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Right-lobe live donor liver transplantation improves survival of patients with acute liver failure.

BACKGROUND: Right-lobe live donor liver transplantation (LDLT) is used by many liver transplant centres for treating adult patients with terminal liver disease, but its incremental benefit for the intended recipient over cadaveric liver graft transplantation has not been determined. The impact of LDLT as a proactive approach on the outcome of patients with acute liver failure was analysed. METHODS: From January 1999 to March 2001, right-lobe LDLT was offered proactively to 50 consecutive patients with acute liver failure and their families. The outcome of those who opted for right-lobe LDLT (n = 34) was compared with that of those who did not opt for LDLT (n = 16). RESULTS: In the group that opted for right-lobe LDLT, 16 patients eventually received a live donor right-lobe graft (14 patients survived) and three patients received a cadaveric liver graft that became available while the potential live donor was undergoing evaluation (all three patients survived). Among the group who did not opt for LDLT, only one patient received a cadaveric liver graft and survived. The former group had a higher overall survival rate (17 of 34 versus one of 16). With a proactive approach, the overall transplant rate was increased from four of 50 to 20 of 50. The morbidity rate among donors was low and none died. CONCLUSION: Right-lobe LDLT improves the overall survival rate of patients with acute liver failure and should be considered as one of the treatment options for adult patients with acute liver failure.

Adolescent↗

Peritoneoscopic findings and liver function in chronic liver disease.

In 100 cases with chronic liver disease, peritoneoscopy and liver biopsy were performed, and the association between peritoneoscopic findings and liver function was studied. With respect to liver function, a series of tests which seem to indicate residual liver function were selected as follows; dye excretion, serum levels of albumin and cholinesterase, and subfractions of serum proteins. In evaluating the periotoneoscopic view, new criteria for the classification of liver surface findings are proposed. All cases were divided into 5 types in accordance with these criteria. Analysis of the correlation between peritoneoscopic findings and liver function showed that the degree of liver dysfunction was clearly indicated by liver surface alterations. As a result, the residual liver function may be determined quite well by using this classification.

Biopsy↗

Auxiliary partial liver transplantation for end-stage chronic liver disease.

Auxiliary heterotopic liver transplantation is theoretically attractive because it leaves the recipient's liver in place. The surgical trauma of hepatectomy is avoided, and failure of the graft does not necessarily lead to the death of the patient or a second, emergency transplantation. Another advantage is that matching the body sizes of the donor and the recipient is not mandatory, which increases the number of possible donors. However, previous clinical results of auxiliary liver transplantation have been poor. We performed auxiliary partial liver transplantation in six consecutive patients with end-stage chronic liver disease who were not accepted for orthotopic liver transplantation because they had massive ascites, deficient clotting function, cachexia, or poor pulmonary reserve. The donor liver was transplanted to the right subhepatic region after removal of segments II and III, and it was provided with portal and arterial blood. There were no major changes in hemodynamic measurements during surgery. The mean hospital stay after transplantation was 22.7 days (range, 14 to 29). After a mean follow-up period of 14 months (range, 5 to 23), all patients were alive, with good graft function as demonstrated by scintigraphy, Doppler ultrasonography, and synthesis of clotting factors. From these observations we conclude that auxiliary partial liver transplantation is an attractive alternative to orthotopic liver transplantation in high-risk patients. Its role in other patients who need liver transplants remains to be defined.

Adult↗

Utility of Tc-99m GSA SPECT imaging in estimation of functional volume of liver segments in health and liver diseases.

The authors examined whether there was a difference in liver function among hepatic segments in liver cirrhosis cases, and in cases of hepatocellular carcinoma (HCC) associated with liver cirrhosis. If the average counts in the lateral segment of the left lobe were set at 1, the average counts in the right upper and lower segment of the liver were 0.75 approximately 1.02 (0.89 +/- 0.09, mean +/- SD) in normal cases, 0.38 approximately 2.24 (1.01 +/- 0.39) in liver cirrhosis cases, and 0.61 approximately 2.85 (1.15 +/- 0.58) in HCC cases. There is a significant difference between normal cases and liver cirrhosis cases or HCC cases (P < 0.001). Also, in HCC cases, if the average counts in the cancer-bearing segment of the liver were set at 1, the average counts in the noncancerous segment of the liver were 0.55 approximately 2.85 (1.23 +/- 0.58), and many average counts in the cancer-bearing segment were equal to, or lower than those in the noncancerous segment. It has been found that there were significant differences in function among hepatic segments in liver cirrhosis cases, and in HCC cases. Furthermore, the liver function in the cancer-bearing segment tended to be worse due to the existence of carcinoma compared with that in the noncancerous segment.

Adult↗

Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure.

The limited donor organ supply has led to several bridging techniques to sustain patients with acute and subacute liver failure. We report here the prospective, controlled trial of transplanted isolated fresh and cryopreserved human hepatocytes as a bridge to orthotopic liver transplantation. Five hepatocyte transplant recipients with grade IV encephalopathy and multisystem organ failure and four patients of equal illness severity due to liver failure were studied. Medical therapy resulted in a significant (P<0.05), but not normal, fall in blood ammonia, and a significant (P<0.02) resolving biochemical marker of liver injury that did not improve cardiovascular or cerebral stability; this lead to death within 3 days in all control patients. The five hepatocyte-treated patients maintained normal cerebral perfusion and cardiac stability, with withdrawal of medical support for 2 to 10 days before orthotopic liver transplantation. Biochemical evidence of liver injury improved significantly (P=0.004) and blood ammonia levels decreased significantly (P=0.0005) to normal levels in the hepatocyte-treated patients. Three of five patients who successfully bridged to whole liver allograft transplant are alive, home, and normal with more than 20 months of follow-up. No infections or embolic or pulmonary complications resulted from intra-arterial splenic hepatocyte infusion. Specific antiprotease production in a patients with genetically deficient alpha-1-antitrypsin disease, and immunohistochemical and electron microscopic evidence of splenic "hepatization" are presented as evidence of the viability of hepatocyte splenic seeding. In conclusion, splenic transplantation of differentiated adult hepatocytes can control hyper-ammonemia, correct genetic defects in liver function, and bridge life to orthotopic liver transplantation in human liver failure.

Adult↗

Haemostatic abnormalities in liver disease: could some haemostatic tests be useful as liver function tests?

The liver plays a central role in haemostasis, being the site of synthesis of most of the clotting factors, coagulation inhibitors and fibrinolytic parameters, in addition to its clearance of activated clotting and fibrinolytic factors. Nonetheless, no haemostatic test(s) is included among the routine liver function tests and this study aims to probe this possibility. The liver disease group (n=258) included acute hepatitis (n=25), chronic viral hepatitis (n=128), hepatitis B (HB) carriers (n=25), liver cirrhosis (n=67), and hepatocellular carcinoma (HCC) (n=13). The prothrombin time was significantly prolonged in acute hepatitis, liver cirrhosis and HCC. However, the reptilase time was prolonged in all the groups except in HB carriers, while the thrombin time was prolonged only in the HCC group. Antithrombin III and protein C levels exhibited significant reduction in acute hepatitis, liver cirrhosis and HCC. On the other hand, protein S levels (total and free) were reduced significantly in all the patients groups, including HB carriers when compared with healthy controls. Derangement of haemostatic tests is a common feature in liver disease, being most significant in acute hepatitis, liver cirrhosis and hepatocellular carcinoma. The most sensitive markers of hepatocyte malfunction are protein S (total and free) and the reptilase time as they were abnormal, in the mildest liver affections, when other biochemical tests as well as other haemostatic tests were normal. Further studies are needed to see whether these two tests qualify for inclusion among the routine liver function tests.

Adolescent↗

Antipyrine clearance per unit volume liver: an assessment of hepatic function in chronic liver disease.

Liver size has been estimated clinically and by a non-invasive ultrasound technique in 16 normal subjects, 16 patients with cirrhosis, 10 patients with chronic biliary obstruction, and three patients with primary hepatoma. Antipyrine disposition was also measured in each subject. Hepatomegaly was not clinically detectable until there was approximately a 20% increase in liver size. Additional increases in size correlated significantly with clinical estimates of hepatomegaly. Antipyrine clearance had a three-fold range in normal subjects. Its mean value was significantly reduced in each subgroup of patients with liver disease. However, 48% of patients with liver disease had values within the normal range. In normal subjects there was a significant correlation between antipyrine clearance and liver volume. Thus, intersubject variation in clearance normalised for liver volume was less than clearance alone. Antipyrine clearance normalised for liver volume in patients with liver disease was significantly lower than in normal subjects and there was no overlap with normal subjects. In conclusion, assessment of drug metabolising efficiency per unit volume of liver increased the discrimination in differentiating subjects with normal from abnormal livers.

Aged↗

Liver histology and follow up of 68 patients with ulcerative colitis and normal liver function tests.

Hepatobiliary disorders are well known complications in patients with ulcerative colitis but it is not possible to predict those patients with ulcerative colitis who will eventually develop liver disease. In this study, liver biopsies from 74 patients with ulcerative colitis have been reevaluated. None of the patients showed clinical or biochemical signs of liver disease at the time of biopsy. Thirty seven (50%) had a completely normal liver biopsy. The others showed minimal portal inflammation or fatty infiltration. The biopsies of three patients displayed concentric, periductular fibrosis, or so called 'onion skin' lesions. None showed other signs of fibrosis or cirrhosis. The histological findings were unrelated to either activity or extent of colitis, except for the onion skin lesions which were seen exclusively in biopsies of patients with involvement of the total colon. Sixty eight of the 74 patients were reviewed after a mean interval of 18 years. The majority had no symptoms of hepatobiliary disorders and only two had developed liver disease; one suffered from cryptogenic cirrhosis, possibly due to non-A, non-B hepatitis and the other of an autoimmune liver disease and later developed a bile duct carcinoma. Both were women with total colonic involvement. At the time of the first liver biopsy one showed no histological abnormalities and the other only minor fatty infiltration. Thus, minor abnormalities in liver tissue are common in patients with ulcerative colitis without biochemical evidence of liver disease. The morphological changes are of little help in predicting the future risk of a patient with ulcerative colitis developing a clinically relevant hepatobiliary complication. The absence of biochemical parameters for liver disease during the early years of ulcerative colitis predict a favourable longterm diagnosis as regards hepatobiliary complications.

Adolescent↗

N-acetylcysteine decreases lactate signal intensities in liver tissue and improves liver function in septic shock patients, as shown by magnetic resonance spectroscopy: extended case report.

BACKGROUND: N-acetylcysteine (NAC) has been shown to improve splanchnic blood flow in experimental studies. This report evaluates the effects of NAC on liver perfusion and lactate signal intensities in the liver tissue of septic shock patients using proton magnetic resonance imaging and spectroscopy. Furthermore, the monoethylglycinexylidide (MEGX) test was used to investigate hepatic function. METHODS: Five septic shock patients received 150 mg/kg body weight NAC as an intravenous bolus injection over 15 min. Lidocaine was injected both prior to and following NAC administration in order to determine MEGX formation. Measurements (hemodynamics, oxygen transport-related variables, blood samples for lactate, liver-related markers) were performed 1 hour before and 1 hour after NAC injection. In addition to the proton magnetic resonance imaging patients received two proton magnetic resonance spectra, one prior to and one 30 min subsequent to the onset of the NAC infusion at a 1.5 Tesla clinical scanner, for measurement of liver perfusion and liver lactate signal intensity. MAIN FINDINGS: Following NAC infusion, the lactate signal intensity in the liver tissue showed a median decrease of 89% (11-99%), there was a median increase in liver perfusion of 41% (-14 to 559%), and the MEGX serum concentration increased three times (1.52-5.91). CONCLUSIONS: A decrease in the lactate signal intensity in the liver tissue and an increase in the MEGX serum concentration and in liver perfusion might indicate improved liver function as a result of NAC administration. Patients with compromised hepatosplanchnic function, such as patients with septic shock due to peritonitis, may therefore benefit from NAC therapy.

Acetylcysteine↗

Effect of surgery on liver function in patients with liver cancer.

The effect of hepatic resection, hepatic artery ligation (HAL), and artery ligation combined with regional infusion of 5-fluorouracil (HAL + 5-FU) on liver function was investigated by liver tests including antipyrine in 20 patients with liver cancer. One month after resection the conventional liver tests except serum albumin were normalized, but the rate of antipyrine elimination was still significantly reduced. This suggests that the oral antipyrine test may be a sensitive reflector of the reserve capacity of the liver. Palliative procedures (HAL +/- 5-FU) had a transient effect on conventional liver tests and a negligible effect on functional liver capacity as determined by the antipyrine test or serum albumin concentration. On the basis of our results it remains unknown whether antipyrine determination provides any additional advantage over serum albumin as a measure of functional liver capacity in localized liver diseases, such as liver tumours.

Adult↗

[De novo hepatitis B infection after liver transplantation--evidence for the need of active hepatitis B vaccination of liver transplantation candidates].

BACKGROUND: Liver transplantation (LTX) is a generally accepted therapy in the treatment of acute and chronic end-stage liver diseases. Recurrent and de-novo hepatitis B and C virus infection following liver transplantation have been shown. PATIENTS AND METHODS: We analyzed retrospectively the course of patients treated at our transplant center between 01.01.1992 and 31.12.1997, who does not show any markers of an active hepatitis B (HBV) infection prior to liver transplantation but developed replicative HBV infection afterwards. During this period 544 liver transplantations were performed in 452 patients, 395 of whom were HBs-Ag negative prior to transplantation. RESULTS: Six patients were identified who underwent LTX for non-hepatitis B-induced liver disease, and who subsequently developed a highly replicative de-novo HBV-infection six to twelve months (mean 8.5 months) after LTX. In each of the patients HBV de-novo infection showed clinically and biochemically a mild but chronic course without evidence of liver failure during a maximum follow-up period of 14 to 37 months (mean 26 months). Liver biopsies taken in four patients nine to 22 months after LTX showed chronic active hepatitis (n = 2), chronic portal hepatitis (n = 1), and a mild rejection (n = 1). The source of de-novo HBV infections remained unclear, but inapparent infection of patients pre-LTX was ruled out so that the donor livers or postoperative infection appear to be the likely source. CONCLUSION: In our center the number of HBV de-novo infections (1.5%, 6/395) following liver transplantation was comparable to the results published by other centers, but in our center no inapparent infection of patients prior to LTX was observed. For further minimization of HBV de-novo infection following LTX active HBV immunization of patients awaiting LTX is recommended.

Adult↗

[Evaluation of the liver uptake rate measured by 99mTc-GSA SPECT to assess liver function].

Whether the global liver uptake rate of 99mTc-GSA directly measured by SPECT is useful as a new index of liver function was evaluated in comparison with biochemical test results (PT%, ChE, Alb, ICG R15, KICG) and Child classification. 99mTc-GSA SPECT was performed in 157 patients with diffuse hepatic disease or hepatobiliary tumor, and two indices, namely the global liver uptake rate measured by SPECT 15 minutes after intravenous injection of 99mTc-GSA (LUS 15) and liver uptake per volume (liver uptake density) were examined. Both LUS 15 and liver uptake density were significantly correlated with biochemical test results and Child classification. In particular, close relationships between LUS 15 and ICGR15 (r = -0.720, p < 0.0001), LUS 15 and KICG (r = -0.750, p < 0.0001), and between LUS 15 and ChE (r = 0.720, p < 0.0001), indicate that LUS 15 is a useful index to evaluate liver function. Moreover, the local liver uptake rate measured by SPECT represented regional liver function and was considered a useful index to predict the function of the remnant liver after invasive treatment such as surgery.

Adult↗

Living-related auxiliary partial orthotopic liver transplantation for primary sclerosing chonangitis--subsequent removal of the native liver.

In Japan, living-related auxiliary partial orthotopic liver transplantation (APOLT) is mainly indicated for small-for-size grafts. We present the case of a 24 year-old patient with primary sclerosing cholangitis (PSC) who underwent a living-related auxiliary partial orthotopic liver transplantation for a small-for-size graft, that was subsequently excised. During the transplantation procedure, the native liver was freed from the surrounding tissues, and was only connected to the body by the right hepatic artery and right hepatic vein. The auxiliary extended left lobe graft, corresponding to 22% of the estimated recipient liver volume, was orthotopically transplanted after extended left lobectomy of the recipient native liver. Post-transplant CT-volumetry showed rapid increase of the graft volume with atrophy of the native liver, and GSA scintigraphy showed dominant function of the graft. Although hyper-bilirubinemia was prolonged by the removal of the native liver on the 18th post-transplantation day, it gradually subsided after plasmapheresis was performed twice, and the patient was discharged on the 77th post-transplantation day. We conclude, based on this case, that subsequent removal of the native liver is necessary in APOLT for patients with potential hepatic malignancies. The optimal timing of the removal of the remnant native liver should be determined based on CT-volumetry, GSA scintigraphy, and the liver biopsy specimen of the graft.

Adult↗

Role of tissue trace elements in liver cancers and non-cancerous liver parenchyma.

BACKGROUND/AIMS: The role of trace elements in liver fibrosis, carcinogenesis and progression of hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to analyze the characteristics of trace elements in liver cancers and non-cancerous liver and to discuss their role in hepatic fibrosis, hepatocarcinogenesis and progression of HCC. METHODOLOGY: The amount of zinc (Zn), iron (Fe), and copper (Cu) in 20 HCCs, 2 cholangiocellular carcinomas (CCC), 7 metastatic liver cancers (Meta) and their non-tumorous liver parenchyma were measured using an atomic absorption spectrophotometer. RESULTS: The amounts of Zn and Fe in non-tumorous liver parenchyma were reduced by liver fibrosis, and the amounts were lower in HCC tissue compared to non-tumorous liver parenchyma. The amounts of Zn and Cu were higher in HCC than the amounts found in CCC and Meta. The amount of Zn in HCC tissue decreased, but the amount of Fe increased in tumors more than 4cm in diameter. CONCLUSIONS: These results suggest that the decrease in the amount of Zn and Fe found in non-tumorous liver parenchyma correlates with liver fibrosis leading to cirrhosis and hepatocarcinogenesis. Also that decreases in Zn and increases of Fe in HCC tissue correlates with HCC tumor progression.

Carcinoma, Hepatocellular↗

[Evaluation of the liver reserve using lidocaine test on experimental liver injuries in rats].

OBJECTIVES: To study the effectiveness of the lidocaine test in evaluating the liver reserve of rats with experimental liver injury in different phases. METHODS: 40 healthy male Wistar rats were divided randomly into experimental and control groups. Rats of the experimental group received subcutaneous CCl4 in oil injection, and rats of the control group received saline injections. Monoethylglycinexylidide (MEGX) test, common hepatic function tests and histological examination of the livers were performed on all the rats. RESULTS: With the development of the severity in liver injury, the concentrations of the serum MEGX in lidocaine test decreased gradually, which were consistent with liver histological changes. However, the results from the common liver function tests were all abnormal in the experimental group and were not consistent with the liver histological changes. CONCLUSION: The results obtained from the MEGX test are more agreeable to liver histological changes than those from common liver function tests. The results from the MEGX test can represent liver histological changes concisely.

Animals↗

The expression of c-myc and c-N-ras in human cirrhotic livers, hepatocellular carcinomas and liver tissue surrounding the tumors.

To study the possible role of proto-oncogenes in the multistep process of human liver hepatocarcinogenesis, we have examined the expression of c-N-ras and c-myc in human hepatocellular carcinomas and liver tissue surrounding the tumors as well as cirrhotic livers which are generally considered to precede the formation of human hepatocellular carcinoma. One to four-fold higher expression of the c-N-ras proto-oncogene was observed in twelve hepatoma patients as compared to normal liver. Increased expression of c-N-ras was also observed in liver tissue surrounding these tumors. Eight patients exhibited an apparent higher expression of the c-N-ras oncogene in adjacent liver tissue than in their corresponding tumor tissues. Six human liver cirrhosis patients also exhibited a slight increase in c-N-ras expression. Southern blot analysis demonstrated an amplified c-N-ras sequence in these tissues surrounding the tumors. In the study of the c-myc gene, variable degrees of highly enhanced expression were found in all twelve hepatoma patients as compared to normal liver. The c-myc gene was also expressed in the adjacent liver tissue and in some of the human cirrhotic livers. Our studies give further evidence that the expression of c-N-ras and c-myc proto-oncogenes are involved in the process of human hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

[Regeneration ability of ischemic liver and the effect of liver resection and extracts stimulating proliferation].

DNA synthesis was studied in liver nuclei of Wistar rats after 30% liver tissue resection, 2 hr ischemia of 70% liver tissue or 2 hr ischemia of 70% liver tissue with resection of intact lobes. DNA synthesis was markedly increased in ischemic lobes and was especially high in ischemic lobes if simultaneous resection of intact lobes occurred; maximum of the synthesis was observed within 32 hrs after the operation. Proliferation stimulating extracts, isolated from liver tissue within 48 hrs after the resection or after ischemia, intensified the regenerating processes in the resected liver tissue; the first preparation (from resected liver tissue) exhibited the most distinct effect as compared with the second extract (from ischemic liver tissue). Proliferation stimulating extracts did not affect the cytochrome P-450, content of which was decreased after resection and ischemia. The data obtained suggest the important role of proliferation stimulating factors in regeneration of liver tissue after ischemia or resection; these factors proved to be possible to isolate from ischemized and reperfused liver tissue; the medicinal effect of resection was shown.

Animals↗

Characterization of nucleolar antigens of normal rat liver, regenerating rat liver, and Novikoff ascites hepatoma cells following in vitro translation of polyadenylic acid-containing messenger RNA.

Nucleolar antigens of normal rat liver, regenerating liver, and Novikoff ascites hepatoma cells were transplanted in vitro from polyadenylic acid-containing messenger RNAs isolated from the respective tissues and immunoprecipitated with specific antinucleolar antibodies and Protein A. By two-dimensional gel electrophoresis of the translation products, five antigens were detected in normal rat liver. The antigens detected in 18-hr regenerating rat liver were the same as those of normal rat liver when immunoprecipitated with the anti-liver nucleolar antibodies. In the Novikoff tumor, 11 antigens were detected with anti-Novikoff nucleolar antibodies. Of these, two were not found in either normal or regenerating liver. Four major antigens were detectable in both Novikoff hepatoma and regenerating liver messenger RNA translation products with anti-Novikoff nucleolar antibodies. Two antigens were found in normal and regenerating liver that were not found in Novikoff hepatoma. In agreement with previous results, these immunoprecipitation analyses provide further evidence that some nucleolar antigens are present in Novikoff hepatoma that are not found in either normal or regenerating rat liver.

Animals↗