Congenital Liver Disease Research Articles

Surveillance of epstein-barr virus loads in adult liver transplantation: Associations with age, sex, posttransplant times, and transplant indications

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication after adult orthotopic liver transplantation (AOLT). Besides EBV and immunosuppression, relatively little is known about the pretransplant clinical parameters associated with the risk of PTLD, and the benefit of using EBV surveillance to predict EBV-associated disease in AOLT patients is uncertain. The aims of this single-center study were to monitor EBV viral loads (VLs) in AOLT patients and to investigate any associations with age, sex, cytomegalovirus (CMV) serostatus, posttransplant times, and indications for transplantation. 1275 blood samples that were collected from 197 AOLT patients 1 day to more than 15 years after transplantation were investigated with quantitative polymerase chain reaction for EBV and CMV DNA. Seventy-two percent of the patients had EBV DNAemia less than 100 days after transplantation without clinical manifestations. No association was observed between the EBV copy numbers and the time since transplantation. EBV DNAemia was weakly associated with male sex but was not associated with age, CMV serostatus, or indications for AOLT. The highest EBV VL levels were observed in patients who presented with congenital liver diseases, whereas patients with viral hepatitis maintained high EBV VLs after transplantation. None of the patients developed PTLD during the study period; however, 3 patients presented with EBV-associated diseases. In conclusion, EBV DNAemia is common in AOLT patients, and routine EBV surveillance has limited value for predicting EBV-associated morbidity or mortality.

The utility of uric acid assay in dogs as an indicator of functional hepatic mass

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.

Congenital fibrocystic liver diseases

Fibrocystic diseases affecting the liver and often also other organs like the kidneys are a clinically and genetically heterogeneous group of disorders that may present in utero or remain clinically silent into late adulthood. During recent years, substantial progress has been made in unravelling the aetiology with primary cilia playing a central pathogenic role in many if not all of these diseases. The fibrocystogenic process shares some common features including proliferation and dilatation of epithelial bile ducts with concomitant abnormal apoptosis, fluid secretion and extracellular matrix deposition. In this review, we summarise clinical and diagnostic aspects, mechanisms of hepatic cystogenesis, and recent knowledge on potential therapies for these conditions.

Hepatocellular carcinoma in two patients with cardiac cirrhosis

Hepatocellular carcinoma has been commonly associated with multiple etiologic factors including hepatitis B and C, alcoholic liver disease, and more rarely congenital metabolic liver diseases. 'Cardiac cirrhosis' is the cirrhosis resulting from prolonged passive liver venous congestion secondary to right-sided congestive heart failure; hepatocellular carcinoma is a rarely reported outcome. In this study we present two female patients with congenital heart defects treated with the Fontan procedure who survived into their third decade, and developed hepatocellular carcinoma in the setting of cardiac cirrhosis. The Fontan procedure diverts blood from the inferior vena cava and superior vena cava to the pulmonary arteries, thereby increasing survival in infants born with a single effective ventricle. As such patients live longer, however elevated pulmonary and right-sided heart pressures cause chronic passive liver congestion and eventual cardiac cirrhosis. The two patients in this study had no risk factors for hepatocellular carcinoma other than cardiac cirrhosis secondary to their prolonged survival after their Fontan procedure. In conclusion, we suggest that cardiac cirrhosis may be a risk factor for developing hepatocellular carcinoma and recommend close follow-up and hepatocellular carcinoma screening for patients with known right heart failure and passive hepatic congestion.

New school in liver development: Lessons from zebrafish #

There is significant overlap in the genes and pathways that control liver development and those that regulate liver regeneration, hepatic progenitor cell expansion, response to injury, and cancer. Additionally, defects in liver development may underlie some congenital and perinatal liver diseases. Thus, studying hepatogenesis is important for understanding not only how the liver forms, but also how it functions. Elegant work in mice has uncovered a host of transcription factors and signaling molecules that govern the early steps of hepatic specification; however, the inherent difficulty of studying embryogenesis in utero has driven developmental biologists to seek new systems. The rapidly developing vertebrate zebrafish is a favorite model for embryology. The power of forward genetic screens combined with live real-time imaging of development in transparent zebrafish embryos has highlighted conserved processes essential for hepatogenesis and has uncovered some exciting new players. This review presents the advantages of zebrafish for studying liver development, underscoring how studies in zebrafish and mice complement each other. In addition to their value for studying development, zebrafish models of hepatic and biliary diseases are expanding, and using these small, inexpensive embryos for drug screening has become de rigueur. Zebrafish provide a shared platform for developmental biology and translational research, offering innovative methods for studying liver development and disease. The story of hepatogenesis has something for everyone. It involves transcriptional regulation, cell-cell interaction, signaling pathways, control of cell proliferation and apoptosis, plus morphogenic processes that sculpt vasculature, parenchymal cells, and mesenchyme to form the multifaceted liver. Decades of research on liver development in mice and other vertebrates offer valuable lessons in how the multipotent endoderm is programmed to form a functional liver. Of equal importance are insights that have illuminated the mechanisms by which hepatic progenitors are activated in a damaged liver, how the adult liver regenerates, and, possibly, the basis for engineering liver cells in vitro for cell transplantation to sustain patients with liver failure. Moreover, processes that are key to liver development are often co-opted during pathogenesis. Therefore, reviewing hepatogenesis is informative for both basic and translational researchers. In this review, we bring to light the many advantages offered by the tropical freshwater vertebrate zebrafish (Danio rerio) in studying hepatogenesis. By comparing zebrafish and mice, we highlight how work in each system complements the other and emphasize novel paradigms that have been uncovered using zebrafish. Finally, we highlight exciting efforts using zebrafish to model hepatobiliary diseases.

Pediatric liver transplantation in 31 consecutive children

Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Thirty-one children (< or = 18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively. The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The early postoperative management is the key to success. Postoperative bile leak was common, but most patients underwent liver transplantation had a better prognosis.

Mortality in Women with Turner Syndrome in Great Britain: A National Cohort Study

Turner syndrome is characterized by complete or partial X chromosome monosomy. It is associated with substantial morbidity, but mortality risks and causes of death are not well described. Our objective was to investigate mortality and causes of death in women with Turner syndrome. We constructed a cohort of women diagnosed with Turner syndrome at almost all cytogenetic centers in Great Britain and followed them for mortality. A total of 3,439 women diagnosed between 1959-2002 were followed to the end of 2006. Standardized mortality ratios (SMRs) and absolute excess risks were evaluated. In total, 296 deaths occurred. Mortality was significantly raised overall [SMR = 3.0; 95% confidence interval (CI) = 2.7-3.4] and was raised for nearly all major causes of death. Circulatory disease accounted for 41% of excess mortality, with greatest SMRs for aortic aneurysm (SMR = 23.6; 95% CI = 13.8-37.8) and aortic valve disease (SMR = 17.9; 95% CI = 4.9-46.0), but SMRs were also raised for other circulatory conditions. Other major contributors to raised mortality included congenital cardiac anomalies, diabetes, epilepsy, liver disease, noninfectious enteritis and colitis, renal and ureteric disease, and pneumonia. Absolute excess risks of death were considerably greater at older than younger ages. Mortality in women with Turner syndrome is 3-fold higher than in the general population, is raised for almost all major causes of death, and is raised at all ages, with the greatest excess mortality in older adulthood. These risks need consideration in follow-up and counseling of patients and add to reasons for continued follow-up and preventive measures in adult, not just pediatric, care.

DOUBLE HOMOZYGOSITY FOR MUTATIONS OF AGL AND SCN9A MIMICKING NEUROHEPATOPATHY SYNDROME

Congenital indifference to pain (CIP, MIM #243000) is rare (<30 cases reported). We describe a consanguineous family from Egypt with the index patient displaying lesions typical of CIP. In addition, he had short stature, myopathy, and liver dysfunction—a combination typical of Navajo neurohepatopathy (NNH, MIM #256810). No mutation was found in MPV17 , the gene primarily involved in NNH.1 Pain perception was normal in a sister with congenital liver disease. Detailed genetic and clinical investigation revealed two separate rare disorders in the index patient, glycogen storage disease type 3 (GSD III; MIM #232400) and CIP, based on homozygous mutations in the genes AGL and SCN9A . ### Case report. The index patient (IV-10, age 11 years) and his sister (IV-11, age 1 year 10 months) underwent detailed clinical assessment. Starting at 2 years of age, IV-10 developed frequent painless fractures of legs and arms, bruises, cuts, and abdominal enlargement. On recent examination, he had short stature (<3 SD), corneal ulcerations, self-mutilative injuries of lips, skin, and fingers, and limb deformities due to untreated fractures (figure). There was mild hypotonia in lower limbs, flexors of hips and trunk muscles, and hypesthesia in both arms. Liver enzymes (AST: 260 U/L, ALT: 607 U/L), creatine phosphokinase (CPK: 341 U/L), and serum triglycerides (214 mg%) were markedly elevated. Generalized decrease of bone density was noted (dual energy X-ray absorptiometry). Hepatosplenomegaly, hepatocyte swelling, and periportal fibrosis were consistent with GSD (ultrasonography, …

Significance and specificity of vascular anastomosis in liver transplantation: Our experience

Transplantation is the method of choice in the treatment of terminal liver diseases with acute and structural damage of liver tissue and congenital liver diseases. The aim of our study was to determine specificity and significance of vascular anastomosis in liver transplantation by postoperative evaluation of vascular anastomosis function. The study included 16 patients with 16 liver transplantations and one re-do liver transplantation. In all patients, preoperative angiography and postoperative duplex sonographic and angiographic evaluation of vascular anastomosis were performed. Preoperative angiographic evaluation did not reveal anomalies in liver blood vessels of transplant candidates. In one patient, we identified and angiographically confirmed stenosis on anastomosis of the hepatic artery on the 7th postoperative day. In another patient, we had artificial thrombosis of the hepatic artery branch due to the liver biopsy. The successful performance of vascular anastomosis in liver transplantation is significant for adequate liver graft perfusion, good postoperative graft function and overall outcome of the liver transplantation.

Management of a cadaveric orthotopic liver transplantation in a pediatric patient with complex congenital heart disease

Pediatric orthotopic liver transplantations (OLT) are commonly performed nowadays. Two primary reasons for OLT in children are complications from either extrahepatic biliary atresia (EHBA) or inborn errors of metabolism. However, congenital liver disease may be associated with significant other congenital abnormalities. We present a case of a successful OLT in a pediatric patient with a history of EHBA, situs inversus, and complex congenital heart disease. The cardiac anomalies include dextrocardia, absence of the atrial septum (single atrium), single atrioventricular valve (a-v canal), and an incomplete ventricular septum. Prior surgery include a Kasai procedure for EHBA, banding of the proximal main pulmonary artery, and Broviac catheter placement. We present the anesthesia concerns and management for this complicated case.

Successful Treatment of UGT1A1 Deficiency in a Rat Model of Crigler–Najjar Disease by Intravenous Administration of a Liver-Specific Lentiviral Vector

Treatment of congenital and acquired liver disease is one of the main issues in the field of gene therapy. Self-inactivating lentiviral vectors have several potential advantages over alternative systems. We have constructed a self-inactivating lentiviral vector (LV-ALBUGT) that expresses the human bilirubin UDP-glucuronosyltransferase (UGT1A1) from a liver-specific promoter. UGT1A1 is involved in the clearance of heme metabolites in the liver. This enzyme is deficient in Crigler–Najjar disease, a recessive inherited disorder in humans characterized by chronic severe jaundice, i.e., high plasma bilirubin levels. Gunn rats suffer from the same defect and are used as an animal model of this disease. We have treated juvenile Gunn rats by single intravenous injection with the LV-ALBUGT vector. Over 1 year after treatment with the highest dose (5 × 108 transducing units), we observed a stable reduction of bilirubin levels to near normal levels and normal secretion of bilirubin conjugates in the bile, in contrast to untreated animals. In situ hybridization showed expression of the therapeutic gene in more than 30% of liver parenchymal cells. Thus, we demonstrate stable and complete clinical remission of a congenital metabolic liver disease in an animal model, after systemic administration of a therapeutic lentiviral vector.

Analysis of some clinical and laboratory aspects of adolescent patients with thrombosis

A total of 360 pediatric patients aged 1 month to 18 years were diagnosed as having thrombosis between January 1998 and April 2003. Of these patients, those aged 11-18 years (n=131) were regarded as adolescents and the rest as children. The proportion of adolescents in the whole group excluding the neonates was 36%. The peak age of diagnosis in adolescents was 11-14 years, comprising 58% of all thrombotic events in adolescents. In 73% of the adolescents, there was at least one risk factor. The four most common underlying disorders were infection, malignancy, connective tissue and cardiac disorders, in decreasing order of frequency. In children, on the other hand, infection was followed by congenital heart disease, malignancy and liver disease. Three common types of thrombosis in adolescents were deep venous thrombosis, cerebro-vascular events and portal venous thrombosis, while cerebro-vascular events were the most common in children. The frequency of factor V G1691A mutation in the adolescents (22.1%) was significantly higher than that found in a group of healthy controls (7.4%) and this mutation was associated with a 3.6-fold increase in the risk of developing thrombosis (95% confidence interval, 1.4-9.0). The carrier frequency of prothrombin G20210A mutation (3.1%) in adolescents did not differ significantly from that of the healthy population (2.3%) and no association was observed between this mutation and a risk of developing thrombosis in this group (odds ratio, 1.3; 95% confidence interval, 0.2-7.5). The rate of recurrent thrombosis was 6%.

O0008 SUCCESSFUL TREATMENT OF CRIGLER-NAJJAR DISEASE BY INTRAVENOUS APPLICATION OF A LIVER-SPECIFIC LENTIVIRAL VECTOR IN A RAT MODEL.

Introduction: Treatment of congenital and acquired liver disease is one of the main issues in the field of gene therapy. HIV-1 derived lentiviral vectors of the latest generation have several potential advantages over alternative systems. We have tested such a vector in a rat model (Gunn rat) of Crigler-Najjar disease (CN). CN is a recessive inherited disorder in humans characterized by chronic severe jaundice. CN is caused by mutations in the bilirubin UDP glycosyltransferase gene (hUGT1A1) that is involved in the clearance of heme metabolites in the liver. Present treatment by light therapy is cumbersome and insufficient. The only known effective remedy is liver transplantation, which requires high-risk surgery and cyclosporin treatment. Therefore, gene therapy is considered as an alternative. Methods: We have constructed and produced a self-inactivating VSV-G pseudotyped lentiviral vector LV ALBUGT, which is designed to express the human UGT1A1 gene specifically in liver parenchymal cells. Juvenile Gunn rats were treated with this preparation by intravenous injection (108–109 transforming units). Results: Eight weeks after treatment with the highest vector dose we observed a complete normalisation of bilirubin levels, and normal secretion of bilirubin conjugates in the bile, in contrast to untreated animals. In situ hybridisation showed expression of the therapeutic gene in up to thirty percent of liver parenchymal cells. No adverse effects, such as transient inflammation morbidity or mortality, were observed. Conclusion: To our knowledge this is the first demonstration in an animal model of complete remission of a congenital liver disease, after systemic application of a lentiviral vector. These encouraging results suggest that clinical application of this vector would be feasible

Lathosterolosis, a Novel Multiple-Malformation/Mental Retardation Syndrome Due to Deficiency of 3β-Hydroxysteroid-Δ 5-Desaturase

We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis.

Nutritional Management of Neonatal and Infant Liver Disease

After completing this article, readers should be able to: 1. Describe the caloric requirements of a neonate who has chronic liver disease. 2. Identify the vitamin and mineral deficiencies associated with cholestasis and the methods used to correct these deficits. 3. Describe the relationship between total parenteral nutrition and the development of chronic liver disease. 4. Delineate the relationship between malnutrition at the time of liver transplantation and subsequent morbidity and mortality. 5. List the best measurements of nutrition assessment in infants who have chronic liver disease. The liver is involved in many of the body’s metabolic processes, including: regulation of protein, fat, and carbohydrate metabolism; vitamin storage and activation; and detoxification and excretion of waste products. The healthy liver synthesizes and excretes bile salts. With cholestatic liver diseases, poor bile flow results in fat malabsorption because micelles, which solubilize long-chain fatty acids, cannot form without bile salts. Fat malabsorption results in enteric losses of the fat-soluble vitamins A, D, E, and K. Impaired liver function can lead to nutrient deficiencies and eventually protein-energy malnutrition. All of these factors, combined with the common symptoms of anorexia and poor dietary intake, make malnutrition common in chronic liver disease, particularly if it occurs in infants, who are more vulnerable to the debilitating effects of malnutrition because of their higher energy and growth requirements. A wide range of deficits occurs in most chronic liver diseases of children (Table 1⇓ ). Malnutrition itself may induce further derangements of liver function because the liver requires energy for a number of synthetic, storage, and detoxification functions. View this table: Table 1. Nutritional Risk Factors in Acute and Chronic Liver Disease The need for aggressive, early nutrition support in neonates has been well established and discussed extensively. Some centers routinely use a “standardized” approach to nutrition support; we use a “tailored” approach that entails parenteral or …

Expression of neural cell adhesion molecule in human liver development and in congenital and acquired liver diseases.

In the liver, neural cell adhesion molecule (NCAM) is a marker of immature cells committed to the biliary lineage and is expressed by reactive bile ductules in human liver diseases. We investigated the possible role of NCAM in the development of intrahepatic bile ducts and aimed at determining whether immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases. Therefore, we performed immunohistochemistry for NCAM and bile duct cell markers cytokeratin 7 and cytokeratin 19 on frozen sections of 85 liver specimens taken from 14 fetuses, 10 donor livers, 18 patients with congenital liver diseases characterized by ductal plate malformations (DPMs), and 43 cirrhotic explant livers. Duplicated ductal plates and incorporating bile ducts during development showed a patchy immunoreactivity for NCAM, while DPMs were continuously positive for NCAM. Bile ducts showing complete or patchy immunoreactivity for NCAM were found in cirrhotic livers, with higher frequency in biliary than in posthepatitic cirrhosis. Our results suggest that NCAM may have a function in the development of the intrahepatic bile ducts and that NCAM-positive immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases.

Transplantation of isolated hepatocytes and their role in extrahepatic life support systems.

Transplantation of isolated hepatocytes for the replacement of liver function and the use of isolated hepatocytes as a bridge-to-transplantation in extrahepatic bioartificial liver support devices offer important therapeutic advances for treating severe liver disease. Progress in cell biology, tissue culture techniques and biotechnology have led the way for the potential therapeutic use of isolated hepatocytes in a wide array of liver disorders. Transplanted hepatocytes show considerable promise of performing the full range of liver functions in several animal models of liver disease, ranging from fulminant hepatic failure to congenital metabolic liver disease. Recently, several interesting designs for extrahepatic liver support systems have been proposed. Although there is no current consensus on its eventual design configuration, the hollow fiber hepatocyte bioreactor design has the greatest potential for therapeutic benefit.

Improved function of microencapsulated hepatocytes in a hybrid bioartificial liver support system.

Conventional methods of microencapsulating isolated hepatocytes with Type I collagen matrix have provided metabolic liver support in experimental animal models of acute liver failure and congenital metabolic liver disease. We compared the biological function of transplanted microencapsulated hepatocytes cultured on standard Type I collagen (Vitrogen) and a commercially available liver basement-membrane-like extract from a mouse sarcoma (Matrigel). Isolated hepatocytes were microencapsulated with Matrigel and Vitrogen within an alginate-poly-L-lysine composite membrane. Isolated encapsulated hepatocytes (IEH) were transplanted intraperitoneally into homozygous Gunn rats that exhibit congenital hyperbilirubinemia. Control Gunn rats received empty or no microcapsules. Total serum bilirubin and conjugated bilirubin in bile were measured at weekly intervals for one month. Significant (p < 0.01) decreases in total serum bilirubin were observed in all IEH transplanted animals. No such decrease was seen in control animals. Gunn rats that received Matrigel had significantly (p < 0.05) lower serum bilirubin values and significantly (p < 0.05) higher conjugated bilirubin in bile than those that received Vitrogen. We conclude that hepatocytes microencapsulated with Matrigel functioned better than those with Vitrogen. This improved in vivo biological response underscores the importance of using the appropriate cell attachment substratum to enhance the function of a hybrid bioartificial liver support system based on transplanted hepatocytes.

Repeated transplantation of microencapsulated hepatocytes for sustained correction of hyperbilirubinemia in Gunn rats.

In previous studies we demonstrated that transplantation of microencapsulated hepatocytes could correct congenital hyperbilirubinemia in Gunn rats for 4 to 6 wks. Reduction in hyperbilirubinemia followed a single transplantation of isolated encapsulated hepatocytes (IEH). After 4 to 6 wks of transplantation IEH gradually lose their functionality. To sustain long-term supplementation of liver function we have investigated the efficacy of monthly IEH transplantation for 6 mo. Hepatocytes, isolated from young Wistar rats, were microencapsulated with a collagen matrix within an alginate-poly L-lysine composite membrane. We transplanted IEH intraperitoneally into homozygous Gunn rats at monthly (4-wk) intervals for 6 mo. Control Gunn rats received intraperitoneal transplantations of empty microcapsules. Total serum bilirubin was measured in the IEH-transplanted and control Gunn rats at weekly intervals for the duration of the 6-month study. A significant (p < 0.01) and sustained decrease (by nearly 50%) in total serum bilirubin levels was observed following monthly IEH transplantations in Gunn rats for the duration of the study. No such decrease in total serum bilirubin levels was seen in the controls. The Gunn rats exhibited good tolerance for the multiple IEH transplantations. Thus, repeated IEH transplantation may be one strategy for providing long-term supplementation of liver function in congenital metabolic liver disease.

Gray scale ultrasonographic evaluation of hepatic cystic disease

Eight patients with various forms of hepatic cystic disease studied with gray scale ultrasonography are described. Four had solitary cysts, two had multiple simple liver cysts, and two had congenital polycystic liver and kidney disease. The spectrum of ultrasonographic features in benign cystic disease of the liver is discussed. All eight patients were felt to have malignant disease in the liver prior to ultrasonographic evaluation. The value of gray scale ultrasound as a noninvasive means of differentiating cystic disease from suspected metastatic disease is emphasized.