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Biomedical subjects

T D Schiano

Publications and source records attributed to T D Schiano.

At least 19 recordsLinked to original sources
PubMed2005

Identification of ultrastructural changes in liver allografts of patients experiencing primary nonfunction.

BACKGROUND: Primary nonfunction (PNF) after liver transplantation is fatal without timely retransplantation. PNF has been associated with many risk factors, but the etiology remains unknown in most cases. Using electron microscopy, we examined the hepatic ultrastructure of donor allografts in patients experiencing PNF and compared the findings with a well-matched group of other donor allografts. MATERIALS AND METHODS: Archival paraffin-embedded pre- and post-reperfusion donor liver biopsies were examined by electron microscopy in 10 patients with PNF and in 10 controls, matched by donor age +/- 5 years, gender, cold ischemic time +/- 1 hour, and donor cause of death. Mitochondria, endoplasmic reticulum, sinusoidal endothelial cells, and the glycogen content of the cells were assessed. The donors' serum peak transaminases, bilirubin and sodium levels, as well as the recipient age and serum creatinine were compared. RESULTS: There were no significant differences in recipient age at the time of transplantation, peak recipient serum creatinine, donor peak serum transaminase, sodium or bilirubin levels. In all cases, the endoplasmic reticulum and sinusoidal endothelial cells were ultrastructurally normal. Hepatocytes had variable degrees of glycogen pooling. Hepatic steatosis and intramitochondrial inclusions cells were present in 5/10 PNF compared to 0/10 controls patients on preperfusion liver biopsy (P = .17). CONCLUSION: Liver allografts from patients suffering from PNF can have mitochondrial ultrastructural changes on preperfusion biopsies.

Adult↗
PubMed2001

Results of steroid-based therapy for the hepatitis C-autoimmune hepatitis overlap syndrome.

OBJECTIVE: Overlap syndromes in which persons manifest clinical, histological, or immunological features of both hepatitis C infection and autoimmune hepatitis are well described. The discordant forms of treatment for hepatitis C and autoimmune hepatitis have made medical management of these patients difficult. We report our experience in using corticosteroids as first line therapy for the hepatitis C-autoimmune hepatitis overlap syndrome. METHODS: Seven patients with this overlap syndrome (diagnosis based on the presence of serum hepatitis C antibody by RIBA and serum hepatitis C RNA by polymerase chain reaction, and serum hypergammaglobulinemia, elevated ANA or ASMA titers, or histological findings consistent with autoimmune hepatitis) were treated with prednisone with or without azathioprine or cyclosporine, and followed for a median duration of 44.5 months. RESULTS: Five patients (71%) showed improvement of median serum ALT level from 162 U/L to 38 U/L (p = 0.04) and median serum gamma-globulin from 2.1 g/dl to 1.4 g/dl (p = 0.04) by 6 months of therapy. The mean modified histological activity index score also decreased from 11.4 +/- 2.5 to 6.6 +/- 2.6 (p = 0.04) by at least 1 yr of therapy. One patient discontinued prednisone while taking azathioprine and experienced a rebound elevation of serum ALT that did not respond to retreatment with prednisone. Antiviral therapy was subsequently administered and resulted in biochemical and virologic response. Hepatitis C virus RNA remained detectable in all other patients. CONCLUSION: Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis C-autoimmune overlap syndrome, resulting in appreciable biochemical and histological response but without viral eradication.

Adult↗
PubMed2000

Donor liver uridine diphosphate (UDP)-glucuronosyltransferase-1A1 deficiency causing Gilbert's syndrome in liver transplant recipients.

BACKGROUND: Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, has been attributed to two extra (TA) bases in the TATAA-box of the promoter region of its gene, where the A(TA)6TAA allele corresponds to the normal gene and A(TA)7TAA corresponds to a gene with reduced expression. Our aim was to determine whether isolated hyperbilirubinemia in liver transplant recipients was due to Gilbert's syndrome acquired through the liver allograft. METHODS: From 305 patients followed in our Liver Transplant Clinic, five patients with isolated unconjugated hyperbilirubinemia in the absence of hemolysis, recurrent viral hepatitis, and biliary tract pathology were identified; 10 other post-orthotopic liver transplantion patients with normal liver chemistry tests were randomly selected as a control group. DNA was extracted from paraffin-embedded liver allograft tissue and peripheral lymphocytes and was genotyped for the TA repeat at the uridine diphosphate glucononosyltransferase-lA1 promoter region by polymerase chain reaction and acrylamide gel electrophoresis. Homozygosity for the (TA)7 allele was considered diagnostic of Gilbert's syndrome. RESULTS: The mean serum total bilirubin level of the study patients was 2.28 mg/dl (range 1.8-3.0), consisting predominantly of the unconjugated form; that of the control patients was 0.76 mg/dl (range 0.4-1.1). The liver tissue from all five patients in the study group possessed the homozygous A(TA)7TAA genotype that was not observed in their lymphocytes. None of the liver tissue from the control patients demonstrated homozygosity for the A(TA)7TAA allele. CONCLUSION: Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, may be carried by the donor liver and present with isolated unconjugated hyperbilirubinemia in liver transplant recipients.

Adult↗
PubMed2000

Accuracy and significance of computed tomographic scan assessment of hepatic volume in patients undergoing liver transplantation.

BACKGROUND: A small liver volume is considered to be a poor prognostic factor in cirrhosis, often indicative of advanced liver disease. Radiologic assessment of liver volume before liver transplant is routinely performed in many transplant centers. We sought to assess the accuracy and significance of computed tomographic (CT) scanning in hepatic volumetric analysis by correlating CT-derived estimation of liver volume with that of corresponding liver explants. METHODS: A chart review of all patients aged 17 years or older undergoing liver transplant at Mount Sinai Medical Center between 1989 and 1995 was performed. Each patient underwent conventional CT scanning with measurement of liver volume (CTLV). Recipient liver volume (RLV) was defined as weight of liver explant after all attached ligaments, portal structures, and gallbladder were dissected free. Expected liver volume was calculated pretransplant based on age, gender, height, and weight. Patients were categorized into three groups based on etiology of liver disease: (1) hepatocellular (e.g., viral hepatitis, alcohol-related), (2) cholestatic (e.g., primary biliary cirrhosis), and (3) cryptogenic. The ratio of CTLV to RLV was used as a measure of the accuracy of CT volumetric analysis. RESULTS: A total of 579 patients was studied (group 1=376, group 2=139, group 3=64). All three groups were statistically similar with regard to age, prothrombin time and total bilirubin. Median CT liver volume was 1308 ml (range: 338-3847), 1651 ml (range: 641-3861), and 1210 ml (range: 348-2575) in groups 1-3, respectively; median ratio of CTLV to RLV was 1.02 (range: 0.50-2.31), 1.05 (range: 0.52-2.22), and 1.05 (range: 0.50-1.56) for groups 1-3, respectively. When RLV was small, it tended to be overestimated by CTLV. In contrast, when RLV was large, it was often underestimated. Clinical features such as history of esophageal variceal bleed, encephalopathy or ascites, and laboratory data did not influence accuracy of CT volumetric analysis. CONCLUSIONS: CT-derived estimation of liver volume appears to correlate closely with actual weight of liver explant regardless of the etiology of chronic liver disease. With extremes in CT volumetric analysis, actual liver volume tends to be under- or overestimated. For patients with end-stage liver disease, both CT-derived and actual liver volume are greater in cholestatic than in hepatocellular disorders.

Adolescent↗
PubMed2000

Alpha1-antichymotrypsin globules within hepatocytes in patients with chronic hepatitis C and cirrhosis.

Alpha1-antichymotrypsin (A1AC) is an acute phase serine protease inhibitor, similar to alpha1-antitrypsin (A1AT) in amino acid sequence. A1AT deficiency is known to be associated with emphysema and cirrhosis; deficiency of serum A1AC has been reported to be associated with emphysema, childhood asthma, and cryptogenic cirrhosis. The hepatocyte globules associated with A1AT deficiency have been well described; A1AC deficiency also has been reported to be associated with hepatocyte globules. The aim of this study was to describe the globules of A1AC and to compare them with A1AT globules. Immunohistochemistry for A1AC and A1AT was performed on liver biopsy specimens from 15 hepatitis C virus (HCV)-positive cirrhotic patients, 14 non-HCV cirrhotic patients, and 12 other patients with chronic hepatitis C but no cirrhosis, all of whom had known serum levels of A1AC; most had known serum levels of A1AT. Five of 15 HCV-positive cirrhotic patients, 1 of 14 non-HCV cirrhotic patients, and 1 of 12 noncirrhotic chronic hepatitis C patients had A1AC globules. Two of 15 HCV-positive cirrhotic patients and 2 of 14 non-HCV cirrhotic patients had A1AT globules. Histologically, the globules of A1AC were similar to those of A1AT but were smaller and fewer; the PAS/D stain was not as helpful for A1AC as it was for A1AT; immunohistochemistry was most useful. There was not a good correlation between serum levels of A1AC and its globules in hepatocytes. A1AC globules should be included in the differential diagnosis of hepatocyte inclusions.

Adult↗
PubMed2000

Portal hypertension and hepatopulmonary syndrome in a middle-aged man with hepatitis B infection.

A 55-year-old Turkish man with a history of chronic hepatitis B for 35 years, presented with incapacitating fatigue and worsening shortness of breath. He was hospitalized several times because of hepatic encephalopathy. He underwent liver transplantation for a clinical diagnosis of Child's C cirrhosis complicated by hepatopulmonary syndrome. The explanted liver, however, was not cirrhotic and demonstrated features of hepatoportal sclerosis. Although treatment for hepatoportal sclerosis is relief of portal hypertension; in rare cases such as in this patient with liver failure, liver transplantation is indicated.

Hepatitis B, Chronic↗
PubMed2000

Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease.

OBJECTIVE: Methotrexate is currently used as a treatment for refractory inflammatory bowel disease. This study sought to evaluate the hepatic effects of long-term methotrexate therapy in patients with inflammatory bowel disease and to determine whether the established guidelines for monitoring methotrexate-related hepatotoxicity with surveillance liver biopsy in patients with psoriasis or rheumatoid arthritis are applicable to these patients. METHODS: Thirty-two patients with inflammatory bowel disease receiving cumulative methotrexate doses of > or = 1500 mg were studied. Liver chemistry tests were obtained before and during therapy. Twenty patients underwent liver biopsies as recommended for methotrexate-treated patients with psoriasis; the biopsies were reviewed and graded according to Roenigk's criteria for methotrexate-induced hepatotoxicity (a grading system for methotrexate hepatotoxicity in psoriasis patients) by a liver pathologist blinded to the methotrexate dose. RESULTS: In patients who had liver biopsies, the mean cumulative methotrexate dose was 2633 mg (range, 1500-5410 mg), given for a mean of 131.7 wk (range, 66-281 wk). Nineteen of 20 patients (95%) had mild histological abnormalities (Roenigk's grade I and II), and one patient had hepatic fibrosis (Roenigk's grade IIIB). Abnormal liver chemistry tests, present in 6 of 20 (30%) patients, did not identify the patient with Roenigk's grade IIIB hepatotoxicity. CONCLUSIONS: Cumulative methotrexate doses up to 5410 mg given up to 281 wk in patients with inflammatory bowel disease are associated with little hepatotoxicity. Surveillance liver biopsies based on cumulative methotrexate doses are not warranted in these patients.

Adult↗
PubMed2000

Increased hepatic iron deposition resulting from treatment of chronic hepatitis C with ribavirin.

Increased levels of hepatic iron may impair the response of patients with chronic hepatitis C to treatment with interferon-alfa, but combination therapy with ribavirin has demonstrated efficacy in the treatment of hepatitis C. When used alone or with interferon-alfa, ribavirin may cause a dose-dependent reversible hemolytic anemia. We compared the extent and cellular localization of iron deposition in liver tissue from biopsy specimens obtained before and after 36 weeks of therapy with ribavirin or placebo for 59 patients with chronic hepatitis C. Paired slides were available for review from 26 ribavirin and 27 placebo recipients. Iron deposition was assessed using coded slides stained with Perls Prussian blue and was semi-quantitated in hepatocytes, Kupffer cells, and areas of fibrosis. The overall iron score fell by 0.96 in the placebo group and increased 1.69 in the ribavirin recipients. Iron was deposited mainly in hepatocytes; the hepatocyte iron score increased from 2.19 to 3.81 in the ribavirin group. The amount of iron staining in Kupffer cells declined in the placebo group and increased slightly in the ribavirin group. Iron changes in areas of fibrosis were minor and did not differ between groups. Increased total hepatic iron deposition occurred during a 9-month course of ribavirin. Ribavirin-associated hemolysis deposits iron preferentially in hepatocytes. This increased deposition of hepatic iron does not seem to affect the biochemical or histologic response to ribavirin therapy but may have implications for hepatocyte susceptibility to future injury.

Alanine Transaminase↗
PubMed2000

Correlation between increased colloid osmotic pressure and the resolution of refractory ascites after transjugular intrahepatic portosystemic shunt.

BACKGROUND: This study compared the changes in serum albumin, globulin, and colloid osmotic pressure (COP) before and after transjugular intrahepatic portosystemic shunt (TIPS) or large volume paracentesis (LVP) in patients with ascites. METHODS: Of 23 patients with refractory ascites, 17 had TIPS and 6 had LVP with infusion of albumin. Colloid osmotic pressure measurements were calculated, using the formula previously proposed by Hoefs: COP = A (1.058G + 0.163A + 3.11) where A = serum albumin and G = serum globulin. RESULTS: After 1 month, ascites resolved in 9 of the 17 patients who had TIPS and in none of the 6 who had LVP. Colloid osmotic pressure increased significantly in patients whose ascites resolved after TIPS. Colloid osmotic pressure did not change in the patients whose ascites did not resolve after TIPS, and COP decreased significantly in the LVP group. A statistically significant difference was found in the pre-TIPS COP measurements between those patients who had resolution of ascites and those who did not. A pre-TIPS COP of < or =20 mm Hg predicted resolution of ascites with an 88% sensitivity and a 78% specificity. CONCLUSIONS: Serum COP increased significantly in patients with resolution of ascites but remained unchanged in patients with persistent ascites after TIPS. Serum COP decreased after LVP. A statistically significant difference in the pre-TIPS COP was found between patients whose ascites resolved and patients having persistent ascites.

Adult↗
PubMed1999

Successful combined liver-heart transplantation in adults: report of three patients and review of the literature.

BACKGROUND: Three patients received liver/heart transplantation, and we report their successful outcome. METHODS: Two patients had alcoholic cirrhosis and dilated cardiomyopathy; one had cryptogenic liver disease and idiopathic cardiomyopathy. RESULTS: All patients had evidence of portal hypertension and coagulopathy. The cardiac transplants were performed first. Cardiopulmonary bypass was discontinued in favor of venovenous bypass, and liver transplantation was then performed. All patients developed acute tubular necrosis; two required a brief period of hemodialysis. There was only one episode of acute cellular rejection of the liver. Protocol endomyocardial biopsies in all three patients revealed no evidence of rejection. All patients are currently using low doses of immunosuppressive medications and have normal liver chemistry tests and cardiac function; two patients have mild renal insufficiency. CONCLUSION: In selected patients with severe cardiac dysfunction and advanced liver disease, liver/heart transplantation can be successfully performed even in the face of portal hypertension and coagulopathy.

Adult↗
PubMed1999

Rapidly progressive liver injury and fatal alcoholic hepatitis occurring after liver transplantation in alcoholic patients.

Alcohol-related liver disease (ALD) is a common indication for orthotopic liver transplantation (OLT) in adults. Although return to 'heavy drinking' post-OLT is believed to be uncommon, the prevalence and severity of alcohol-related liver injury in such patients is not well characterized. We retrospectively reviewed the records of 68 adult patients who underwent OLT for ALD to determine the incidence of return to heavy drinking and to assess their clinical outcome. Follow-up ranged from 8-99 months (mean 42) post-OLT; 54 patients were followed for > or = 12 months. Ten patients (15%) had evidence of coexisting viral hepatitis (hepatitis C in 9 and hepatitis B in 1) before OLT. Six of 68 patients (8%) returned to heavy drinking post-OLT, and three of those died of alcoholic hepatitis at nine months, 2.5 and 3.5 years after OLT. In two of these three patients, premortem liver biopsy showed histologic features of alcoholic hepatitis in addition to bridging fibrosis or cirrhosis. None of the three patients who died of ALD had coexisting viral hepatitis. Of the 57 patients surviving for > or = 3 months post-OLT, 4 of 8 patients (50%) with steatosis and Mallory bodies in their native livers returned to heavy drinking compared to only 2/49 (4%) without these histologic findings (P<0.05). In conclusion, the incidence of heavy drinking post-OLT was uncommon, however, it was associated with fatal alcoholic hepatitis in 50% of patients. Rapidly progressive alcohol-related liver injury was seen even in the absence of coexisting viral hepatitis. The presence of steatosis and Mallory bodies in the native liver, which suggests recent or ongoing alcohol-related liver injury, predicted a return to heavy drinking post-OLT.

Adult↗
PubMed1999

Absence of hepatitis G virus within liver tissue of patients undergoing liver transplantation for cryptogenic cirrhosis.

BACKGROUND: Epidemiological studies have detected up to a 9% incidence of hepatitis G (HGV)-RNA in patients with acute and chronic liver disease of unknown etiology. We sought to clarify the role of HGV as a causative agent in cryptogenic cirrhosis by analyzing archival liver tissue for HGV-RNA in patients undergoing orthotopic liver transplantation. METHODS: Using a computer database, we identified 54 patients who underwent orthotopic liver transplantation for cryptogenic cirrhosis. After using rigorous serologic and histopathologic screening guidelines, 20 patients were studied, 7 of whom had concurrent hepatocellular carcinoma (HCC). RNA was extracted from archival paraffin-embedded liver tissue; HGV sequences were amplified by nested reverse transcription-polymerase chain reaction using primers designed from the 5' noncoding region. RESULTS: HGV-RNA was absent from all 20 liver specimens, including those 7 with HCC. Beta-actin RNA, used as a positive control for cellular RNA, was isolated from all 20 liver specimens, including the 7 with HCC. CONCLUSIONS: Utilizing a highly sensitive reverse transcription-polymerase chain reaction assay for HGV-RNA, we were unable to detect HGV-RNA within the livers of patients with cryptogenic cirrhosis or in the HCC arising within them. This lends further evidence to HGV infection not being a cause of cryptogenic cirrhosis and not being associated with the development of HCC in cryptogenic cirrhosis.

Actins↗
PubMed1999

Hereditary hemochromatosis in liver transplantation.

A candidate gene, HFE, was recently described in patients with hereditary hemochromatosis (HH) and found to contain a missense mutation leading to a cysteine to tyrosine substitution (C282Y). A second mutation, H63D, was also found in the gene. This study was undertaken to determine the HFE genotype in liver transplant recipients clinically diagnosed with HH and those incidentally found to have increased iron deposition in their explanted livers and to evaluate whether biochemical or histological hepatic iron indices (HIIs) correlated with homozygosity for the C282Y mutation. We identified 15 patients clinically diagnosed with various liver disorders other than HH who had increased liver iron deposits among 918 adult patients who underwent liver transplantation from 1988 to 1995. Four additional patients were clinically diagnosed as having HH. Archival explant liver tissue was evaluated for the histological HII according to the method of Deugnier et al, in which an index greater than 0.15 suggests homozygosity for HH. The HII was computed according to established methods, with a value greater than 1.9 suggesting homozygosity for HH. A portion of liver tissue was subjected to DNA genotyping using polymerase chain reaction-amplified products. Two of 4 patients with clinically suspected HH were homozygous for C282Y, and 2 patients had neither mutation. One of the 15 patients not suspected to have HH was a C282Y homozygote, 1 was a C282Y heterozygote, 6 were H63D heterozygotes, and 7 had neither mutation. The histological HII was consistent with HH in 13 patients, whereas the HII was consistent with HH in 6 patients. Thus, in patients with end-stage liver disease, despite fulfilling the established clinical criteria for HH using biochemical and histological parameters, only a minority of patients were homozygous for the C282Y mutation. Hepatic iron overload may result from other causes, and in end-stage liver disease, an elevated HII may not accurately predict HH. Other factors that either control or lead to iron absorption may explain iron overload in these patients.

Adult↗
PubMed1999

High-resolution endoluminal sonography assessment of the hematocystic spots of esophageal varices.

BACKGROUND: Many variables are associated with an increased potential for esophageal variceal rupture, especially the presence of hematocystic spots and other red signs on upper endoscopy. The etiology of hematocystic spots is unknown. High-resolution endoluminal sonography has been shown to be an accurate and sensitive imaging modality for detection, as well as the qualitative and quantitative assessment of esophageal varices. Because the high-resolution endoluminal sonography transducer permits detailed resolution of submucosal structures thereby allowing more precise examination of the actual wall of the varix, we sought to image variceal hematocystic spots in an effort to better define their anatomy. METHODS: Simultaneous upper endoscopy and high-resolution endoluminal sonography were performed in 68 patients with cirrhosis. Endoscopy was performed as part of screening for varices during evaluation for liver transplantation or in patients with previous presumed variceal bleeding. On endoscopy and high-resolution endoluminal sonography, two independent reviewers identified the same 10 patients having esophageal varices with hematocystic spots. The patients who had bled from their varices had not received prior endoscopic treatment. RESULTS: Hematocystic spots as seen with high-resolution endoluminal sonography imaging appeared as saccular aneurysm like projections on the variceal surface in 6 of 10 patients. Four of six patients would later have recurrent bleeding; two of these patients were again noted to have hematocystic spots on endoscopy with a similar corresponding high-resolution endoluminal sonography appearance. Patients without hematocystic spots did not have similar high-resolution endoluminal sonography imaging. CONCLUSION: Aneurysm-like projections in the wall of varices may represent focal weaknesses of the variceal wall and thus play a role in the pathophysiology of esophageal variceal rupture. The present findings may help to explain why there is an increased risk of variceal hemorrhage associated with the presence of hematocystic spots on esophageal varices.

Endoscopy, Digestive System↗
PubMed1999

Recurring fibro-obliterative venopathy in liver allografts.

Recurrent diseases in liver allografts are not uncommon. These occur most frequently in those transplanted for viral hepatitis B and C. We report an unusual case of recurrent process in two consecutive liver allografts received by a 37-year-old woman, who previously had an unremarkable past medical history but developed a rapidly progressive cholestatic liver failure. Histopathologic examination of the native liver showed fibroocclusive lesions of both terminal hepatic venules and portal vein branches. The exuberant fibroobliterative process created dense fibrosis with whorled appearance, and broad fibrous septa connecting adjacent central areas, and sometimes bridging portal to central areas. Dense portal fibrosis resulted in compression atrophy and loss of bile ducts. The first allograft, which failed within 3 months, showed histopathologic findings similar to that of the native liver. A liver biopsy that was performed 20 months after the second liver transplant again showed similar histopathology. The histopathologic features and clinical presentation of this patient suggest an unusual form of recurring progressive fibroobliterative venopathy causing liver failure.

Adult↗
PubMed1999

Fulminant hepatic failure secondary to malignant melanoma: case report and review of the literature.

Malignant melanoma has a propensity to metastasize widely to many organs, involving the liver in up to one-third of cases. Fulminant hepatic failure is an unusual presentation of hepatic neoplasms, whether primary or metastatic. We describe a case of malignant melanoma with liver metastases that rapidly progressed to fulminant hepatic failure and death. Striking elevations of liver tests, particularly lactate dehydrogenase, were seen. Liver biopsy showed diffuse intrasinusoidal infiltration with melanoma cells. In patients with malignant melanoma, raised serum lactate dehydrogenase levels may suggest hepatic involvement, with extreme elevations possibly predictive of liver failure.

Hepatic Encephalopathy↗