Protective effect and mechanism of stronger neo-minophagen C against fulminant hepatic failure

AIM： To investigate the protective effect of stronger neo-minophafen C （SNMC） on fulminant hepatic failure （FHF） and its underlying mechanism. METHODS： A mouse model of FHF was established by intraperitoneal injection of galactosamine （D-Gal N） and lipopolysaccharide （LPS）. The survival rate, liver function, inflammatory factor and liver pathological change were obtained with and without SNMC treatment. Hepatoo/te survival was estimated by observing the stained mitochondria structure with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling （TUNEL） method and antibodies against cytochrome C （Cyt-C） and caspase-3. RESULTS： The levels of plasma tumor necrosis factor alpha （TNF-α）, nitric oxide （NO）, ET-1, interleukin-6 （IL-6）, and the degree of hepatic tissue injury were decreased in the SNMC-treated groups compared with those in the model group （P 〈 0.01）. However, there were no differences after different dosages administered at different time points. There was a significant difference in survival rates between the SNMC-treated groups and the model group （P 〈 0.01）. The apoptosis index was 32.3% at 6 h after a low dose of SNMC, which was considerably decreased from 32.3% ± 4.7% vs 5% ± 2.83% （P 〈 0.05） to 5% on d 7. The expression of Cyt-C and caspase-3 decreased with the prolongation of therapeutic time. Typical hepatocyte apoptosis was obviously ameliorated under electron microscope with the prolongation of therapeutic time. CONCLUSION： SNMC can effectively protect liver against FHF induced by LPS/D-Gal N. SNMC can prevent hepatocyte apoptosis by inhibiting inflammatory reaction and stabilizing mitochondria membrane to suppress the release of Cyt-C and sequent activation of caspase-3.

TypeⅠinositol 1, 4, 5-triphosphate receptors increase in kidney of mice with fulminant hepatic failure

AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.

Role of cathepsin B-mediated apoptosis in fulminant hepatic failure in mice

AIM: To investigate the pathogenic role of cathepsin B and the protective effect of a cathepsin B inhibitor (CA074Me) in fulminant hepatic failure in mice. METHODS: LPS/D-Gal N was injected into mice of the model group to induce fulminant hepatic failure; the protected group was administered CA-074me for 30 min before LPS/D-Gal N treatment; the normal group was given isochoric physiologic saline. Liver tissue histopathology was determined with HE at 2, 4, 6 and 8 h after Lps/D-Gal injection. Hepatocyte apoptosis was examined by TUNEL method. The expression of cathepsin B in liver tissues was investigated by immunohistochemistry, Western blot and RT-PCR. RESULTS: Compared with the normal group, massive typical hepatocyte apoptosis occurred in the model group; the number of apoptotic cells reached a maximum 6 h after injection. The apoptosis index (AI) in the protected group was clearly reduced (30.4 ± 2.8 vs 18.1 ± 2.0, P < 0.01 ). Cathepsin B activity was markedly increased in drug-treated mice compared with the normal group (P < 0.01). Incubation with LPS/D-Gal N at selected time points resulted in a timedependent increase in cathepsin B activity, and reached a maximum by 8 h. The expression of cathepsin B was significantly decreased in the protected group (P < 0.01). CONCLUSION: Cathepsin B plays an essential role in the pathogenesis of fulminant hepatic failure, and the cathepsin B inhibitor CA-074me can attenuate apoptosis and liver injury.

Tumor necrosis factor-alpha induces apoptosis of enterocytes in mice with fulminant hepatic failure

AIM: To explore the alterations of intestinal mucosa morphology, and the effects of tumor necrosis factor a (TNFα) on enterocyte apoptosis in mice with fulminant hepatic failure (FHF). METHODS: Liver damage was induced by lipopolysaccharide (LPS)/TNF-α in D-galactosamine (GaIN) sensitized BALB/c mice. There were 40 mice in normal saline (NS)-treated group, 40 mice in LPS-treated group, 40 mice in GaIN-treated group, 120 mice in GaIN/ LPS-treated group and 120 mice in GaIN/ TNFα-treated group. Each group was divided into five subgroups of eight mice each. Serum samples and liver, intestinal tissues were respectively obtained at 2, 6,9,12 and 24 h after administration. Anti-TNFa monoclonal antibody was injected intravenously into GaIN/LPS-treated mice. Serum TNFα levels were determined by enzyme linked immunosorbent assays (ELISA). Serum ALT levels were determined using an automatic analyzer. The intestinal tissues were studied under light microscope and electron microscope at 2, 6, 9,12 and 24 h in mice with fulminant hepatic failure, respectively. Enterocyte apoptosis was determined by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method. The expression of tumor necrosis factor receptor 1 (TNFR1) in intestinal tissue was tested by immunohistochemistry Envision Two Steps. RESULTS: Gut mucosa was morphologically normal at all time points in all groups, but typical apoptotic cells could be seen in all experimental groups under electron microscope. Apoptosis rate of gut mucosal epithelial cells were significantly increased at 6, 9 and 12 h, peaked at 12 h in mice with fulminant hepatic failure. TNFa induced apoptosis of enterocytes in mice with FHF. The integrated OD (IOD) levels of TNFa receptor 1 protein expressed in the intestine of mice with GaIN/LPS and GaIN/ TNFα induced FHF at 2, 6, 9, 12 and 24 h after GaIN/LPS and GaIN/TNFα administration were 169.54±52.62/905.79±111.84,11 350.67±2 133.26/28 160.37±4 601.67, 25 781.00±2 277.75/122 352.30±49 412.40, 5 241.53±3 007.24/ 49 157.93±9 804.88, 7 086.13±1 031.15/3 283.45±127.67, respectively, compared with those in control groups (with NS, LPS and GaIN administration, respectively). IOD level of TNFR1 changed significantly at 6, 9 and 12 h after GaIN/LPS and GalN/TNFa administration. The expression of TNFR1 protein was significantly higher at 9 h after GaIN/LPS and GaIN/TNFα administration than that in control groups. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis. CONCLUSION: TNFα can induce apoptosis of enterocytes in mice with FHF. Anti-TNFα IgG can inhibit this role.

A Macaca mulatta model of fulminant hepatic failure

AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin.Clinical features,biochemical indexes,histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.RESULTS:Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration.Coagulation activity was significantly decreased.Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h.The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h,respectively.The autopsy showed typical yellow atrophy of the liver.Hepatic encephalopathy of the models was also confirmed by hepatic coma,MRI and pathological changes of cerebral edema.The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices,imaging and histopathology.CONCLUSION:We have established an appropriate large primate model of FHF,which is closely similar to clinic cases,and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.

Etiology of fulminant hepatic failure:experience from a tertiary hospital in Bangladesh

BACKGROUND: Fulminant hepatic failure (FHF) is not uncommon in our clinical practice in Bangladesh. There was a rise in acute hepatitis E virus (HEV) in Bangladesh after the 2004 floods. At that time, most of the country was under water for more than a month, leading to sewage contamination of the water supply. The aim of this study was to investigate the etiology of FHF in Bangladesh. METHODS: In this retrospective study, 23 patients with FHF who presented with severe impairment of hepato- cellular function (i.e. encephalopathy, coagulopathy and jaundice) within 6 months of onset of symptoms were included. There were 17 men and 6 women, aged from 18 to 32 years. Four of the women were pregnant. Patients were tested for markers for common hepatotrophic viruses. A relevant history was taken and the Patient Record Book of the Unit was reviewed. RESULTS: 56.52% patients (13/23) had HEV infection, and all were anti-HEV IgM-positive tested by ELISA. HBV infection was detected in 34.78% patients (8/23), all of whom were tested positive for either HBsAg or anti-HBs IgM by ELISA. 8.7% patients (2/23) had a positive history for intake of alcohol and/or drugs. CONCLUSIONS: Acute HEV infection is the leading cause of FHF in Bangladesh. Sewage contamination of the water supply following floods contributes to a higher incidence of HEV infection. HBV infection is also important.

Fulminant hepatic failure caused by Salmonella paratyphi A infection

We report a case of fulminant hepatic failure associated with Salmonella paratyphi A infection, in a 29-yearold patient who was admitted to the intensive care unit （ICU） with fever of two days, headache and vomiting followed by behavioural changes and disorientation. On examination, the patient appeared acutely ill, agitated, confused, and deeply jaundiced. Temperature 38.5℃, pulse 92/min, blood pressure 130/89 mmHg. Both samples of blood grew S. paratyphi A, which was sensitive to ceftriaxone and ciprofloxacin. Ceftriaxon was administered with high-dose dexamethasone. Two weeks after treatment with ceftriaxon, the patient was discharged in satisfactory condition.

Enhanced expressions and activations of leukotriene C4synthesis enzymes in D-galactosamine/lipopolysaccharide-induced rat fulminant hepatic failure model

AIM： To investigate the expression and activity of leukotriene C4 （LTC4） synthesis enzymes and their underlying relationship with cysteinyl leukotriene （cys-LT） generation in a rat fulminant hepatic failure （FHF） model induced by D-galactosamine/lipopolysaccharide （D-GaIN/ LPS）. METHODS： Rats were treated with D-GaIN （300 mg/kg） plus LPS （0.1 mg/kg） for 1, 3, 6, and 12 h. Enzyme immunoassay was used to determine the hepatic cys-LT content. Reverse transcription-polymerase chain reaction （RT-PCR）, Western blot or immunohistochemical assay were employed to assess the expression or location of LTC4 synthesis enzymes, which belong to membrane associated proteins in eicosanoid and glutathione （MAPEG） metabolism superfamily. Activity of LTC4 synthesis enzymes was evaluated by determination of the products of LTA4 after incubation with liver microsomes using high performance liquid chromatography （HPLC）. RESULTS： Livers were injured after treatment with D-GaIN/LPS, accompanied by cys-LT accumulation at the prophase of liver injury. Both LTC4 synthase （LTC4S） and microsomal glutathione-S-transferase （mGST） 2 were expressed in the rat liver, while the latter was specifically located in hepatocytes. Their mRNA and protein expressions were up-regulated at an earlier phase after treatment with D-GaIN/LPS. Meantime, a higher activity of LTC4 synthesis enzymes was detected, although theactivity of LTC4S played the main role in this case. CONCLUSION： The expression and activity of both LTC4S and mGST2 are up regulated in a rat FHF model, which are, at least, partly responsible for cys-LT hepatic accumulation.

Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic failure and increase survival in mice

BACKGROUND：Cell therapy has been promising for various diseases.We investigated whether transplantation of human umbilical cord mesenchymal stem cells（h UCMSCs）has any therapeutic effects on D-galactosamine/lipopolysaccharide（Gal N/LPS）-induced fulminant hepatic failure in mice.METHODS：h UCMSCs isolated from human umbilical cord were cultured and transplanted via the tail vein into severe combined immune deficiency mice with Gal N/LPS-induced fulminant hepatic failure.After transplantation,the localization and differentiation of h UCMSCs in the injured livers were investigated by immunohistochemical and genetic analy- ses. The recovery of the injured livers was evaluated histologi- cally. The survival rate of experimental animals was analyzed by the Kaplan-Meier method and log-rank test. RESULTS： hUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed adip- ogenic and osteogenic differentiation potential. Hematoxylin and eosin staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival rate of mice with fulminant hepatic failure. Polymerase chain reaction for human alu sequences showed the presence of human cells in mouse livers. Positive staining for human albumin, human alpha-fetoprotein and human cytokeratin 18 suggested the for- mation of hUCMSCs-derived hepatocyte-like cells in vivo.CONCLUSIONS： hUCMSC was a potential candidate for stem cell based therapies. After transplantation, hUCMSCs partially repaired hepatic damage induced by GalN/LPS in mice. hUC- MSCs engrafted into the injured liver and differentiated into hepatocyte-like cells.

Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg·d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg·d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α (TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNPa (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.

Fulminant hepatic failure resulting from small-cell lung cancer and dramatic response of chemotherapy

Prompt treatment in tumor-associated encephalopathy may prolong survival. We describe a 69-year-old male patient who was presented with fulminant hepatic failure, secondary to small-cell lung carcinoma with rapidly progressing encephalopathy. Both symptoms remitted following chemotherapy, suggesting swift diagnosis and administration of chemotherapy to be effective in treatment of fulminant hepatic failure and encephalopathy.

Inhibiting the expression of hepatocyte nuclear factor 4 alpha attenuates lipopolysaccharide/ D-galactosamine-induced fulminant hepatic failure in mice

BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN). METHODS: The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4α short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed. RESULTS: The expression of HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4α expression was inhibited in mice with FHF. CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.

Multimodal brain monitoring in fulminant hepatic failure

Acute liver failure, also known as fulminant hepatic failure(FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting.

An Experimental Study on the Disorders of Hepatic Hemodynamics and Changes of Plasma Histamine in Dogs with Fulminant Hepatic Failure

The model of fulminant hepatic failure induced by acetaminophen was established in dogs to observe the changes of hepatic hemodynamics and plasma histamine levels in portal vein (PV), hepatic vein (HV), abdominal aorta (AA) and inferior vena cava (ICV). The results showed that the portal vein resistance (PVR) was elevated and portal venous blood flow (PVF) was decreasedl hepatic artery resistance (HAR) was decreased and the hepatic artery blood flow (HAF),portal venous pressure (PVP), wedged hepatic venous pressure (WHVP) and inferior vena cava pressure (ICVP) had no changes. The histamine of the PV, HV,ICV and AA were all elevated after formation of fulminant hepatie failure. And the increasing wave Of the HV was the highest. The increased histamine in HV may be mediated by H, receptor.causing the contraction of hepatic venulae, result ing liver sinusoid congestion, increasing PVR and decreasing PVF which exacerbate the liver cell damage. Moreover, the more selvere liver damage, the more histamine was released, and a vicious circle may ensue. Our results also suggest the possibility of using,H1 receptor antagonist to treat the disturbance of liver hemodynamfics in severe acute liver damage. The increased histamine in systematic circulation as a vasodilator may lower blood pressure and accelerate heart beats.The increase of plasma histamine may play an important role in the changes of hepatic and systemic hemodynamics in fulminant hepatic failure.

Rapid onset Chilaiditi's sign on top of fulminant hepatic failure

ABSTRACT: Fulminant hepatic failure is a medical emer-gency. When this condition declared itself irreversible, atimely liver transplantation is the only effective treatment.A 34-year-old Chinese with fulminant hepatic failure wasevaluated as a potential liver transplantation candidate. Onthe erect chest radiograph, Chilaiditi' s sign has developedover a very short period of a week due to rapid shrinkage ofthe liver. Awareness of Chilaiditi' s sign facilitated distin-guishing the condition of free gas under the diaphragm dueto bowel perforation and subphrenic abscess by gas formingmicro-organisms. Rapidity of onset of this sign parallels thedeterioration of liver function and reflects the urgency ofcondition.

Protection of plasma transfusion against lipopolysaccharide/D-galactosamine-induced fulminant hepatic failure through inhibiting apoptosis of hepatic cells in mice

Fulminant hepatic failure is a severe clinical condition associated with extremely poor outcomes and high mortality. A number of studies have demonstrated the ability of plasma transfusion to successfully treat fulminant hepatic failure, but the underlying mechanisms are not well understood. The aim of the present study is to define the mechanisms of plasma transfusion treatment in lipopolysaccharide/D-galactosamine(LPS/D-Gal N)-induced mice. LPS/D-Gal N treatment in mice causes significant hepatic failure, including increasing serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) levels, histopathological changes in centrilobular necrosis and inflammatory cells, and the up-regulation of inflammation(tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)). When LPS/D-Ga IN-induced mice were treated with plasma, these changes were halted. Results showed that plasma transfusion significantly reduced mortality, and decreased the levels of AST, ALT, and inflammation factors such as TNF-α and IL-6. The expression levels of cleaved Caspase-3, BAX, and p53 were down-regulated and Bcl-2 was up-regulated, suggesting that plasma can reduce LPS/D-Gal N-induced apoptosis. The protective mechanism of plasma against LPS/D-Gal N-induced fulminant hepatic failure is related to the inhibition of the inflammatory response and the reduction in apoptosis through the down-regulation of the p53-induced apoptotic pathway.

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, how ever, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

Parvovirus B19 induced hepatic failure in an adult requiring liver transplantation

Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported, mainly in children. Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation. We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation. This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation. This case suggests that Parvovirus B19 induced liver disease can affect adults, can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation.

Diagnostic criteria for acute liver failure due to Wilson disease

AIM： To describe the diagnostic criteria for acute liver failure due to Wilson disease （WD）, which is an uncommon cause of acute liver failure （ALF）. METHODS： We compared findings of patients presenting with ALF due to WD to those with ALF of other etiologies. RESULTS： Previously described criteria, such as low alkaline phosphatase activity, ratio of low alkaline phosphatase to total bilirubin or ratio of high aspartate arninotransferase （AST） to alanine arninotransferase （ALT）, failed to identify patients with ALF due to WD. There were significant differences in low ALT and AST activities （53 ± 43 vs 1982 ± 938, P 〈 0.0001 and 87 ± 44 vs 2756 ± 2941, P = 0.037, respectively）, low choline esterase activity （1.79 ± 1.2 vs 4.30 ± 1.2, P = 0.009）, high urine copper concentrations （93.4 ± 144.0 vs 3.5 ± 1.8, P = 0.001） and low hemoglobin （7.0 ± 2.2 vs 12.6 ± 1.8, P 〈 0.0001） in patients with ALF caused by WD as compared with other etiologies. Interestingly, 4 of 7 patients with ALF due to WD survived without liver transplantation. CONCLUSION： In ALF, these criteria can help establish a diagnosis of WD. Where applicable, slitlamp examination for presence of Kayser-Fleischer rings and liver biopsy for determination of hepatic copper concentration still remain important for the diagnosis of ALF due to WD. The need for liver transplantation should be evaluated carefully as the prognosis is not necessarily fatal.

Successful disintegration,dissolution and drainage of intracholedochal hematoma by percutaneous transhepatic intervention

Hemobilia is a rare biliary complication of liver transplantation.The predominant cause of hemobilia is iatrogenic,and it is often associated with traumatic operations,such as percutaneous liver intervention,endoscopic retrograde cholangiopancreatography,cholecystectomy,biliary tract surgery,and liver transplantation.Percutaneous transhepatic cholangiography and liver biopsy are two major causes of hemobilia in liver transplant recipients.Hemobilia may also be caused by coagulation defects.It can form intracholedochal hematomas,causing obstructive jaundice.Herein we describe a patient with an intracholedochal hematoma resulting in significant obstructive jaundice after liver transplantation for fulminant hepatic failure.Previous studies have shown that percutaneous transhepatic manipulation is a major cause of hemobilia after liver transplantation,but in our case,percutaneous transhepatic intervention was used to relieve the biliary obstruction and dissolve the biliary clot,with a good outcome.