Chronic Liver Insufficiency Research Articles

Performance of Baveno VII criteria for the screening of varices needing treatment in patients with biliary atresia.

Biliary atresia (BA) is the leading cause of liver cirrhosis and chronic liver insufficiency in children in the world. Gastroesophageal varices bleeding is an ominous complication of cirrhosis in BA patients and is associated with high morbidity and mortality. In this study, we aimed to investigate the utility of noninvasive Baveno VIand Baveno VII criteria for the screening of varicesneed treatment (VNT) and the need for liver transplantation in BA patients. This study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years; the clinical data were surveyed in a retrospective design. The sensitivity and negative predictive valueof Baveno VI and Baveno VII criteria for the prediction of VNT in BA patients are both 100% and 100%, respectively. The VNT missing rate of Baveno VI and Baveno VII criteria are both 0% in our cohort. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are also predictive of the need for liver transplantation in our cohort (OR = 10.33, 4.24, and 21.33; p = 0.009, 0.03, and 0.007, respectively). The Baveno VI and Baveno VII criteria are useful for the screening of VNT and minimize non-necessary invasive EGD in BA patients with low VNT missing rates. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are associated with the need for liver transplantation.

Reduction of oxidative stress response and protection of liver and renal cell functions by reduced glutathione in lower limb arterial ischemia–reperfusion in New Zealand white rabbits with high triglyceride levels

ObjectiveAcute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia–reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated. MethodsNew Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated. ResultsAfter IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted. ConclusionThis study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

To Study the Clinical and Etiological Profile of Patients with Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a term used to describe a reversible syndrome of impaired brain function involvinga complex spectrum of nonspecific neurological and psychiatric manifestations occurring in patients of severeacute or chronic liver insufficiency. Hepatic encephalopathy (HE) is one of the most devastating complication ofcirrhosis having high morbidity and mortality. There is very limited data regarding the incidence and risk factorsof hepatic encephalopathy so this study is to find the clinical and etiological profile of hepatic encephalopathy.Methodology: The study was conducted in patients visited in OPD/IPD of medicine department, SGRDIMSR,Amritsar (Punjab) in the time period from 1 April 2021 to 31 July 2022. A total of 150 patients were taken up forthis study. All the diagnosed patients of liver cirrhosis of any etiology (Recently detected or old patients) wereincluded in the study.FindingsIn this study most of patients were males (81%) in the age group of 31 to 60 yrs (65%). Most common etiologyfound to be alcoholic (53%) with presenting symptoms of altered talks(51%).Conclusion: Education of the society about the precipitating factors can lead to early detection of hepaticencephalopathy and thus decrease the morbidity and mortality related to it. So there is need for Screeningprograms and education.

Elevated serum tyrosine concentration is associated with a poor prognosis among patients with liver cirrhosis.

Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis. This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio, were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios for factors that were associated with mortality or liver transplantation. Among the 158 patients, baseline measurements showed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BCAA-to-tyrosine ratio for 114 patients (72.2%). During a median follow-up period of 3.0years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis showed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis showed that a serum tyrosine concentration of >110µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted hazard ratio 1.89, 95% confidence interval 1.15-3.11, p=0.012). Kaplan-Meier analysis showed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, p<0.001). Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BCAA-to-tyrosine ratio, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis.

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy.

Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis. A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched-chain amino acids and tyrosine, and branched-chain amino acid-to-tyrosine ratio were determined. The hazard ratios of factors associated with liver-related events were analyzed by Cox proportional hazard analysis. Of the 75 patients enrolled, 12 showed a decrease in serum branched-chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched-chain amino acid-to-tyrosine ratio decreased in 16 patients. During a median 5.6-year follow up, liver-related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110μmol/L was identified as a cut-off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3-101.5, P < 0.001). Kaplan-Meier analysis showed that the 5-year cumulative incidences of event occurrence in patients with high and low serum tyrosine concentration were 56.5% and 5.5%, respectively (P < 0.001). The 10-year survival probabilities also showed significant differences between patients with high and low serum tyrosine concentration (44.9% vs. 92.0%, P < 0.001). Elevation of serum tyrosine concentration indicates a high risk of liver-related events in primary biliary cholangitis patients receiving urusodeoxycholic acid therapy.

Reactive cholangiocytes differentiate into proliferative hepatocytes with efficient DNA repair in mice with chronic liver injury

Chronic liver diseases are characterized by expansion of the small immature cholangiocytes - a mechanism named ductular reaction (DR) - which have the capacity to differentiate into hepatocytes. We investigated the kinetics of this differentiation, as well as analyzing several important features of the newly formed hepatocytes, such as functional maturity, clonal expansion and resistance to stress in mice with long-term liver damage. We tracked cholangiocytes using osteopontin-iCreERT2 and hepatocytes with AAV8-TBG-Cre. Mice received carbon tetrachloride (CCl4) for >24 weeks to induce chronic liver injury. Livers were collected for the analysis of reporter proteins, cell proliferation and death, DNA damage, and nuclear ploidy; hepatocytes were also isolated for RNA sequencing. During liver injury we observed a transient DR and the differentiation of DR cells into hepatocytes as clones that expanded to occupy 12% of the liver parenchyma by week 8. By lineage tracing, we confirmed that these new hepatocytes derived from cholangiocytes but not from native hepatocytes. They had all the features of mature functional hepatocytes. In contrast to the exhausted native hepatocytes, these newly formed hepatocytes had higher proliferative capability, less apoptosis, a lower proportion of highly polyploid nuclei and were better at eliminating DNA damage. In chronic liver injury, DR cells differentiate into stress-resistant hepatocytes that repopulate the liver. The process might account for the observed parenchymal reconstitution in livers of patients with advanced-stage hepatitis and could be a target for regenerative purposes. During chronic liver disease, while native hepatocytes are exhausted and genetically unstable, a subset of cholangiocytes clonally expand to differentiate into young, functional and robust hepatocytes. This cholangiocyte cell population is a promising target for regenerative therapies in patients with chronic liver insufficiency.

Gut Lymphangiopathy: Adding Fuel to the Fire in Chronic Liver Disease

The splanchnic inflammation inchronic liver disease increases intestinal angiogenesis. In the current study our aim was demonstrating that the small bowel lymphangiogenesis is associated with angiogenesis in chronic cholestasis in the rat. A stereological study of the lymphatic microcirculation in the small intestine was performed in cholestatic rats. Portal enteropathy in cholestasis increases lymphatic microvessels in the mucosa and submucosa layers. Thus, the lymphatic microvessel volume fraction was superior (p -2; p -2; p -2). These alterations predominate in the duodenum (volume fraction: 0.10 ± 0.01 and length density: 33.55 ± 5.98 mm-2) and ileum (volume fraction: 0.16 ± 0.01 and length density: 38.62 ± 6.07 mm-2). This study demonstrates the predominance of an increased lymphangiogenic response in both end sides of the small bowel associated with chronic liver disease. Since the porto-systemic venous collateral circulation in the chronic liver insufficiency is developed in the ends of the gastrointestinal tract, the excessive duodeno-ileal lymphangiogenesis could suggest the development of amesenteric-systemic lymphatic bypass in the chronic portal hypertension.

Lower values of handgrip strength and adductor pollicis muscle thickness are associated with hepatic encephalopathy manifestations in cirrhotic patients

Hepatic encephalopathy (HE) is a late complication of liver cirrhosis and is clearly associated with poor outcomes. Chronic liver insufficiency leads to progressive muscle wasting, impairing ammonia metabolism and thus increasing the risk for HE. Given the association between lean mass and adductor pollicis muscle thickness (APMT), it has been used to predict outcome and complications in many conditions, but not yet in cirrhotic patients. Therefore, this article aimed to study the association between HE manifestations and measures related to muscle mass and strength. This cross-sectional study included 54 cirrhotic outpatients with HE varying from subclinical to grade II according to the West-Haven criteria, who were submitted to neuropsychometric tests, electroencephalogram, brain Single Photon Emission Computed Tomography (SPECT), anthropometric measurements, handgrip strength (HGS) and dual energy X-ray absorptiometry exam (DXA). Multiple logistic regression analysis was performed to investigate the association between body composition measures and HE grade. Analysis of the area under the receiver operator characteristic (AUROC) curve revealed the values related to neurological manifestations (HE grades I and II). Reductions in APMT and HGS were associated with higher HE grades, suggesting a big impact caused by the loss of muscle mass and function on HE severity. The link between HE manifestations and anthropometric measures, namely APMT and HGS, point to a significant relation concerning skeletal muscles and the neurological impairment in this population.

Hepatic differentiation of human amniotic epithelial cells and in vivo therapeutic effect on animal model of cirrhosis

Human amniotic epithelial cells (hAECs) have been touted as an ideal stem cell candidate, being ethically neutral, immunologically naïve, plentiful in origin, and retaining plasticity in its fetal stage. We hypothesized that by applying natural physiological signals of the developing liver, hAECs can be coaxed into becoming functional immunopermissive hepatocyte-like cells. These cells would have tremendous potential for allogenic cellular transplantation in the treatment of chronic liver insufficiency. hAECs were obtained from term placentas and subjected to hepatic trans-differentiation. Hepatic differentiated cells were analyzed with immunophenotyping, electron microscopy, reverse transcription-polymerase chain reaction as well as characterized for hepatic metabolic function. In vivo efficacy was tested using intrasplenic transplantation into non-obese diabetic (NOD) Scid Gamma mice with thioacetamide-induced chronic liver failure and analyzed for engraftment and improvement in liver indices. With hepatic differentiation, hAECs assumed a hepatocytic polygonal morphology with upregulation of transcription factors responsible for liver specification. These hepatic differentiated-hAECs (HD-AECs) demonstrated bile canaliculi formation, secreted albumin, eliminated indo-cyanine green, uptook low-density lipoprotein, and inducible CYP3A4 and CYP2C9 enzymatic activities. Transplantation of HD-AECs and de novo hAECs in mice model of cirrhosis showed successful in vivo engraftment and differentiation into functional hepatocytes positive for human-specific albumin. HD-AEC cells that had undergone hepatic differentiation showed the greatest improvement in albumin function while preserving human leukocyte antigen-G expression postdifferentiation. hAECs were able to differentiate into functional hepatocyte-like cells both in vivo and in vitro. They showed therapeutic efficacy after transplantation in mice model of cirrhosis, offering an exciting source of cells for generation of functionally useful hepatocytes.

Pre-analytic factors and initial biomarker levels in community-acquired pneumonia patients.

BackgroundBlood biomarkers are increasingly used to diagnose, guide therapy in, and risk-stratify community-acquired pneumonia (CAP) patients in emergency departments (EDs). How pre-analytic factors affect these markers’ initial levels in this population is unknown.MethodsIn this secondary analysis of consecutive ED patients with CAP from a large multicentre antibiotic stewardship trial, we used adjusted multivariate regression models to determine the magnitude and statistical significance of differences in mean baseline concentrations of five biomarkers (procalcitonin [PCT], C-reactive protein [CRP], white blood cells count [WBC], proadrenomedullin [ProADM], copeptin) associated with six pre-analytic factors (antibiotic or corticosteroid pretreatment, age, gender, chronic renal failure or chronic liver insufficiency).ResultsOf 925 CAP patients (median age 73 years, 58.8% male), 25.5% had antibiotic pretreatment, 2.4%, corticosteroid pretreatment, 22.3%, chronic renal failure, 2.4% chronic liver insufficiency. Differences associated with pre-analytic factors averaged 6.1% ±4.6%; the three largest statistically significant changes (95% confidence interval) were: PCT, +14.2% (+2.1% to +26.4%, p = 0.02) with liver insufficiency; ProADM, +13.2% (+10.2% to +16.1%, p < 0.01) with age above median; CRP, -12.8% (-25.4% to -0.2%, p = 0.05) with steroid pretreatment. In post hoc sensitivity analyses, reclassification statistics showed that these factors did not result in significant changes of biomarker levels across clinically used cut-off ranges.ConclusionsDespite statistically significant associations of some pre-analytic factors and biomarker levels, a clinically relevant influence seems unlikely. Our observations reinforce the concept of using biomarkers in algorithms with widely-separated cut-offs and overruling criteria considering the entire clinical picture.Trial registrationIdentifier ISRCTN95122877.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2253-14-102) contains supplementary material, which is available to authorized users.

Allogenic hepatocyte transplantation in immunomodulated Lewis rats with acute liver insufficiency following hepatectomy.

Orthotropic Liver transplantation (OLT) is a conventional management for end-stage acute or chronic liver insufficiency, but the shortage of donor organs continues to be the restrictive factor throughout the world. Hepatocyte transplantation (HCTx) might be the promising treatment for several liver diseases and can be used as a "bridge" to OLT. Hepatocytes transplantation can protect and even save human lives, its' applicability remains limited by the large deficiency of liver organs and hepatocytes (HC), and cellular loss after engraftment. Host elimination of grafted cells is called Early Graft Dysfunction. This study was developed for an efficient protocol of HCT. Several conditions have been met in order to achieve a high yield of harvested viable HC, overcome the detached-cell apoptosis, attenuation of innate immune reaction against transplanted cells and a receptive cell environment. HC were isolated from Lewis rats (n = 8) weighing 250 gm, by the 2 step collagen a seper fusion technique, and bone marrow cells (BMCs) were obtained from the rats tibia and femur by centrifugation in a buffer solution. The mean viability of harvested HC and BMCs were 90% and 95% respectively. To minimize the rejection of HC, Lewis rat recipients (n = 14) weighing 250 gm, were irradiated with 6 Gy and received 0.1 mg of anti-aisle GMI antiserum intravenously as immunosuppressive drug. The isolated HC were intra-splenically transplanted and 10(7) bone marrow cells were injected in a penile vein into the recipients on the third day. Simultaneously, 70% hepatectomy and ligation of common bile duct were done. Thirty days later; the grafted spleen had areas with external appearance of a normal liver in ten out of 14 surviving rats (71%). Hematoxlin and eosin (H & E) staining of sections from these fragments showed sinusoids and portal areas, an evidence of successful hepatocyte engraftment and bile canaliculea formation. Large number of HC clusters of 15 to 20 cells and 2 to 4 distended small bile canaliculea were seen per 50 HC. The intrasplenic route for transplanting freshly isolated HC in an immune-compromised animal model was found to give good results regarding cell engraftment and tissue formation.

Comparative assessment of hepatoprotective effects of various liposome formulations in experimental venous congestion-induced chronic liver insufficiency

Comparative assessment of hepatoprotective effects of various liposome formulations in experimental venous congestion-induced chronic liver insufficiency

Liver impairment after portacaval shunt in the rat: The loss of protective role of mast cells?

Mast cells are involved in various liver diseases and appear to play a broader pathogenic role than originally thought. They may participate in the splanchnic alterations related to a porto-systemic shunt. To verify this hypothesis we studied the serum and hepatic histological changes in rats four weeks after an end-to-side portacaval shunt. In this experimental model of chronic liver insufficiency we also assessed the mucosal mast cells (MMC) and connective tissue mast cells (CTMC) in the liver, mesenteric lymph nodes and small intestine, as well as the serum levels of rat mast cell protease-II (RMCP-II). The results show liver and testes atrophy, with hypoalbuminemia (p=0.0001), hyperbilirubinemia (p=0.0001) and increase in aspartate aminotransferase (p=0.004) and alanine aminotransferase (p=0.0001). Hepatic histopathology demonstrates hepatocytic necrosis and apoptosis, portal inflammation, biliary proliferation, steatosis and fibrosis. There is a decrease of MMCs and CTMCs in the liver, while in the ileum CTMCs increase and MMCs decrease. These results suggest the involvement of mast cells in the pathophysiological splanchnic impairments in this experimental model. In particular, the decreased number of liver mast cells may be associated with the hepatic atrophy. If this is the case, we propose that the disruption of the hepato-intestinal axis after a portocaval shunt in the rat could inhibit the ability of the liver to developing an appropriate repair response mediated by mast cells.

Influence of leukotriene biosynthesis inhibition on heart rate in patients with atrial fibrillation

Atrialfibrillation (AF) is themost common cardiac arrhythmia. There is an increasing evidence linking systemic and/or local inflammation to AF pathogenesis [1–3]. Leukotrienes (LT) are potent proinflammatory mediators produced via 5-lipoxygenase (5-LO) pathway of arachidonic acid. Both experimental [4,5] and clinical [6,7] data point to their role in cardiac pathology. Our recent results [8] indicate that pharmacological inhibition of LT biosynthesis is associatedwith decrease in the heart rate and enhanced heart rate variability in patients with stable angina pectoris undergoing elective coronary catheterization or angioplasty. This suggested to us that LT biosynthesis inhibition could be of potential interest in patients with AF. We studied49 subjects, recruited from103 consecutive patientswith permanent AF, hospitalized in the Department of Medicine. Exclusion criteria encompassed: age over 80 years, heart failure, asthma, acute or chronic inflammatory diseases, renal or liver insufficiency, hyperthyroidism and pacemaker implantation. The clinical characteristics of the patients are presented in Table 1. Informed written consent was obtained from all patients. The study protocol, that complied with the Helsinki Declaration, was approved by the local Ethics Committee. The participants underwent a single-blind, placebo-controlled study with the inhibitor of 5-lipoxygenase (zileuton; Zyflo, Cornerstone Therapeutics Inc., Cary, NC USA). The study lasted 2 days; placebo was administered on the first day (4×1 tablets/day) and zileuton – in its standard daily dosage (4×600 mg/day) – on the second day. Measurements of the urinary leukotriene E4 , considered to reflect global leukotriene production (uLTE4) (ELISA; Cayman Chemicals, Ann Arbor, MI, USA) were carried out twice; at base and after zileuton treatment. They were expressed as LTE4 pg/mg of creatinine [9]. 24-h, threechannel digital ECG Holter recordings (Aspel, HolCARD 24W, Poland) were performed in all patients on thefirst and the second study day. The mean values of 24-h heart rate (HR), the number of ventricular extrasystoles (VEs), ST-segment depression, as well as episodes of tachycardia, bradycardia and pauses were evaluated. Echocardiography was performed to assess left ventricular ejection fraction and left atrial area. Datawere analyzedusing StatSoft, Inc. STATISTICA software. Theyare presented as mean±SD or median with interquartile range and log transformed when applicable. For comparisons between groups,

Control of acute, chronic, and constitutive hyperammonemia by wild‐type and genetically engineered Lactobacillus plantarum in rodents†

Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed. Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut.

Early Results of Orthotopic Liver Transplantations Using the Technique of Inferior Vena Cava Anastomosis

Introduction We compared early results of orthotopic liver transplantation (OLT) in adults using the classic versus piggyback technique of inferior vena cava anastomosis. Patients and Methods We analyzed 100 consecutive patients who underwent OLT from 2000 to 2003. Group A included 50 patients operated with the classic technique with venovenous extracorporeal bypass, and group B, 50 patients with the piggyback technique. The age range of the patients in group A was 21 to 63 years (mean, 43.5 years) and in group B, 20 to 65 years (mean, 46 years). The gender F/M distribution in group A was 24/26 and in group B, 28/22. The indications for OLT were acute hepatic failure (8%), chronic liver insufficiency (77%), liver tumors (8%), metabolic diseases (5%), and Budd-Chiari syndrome (2%). The degrees of liver insufficiency evaluated according to the Child classification were A, 18; B, 52; and C, 30 patients. The urgency for OLT on the United Network for Organ Sharing (UNOS) scale was UNOS 1—group A, 2 patients; group B, 7 patients; UNOS 2a—group A, 7 patients; group B, 6 patients; UNOS 2b—group A, 29 patients; group B, 30 patients; UNOS 3—group A, 12 patients; group B, 7 patients. Results The average cold ischemia time in group A was 530 minutes and in group B, 515 minutes. The average results on the 10th postoperative day: aspartate transaminase (AST)—group A, 52.5 U/L; group B, 54.5 U/L; alanine transaminase (ALT)—group A, 131.5 U/L; group B, 153 U/L; gamma glutyl transpeptidase (GGTP)—group A, 299 U/L; group B, 285.5 U/L; alkaline phosphatase (ALP)—group A, 164 U/L; group B, 150.5 U/L; bilirubin—group A, 4.37 mg%; group B, 2.71 mg%; activated partial thromboplastin time (APTT)—group A, 37.6 seconds; group B, 34.8 seconds; platelets (PLT)—group A, 167 10 2/mm 2; group B, 171 10 2/mm 2. The incidence of postoperative complications was 36% in group A; it was 30% in group B. The mean hospitalization times in the surgical department were 17 days in group A and 16 days in group B. Conclusions The early results, morbidity and mortality with both applied techniques were similar. Individualization in qualifying the patients for a given operative technique is important. The lower complication rate and reduced treatment cost of the piggyback technique group suggested advantages of this technique when compared with the classical OLT technique.

Morphometric and immunohistochemical patterns of duodenal CCK-cells in rats with portacaval shunts

End-to-side portacaval shunt (PCS) performed in rats is an appropriate experimental model of chronic liver insufficiency. Functional hepatic injury followed by numerous metabolic and endocrine disorders develops, as well. Due to impaired functional hepatic activity in PCS and to the well known role of the liver in CCK metabolism and elimination, delayed CCK bloodstream elimination may be responsible for increased CCK-A receptor activity. Therefore, we investigated immunohistochemical and morphometric features of duodenal CCK-cells in rats with PCS. Male Wistar rats (180 - 250g body weight) were used in this experiment. The animals were divided into two groups: PCS-animals (experimental group (n=27) which underwent an operation) and C - unoperated animals [control group (n=11)]. End-to-side portacaval anastomosis was created using the technique of Lee and Fisher, modified by Bismuth et al. Eight weeks, after the operation, animals were sacrificed. Pancreatic and hepatic weights were measured and samples taken from appropriate segments of the small intestine were used for morphometric and immunohistochemical CCK-cells determination. IMMUNOHISTOCHEMICAL TECHNIQUE: Peroxidase-antiperoxidase (PAP) technique described by Stenberger was applied for detection of intestinal CCK-immunoreactive cells. Our results indicate that eight weeks after operation liver weight was reduced in animals with PCS compared to control animals (p<0.01). To the contrary, in comparasion with control animals, the pancreatic wight was increased (p<0.01). In the exocrine pancreas of rats with PCS there were lipid droplets and hypertrophy of the acinus cells. The morphometric analysis of CCK-immunoreactive cells in different small intestine segments indicates that in the duodenum of animals with PCS there was a significant cell increase compared to control, unoperated animals. In liver cirrhosis, plasma CCK-8 concentration increases. In PCS, performed in rats, as an experimental model of chronic liver insufficiency, proliferation of CCK-cells in the small intestine leads to pancreatic hypertrophy and hyperplasia.

Sistemas de soporte hepático artificial: estado actual del tratamiento con diálisis de albúmina (MARS)

Mortality among patients with liver insufficiency continues to be unacceptably high. The prognosis of patients with acute episodes of chronic liver insufficiency is almost as poor as that of patients with acute liver failure. Therefore, systems that support liver function, either until liver transplantation can be performed or until resolution of the situation before acute injury occurs, are essential. Albumin dialysis is a system of artificial liver support that allows detoxification of albumin-related and hydrosoluble substances, thus maintaining the patient's homeostasis. Current clinical experience of this therapy is still limited, although beneficial effects on clinical, laboratory and hemodynamic parameters have been demonstrated. Multicenter, controlled trials to evaluate the effect of this therapy on survival in distinct diseases are needed.

À propos de trois grossesses consécutives chez une patiente cirrhotique

We report the case of a patient suffering from an immune liver cirrhosis with chronic liver insufficiency and a portal hypertension, presenting with three consecutive pregnancies. During the first pregnancy, stillbirth occurred at 34 weeks gestation (WG) with a justified vaginal delivery. There was no liver deterioration during the second pregnancy until 36 WG when fetal distress occurred, requiring a caesarean section under general anaesthesia. During the third pregnancy, fetal distress and maternal hepatic failure occurred at 35 WG, requiring an emergency caesarean section complicated with post partum haemorrhage and an episode of encephalopathy.

Bioartificial liver support anno 2001.

Despite maximal intensive care, mortality of acute fulminant hepatic failure is high: 60%-75% in several studies. In addition patients with chronic liver insufficiency suffer from a bad quality of life: all patients suffer from fatigue; symptoms of hepatic encephalopathy, jaundice, and itching are often present. Analogous to artificial kidney treatment in patients with renal failure, an artificial liver assist device is needed not only to bridge patients with fulminant hepatic failure to liver transplantation or own liver regeneration, but also to improve the quality of life of patients with chronic liver insufficiency. Several modalities of artificial liver support are under investigation, like plasma exchange, haemodialysis, haemadsorption, albumin dialysis, liver cell transplantation, and the bioartificial liver. Artificial livers based on only supportive detoxification function do not show significant improvement of survival in controlled studies. Bioartificial liver support systems have also the potential to support hepatic synthetic functions. Bioreactors can be charged with freshly isolated or cryopreserved porcine hepatocytes, but also by human hepatoma cell lines. Several uncontrolled studies in humans show safety of such a treatment, even by using porcine cells. Transmission of porcine endogenous retrovirus to recipients has not been found. Furthermore, beneficial effects have been reported on symptoms of hepatic encephalopathy, on the height of intracranial pressure and on hemodynamic parameters. By using porcine cells immunological problems (e.g., serum sickness) can be expected during treatments longer than one week. However, "proof of the pudding" in the sense of improvement of survival is not yet available. The creation of a "liver dialysis unit" in the near future depends mainly on the development of well-differentiated immortalized human hepatocytes. Some progress in this field has already been obtained.