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[Quantitative evaluation of liver function with 99mTc-GSA scintigraphy using extraction index].

Extraction index (EI5) was introduced to evaluate liver function quantitatively with 99mTc-GSA (GSA) scintigraphy, and it was compared with conventional indices; receptor index (LHL15) and clearance index (HH15). EI5 is expressed as following equation: EI5 = (L5 - L3)/(H3 + H5) * PH/PL where L3, L5: counts at 3 or 5 minutes after the injection in the liver ROI, respectively, H3, H5: counts at 3 or 5 minutes in the heart ROI, respectively; PL, PH: numbers of pixels in the liver- and heart-ROI, respectively. We performed GSA scintigraphy in 40 patients with liver dysfunction and calculated values of the indices. Good correlations were observed between EI5 and liver function tests. Correlation coefficients were almost equal to or higher than those between conventional parameters and liver functional tests. EI5 was thought to be a practical index, and it could be calculated in a short time without aid of computer. Evaluation of local liver function may be possible, because EI5 was corrected with numbers of pixels in the liver- and heart-ROI; which was not considered in the conventional parameters.

Adult↗

Aminopyrine breath test: development of a 13C-breath test for quantitative assessment of liver function in humans.

BACKGROUND/AIM: 14C-aminopyrine breath test (ABT) has been shown to be well correlated to the severity of liver diseases, but its use is limited in countries where radioactive isotopes are severely controlled. The goal of this study was to develop a 13C-ABT based on a highly sensitive method to measure 13CO2 in breath samples. MATERIALS AND METHODS: The relevant parameters were studied in 26 controls and 27 patients: the 13CO2 enrichment of expired breath between t-10 and t+60 minutes was determined as the most simple and clinically useful parameter. The 13C-ABT was then prospectively compared to clinico-biological data and the galactose elimination capacity (GEC) in 82 patients. RESULTS: The 13C-ABT was well correlated to: i) the Child-Pugh classification; ii) GEC results; iii) the hepatic volume. The presence of ascites or alcoholic consumption did not alter significantly the results of the test. 13C-ABT appeared more sensitive than GEC to evaluate minor liver dysfunctions. CONCLUSIONS: The 13C-ABT is a simple and sensitive test to measure liver function. The use of the stable isotope 13C ensures the harmlessness of the test and the possibility to repeat it in a given patient.

Adult↗

Three brothers with progressive hepatic dysfunction and severe hepatic steatosis due to a patent ductus venosus.

Three Japanese brothers with progressive deterioration of hepatic function and fatty degeneration of the liver eventually leading to hepatic encephalopathy were recently encountered. Each of them had a congenital intrahepatic portosystemic venous shunt due to a patent ductus venosus. Liver dysfunction and hepatic steatosis reverted to normal with surgical correction of the ductus venosus. Our observations suggest that impairment of liver function occurs first in the presence of malnutrition related to a reduction of blood in the portal vein. Hepatic steatosis is a consequence of a depleted metabolism of hepatocytes. Congenital portosystemic venous shunt due to a patent ductus venosus in this family has a genetic background.

Angiography↗

Prevention of hepatic infarction as acute-phase complication of TIPS by temporary balloon occlusion in a patient with primary myelofibrosis.

Severe acute liver dysfunction occurred following transjugular intrahepatic portosystemic shunt (TIPS) creation in a patient with massive ascites due to portal hypertension associated with primary myelofibrosis. On US and TIPS venography, we considered that the acute liver ischemia was induced by TIPS. To avoid diffuse hepatic infarction and irreversible liver damage, a balloon catheter was inserted transjugularly into the TIPS tract and occluded it to increase portal venous flow toward the peripheral liver parenchyma. The laboratory data indicating hepatic dysfunction were improved after the procedure. We should pay attention to the possible occurrence of acute hepatic ischemia and infarction after TIPS creation even in a case of noncirrhotic portal hypertension. In such cases, temporary balloon occlusion of TIPS is an effective therapeutic method, probably as a result of inducing the development of arterial compensation through the peribiliary plexus.

Acute-Phase Reaction↗

Characteristics of liver grafts in living-donor adult liver transplantation: comparison between right- and left-lobe grafts.

HYPOTHESIS: Few studies have investigated the results of research focused on living-donor adult liver transplantation. Different characteristics between right- and left-lobe grafts have not yet been clarified in living-donor adult liver transplantation. Left-lobe graft remains an important option, even in adult recipients. SETTING: A single liver transplantation center with a long history of hepatic resection. PATIENTS: Forty-five donors received left-lobe (n = 39) and right-lobe (n = 6) grafts. The clinicopathological data for the donor, graft, and recipient were compared. All left-lobe grafts were extended grafts that included the middle hepatic vein, and 24 of the 39 left-lobe grafts included the left caudate lobe. No right-lobe graft included a middle hepatic vein. RESULTS: The postoperative aspartate aminotransferase and total bilirubin values of the donor in the right-lobe graft group were higher, and the postoperative hospital stay was longer than in the left-lobe graft group. Graft weight in the left-lobe graft group was lighter than in the right-lobe graft group (median weight, 450 vs 675 g). The median graft weight divided by the standard liver volume in the left-lobe graft group was 41% (range, 21%-66%), compared with 52% (range, 47%-75%) in the right-lobe graft group. We found no difference in terms of the incidence of postoperative complications between groups. No difference in induced complications of small-for-size grafts such as intractable ascites and persistent hyperbilirubinemia was evident between groups. The survival rate for grafts at 18 months was 75.0% in the right-lobe graft group compared with 85.6% in the left-lobe group. In the right-lobe graft group, we found a few cases in which a marked poor-perfusion area in the anterior segment caused liver dysfunction. CONCLUSIONS: Left-lobe grafts are a feasible option for living-donor adult liver transplantation, and in the case of right-lobe grafts, hepatic venous drainage is one of the most critical problems.

Adult↗

Severe fatty change of the graft liver caused by a portosystemic shunt of mesenteric varices.

Portosystemic shunt is a common complication in patients with portal hypertension. Mesenteric varix is one of the collaterals that can cause post-transplant liver dysfunction. In this case report, a 45-year-old woman underwent living relative donor liver transplantation for alcoholic cirrhosis. Although the early postoperative course was uneventful, she was readmitted for treatment of liver hypofunction. Fatty change in the graft liver was confirmed by histopathology of the biopsy specimen. The venous phase of a superior mesenteric angiogram revealed large-caliber mesenteric varices comprising portosystemic venous shunts. Surgery was performed to ligate the shunts. The intraoperative color Doppler ultrasonography showed hepatofugal portal blood flow, which was corrected to hepatopetal blood flow by clamping the shunt vessels. The portal pressure was moderately elevated from 13.6 cm to 21.8 cm H(2)O. Two shunt vessels were ligated and divided. Her liver function returned to nearly normal thereafter. We recommend that descending collaterals be divided during liver transplantation.

Fatty Liver↗

The decrease in total collagen fibers in the liver by hepatocyte growth factor after formation of cirrhosis induced by thioacetamide.

Liver cirrhosis is an inveterate disease accompanying fibrosis, hepatocyte damage, and liver dysfunction. In this study, the therapeutic effects of recombinant human hepatocyte growth factor (rhHGF) on liver cirrhosis were examined in rats administered thioacetamide (TAA). Repeated administration of TAA for 10 weeks to rats induced liver cirrhosis with collagen nodes and pseudo-lobe generation, a condition that was pathologically similar to that in humans. Administration of rhHGF after the formation of liver cirrhosis markedly decreased the incidence of pathological fibrosis and the degree of fibrosis as measured by a computed image analysis system. Continuous administration of rhHGF by infusion pump was more effective than bolus administration. Northern blotting analysis showed that rhHGF reduced mRNA levels of procollagen alpha2(I), alpha1(IV), and transforming growth factor-beta1 (TGF-beta1) that were stimulated in the TAA-treated liver. The labeling index of hepatocytes increased following administration of rhHGF in this model. These observations suggest that the pathological recession of liver fibrosis is the result of the reduction of TGF-beta1 and collagen synthesis and, in part, of the stimulation of mitosis of hepatocytes directly by rhHGF and indirectly by TGF-beta1 reduction in the cirrhotic liver. These results demonstrate the usefulness of rhHGF as a therapeutic agent in liver cirrhosis.

Animals↗

Domino liver transplants for metabolic disorders: experience with familial amyloidotic polyneuropathy.

BACKGROUND: Shortage of liver donors means that new methods of liver procurement must be explored. In domino transplantation, organs explanted during transplantation in one patient are transplanted into a second patient. Domino procedures can be performed with livers from patients having transplantation for hepatic metabolic disorders that cause systemic disease without affecting other liver functions. Familial amyloidotic polyneuropathy (FAP) type I is one of these. STUDY DESIGN: We reviewed the Paul Brousse experience with a domino liver transplant program for FAP, hoping to extend the approach to other metabolic disorders. RESULTS: Livers from 10 patients transplanted for FAP type 1 were used for domino transplants to patients with unresectable primary or metastatic liver cancers. There was no perioperative mortality. Neuropathy or cardiomyopathy did not increase the morbidity of the domino liver explant and transplant procedures. Morbidity for the domino recipients did not appear to be increased. Variant transthyretin was detected in the serum in FAP liver recipients, with no immediate clinical consequences. CONCLUSIONS: The domino approach is feasible and requires careful planning of the surgical procedures for liver explantation, particularly for the nature and site of vascular anastomoses. Domino transplantation of metabolically dysfunctional livers creates new categories of potential donors and potential recipients. It raises new ethical, technical, and societal issues. The domino approach could be used in several genetic or biochemical disorders now treated by liver transplantation. It has the potential to increase the number of liver grafts available for transplantation.

Adult↗

Sequential measurement of human herpesvirus 6 DNA with polymerase chain reaction method in pediatric living-related liver transplantation.

BACKGROUND: Human herpesvirus 6 (HHV-6), a causative virus of exanthem subitum, may occasionally present with a severe clinical form in immunosuppressed patients after transplantation. In this study, HHV-6 DNA was sequentially measured with a polymerase chain reaction (PCR) method, a quick and sensitive modality in pediatric living-related liver transplantation (LTx). METHODS: Subjects consisted of 5 post-operative biliary atresia patients undergoing living-related LTx at ages from 8 months to 4 yr. Immunosuppression was performed with Tacrolimus (blood trough level 8-18 within 1 month and 5-10 ng/mL thereafter) and low-dose steroid. Specimens were peripheral blood mononuclear cells (PBMC), plasma, and liver biopsy tissue. The amount of HHV-6 DNA was semiquantified as follows: 1+, 1-10; 2+, 10-100; 3+, 100-1000; 4+, over 1000 copies/105 PBMCs. RESULTS: A total of 69 blood samples and three liver biopsies were provided for the examination. HHV-6 DNA in PBMC was positive in 2 donors and 3 recipients before LTx. Two patients with negative DNA were converted to 3+ at 2-3 wk after LTx and 3 with positive DNA remained 2+ to 3+ throughout the post-LTx period. Only 1 patient developed clinical symptoms, such as fever, liver dysfunction, petechiae, idiopathic thrombocytopenic purpura, and finally bone marrow suppression. HHV-6 DNA in the liver biopsy tissue and plasma in this patient were 4+ and 2+, respectively. CONCLUSION: HHV-6 DNA in PBMC measured by the PCR method may be persistently high in pediatric recipients after living-related LTx. Although HHV-6 DNA in PBMC may be positive in case of evident infection, positivity in PBMC may not be always associated with the clinical symptoms.

DNA, Viral↗

Arteriovenous haemangioma in chronic liver disease: clinical and histopathological features of four cases.

Chronic liver diseases are known to cause several skin manifestations, including cutaneous vascular changes such as spider naevus and palmar erythema. Arteriovenous haemangioma (AVH), a benign acquired cutaneous vascular lesion, has also been reported to be associated with chronic liver disease. We report here four cases of AVH in patients with chronic liver disease: (i) a 59-year-old man who had suffered from chronic active hepatitis associated with hepatitis C virus for 15 years; (ii) a 48-year-old man who had suffered from alcoholic hepatitis for 3 years and was diagnosed with liver cirrhosis 1 year ago; (iii) a 69-year-old female who had had chronic active hepatitis associated with hepatitis C virus infection for 20 years and was diagnosed with liver cirrhosis 7 years ago; and (iv) a 48-year-old man who had had chronic active hepatitis associated with hepatitis B virus infection for about 20 years. All patients showed an asymptomatic solitary dome-shaped reddish papule, 5-10 mm in diameter, on the face (first, second and third patients) or chest (fourth patient). Histopathological examination of the tumours revealed features of AVH, namely a well-circumscribed lesion composed of vascular structures of various sizes reminiscent of arteries and veins. In all four cases, elastic-van Gieson stain showed the absence of an internal elastic lamina in the thick-walled vessels as well as the thin-walled vessels. Examination of multiple sections demonstrated glomus cells and an ascending artery feeding the tumour vessels in only one case. Slight inflammatory cell infiltration was seen in the stroma of three patients while Toluidine blue staining revealed an increased number of mast cells in the stroma in all lesions. The present cases suggest that the occurrence of AVH associated with chronic liver disease is not related to any specific liver disease, but may be related to chronic liver dysfunction itself.

Hemangioma↗

[Congenital hypopituitarism and giant cell hepatitis in a three month old girl].

CASE REPORT: A three month old girl, with recurrent hypoglycemia and neonatal cholestasis, is reported. A metabolic disease could be excluded. The liver biopsy revealed giant cell hepatitis and intrahepatic bile duct hypoplasia. ACTH, Cortisol and hGH measured during hypoglycemia were low. Magnetic tomography (MR) of the brain showed an "empty sella". After beginning a replacement therapy with hydrocortisone, growth hormone and thyroxine there was no further episode of hypoglycemia. Transaminases and bilirubin levels normalized. The girl is in good condition, growth and development are normal. DISCUSSION: Hypoglycemia is often the first sign in childrens with neonatal hypopituitarism. The association of liver disease and hypopituitarism has been documented in a few reports. The pathophysiological mechanism leading to the liver dysfunction is not well understood. The prognosis of neonatal hypopituitarism as well as the concomitant liver disease is good under sufficient replacement therapy.

Bile Ducts, Intrahepatic↗

Transient focal hepatic defects related to sustained-release niacin.

Hepatotoxicity is a potential side effect of niacin therapy for hypercholesterolemia, ranging from mild aminotransferase elevation to fulminant hepatic failure. Although uncommon with plain forms, liver dysfunction has increasingly been associated with sustained-release preparations. This case illustrates transient focal liver defects seen on computed tomography with symptomatic elevation of liver-associated enzymes during treatment with sustained-release niacin. The masses were not evident on radionuclide liver scan, suggesting focal fatty liver. After niacin was discontinued, these abnormalities resolved, and aminotransferases returned to normal. This is the first such reported case.

Adult↗

Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver.

The organization of the hepatic microvascular network has been widely studied in recent years, especially with regard to cirrhosis. This research has enabled us to recognize the distinctive vascular patterns in the cirrhotic liver, compared with the normal liver, which may explain the cause of liver dysfunction and failure. The aim of this study was to compare normal and cirrhotic rat livers by means of a quantitative mathematical approach based on fractal and Fourier analyses performed on photomicrographs and therefore on discriminant analysis. Vascular corrosion casts of livers belonging to the following three experimental groups were studied by scanning electron microscopy: normal rats, CCl(4)-induced cirrhotic rats and cirrhotic rats after ligation of the bile duct. Photomicrographs were taken at a standard magnification; these images were used for the mathematical analysis. Our experimental design found that use of these different analyses reaches an efficiency of over 94%. Our analyses demonstrated a higher complexity of the normal hepatic sinusoidal network in comparison with the cirrhotic network. In particular, the morphological changes were more marked in the animals with bile duct-ligation cirrhosis compared with animals with CCl(4)-induced cirrhosis. The present findings based on fractal and Fourier analysis could increase our understanding of the pathophysiological alterations of the liver, and may have a diagnostic value in future clinical research.

Algorithms↗

Liver disease in pregnancy.

Liver dysfunction during pregnancy can be caused by conditions that are specific to pregnancy or by liver diseases that are not related to pregnancy itself. This review attempts to summarize the epidemiology, pathophysiology, and management of the different pregnancy-related liver diseases, and to review different liver diseases not related to pregnancy and how they may affect or be effected by pregnancy. Some of the liver diseases specific to pregnancy can cause significant morbidity and mortality both to the mother and to the fetus, while most of the liver diseases not specific to pregnancy do not have a deleterious effect on the pregnancy itself.

Female↗

Ischaemic hepatitis in the elderly.

BACKGROUND: Ischaemic hepatitis is centrilobular necrosis which is usually associated with an acute cardiovascular event and in a general hospital setting has been considered to be a rare condition. It is though thought to be frequently unrecognized, which is important as it has implications for both investigations and drug therapy. Previous reports have not focused on the elderly. OBJECTIVES: (1) To determine the incidence of ischaemic hepatitis in elderly patients admitted to a Department of Geriatric Medicine and (2) to assess both the clinical and biochemical features of the condition. METHODS: 1,905 elderly patients (1,270 F, 635 M) admitted consecutively to our department over a 2-year period were assessed prospectively. All were aged > or =65 years (mean 78, range 65-98). Ischaemic hepatitis was diagnosed by a rapid development of abnormal liver function tests of hepatocellular type in acutely ill patients in whom a fall in blood pressure occurred and other causes of liver dysfunction were excluded. The admission, lowest and subsequent blood pressures were recorded. Daily renal and liver function tests, including prothrombin times, were measured during the acute illness. RESULTS: Nineteen patients (1%) developed ischaemic hepatitis. The clinical picture was dominated by the causal condition, the commonest being left ventricular failure (12 patients). The mean fall in systolic, diastolic and mean blood pressures were 61, 44 and 48 mm Hg, respectively. Within 3 days the alanine aminotransferase increased to more than 5 times normal and there were marked elevations of the lactic dehydrogenase. In those who survived, the liver enzymes returned to normal within 7-22 days (mean 13). The prothrombin time was prolonged to >20 s in 6 patients (32%). Six patients died, 5 from left ventricular failure; the mean creatinine in 5 of those who died was 244 micromol/l (range 174-355) and in each the urea was >25 micromol/l. CONCLUSION: Ischaemic hepatitis is an uncommon but not rare condition in elderly patients admitted acutely to a Department of Geriatric Medicine. There was a dramatic rise in liver enzymes which in survivors returned to normal within 3 weeks. Clinical features were dominated by the causal condition and a third of the patients died.

Aged↗

Polymyositis associated with asymptomatic primary biliary cirrhosis.

We studied a 67-year-old female who suffered from polymyositis associated with primary biliary cirrhosis (PBC). Liver dysfunction was revealed by a screening test. Antimitochondrial antibodies (AMA) and antinuclear antibodies were positive. Liver biopsy was compatible with PBC (Scheuer stage I). Four years later she showed severe weakness and atrophy on her four extremities. Laboratory examination showed a creatinine kinase level of 312 IU/l, IgM 416 mg/dl, and AMA titer 1:320. Muscle biopsy findings were compatible with polymyositis. Electron microscopic examination disclosed diffuse increase of mitochondria in subsarcolemma and intermyofibrils, which has not been reported until now in polymyositis associated with PBC.

Aged↗

Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion.

Graft-versus-host disease (GVHD) of the liver is characterized by bile duct damage and portal lymphocytic infiltrate. We report acute hepatitislike presentation of GVHD after donor lymphocyte infusion (DLI). Between April 1998 and September 2001, 73 patients received 94 DLI treatments. Liver GVHD developed after DLI in 22 (30%) patients whose median age was 43 years (range, 21 to 61 years). Onset of liver dysfunction was at 35 days (range, 11 to 406 days) after DLI. Fifteen patients underwent liver biopsy, and the diagnosis of liver GVHD was confirmed in 13 (87%) patients. After viral hepatitis and recent drug exposure were excluded, 11 (50%) patients were given a diagnosis of a hepatitic variant of GVHD based on histologic evidence of lobular hepatitis (n = 5), elevation of maximum serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level more than 10 times the upper normal limit (n = 9), or both. There was a significant difference in maximum ALT (P =.002) and AST (P =.01) level between the hepatitic-variant and classical GVHD groups. GVHD progressed in 14 (64%) patients, and 10 patients died after a median follow-up of 221 days (range, 31-1284 days). These observations suggest that GVHD that occurs after DLI may have distinct clinical features. Hepatitic-variant GVHD should be considered in the differential diagnosis in DLI recipients with unexplained hepatitis.

Adult↗

CD8-positive T cell-induced liver damage was found in a patient with polymyositis.

We describe a case of polymyositis (PM) with liver injury that occurred in a patient with rheumatoid arthritis (RA). A 74-year-old woman who had a 12-year history of RA was admitted to our hospital because of muscle weakness and liver dysfunction. CD8-positive T cell infiltration was found in the interstitium of both the liver and muscle. In addition to the administration of a large amount of prednisolone (PSL), high-dose intravenous immunoglobulin (IVIG) successfully improved myositis and hepatitis. Our case indicates the pathogenic potential of CD8-positive T cells in PM-associated liver injury.

Aged↗