An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure

AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.

Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50μg/kg pcDNA3-ALR DNA.The effect of intravenous injection of recombinant pcDNA3ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid,the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P＜0.01).CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level ofAST and ALT in CCl4-intoxicated rats.

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

While cardiopulmonary symptoms are common in patients undergoing dassical 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.

Ex vivo-expanded bone marrow stem cells home to the liver and ameliorate functional recovery in a mouse model of acute hepatic injury

BACKGROUND:Stem cell transplantation provides a theoretical approach for liver regeneration medicine;it may promote liver regeneration and self-repair.However,the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated.This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl 4 injury.METHODS:Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation,characterized by cytoflow immunofluorescence,and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl 4.The integration of bone marrow cells into the liver was examined microscopically,and plasma hepatic enzymes were determined biochemically.RESULTS:Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells.Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl 4 -treated mice.Densitometry showed increased in situ cell proliferation (50±14 vs 20±3 cells/high-power field,P<0.05) and albumin expression (149±25 vs 20±5 cells/high-power field,P<0.05) in the liver,as well as reduced serum aminotransferase levels (P<0.05) and better survival rates (P<0.05) in animals receiving cultured bone marrow cells relative to controls.CONCLUSIONS:Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically- injured liver.Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.

Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages

AIM To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells(MSCs) in acute hepatic failure(AHF).METHODS MSCs were transfused into rats with AHF induced by D-galactosamine(DGal N). The therapeutic effects of MSCs were evaluated based on survival rate and hepatocyte proliferation and apoptosis. Hepatocyte regeneration capacity was evaluated by the expression of the hepatic progenitor surface marker epithelial cell adhesion molecule(Ep CAM). Macrophage polarization was analyzed by M1 markers [CD68,tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),inducible nitric oxide synthase(INOS)] and M2 markers [CD163,interleukin(IL)-4,IL-10,arginase-1(Arg-1)] in the survival and death groups after MSC transplantation.RESULTS The survival rate in the MSC-treated group was increased compared with the DPBS-treated control group(37.5% vs 10%). MSC treatment protected rats with AHF by reducing apoptotic hepatocytes and promoting hepatocyte regeneration. Immunohistochemical analysis showed that MSC treatment significantly increased the expression of Ep CAM compared with the control groups(P < 0.001). Expression of Ep CAM in the survival group was significantly up-regulated compared with the death group after MSC transplantation(P = 0.003). Transplantation of MSCs significantly improved the expression of CD163 and increased the gene expression of IL-10 and Arg-1 in the survival group. IL-4 concentrations were significantly increased compared to the death group after MSC transplantation(88.51 ± 24.51 pg/m L vs 34.61 ± 6.6 pg/m L,P < 0.001). In contrast,macrophages showed strong expression of CD68,TNF-α,and INOS in the death group. The concentration of IFN-γ was significantly increased compared to the survival group after MSC transplantation(542.11 ± 51.59 pg/m L vs 104.07 ± 42.80 pg/m L,P < 0.001).CONCLUSION M2 polarization contributes to the therapeutic effects of MSCs in AHF by altering levels of anti-inflammatory and pro-inflammatory factors.

Hepatoprotective effects of cathepsin B inhibitor on acute hepatic failure induced by lipopolysaccharide/D-galactosamine in mice

BACKGROUND:Increasing evidence suggests that the inactivation of cathepsin B attenuates hepatocyte apoptosis and liver damage.This study aimed to investigate the protective effects of a cathepsin B inhibitor(CA-074me) on lipopolysaccharide(LPS)/D-galactosamine(D-GalN)-induced acute hepatic failure(AHF) in mice.METHODS:Mice were intraperitoneally injected with a combination of LPS/D-GalN to induce AHF with or without CA-074me pretreatment.The cumulative survival rates were calculated 48 hours after the induction of AHF.As well as changes in biochemical indicators and liver histology,hepatocyte apoptosis was assessed using a TUNEL method.Serum tumor necrosis factor-α(TNF-α) production,caspase-3,caspase-8,and caspase-9 activity was evaluated.Cytosolic cytochrome c and Bcl-2 expression were measured by Western blotting.RESULTS:The marked elevation in serum aminotransferase activity and prothrombin time found in LPS/D-GalN-treated mice was significantly improved by pretreatment with CA074me.The efficacy of CA-074me was also confirmed by histological analysis and TUNEL assay.The survival rate significantly improved in LPS/D-GalN-induced mice given CA-074me compared with untreated mice.LPS/D-GalNinduced caspase-3 and caspase-9 activation was remarkably suppressed by CA-074me.However,the increased levels of serum TNF-α and elevated caspase-8 activity in AHF mice were not significantly reduced by CA-074me.Moreover,CA074me sharply reduced the increased expression of cytosolic cytochrome c and markedly augmented Bcl-2 expression.CONCLUSION:These results suggest that CA-074me has a protective effect in acute hepatic failure induced by LPS/D-GalN.

Efficacy of liver transplantation for acute hepatic failure:asingle-center experience

BACKGROUND:Acute hepatic failure (AHF) is a devastating clinical syndrome with a high mortality rate.The outcome of AHF varies with etiology,but liver transplantation (LT) can significantly improve the prognosis and survival rate of such patients.This study aimed to detect the role of LT and artificial liver support systems (ALSS) for AHF patients and to analyze the etiology and outcome of patients with this disease.METHODS:A retrospective analysis was made of 48 consecutive patients with AHF who fulfilled the Kings College Criteria for LT at our center.We analyzed and compared the etiology,outcome,prognosis,and survival rates of patients between the transplantation (LT) group and the non-transplantation (N-LT) group.RESULTS:AHF was due to viral hepatitis in 25 patients (52.1%;hepatitis B virus in 22),drug or toxic reactions in 14 (29.2%;acetaminophen in 6),Wilson disease in 4 (8.3%),unknown reasons in 3 (6.3%),and miscellaneous conditions in 2 (4.2%).In the LT group,36 patients (7 underwent living donor LT,and 29 cadaveric LT) had an average model for endstage liver disease score (MELD) of 35.7.Twenty-eight patients survived with good graft function after a follow-up of 27.3± 4.5 months.During the waiting time,6 patients were treated with ALSS and 2 of them died during hospitalization.The 30-day,12-month,and 18-month survival rates were 77.8%,72.2%,and 66.7%,respectively.In the N-LT group,12 patients had an average MELD score of 34.5.Four patients were treated with ALSS and all died during hospitalization.The 90-day and 1-year survival rates were only 16.7% and 8.3%,respectively.CONCLUSIONS:Hepatitis is the most prominent cause of AHF at our center.Most patients with AHF,who fulfill the Kings College Criteria for LT,did not survive longer without LT.ALSS did not improve the prognosis of AHF patients,but may extend the waiting time for a donor.Currently,LT is still the most effective way to improve the prognosis of AHF patients.

Differential Gene Expression Profiles in Acute Hepatic Failure Model in Mice Infected with MHV-3 Virus Intervened by Anti-hepatic Failure Compound

Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure infected with MHV-3 virus intervened by anti-hepatic failure compound （AHFC） and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% respectively 48 h after intraperitoneal injection of MHV-3 （P〈0.05）. Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oligonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fgl2, IL-8, IL-6, IFN-7, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure

AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF).

Characteristics and Outcome of Exertional Heatstroke Patients Complicated by Acute Hepatic Injury:A Cohort Study

Background and Aims:Exertional heatstroke(EHS)is associated with strenuous physical activity in hot environments.The present study aimed to investigate dynamic changes of hepatic function indices in EHS patients and determine risk factors for death.Methods:This single-center retrospective cohort study considered all patients with EHS admitted to the intensive care unit at the General Hospital of Southern Theater Command of PLA from October 2008 to May 2019.Data on general characteristics,organ function parameters,and the 90-day outcome of enrolled patients were collected.Hepatic indices were collected dynamically,and patients with acute hepatic injury(AHI)were identified by plasma total bilirubin(TBIL)≥34.2μmol/L and an international normalized ratio≥1.5,or with any grade of hepatic encephalopathy.Results:In patients who survived,TBIL,alanine aminotransferase and aspartate aminotransferase were increased at 24 h,peaked at 2–3 days,and began to decrease at 5 days.In non-survivors,TBIL continuously increased post-admission.The area under the receiver operating characteristic curve for the prediction of mortality based on sequential organ failure assessment(SOFA)scores was 89.8%,and the optimal cutoff value was 7.5.Myocardial injury and infection were identified as independent risk factors for death in EHS patients with AHI.Conclusions:In EHS patients,hepatic dysfunction usually occurred within 24 h.Patients with AHI had more severe clinical conditions,and significantly increased 90-day mortality rates.SOFA scores over 7.5,complicated with myocardial injury or infection,were found to be risk factors for death in EHS patients with AHI.

Subacute fulminant hepatic failure with intermittent fever

BACKGROUND: Viral hepatitis B accounts for over 80% of acute hepatic failures in China and the patients die mainly of its complications. A patient with hepatic failure and fever is not uncommon, whereas repeated fever is rare. METHODS: A 32-year-old female was diagnosed with subacute hepatic failure and hepatitis B viral infection because of hyperbilirubinemia, coagulopathy, hepatic encephalopathy, serum anti-HBs-positive without hepatitis B vaccination, and typical intrahepatic pathological features of chronic hepatitis B. Plasma exchange was administered twice and she awoke with hyperbilirubinemia and discontinuous fever. RESULTS: Urethritis was confirmed and medication-induced fever and/or spontaneous bacterial peritonitis (Gram-negative bacillus infection) was suspected. The patient was treated with antibiotics, steroids and a Chinese herbal medicine, matrine, for three months and she recovered. CONCLUSION: The survival rate of patients with hepatic failure might be improved with comprehensive supporting measures and appropriate, timely management of complications.

“Pseudotumoral” hepatic pattern in acute alcoholic hepatitis:A case report

In acute alcoholic hepatitis (AAH), a "pseudotumoral" appearance of the liver parenchyma on computed tomography (CT) scan has been reported. The main findings are hypervascularized areas closely similar to those observed in large hepatocellular carcinomas. We report a case of a patient affected by AAH with an unusual appearance of these "pseudotumoral" areas on CT scan, close resembling a metastatic cancer rather than a primary hepatocellular carcinoma. In fact, in contrast with previous reports, the picture was characterized by the presence of many inhomogeneous, hypoattenuated areas highlighted during both pre- and post-contrast phases. Moreover, we report the first description of "pseudotumoral" lesions on ultrasound scan. This patient was successfully treated with corticosteroids, even if many controversies still exist regarding their efficacy in this setting.

Hepatic artery pseudoaneurysm caused by acute idiopathic pancreatitis

Hepatic artery pseudoaneurysm(HAP) is a very rare disease but in cases of complication,there is a very high mortality.The most common cause of HAP is iatrogenic trauma such as liver biopsy,transhepatic biliary drainage,cholecystectomy and hepatectomy.HAP may also occur with complications such as infections or inflammation associated with septic emboli.HAP has been reported rarely in patients with acute pancreatitis.As far as we are aware,there is no report of a case caused by acute idiopathic pancreatitis,particularly.We report a case of HAP caused by acute idiopathic pancreatitis which developed in a 61-year-old woman.The woman initially presented with acute pancreatitis due to unknown cause.After conservative management,her symptoms seemed to have improved.But eight days after admission,abdominal pain abruptly became worse again.Abdominal computed tomography(CT) was rechecked and it detected a new HAP that was not seen in a previous abdominal CT.Endoscopic retrograde cholangiopancreatography(ERCP) was performed because of a suspicion of hemobilia as a cause of aggravated abdominal pain.ERCP confirmed hemobilia by observing fresh blood clots at the opening of the ampulla and several filling defects in the distal common bile duct on cholangiogram.Without any particular treatment such as embolization or surgical ligation,HAP thrombosed spontaneously.Three months after discharge,abdominal CT demonstrated that HAP in the left lateral segment had disappeared.

May 2022 acute hepatitis outbreak,is there a role for COVID-19 and other viruses?

There has been an increasing number of reported cases of acute hepatitis of unknown origin in previously healthy children since first reported on March 31,2022.This clinical syndrome is identified by jaundice and markedly elevated liver enzymes with increased aspartate transaminase and/or alanine aminotransa-minase(greater than 500 IU/L).We conducted an inclusive literature review with respect to acute hepatitis outbreaks in children using the search terms acute hepatitis,outbreak,children,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),coronavirus disease 2019(COVID-19),and adenovirus.According to the cumulative data presented in four main studies,the median age is 4 years,with a male predominance(1.3:1).Jaundice was the most common clinical manifestation(69%),followed by vomiting(63%),anorexia(52.9%),diarrhea(47.2%),abdominal pain(39%),pyrexia(33.3%),pale stool(30%),and dark urine(30%).Coryza and lethargy were reported in 16.6%,while pruritus was reported in 2%of cases.Acute liver failure was observed in 25%of cases.The exact mechanism of this acute hepatitis outbreak is still not entirely clear.Adenoviruses and SARS-CoV-2 were detected in a significant number of patients.Coinfection with adenovirus and SARS-CoV-2 could be a possible underlying mechanism.However,other possible infections and mechanisms must be considered in the pathogenesis of this condition.Acute hepatitis of unknown origin in children has been a serious problem since the start of the COVID-19 pandemic but has not yet been sufficiently addressed.Many questions remain regarding the underlying mechanisms leading to acute liver failure in children,and it is likely that extensive future research is needed.

Acute hepatitis of unknown etiology in an adult female:A case report

BACKGROUND Acute liver injury(ALI)refers to inflammation of the hepatic parenchyma without hepatic encephalopathy that lasts less than 6 mo.When the etiology is unknown,Acute Hepatitis of Unknown Origin(AHUO)can present as a diagnostic and treatment challenge.AHUO in the adult population is unusual and poorly documented.It has an incidence between 11%and 75%.Currently,no treatment guidelines exist.With no identified cause,treatment is often blind,and the wrong treatment plan may have unintended consequences.CASE SUMMARY We present the case of a 58-year-old woman who presented to the emergency room for elevated liver function tests(LFTs).Her symptoms started 10 d prior to admission and included nausea,vomiting,jaundice,decreased appetite,weight loss of 10 lbs,and dark urine.She denied drinking alcohol or taking any hepatotoxic agents,including acetaminophen,statins,vitamins,or supplements.She was admitted to the hospital,and an etiologic work-up was carried out.Her initial bloodwork revealed elevated liver enzymes(alanine aminotransferase 2500 U/L,aspartate aminotransferase 3159 U/L,and alkaline phosphatase 714 U/L)and elevated total bilirubin of 6.4 mg/dL.She tested negative for common infectious etiologies such as hepatotropic viruses A,B,C,and E.Further infective work-up revealed negative serology for cytomegalovirus,Epstein-Barr virus,herpes simplex virus 1&2,and human immunodeficiency virus.Her autoanti-body test results were negative,including anti-smooth muscle antibody,anti-mitochondrial antibody,and anti-liver kidney microsome 1 antibody.Magnetic resonance cholangiopancreatography ruled out biliary causes of elevated LFTs,and her core liver biopsy proved inconclusive.Over the course of her hospital stay,the patient's LFTs improved with supportive care and without steroids.CONCLUSION Idiopathic hepatitis makes treatment challenging.It can leave patients feeling confused and unfulfilled.Thus,educating the patient thoroughly for shared decision-making and management becomes essential.

Transplantation of microencapsulated umbilical-cord-blood-derived hepatic-like cells for treatment of hepatic failure

AIM: To investigate intraperitoneal transplantation of microencapsulated hepatic-like cells from human umbilical cord blood for treatment of hepatic failure in rats. METHODS: CD34+ cells in umbilical cord blood cells were isolated by magnetic cell sorting. In the in vitro experiment, sorted CD34+ cells were amplified and induced into hepatic-like cells by culturing with a combination of fibroblast growth factor 4 and hepatocyte growth factor. Cultures without growth factor addition served as controls. mRNA and protein levels for hepatic-like cells were analyzed by reverse transcription-polymerase chain reaction, immunohistochemistry and immunofluorescence. In the in vivo experiment, the hepatic-like cells were encapsulated and transplanted into the abdominal cavity of acute hepatic failure (AHF) rats at 48 h after D-galactosamine induction of acute hepatic failure. Transplantation with PBS and unencapsulated hepatic-like cells served as controls. The mortality rate, hepatic pathological changes and serum biochemical indexes were determined. The morphology and structure of microcapsules in the greater omentum were observed. RESULTS: Human albumin, alpha-fetoprotein and GATA-4 mRNA and albumin protein positive cells were found among cultured cells after 16 d. Albumin level in culture medium was significantly increased after culturing with growth factors in comparison with culturing without growth factor addition (P < 0.01). Compared with the unencapsulated group, the mortality rate of the encapsulated hepatic-like cell-transplanted group was significantly lower (P < 0.05). Serum biochemical parameters, alanine aminotransferase, aspartate aminotransferase and total bilirubin in the encapsulated group were significantly improvement compared with the PBS control group (P < 0.01). Pathological staining further supported these findings. At 1-2 wk post-transplantation, free microcapsules with a round clear structure and a smooth surface were observed in peritoneal lavage fluid, surviving cells inside microcapsules were found by trypan blue staining, but some fibrous tissue around microcapsules was also detected in the greater omentum of encapsulated group by hematoxylin and eosin staining. CONCLUSION: Transplantation of microencapsulated hepatic-like cells derived from umbilical cord blood cells could preliminarily alleviate the symptoms of AHF rats.

Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984 to 0.85/100000 in 2012,and by the reduced prevalence of hepatitis B surface antigen(HBsAg)-positive cases among chronic hepatitis patients with different etiologies,from 60%in 1975 to about 10%in 2001.The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3%in the 1980s to 1%in 2010.Linked to HBV by its characteristics of defective virus,the hepatitis delta virus(HDV)has shown a similar epidemiological impact on the Italian population over time.The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from24%in 1990 to 8.5%in 2006.Before the beneficial effects of HBV mass vaccination introduced in 1991,the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations,the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size.A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.

Acute transient hepatocellular injury in cholelithiasis and cholecystitis without evidence of choledocholithiasis

AIM： To investigate acute transient hepatocellular injury in patients with cholelithiasis and cholecystitis but no evidence of choledocholithiasis.METHODS： The medical records of patients with cholelithiasis who underwent cholecystectomy between July 2003 and June 2007 were retrospectively reviewed. Imaging studies to detect common bile duct （CBD） stones were performed in 186 patients, who constituted the study population. Biochemical liver tests before and after surgery, and with the presence or absence of CBD stones were analyzed.RESULTS： In 96 patients with cholelithiasis and cholecystitis without evidence of CBD stones, 49 （51.0%） had an alanine aminotransferase level elevated to 2-3 times the upper limit of normal, and 40 （41.2%） had an elevated aspartate aminotransferase level. Similar manifestations of hepatocellular injury were, as would be expected, even more obvious in the 90 patients with CBD stones. These markers of hepatocellular injury resolved almost completely within 2 wk to 1 mo after cholecystectomy. Compared to 59 patients with histologically less severe cholecystitisin the group undergoing urgent surgery （total 74 patients）, the 15 patients with a gangrenous gallbladder had a higher mean level of total bilirubin （2.14 ± 1.27 mg/dL vs 2.66 ± 2.97 mg/dL, P 〈 0.001） and white cell count （9480 ± 4681/μL vs 12840 ± 5273/μL, P = 0.018）.CONCLUSION： Acute hepatocellular injury in cholelithiasis and cholecystitis without choledocholithiasis is mild and transient. Hyperbilirubinemia and leukocytosis may predict severe inflammatory changes in the gallbladder.

Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients

AIM: To determine the clinicopathological characteristics of nonsteroidal anti-inflammatory drug (NSAID)-induced acute hepato-nephrotoxicity among Chinese patients.