposing factors, concurrent clinical manifestations and laboratory data, as possible prognostic factors were evaluated. The survival states of the patients (survivors or non-survivors) as final outcome were also documented. Results: The most common underlying liver diseases were cryptogenic (57.2%), hepatitis A (23.8%), Wilson disease (7.1%), and autoimmune hepatitis (7.1%). The total mortality rate was 54%. There was no statistically significant difference in age, weight and hospital stay between survivors or non-survivors groups. Only gastrointestinal bleeding had significant association with mortality (37% vs 92%; p=0.001). The most common predisposing factor was infection (52.5%). Patients with higher international normalized ratio and partial thromboplastin time and lower serum sodium and bicarbonate on admission and those with higher bilirubin, international normalized ratio, partial thromboplastin time, aspartate aminotransferase and lower platelets and serum bicarbonate level on last day were more likely to die. Conclusion: Poor prognostic factors for hepatic encephalopathy were included gastrointestinal bleeding, higher international normalized ratio, partial thromboplastin time, bilirubin, and aspartate aminotransferase, and lower serum sodium and bicarbonate levels and platelet counts.

Significance of Bioelectrical Impedance Change after Ischemia and Reperfusion Injury in Liver and What it Causes?

Purpose: Ischemia and reperfusion (I/R) injury is a major cause of hepatic failure after liver surgery, but there is no direct method to monitor it in real-time (like an ECG in heart disease) during surgery. Recently we found the possible role of bioelectrical impedance (BEI) to monitor I/R injury in liver, but the mechanism responsible for ischemia-related BEI changes has not been clearly determined. Methods: The authors used a LCR meter to quantify BEI changes at 0.12 KHz. Livers were subjected to 70% partial ischemia for 120 minutes, and ATP content, cation changes in extracellular fluid (ECF; determined using an in vivo intracellular microdialysis technique), hepatocyte sizes, and histological changes were then examined. Results: Liver tissue BEI was found to increase gradually during the first 60 minutes of ischemia and then tended to plateau. During the same period, intracellular ATP content decreased to below 20% of the baseline level, [Na + ] in ECF decreased from 150.4 ± 3.8 to 97.8 ± 10.6 mmol/L, and [K + ] in ECF increased from 7.5 ± 0.3 to 34.3 ± 5.5 mmol/L during the first 60 minutes of ischemia. Hepatocyte diameter increased by approximately 20% during the first 60 minutes of ischemia. Conclusion: This study suggests that BEI changes during hepatic ischemia are probably caused by sodium and potassium concentration changes in the ECF due to reduced intracellular ATP content.

Fulminant hepatic failure in association with quetiapine: a case report.

IntroductionFulminant hepatic failure is a serious disease with significant mortality and morbidity. Identifying the exact cause of hepatic failure and predicting prognosis is of paramount importance in managing such patients. Drug-induced liver injury is a common but challenging entity to treat. The use of newer drugs and medications with previously unknown hepatotoxicity add to the challenges faced by treating physicians. Quetiapine is an antipsychotic that has rarely been linked to acute liver injury. In the present work we describe a case of fulminant hepatic failure secondary to use of quetiapine.Case presentationA 59-year-old Caucasian woman with known Parkinson’s disease was being treated with quetiapine for hallucinations. She was referred to our hospital with yellow discoloration of the sclera and later on developed clinical features suggestive of hepatic encephalopathy. A diagnosis of fulminant hepatic failure was made following her admission to the intensive care unit. Her condition improved after discontinuing the drug and providing the standard supportive treatment.ConclusionsOur findings in the present report emphasize the importance of keeping an open mind in cases of fulminant hepatic failure. As drug-induced hepatotoxicity is the most common cause of fulminant hepatic failure in many parts of the world, consideration should be given to the medication(s) patients receive as the potential cause and a review of this list should be part of the clinical care given.

21-jährige Patientin mit Reye-Syndrom nach grippalem Infekt

A 21-year old woman was referred to the hospital because of progressively deteriorating consciousness. Initially agitation and irritability, later confusion and delirium predominated. Previously influenza with high temperature, headache and vomiting had occurred and been treated with acetylsalicylic acid for some days. Non preliminary diseases were reported. CLINICAL INVESTIGATION: Besides of the deterioration in consciousness no clinical or neurological abnormalities were found. Electroencephalography demonstrated general abnormalities of medium range. Cranial magnetic resonance imaging and liquor investigations showed no pathological findings. In laboratory tests a marked increase of transaminases and ammonia were found. The toxicological screening was normal. A hepatic encephalopathy due to acute hepatic failure was diagnosed and a detoxication of ammonemia with lactulose was started immediately. Transjugular liver biopsy showed a marked fattening of liver tissue without serological or histological findings for a reason. Because of progressive deterioration in consciousness mechanical ventilation became necessary. Despite of a rapid decline of ammonium serum levels further neurological deterioration occurred. Cranial computed tomography showed oedema of the cerebrum with beginning cerebral occlusion. Despite immediate therapy of cerebral oedema the patient died because of secondary cerebral oedema in hepatic encephalopathy. Reye's syndrome is an acute illness characterized by hepatic encephalopathy and fatty degeneration of the liver. It often occurs after viral infections. After a viral infection that was eventually treated with acetylsalicylic acid Reye's syndrome has to be discussed after exclusion of common causes of hepatic failure.

Hepatitis C virus: current concepts and future challenges

Hepatitis C virus (HCV) is a global infection, with an estimated 170 million people affected.1 The geographical distribution is of some interest as it gives clues as to the history and transmission of the virus. It appears there are endemic strains, which have persisted in specific locations for many centuries. These can be readily identified by viral genotype—for example, Genotype 2 is a strain which evolved in West Africa, while Genotype 6 evolved in South East Asia.2 In the last century, there have been iatrogenic outbreaks leading to a massive spread of specific subtypes in countries such as Egypt (Genotype 4A).3 There was also global spread of certain strains, most notably Genotype 1 within Europe and North America, and more recently Genotype 3A in European intravenous drug user (IDU) populations.4 HCV heterogeneity is huge, based on its capacity to develop mutation through its error-prone polymerase, and its very long co-evolutionary history with man. This is a major challenge for drug design and vaccines. Clinically, genotypic information on the virus is of major importance in defining response to conventional as well as newer therapies.1,4 Chronic HCV infection is now a leading cause of hepatic failure requiring transplantation in the west. Cirrhosis associated with HCV is also linked to the development of hepatocellular carcinoma, although unlike hepatitis B virus (HBV) this does not occur in pre-cirrhotic states. Chronic HCV infection is also associated with a number of extra-hepatic diseases, linked to B cell hyper-activation and potentially also chronic antigenemia—most notably mixed essential cryoglobulinaemia.5 Acute hepatitis C is actually a rare clinical presentation, despite the widespread nature of the virus. Typically, acute hepatitis is mild and may be clinically very subtle, with a delay of several weeks before a rise in alanine transaminase (ALT) is …