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PubMed2003

Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants.

The United Network for Organ Sharing (UNOS) reports indicate that mortality on the intestine transplant waiting list is higher than on other transplant waiting lists. The goals of this study were (1) to determine whether most of the intestinal transplant candidate deaths have occurred in those who also need liver transplants, and (2) to compare the waiting list mortality in the liver-intestine candidate subset with the overall liver transplant candidate population. We found that 90% of intestine transplant waiting list deaths have occurred in candidates who also needed liver transplants. Since 1994, annual mortality has been higher in liver-intestine transplant candidates than in the overall liver transplant candidate population, and these differences have been statistically significant since 1996. These mortality differences applied to all age groups. Also, status 2B, 3, and 7 candidate mortality was significantly higher in liver-intestine candidates than in the overall liver transplant candidate population. Because there were so few liver-intestine transplant candidates listed as status 1 or 2A, a meaningful comparison was not possible in these statuses. These data indicate that liver-intestine transplant candidates are a unique subset of liver transplant candidates with a significantly higher risk of dying on the waiting list. Recent changes in UNOS liver allocation policy that gives higher priority to liver-intestine candidates may help to reduce this discrepancy. However, further research into the etiology of liver disease in patients on long-term parenteral nutrition and earlier referral of high-risk short bowel syndrome patients to centers with special expertise in their management are needed for an ultimate solution to this problem.

Adult↗
PubMed1990

Phenotype of preneoplastic and neoplastic liver lesions during spontaneous liver carcinogenesis of LEC rats.

The incidence and phenotype of preneoplastic and neoplastic liver lesions appearing in LEC rats after recovery from severe hereditary hepatitis were studied in comparison with the liver lesions appearing in chemical liver carcinogenesis. The livers of 168 rats (90 male, 78 female) were stained for seven histochemical markers at different time periods from the 20th week to the 122nd week of life. Glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and non-specific esterase (ES) were used as negative markers. Gamma-glutamyltransferase (GGT), glutathione S-transferase placental form (GSTP), esterase isozyme L-1 (L1) and alpha-fetoprotein (AFP) were used as positive markers. The study on the incidence of liver lesions in the LEC rats revealed sequential development of liver foci, nodules and hepatocellular carcinomas (HCCs) similar to those seen in chemically induced liver carcinogenesis. These lesions appeared earlier and more frequently in male LEC rats than in female ones, suggesting the importance of hormonal environment in spontaneous HCC development. The histochemical analysis of spontaneous liver lesions in LEC rats showed that GSTP was the most reliable positive marker as previously reported in chemical liver carcinogenesis. There was no essential difference in the expression of the markers in spontaneous and chemically induced liver lesions except for L1, which is considered to be related to xenobiotic metabolism. The results of this study suggest that both spontaneous and chemically induced liver cancer may develop by passing through phenotypically similar preneoplastic processes. In addition, the LEC rat uniquely showed chronic liver damage (hepatocyte death and regeneration) at the promotion stage of carcinogenesis. Such a natural history of HCC development in LEC rats is similar to that of human HCC which is frequently associated with chronic liver damage. Thus, the LEC rat provides a useful model for studying the process and underlying mechanisms of human liver cancer development.

Adenosine Triphosphatases↗
PubMed1992

Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support).

OBJECTIVE: The primary purpose of this review article is to familiarize critical care practitioners with newly developing techniques of hybrid artificial liver support. Implantable and extracorporeal hepatocyte culture systems are emphasized based on their current experimental and clinical status. DATA SOURCES: Data used to prepare this document were obtained from the authors' personal files, as well as the computerized MEDLINE database. Medical headings used include: liver, artificial organs, cell culture, growth hormones, extracellular matrix, and transplantation. Only articles published in English have been cited. STUDY SELECTION: All studies are discussed in which hepatocyte culture systems have been used to support human patients with liver failure. All studies reported the patient's condition before therapy, duration of therapy, and outcome after therapy in order to be included in this review. Since the number of clinical trials is small at this time, animal studies were used to demonstrate application of other systems in the treatment of experimentally induced liver failure. Similar selection criteria were used to select animal studies for review. All initially identified human studies met these selection criteria. DATA EXTRACTION: Independent extraction by multiple observers. DATA SYNTHESIS: Liver failure, resulting from infection, drugs, or as a part of the multiple organ failure syndrome, remains a major cause of morbidity, mortality, and resource allocation. Current therapy is limited to supportive care, along with liver transplantation. Because of these therapeutic limitations, hybrid artificial liver systems have been proposed for temporary and long-term hepatic support. Several animal studies and a small number of preliminary human studies indicate that hepatocyte culture systems are capable of supporting nearly all essential hepatic functions and may supply biologically active substances that promote regeneration and repair of the damaged liver being supported. Hybrid systems may be constructed from materials that serve as immunoprotective barriers against host defenses. CONCLUSIONS: During the past decade, important progress has been made with hybrid artificial liver support systems. Cell culture technology has progressed sufficiently so that an artificial liver, composed of metabolically active hepatocytes, may be a potential reality in the foreseeable future. Both implantable and extracorporeal artificial liver support systems have been developed to provide metabolic support during acute liver failure, or to serve as a bridge to solid organ transplantation. Implantable hepatocyte systems, however, require a prolonged period for intraperitoneal engraftment and vascularization, not typically available to patients with acute liver failure. For this reason, extracorporeal hybrid designs offer the greatest hope for on-line treatment of acute liver failure. Such systems are entering the final stages of animal testing.

Animals↗
PubMed2001

Liver and intestinal lactate metabolism in patients with acute hepatic failure undergoing liver transplantation.

OBJECTIVE: To determine the relative contribution of the gastrointestinal tract and the liver in lactate metabolism in patients with acute liver failure (ALF) and the effect of liver transplantation on this. We hypothesized that the liver and gut are net producers of lactate in ALF and that this is reversed after liver transplantation. SETTING: A university-affiliated specialist liver transplant operating theater. SUBJECTS: Eleven patients with ALF undergoing liver transplantation. MEASUREMENTS AND INTERVENTIONS: After ethical approval, 11 patients with ALF listed for orthotopic hepatic transplantation were studied. Whole blood was analyzed for lactate concentration from radial artery (RA) catheter, portal vein (PV), and hepatic vein (HV) during the dissection phase and was repeated postreperfusion of the liver graft. Gradients across the gut and the liver were calculated to see if there was net production or consumption. RESULTS: HV lactate was significantly higher than arterial (p =.028) in patients with ALF before liver transplantation, suggesting splanchnic production of lactate. Total splanchnic lactate gradient (HV-RA) is positive in ALF. Both the gut (PV-RA) and the liver (HV-PV) were net producers of lactate. After liver transplantation, hepatic venous lactate falls below arterial levels but not significantly. The gradient across the gut (PV-RA) remained positive, but the transhepatic gradient (HV-PV) became significantly negative, showing consumption by the graft (p =.021). The magnitude of lactate consumption after transplantation correlated positively with portal venous lactate concentration (p =.029) and inversely with graft cold ischemic time (p =.007). CONCLUSION: The liver is a net producer of lactate in patients with ALF and an elevated whole blood lactate. After liver transplantation, the graft becomes a consumer of lactate as shown by the negative lactate gradient. The degree of consumption is dependent on portal venous lactate concentration and cold ischemic time.

Female↗
PubMed1988

Diagnostic value of liver biopsy in alcoholic liver disease.

Because it remains debatable whether all patients with a clinical diagnosis of alcoholic liver disease should have a liver biopsy to help confirm the diagnosis, we evaluated the diagnostic value of liver biopsy in alcoholic liver disease. Studied were 108 consecutive patients who had a percutaneous liver biopsy for the first time. In all cases the patient's clinical diagnosis recorded before biopsy was compared with the histological diagnosis of an experienced histopathologist. Prebiopsy clinical data (reported alcohol intake, signs of chronic liver disease) and laboratory data (liver function tests, mean corpuscular volume, ferritin, hepatitis B serology) were reviewed. We found that a prebiopsy clinical diagnosis of alcoholic liver disease (n = 35) was confirmed by biopsy in all but one case. The prebiopsy diagnosis of alcoholic liver disease was significantly associated with a histological diagnosis of alcoholic liver disease (specificity 98%, sensitivity 79%). Individually, alcohol intake, signs of chronic liver disease, the alanine aminotransferase (ALT), the aspartate aminotransferase to ALT ratio, and the mean corpuscular volume were significantly associated with a histological diagnosis of alcoholic liver disease. When clinical and laboratory parameters were considered jointly using stepwise logistic regression, only reported alcohol intake and mean corpuscular volume were significant. Liver biopsy may not always be necessary for the identification of that broad group of patients with alcoholic liver disease.

Alanine Transaminase↗
PubMed2000

Isolated liver transplant and sequential small bowel transplantation for intestinal failure and related liver disease in children.

Liver dysfunction is a well-recognized complication of intestinal failure in children. Advances in total parenteral nutrition (TPN) have allowed these children to survive while their intestinal tract gradually adapts. Unfortunately TPN may lead to cholestatic liver disease particularly in the young children. Progression of liver disease is associated with a poor prognosis and is an indication for small bowel transplantation. We report our experience of orthotopic liver transplantation in four children with short gut and sequential liver and small bowel transplantation in one child. All children had TPN-related liver failure. Causes of intestinal failure included necrotising enterocolitis (n=2), gastroschisis (n=1), intestinal atresia (n=1), and megacystic, microcolon syndrome (n=1). At the time of liver transplantation the children's mean age was 10.9 months (2.5-24) and weight 6.7 kg (4.8-10.1). The mean serum bilirubin was 522 micromol/liter (299-823), aspartate transaminase 423 IU/liter (49-1024) and international normalized ratio 2.8 (2-3.9). There were two deaths both from respiratory failure secondary to adenovirus pneumonia including the child who received a sequential small bowel transplant. Three children with isolated liver grafts are alive and off TPN at 20 months (mean) follow up (range 6-35). Isolated orthotopic liver transplantation has a role in selected children with intestinal failure, particularly those with short but normally functioning gut and progressing with satisfactory intestinal adaptation but developing liver disease. Those children with TPN-related liver disease and unadapted gut or irreversible intestinal disease need combined liver and small bowel transplantation. Sequential small bowel transplantation is feasible after orthotopic liver transplantation and may provide an option for the child with terminal liver and small bowel failure.

Adolescent↗
PubMed2006

Liver and kidney transplantation for polycystic liver and kidney-renal function and outcome.

BACKGROUND: Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation. METHODS: Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation. RESULTS: Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8+/-25.4 ml/min/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7+/-54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4+/-68.6 months (n=9) (P=0.36). CONCLUSION: Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Adult↗
PubMed2006

Living donor liver transplantation: histological abnormalities found on liver biopsies of apparently healthy potential donors.

OBJECTIVE: With the continued shortage of deceased donor grafts, living donor liver transplantation has become an option for adult liver transplant candidates. In the non-transplant setting, liver biopsy is typically carried out to evaluate clinical or biochemical hepatic dysfunction. In living donor liver transplantation, assessment of histological abnormalities that are undetectable by serological, biochemical and radiological methods might play an important role in donor and recipient outcome. METHODS: Seventy consecutive liver biopsies carried out as part of our evaluation of potential donor candidates for adult-to-adult or adult-to-child living donor liver transplants were analyzed. RESULTS: Of the 70 potential donor candidates who underwent liver biopsy for evaluation for living donor liver transplantation, 67% had an unexpected abnormality, of which steatosis was the most common abnormality (38.5%). A variety of other histopathological abnormalities were found including granulomas of unknown etiology (7%), chronic hepatitis (6%) and a microabscess. None of the histological abnormalities had been suspected despite extensive clinical, serological or radiological investigation. CONCLUSIONS: Among the 70 potential donor candidates for living donor liver transplantation, 34% had unremarkable liver biopsies. The most common abnormality was steatosis (38.5%). These findings suggest that all potential candidates for living donor liver transplants should undergo screening liver biopsies. The precise significance of these changes remains to be determined, including which of these changes are contraindications to liver transplantation. These findings may also have implications in the non-transplant setting as changes ascribed to specific etiologies for liver disease might include changes occurring in apparently healthy individuals.

Adult↗
PubMed2006

Safety limit of the extent of hepatectomy for rats with moderately fatty liver: experimental study concerning living liver donor safety.

INTRODUCTION: The aim of the present study was to determine whether rats with moderately fatty liver could withstand a 90% hepatectomy, which rats with normal livers can survive. MATERIAL AND METHODS: Nine-week-old male Wistar rats were used. Normal rat chow was fed to the normal liver group, and fat-enriched rat chow was fed to the fatty liver group for 4 weeks to induce a moderately fatty liver. The authors have previously reported that this fatty liver rat model can cause fatal liver dysfunction after reduced-size-liver transplantation. A 90% and 95% hepatectomy were performed using rats of both groups to evaluate posthepatectomized liver function. RESULTS: All rats undergoing a 90% hepatectomy were still alive 30 days after the hepatectomy, but the rats that underwent a 95% hepatectomy were all dead within 4 days regardless of group. Increases in the liver remnant wet weight measured until 7 postoperative days after 90% hepatectomy were almost similar among the two groups. Alanin aminotransferase measured at 24, 48, 72, and 168 h after a 90% hepatectomy were significantly higher in the fatty liver group than in the normal liver group. Similarly, at up to 72 h postoperatively, the serum hyarulonic acids were significantly higher in the fatty liver group. CONCLUSION: A moderately fatty liver did not cause mortality in 90% hepatectomized rats. However, it caused a higher degree of hepatic parenchymal as well as sinusoidal injury.

Animals↗
PubMed1998

The value of sonography for estimation of liver volume by using a simple geometric formula ascertained in cadaveric livers.

Accurate assessment of liver size and its volume are important. However, as the clinical methods do not produce reliable results especially when the liver is shrunken, and the previous attempts to accurately assess liver volume by radio-isotopes, CT scans and computer assisted ultrasonography have not gained popularity due to high cost and complex techniques, the need to devise a simpler technique for estimation of liver volume continues. In doing so, we estimated volume of 10 cadaveric livers by water displacement technique to serve as the reference value. Thereafter, assuming the shape of liver like a right-angled pyramid, we calculated its volume by a simple geometric formula of '1/2 abc'. However, a reduction of 15% was made from this to compensate for depression on the inferior surface of liver. This method was subsequently implemented to assess liver volume of 14 healthy individuals and 20 patients of fulminant hepatic failure (FHF) by using ultrasonography. Our findings revealed smaller liver volume in Indians as compared to the reported Western figures, and a significantly smaller liver volume in females as compared to males. The liver volume of 6 FHF patients who died was significantly smaller (696.5 +/- 143.5 cm3) as compared to that of the 14 FHF patients who survived (1083 +/- 365.3 cm3). Moreover, mortality rate was 100 per cent in 3 patients of FHF who showed markedly shrunken globular liver with a liver volume of less than 500 cm3. Thus, a markedly reduced liver size in FHF patients suggests a poor prognosis. However, since the number of FHF patients in the present series is small, it is our contention that a larger series is mandatory to confirm the findings of the present study.

Adult↗
PubMed2005

[Granulocyte colony-stimulating factor-mobilized autologous bone marrow stem cells promote the liver regeneration of partial liver transplant: an experiment with rats].

OBJECTIVE: To investigate the effects of granulocyte colony-stimulating factor (G-CSF)-mobilized autologous bone marrow stem cells on the liver regeneration of partial liver transplant. METHODS: A 50% partial liver transplantation model as established by transplanting parts of the liver of female rats to the male rats with the equal weights that had had parts of their livers resected. Then the transplanted male rats were randomly divided into 3 equal groups: G-CSF + PLTx group that was injected hypodermically with recombinant human G-CSF (rhG-CSF) daily for 5 days and then underwent liver resection and 50% partial liver transplantation (PLTx); PLTx + G-CSF group that underwent PLTx and 3 hours after the transplantation received injection of rhG-CSF daily for 5 days, and PLTx control group that underwent PLTx and 3 hours later received injection of normal saline daily for 5 days. One, 3, 5, 7, and 14 days after the PLTx blood samples and livers were collected from 6 rats from each group, and one hour before the liver was taken bromodeoxyuridine (BrdU) was injected intraperitoneally to be integrated into the synthesis of DNA in the liver cells. Immunohistochemistry was used to detect the CD34 and BrdU-positive cells. In situ hybridization was used to detect the sry (sex-determining region) gene so as to determine the origin of the proliferating cells in the transplanted liver. RESULTS: The 14-day survival rate of the G-CSF + PLTx group was 90%, significantly higher than those of the G-CSF + PLTx (60%) and PLTx group (50%) (both P < 0.05) with a significant difference between the latter 2 groups too (P < 0.05). The mitosis index of liver cells 3 days after the transplantation of the PLTx + G-CSF group was 30% +/- 5%, significantly higher than those of the G-CSF + PLTx group (24% +/- 7%) and PLTx group (24% +/- 6%) (both P < 0.05) without a significant difference between the latter 2 groups. The rate of BrdU-positive cells of the PLTx + G-CSF group was 42% +/- 6%, significantly higher than those of the G-CSF + PLTx group (38% +/- 4%) and PLTx group (34% +/- 8%) (both P < 0.05). The transplantation the mitosis index and rate of BrdU-positive cells decreased since the 7th days after transplantation in all 3 groups, however, with the same relationship among them. The numbers of CD34(+) cell around the portal area of the 2 G-CSF groups increased since the 3rd day after transplantation in comparison with the PLTx group, was the highest on the 3rd day for the G-CSF + PLTx group, and continued to increase in the PLTx + G-CSF group. Since the 3rd day after transplantation, sry-positive cells were seen in the hepatic sinusoid and portal area in the 2 G-CSF groups, and were rarely seen in the PLTx group. CONCLUSION: G-CSF treatment after 50% PLTx significantly promotes liver regeneration and ameliorates the liver damage, thus raising the survival rate.

Animals↗
PubMed1979

[Accuracy of liver scintigraphy in focal liver disease; a comparison with postmortem studies in 159 cases (author's transl)].

In recent literature numerous papers have been published concerning the accuracy of scintigraphic detection of liver metastases. Unfortunately however, the problem of false positive results is not particularly discussed in these papers. Because of the lack of information it was our aim to compare our own scintigraphic results with postmortem histopathological findings. Our investigations were carried out in 139 patients with various types of malignancy. Included in the investigations were 20 patients with primary liver tumor. The interval between scintigraphic examination and the histological verification ranged from 3 days to 1 year. In 62 of the patients with liver metastases, histopathology revealed liver metastases, while 77 patients showed no liver involvement. We arrived at the correct diagnosis "liver metastasis" in 50 out of 62 patients (80.6%). False negative scintigrams (19.4%) were found in most of the respective cases when diffuse malignant involvement such as leukemia and Hodgkin's disease was present, and also when the size of the metastases was less than 2 cm in diameter. Fifty six out of 77 patients (72.7%) without histopathological evidence of liver metastases revealed negative scintigrams. Twenty one (27.3%) false positive scintigrams were mostly due to (diffuse) nonmalignant disease e.g. fibrosis and cirrhosis. The overall accuracy of liver scintigraphy in our study was 76.2%. In 18 of 20 (90%) patients with focal liver disease correct diagnosis was established. 7 patients with benign liver tumors and 11 of 13 patients with hepatocellular carcinoma showed focal defects. Considering the fact that liver scintigraphy is a non-invasive procedure, it can be recommended as screening method. In connection with sonography and computer tomography liver scintigraphy can undoubtedly improve the diagnostic accuracy in detecting liver metastases and primary liver tumors.

Autopsy↗
PubMed1983

[Effects of cianidanol on chronic liver injury induced by carbon tetrachloride and on liver regeneration after partial hepatectomy in rats].

Effects of cianidanol on chronic liver injury induced by prolonged administration of carbon tetrachloride (CCl4) and on liver regeneration after partial hepatectomy of normal liver and CCl4 chronically injured liver were investigated by the measurement of plasma and liver biochemical parameters. Cianidanol increased the total plasma protein and 14C-Leu incorporation into plasma protein, while it reduced the contents of liver cholesterol and triglycerides. In rats with chronically injured liver or regenerating liver after partial hepatectomy of chronically injured liver, cianidanol improved the retention rate of BSP and the content of liver sugar. In rats with chronically injured liver, plasma GPT and GOT activities were reduced with the administration of cianidanol. Cianidanol had no effect on the regeneration rate after partial hepatectomy of normal liver, but it increased the regeneration rate after partial hepatectomy of chronically injured liver. These results suggest that cianidanol has the effect of improving the function of liver cells damaged by CCl4 treatment and of promoting the recovery of cell function to a normal level.

Alanine Transaminase↗
PubMed1994

Entactin gene expression in normal and fibrotic rat liver and in rat liver cells.

BACKGROUND: Entactin, a constituent of basement membranes, is a sulfated glycoprotein with binding sites for laminin, collagen type IV, fibronectin, and cell surfaces. As it is known that excess matrix deposition and sinusoidal basement membrane formation is a central characteristic of liver fibrogenesis, we investigated whether the entactin gene is expressed in normal and in damaged rat liver and which cell types are able to express this gene. In addition, we were interested in the cellular origin and time course of laminin synthesis, a matrix protein closely associated with entactin. EXPERIMENTAL DESIGN: Entactin gene expression was analyzed in normal, acutely and chronically damaged rat livers (CCl4-model) by immunohistochemistry and in situ detection of specific transcripts. Rat fat-storing cells (FSC) (Ito), hepatocytes, Kupffer cells, liver endothelial cells, arterial smooth muscle cells (SMC), and skin fibroblasts (SF) were isolated according to standard techniques. Entactin gene expression in cultured cells was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitates, Northern blot analysis, and immunocytochemistry. RESULTS: In normal liver, entactin was detected in the vessel walls as continuous deposits and in a spot-like fashion along the sinusoids. Entactin was detectable among the cells of the inflammatory infiltrates of acutely damaged liver and in connective tissue septa, in the walls of newly formed vessels and bile ducts of fibrotic liver. Laminin distribution in the vessels was similar, but it was additionally present in the space of Dissé of damaged liver. By in situ hybridization, few entactin-positive cells were found in normal liver sections. Strongly positive cells were scattered over the injured parenchyma of acutely and chronically damaged livers. Northern blot analysis of total RNA extracted from normal and damaged liver tissue showed a distinct increase of entactin specific transcripts during development of fibrosis. Hybridization of total RNA from cultured FSC, hepatocytes, Kupffer cells, endothelial cells, SMC, and SF revealed entactin specific mRNA in FSC, SMC, SF, and endothelial cells; laminin mRNA was found in FSC and SF. Synthesis and secretion of both proteins were found in FSC, SMC and SF. Entactin and laminin gene expression increased in parallel to FSC during time in culture. CONCLUSIONS: Among the main liver cells, FSC show the highest entactin gene expression and might therefore play the dominant role in the synthesis of this protein in normal and fibrotic liver. However, endothelial cells and liver myofibroblasts could also contribute to entactin production.

Animals↗
PubMed1998

Perioperative continuous hepatocyte growth factor supply prevents postoperative liver failure in rats with liver cirrhosis.

Insufficient regeneration and dysfunction of cirrhotic liver following partial hepatectomy often make the resection extremely vulnerable to postoperative liver failure, which frequently leads to multiple organ failure. Hepatocyte growth factor (HGF), first identified as the most potent mitogen for primary hepatocytes, not only stimulates hepatic regeneration but also accelerates liver function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the ability of a continuous supply of HGF to cirrhotic livers to prevent postoperative liver failure in rats. After liver cirrhosis was induced in 40 rats by the intraperitoneal injection of dimethylnitrosamine (DMN) for 4 weeks, fibroblasts genetically modified to secret rat HGF or control fibroblasts were implanted in the spleens of 20 syngenic rats per group to supply HGF continuously and directly to the cirrhotic livers. Two weeks after the implantation, all rats underwent a 30% hepatectomy. The HGF administration significantly improved liver fibrosis at the time of operation, attenuated the postoperative hepatic damage on histological examination, markedly accelerated the liver regeneration at 24 h after the hepatectomy. The blood chemical analysis indicated that HGF significantly suppressed postoperative liver failure. Most importantly, the HGF treatment significantly improved the survival rate of the rats at 48 h after the hepatectomy. The perioperative continuous supply of HGF from the spleen effectively prevented liver failure following resection of cirrhotic livers in rats.

Animals↗
PubMed2005

Detrimental effect of sinusoidal overperfusion after liver resection and partial liver transplantation.

Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (II) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 min after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte-endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and III. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants.

Animals↗
PubMed2001

Auxiliary liver transplantation and bioartificial bridging procedures in treatment of acute liver failure.

The aim of this review is to discuss the place of auxiliary liver transplantation (ALT) and other cellular based bridging procedures such as hepatocyte transplantation, ex vivo liver perfusion, and bioartificial livers, in the treatment of acute liver failure, vis à vis conventional orthotopic liver transplantation. Hepacocyte transplantation, and ex vivo pig or human liver perfusion are still experimental procedures. Bioartificial livers using human tumoral hepatocytes or porcine hepatocytes have been used in clinical situations as a bridge to transplantation, i.e. to gain the time required to find a high-quality graft for conventional or auxiliary liver transplantation. None of these techniques have yet proved capable of keeping a patient alive long enough for the native liver to recover. Conversely, ALT has been shown to be effective in the treatment of acute liver failure and now appears to be a satisfactory bridging procedure pending native liver (NL) regeneration. We report personal experience of 18 ALT procedures performed in 17 patients between October 1992 and December 1999. The ALT procedure was indicated when patients met criteria for conventional transplantation; it was ultimately selected when a fresh frozen biopsy of the NL did no show any fibrosis. Six patients died within the first 2 postoperative months. The remaining 11 patients are alive, with a follow-up ranging from 2 to 7 years. Regeneration of the NL occurred in 11 of the 17 patients (65%) and in 8 of the 11 survivors (72%), 6 of whom have permanently stopped immunosuppressive therapy. We conclude that liver failure should no longer be handled outside centers where all types of transplantation can be offered, and where innovative therapies such as hepatocyte transplantation and extracorporeal liver-assist devices are being developed and evaluated.

Adolescent↗
PubMed1984

[Accuracy of sonography in the diagnosis of diffuse liver parenchymal diseases--comparison of sonography and liver histology].

A prospective study has been carried out on 127 patients to test the accuracy of sonography in the diagnosis of diffuse liver diseases compared with histology based on percutaneous liver biopsy. Using sonographic criteria - size, margin, surface, elasticity, echo structure and sonic conductivity of the liver, hepatic veins and portal vein - and measuring the size of the gallbladder and the spleen, the following sonographic diagnoses were made: normal liver, fatty liver, fatty liver fibrosis, alcoholic hepatitis, chronic active hepatitis, cirrhosis. Sonographic diagnosis predicted histological diagnosis in case of normal liver in 56%, fatty liver 70%, alcoholic hepatitis 92%, chronic active hepatitis 63%, cirrhosis 79%. The specificity of sonography was 95%, the overall sensitivity was 82%: e.g. fatty liver 84%, chronic active hepatitis 93% and cirrhosis 79%. We conclude that sonography is an ideal screening method for detecting diffuse liver diseases. In cases of fatty liver and of cirrhosis it can spare the patient further invasive investigation. Furthermore, this method is suitable for evaluating the course of diffuse diseases of the liver, especially of toxic-nutritive liver damage and also of chronic active hepatitis.

Biopsy, Needle↗