bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis C in Hiv–Infected Patients With and Without Aids: Prevalence and Relationship to Patient Survival
Authors: Wright Teresa L. , Hollander Harry , Pu Xiang , Held Michael J. , Lipson Peter , Quan Stella , Polito Alan , Thaler Michael M. , Bacchetti Peter , Scharschmidt Bruce F.
Published: March 2007

Background:

Limited information is available about the prevalence of hepatitis C virus in patients with human immunodeficiency virus in relation to specific risk factors or about the influence of hepatitis C virus coinfection on survival. This retrospective study addressed these questions.

Methods:

The study population consisted of 512 predominantly non–intravenous drug–using male homosexuals, 224 of whom had AIDS. Samples positive for hepatitis C virus antibody by second–generation enzyme immunoassay were further tested by means of strip immunoblot assay, and for hepatitis C virus RNA by means of polymerase chain reaction amplification. A randomly selected set of enzyme immunoassay–negative samples was also tested for hepatitis C virus RNA and, if hepatitis C virus RNA positive, by a second–generation recombinant immunoblot assay.

Results:

The prevalence of hepatitis C virus infection unaccounted for by intravenous drug use or transfusion was 11.7% by enzyme immunoassay, and 87% of sera positive by enzyme immunoassay were also positive by second–generation recombinant immunoblot assay or hepatitis C virus RNA analysis. Hepatitis C virus RNA was detectable in 53% of enzyme immunoassay–positive samples but in only about 1% of enzyme immunoassay–negative samples. Hepatitis C virus coinfection did not influence survival of HIV–infected patients with or without manifestations of AIDS.

Conclusions:

Hepatitis C virus infection in nontransfused, non–intravenous drug–using patients with HIV infection is several times more prevalent than in volunteer blood donors, suggesting homosexual transmission of hepatitis C virus. About half of patients seropositive for hepatitis C virus antibody have detectable hepatitis C virus RNA, and serologically occult hepatitis C virus viremia is rare. Hepatitis C virus coinfection does not appear to adversely influence survival. (Hepatology 1994;20:1152-1155).
Hepatic Preneoplasia in Hepatitis B Virus Transgenic Mice
Authors: Toshkov Iljia , Chisari Francis V. , Bannasch Peter
Published: March 2007

Hepatocarcinogenesis in hepatitis B virus transgenic mice was studied by means of a correlative cytomorphological and cytochemical approach at different time points in animals from 1 to 34 mo old. HBsAg–positive ground–glass hepatocytes emerged throughout the liver parenchyma in nearly all transgenic mice during the first 4 mo after birth. The panlobular expression of HBsAg persisted until foci of altered hepatocytes appeared (6 to 9 mo of age). Three different types of foci of altered hepatocytes-namely, glycogen–storage foci, mixed cell foci and glycogen–poor foci-developed. Hepatocellular adenomas and carcinomas appeared after 11 mo. Orcein staining revealed frequent transitions between ground–glass hepatocytes extensively expressing HBsAg and glycogen–storage (predominantly clear–cell) foci containing HBsAg–positive cytoplasmic components. Similar transitions between ground–glass hepatocytes and glycogenotic (clear) cells were often found in diffuse parenchymal glycogenosis at 11 or 12 mo. Remnants of HBsAg–positive material were also detected in mixed cell foci, glycogen–poor diffusely basophilic cell foci, hepatic adenoma and hepatocellular carcinoma. These findings suggest that ground–glass hepatocytes are the direct precursor of foci of altered hepatocytes and their neoplastic descendants. The extensive expression of HBsAg is gradually down–regulated during neoplastic transformation, just as the morphological the biochemical phenotypes of foci of altered hepatocytes, hepatic adenoma and hepatocellular carcinoma in transgenic mice resemble those described in chemical heterocarcinogenesis. The predominant sequence of cellular changes leading from glycogen–storage (predominantly clear cell) foci to mixed cell foci, hepatic adenoma and hepatocellular carcinoma is characterized by a gradual decrease in the activities of glycogen synthase, phosphorylase, glucose–6–phosphatase and adenylate cyclase, whereas glucose–6–phosphate dehydrogenase and pyruvate kinase activities increase. These alterations indicate a shift from the glycogenotic state toward an increase in the pentose phosphate pathway and glycolysis. (Hepatology 1994;20:1162-1172).
Hereditary Tyrosinemia Type I: A New Clinical Classification With Difference in Prognosis on Dietary Treatment
Authors: Van Spronsen Francjan J. , Thomasse Yolande , Smit Peter G.A. , Leonard James V. , Clayton Peter T. , Fidler Vaclav , Berger Ruud , Heymans Hugo S.A.
Published: March 2007

Hereditary tyrosinemia type I (McKusick 27670) is a heterogeneous disease with poor prognosis, yet there are few reports of the long–term prognosis. It is therefore difficult to decide on the treatment for individual patients. We have conducted an international survey of patients with tyrosinemia type I and examined the probability of survival on dietary treatment and the causes of death in 108 patients with tyrosinemia type I. The survival after the onset of symptoms varied with the age at onset; the earlier the symptoms developed the poorer the outlook. Liver failure and recurrent bleeding (67%), hepatocellular carcinoma (17%) and the porphyria–like syndrome with respiratory failure (10%) were the most common causes of death. The 1–and 2–yr survival probability after the onset of symptoms in patients in whom symptoms developed before 2 mo, between 2 and 6 mo and after 6 mo were 38%/29%, 74%/74% and 96%/96%, respectively. On the basis of these survival rates, a new classification – which is important with respect to choices in treatment — is proposed: very early (onset of symptoms < 2 mo), early (2 to 6 mo) and late presenting form (>6 mo). (Hepatology 1994;20:1187-1191).
Expression of Mucin Core Protein of Mammary Type in Primary Liver Cancer
Authors: Sasaki Motoko , Nakanuma Yasuni
Published: March 2007

Expression of mucin core protein of mammary type (MUC–1 core protein) was investigated in primary hepatic carcinoma (25 cases of cholangiocarcinoma, 15 cases of combined hepatocellular–cholangiocellular carcinoma and 18 cases of hepatocellular carcinoma) with monoclonal antibody DF3 and a standard avidinbiotin complex method. MUC–1 core protein was almost always expressed in cholangiocarcinoma and in the cholangiocarcinoma area of hepatocellular–cholangiocellular carcinoma to a varied degree, whereas such expression was virtually absent in hepatocellular carcinoma and the hepatocellular carcinoma areas of hepatocellular–cholangiocellular carcinoma. Nonneoplastic intrahepatic biliary epithelium, as well as hepatocytes, was virtually negative for this protein. In well–differentiated cholangiocarcinoma, this protein tended to be expressed on luminal surfaces, whereas poorly differentiated cholangiocarcinoma showed cell membranous or diffuse cytoplasmic staining patterns. Double staining with Alcian blue (pH 2.5) and immunostaining for MUC–1 core protein showed that although some parts of cancerous areas were positive for both stains, most cancerous areas were only positive for one. Alcian blue—positive areas were dominant over MUC–1 core protein—expressing areas in well–differentiated cholangiocarcinoma, whereas the reverse was the case in poorly differentiated cholangiocarcinomas and also in cholangiocarcinoma areas of hepatocellular–cholangiocellular carcinoma. This study is the first report to document that cholangiocarcinoma and cholangiocarcinoma areas of hepatocellular–cholangiocellular carcinoma express MUC–1 core protein. In addition, MUC–1 core protein—expressing areas and Alcian blue—positive areas in cholangiocarcinoma and cholangiocarcinoma areas of hepatocellular–cholangiocellular carcinoma were reciprocally distributed in most cancerous areas, suggesting that immunostaining for MUC–1 core protein can be used to supplement conventional mucin histochemical study in cholangiocarcinoma and hepatocellular–cholangiocellular carcinoma. (Hepatology 1994;20:1192-1197).
Specific and Dose–Dependent Enzyme Induction by Omeprazole in Human Beings
Authors: Rost Karl Ludwig , Brösicke Herbert , Heinemeyer Gerhard , Roots Ivar
Published: March 2007

Omeprazole induces hepatic cytochrome P–4501A2. In a previous study this effect was shown to be significant

in vivo

in 6 poor metabolizers, including 1 intermediate metabolizer, but not in 12 extensive metabolizers of

S

–mephenytoin after 7 days of treatment with 40 mg/day omeprazole. In this study, the specificity of the inducing potential of omeprazole was investigated in these volunteers. Furthermore, in eight of the extensive metabolizers the dose–dependence of cytochrome P–450 1A2 induction was evaluated. Cytochrome P–450 1A2 activity was monitored by means of the 13C–[

N3

–methyl]caffeine breath test and by means of plasma caffeine clearance before omeprazole treatment with 120 mg/day, on the seventh day of dosage and after a 7–day washout. Omeprazole plasma concentration was measured. Results were compared with those after 40 mg. γ–Glutamyltransferase activity in serum, as well as urinary excretion of d–glucaric acid and 6β–hydroxycortisol, were measured on the same study days in all study groups (n = 26). In the eight extensive metabolizers the breath test indicated a dose–dependent increase of cytochrome P–450 1A2 activity of 8.5% ± 15.0% (40 mg, mean ± SD, NS) and 27.2% ± 16.5% (120 mg, p = 0.002). Caffeine clearance was increased by 31.6% ± 20.7% (p < 0.001) with the higher dose. None of the study groups exhibited a significant increase of γ–glutamyltransferase activity or urinary excretion of d–glucaric acid or 6β–hydroxycortisol. This was in contrast to the phenobarbital–type induction observed after treatment with antiepileptic drugs. Induction by omeprazole seems to be restricted to cytochrome P–450 1A enzymes. Thus cytochrome P–450 1A2 induction is not clinically relevant with common therapeutic doses in EMs but might be of relevance after extraordinarily high doses or in poor metabolizers of

S

–mephenytoin. (Hepatology 1994;20:1204-1212).
Defining the Immunogenetic Susceptibility to Primary Biliary Cirrhosis
Authors: Mehal Wajahat Z. , Gregory Wendy L. , Lo Dennis Y-M. , Cross Susan J. , Fleming Kenneth A. , Bassendine Margaret F. , James Oliver F.W. , Campbell Duncan R. , Chapman Roger W. , Rosenberg William M.C.
Published: March 2007

Primary biliary cirrhosis is a chronic cholestatic disease, thought to be immune–mediated with genetic susceptibility encoded in the major histocompatibility complex. In northern Europeans, the best established associations are with HLA–DR8 and the complement allele, C4B2. These associations could be due to a single susceptibility locus on an extended haplotype linking HLA–DR8 and C4B2 or to both HLA–DR8 and C4B2 independently conferring disease susceptibility. C4B2 genotyping was performed on 64 patients with primary biliary cirrhosis and 61 controls matched for ethnic background and frequency of HLA–DR8. C4B2 was associated with HLA–DR8 (p < 0.05) in PBC. No difference in the frequency of C4B2 was detected between control and disease populations, suggesting that HLA–DR8 and C4B2 are in linkage disequilibrium and that C4B2 is not a susceptibility locus for PBC.

Taq

I polymorphisms were screened in the disease and control populations with the cosmid probe G91, located midway between the HLA–DR and complement loci. One G91 restriction fragment (G91A) was found to be associated with both HLA–DR8 and C4B2, at equal frequency in health and disease, providing evidence of an HLA–DR8–G91A–C4B2 extended haplotype. The frequency of G91A was the same in the disease and control populations, suggesting that G91A does not confer disease susceptibility. These findings establish G91 as the telomeric boundary for disease susceptibility associated with HLA–DR8, encoded on chromosome six. These studies help define the immunogenetic susceptibility locus for primary biliary cirrhosis. (Hepatology 1994;20:1213-1219).
Pathogenic Factors in Cirrhosis With and Without Hepatocellular Carcinoma: A Multicenter Italian Study
Authors: De Bac Carlo , Stroffolini Tommaso , Gaeta Giovanni B. , Taliani Gloria , Giusti Giuseppe
Published: March 2007

We designed a multicenter cross–sectional study to evaluate the role of alcohol abuse, the hepatitis viruses and other pathogenic factors in cirrhosis and hepatocellular carcinoma. A total of 1,829 consecutive cirrhosis patients, with or without HCC, was enrolled over 6 mo in 21 centers throughout Italy. The etiological categories and diagnostic criteria were preestablished. The median age of the patients was 59 yr (range, 13 to 85 yr); 63.6% of the patients were graded as Child class A, 23.4% as Child class B and 13% as Child class C. Hepatitis C virus antibodies were found in 72.1% of cases (47.7% alone, 21.2% with alcohol abuse, 3.2% with hepatitis B virus); HBsAg was present in 13.8% (4.2% alone, 3.2% with hepatitis D virus, 3.2% with hepatitis C virus, 3% with alcohol abuse), alcohol abuse with no concomitant viral infection was recorded in 8.7%, primary biliary cirrhosis was found in 1.8%, other causes were found in 1.4% and cryptogenic cirrhosis was only present in 5.3%. Hepatocellular carcinoma was detected in 11.9% of patients (217 cases). The presence of hepatocellular carcinoma was more frequent in males than females (14.7% vs. 7.3%; p < 0.001) and increased with worsening Child class (8.3% in Child class A, 16.9% in Child class B, 19.9% in Child class C, p < 0.001). The highest prevalences of hepatocellular carcinoma were observed in hepatitis B virus infection, with or without alcohol abuse (20% and 16%, respectively) and in hepatitis C virus cirrhosis, with or without alcohol abuse (16% and 10.3%, p < 0.005). Our data indicate chronic viral infection to be responsible for most cirrhosis and hepatocellular carcinoma in Italy. This finding may aid development of guidelines for prevention programs. (Hepatology 1994;20:1225-1230).
Evaluation of Vascular Tone in Portacaval Shunts Comparing the Index of Contractility and Resistance in Cats
Authors: Inglés Andrés C. , Legare Dallas J. , Lautt Wayne W.
Published: March 2007

A model of prehepatic chronic portal hypertension in cats was used to determine portacaval shunt responses to infused norepinephrine and to possible transmitter overflow into portal blood from nerves supplying the gut. Responses are compared using a new index of contractility. Four weeks after application of a slowly constricting occluder, the portal vein was completely occluded and acute experiments were carried out under pentobarbital anesthesia. Portal pressure was elevated to 15.0 ± 0.9 mmHg and all portal flow passed through the shunts. In response to intraportal norepinephrine (0.25, 0.5 and 1.25 μg ± min kg-1) shunt resistance rose by 6% ± 3%, 19% ± 4% and 26% ± 5%, respectively, whereas the index of contractility rose (by 22% ± 8%, 46% ± 10% and 89% ± 20%, respectively), the distending blood pressure also rose (5% ± 1%, 7% ± 1% and 14% ± 3%, respectively). The difference in percentage increase of resistance and the index of contractility is a result of the passive dilator effect of the elevated distending pressure acting on the distensible shunt vessels. Stimulation of mesenteric nerves caused the mesenteric artery to constrict, but the shunt vessels showed no effect. In conclusion, the shunt vessels respond actively to norepinephrine and passively to altered distending pressure. However, transmitter overflow from nerves supplying the intestines is unlikely to play a role in determining resistance in the shunts. Vascular resistance is affected by both active and passive effects, so that the active contractile responses are best evaluated using the index of contractility, which is not altered passively. (Hepatology 1994;20:1242-1246).
Expression of Hepatocyte Growth Factor in Normal and Carbon Tetrachloride-Treated Monkeys
Authors: Kawakami Shuichi , Tsubouchi Hirohito , Nakagawa Shiro , Hirono Shuichi , Arakaki Naokatu , Nakamura Osamu , Daikuhara Yasushi , Arima Terukatsu
Published: March 2007

We examined hepatocyte growth factor-producing organs in normal and carbon tetrachloride-treated Japanese monkeys, a species more related to human beings than rats, by measuring hepatocyte growth factor protein and hepatocyte growth factor mRNA in various tissues. Hepatocyte growth factor protein and hepatocyte growth factor mRNA levels were determined by use of an enzyme–linked immunosorbent assay for human hepatocyte growth factor and Northern–blot analysis using human hepatocyte growth factor cDNA as a probe, respectively. Although very slight amounts of hepatocyte growth factor protein were found in various organs of normal monkeys, the hepatocyte growth factor protein levels were remarkably increased only in the livers and spleens of carbon tetrachloride-treated monkeys. Hepatocyte growth factor mRNA was distinctly detected in the livers, spleens, lungs, intestinal tracts, adrenal glands and aortas of normal monkeys. After the administration of carbon tetrachloride, the hepatocyte growth factor mRNA levels in the liver, spleen and gastrointestinal tract were markedly increased; the level in the lung was unchanged, differing from the findings in rats; and the levels in adrenal gland and aorta were unaltered. These results indicate that the liver is an importent hepatocyte growth factor–producing organ in monkeys during liver regeneration and that hepatocyte growth factor induced in the liver may stimulate hepatocyte proliferation by way of a paracrine mode. (Hepatology 1994;20:1255-1260).
Liver Injury Following Normothermic Ischemia in Steatotic Rat Liver
Authors: Hui Ai-Min , Kawasaki Seiji , Makuuchi Masatoshi , Nakayama Jun , Ikegami Toshihiko , Miyagawa Shinichi
Published: March 2007

The influence of normothermic ischemia on steatotic liver was compared with that on healthy liver in rats. Steatotic liver was induced with 4 wk of a cholinedeficient diet. We used a procedure of subcutaneous spleen transposition to develop portosystemic collaterals to avoid splanchnic stasis during total hepatic vascular occlusion. One–week survival rates after 30, 45, and 60 min of normothermic ischemia were 75%, 20% and 0% in the steatotic liver group and 100%, 90% and 70% in the control group, respectively. Significantly poor restoration of energy metabolism was observed in the steatotic liver group. After 1 hr of reflow following 45 and 60 min of ischemia, ATP was restored to 74% and 50%, respectively, of the preischemic level in healthy liver but to only 44% and 27% respectively, in steatotic liver. Microscopically, focal hemorrhage, disruption of the sinusoidal microvasculature and occasional spotty necrosis of hepatocytes were demonstrated after 1 hr of reflow following ischemia in steatotic liver, but no significant changes were evident in healthy liver. This microcirculatory alteration seems to be responsible for the loss of organ viability in steatotic liver. We suggest that steatotic liver is more vulnerable than healthy liver to normothermic ischemia in the rat. (Hepatology 1994;20:1287-1293).
Early Pregnancy Factor in Liver Regeneration After Partial Hepatectomy in Rats: Relationship With Chaperonin 10
Authors: Quinn Kathryn A. , Cavanagh Alice C. , Hillyard Narelle C. , McKay Dorothy A. , Morton Halle
Published: March 2007

Early pregnancy factor is not only a product of dividing embryonic and neoplastic cells, as demonstrated previously, but also of normal proliferating cells. Eight hours after partial hepatectomy in rats, early pregnancy factor was detected in serum. It rose to a peak by 48 hr. Neutralization of early pregnancy factor

in vivo

by passive immunization with specific antibodies, 18 hr after partial hepatectomy, resulted in a significant decrease in the uptake of [H]thymidine by the liver remnant, measured 4 to 6 hr later. These results suggest that during liver regeneration, early pregnancy factor is essential to the sequence of events that culminates in DNA synthesis and cell division. Recently we purified early pregnancy factor from human platelets and determined by mass spectrometry a precise molecular mass of 10,843 Da. Amino acid sequencing (˜72% of the molecule) demonstrated that early pregnancy factor is highly homologous with chaperonin 10, a stress–inducible mitochondrial protein, and that platelet–derived early pregnancy factor and rat chaperonin 10 share similar biochemical and immunological properties. In this study we show that early pregnancy factor, purified from regenerating rat liver and from serum taken 24 hr after hepatectomy, shares these properties. In addition, antibodies to early pregnancy factor, effective in passive immunization studies, recognize chaperonin 10, whereas chaperonin 10 antibodies bind to early pregnancy factor from regenerating liver and posthepatectomy serum. We propose that early pregnancy factor/chaperonin 10 is selectively released from proliferating cells and, in an autocrine or paracrine mode (or both) is involved in DNA synthesis. (Hepatology 1994;20:1294-1302).
Internal Biliary Drainage, Unlike External Drainage, Does Not Suppress the Regeneration of Cholestatic Rat Liver After Partial Hepatectomy
Authors: Suzuki Hideaki , Iyomasa Shinsuke , Nimura Yuji , Yoshida Shonen
Published: March 2007

We previously showed that hepatic cells proliferate in obstructive jaundice alone without partial hepatectomy and found that external biliary drainage for obstructive jaundice markedly suppresses liver regeneration after partial hepatectomy. In this study, we produced a model system for internal biliary drainage in which bile was drained into the stomach of rat fed a liquid diet. The regeneration capacity of the liver was assessed on the basis of the induction of DNA polymerase–α activity, as well as the mitotic index of hepatic cells. A remarkable difference was observed in the regeneration capacities of cholestatic livers between two groups—one in which jaundice was released by the internal and one by external biliary drainage before hepatectomy. After 5 days of internal biliary drainage, the regeneration capacity remained at a level comparable to that of sham–operated control rats, in sharp contrast to the impaired regeneration after external biliary drainage. These results clearly indicate that internal biliary drainage is preferable for release of biliary obstruction before partial resection of cholestatic liver. (Hepatology 1994;20:1318-1322).
Is Liver Cancer A Stem Cell—Derived Disease?
Authors: Faris Ronald A. , Hixson Douglas C.
Published: March 2007

In transgenic mice bearing the Simian Virus 40 large T antigen under the control of the human anti–thrombin III regulatory sequences, a step–wise progression toward hepatocellular carcinoma is observed. We have used two monoclonal antibodies (A6 and G7) developed against a surface antigen expressed in oval cells from dipin–treated mice, to analyze the emergence of such preneoplastic populations in the livers of anti–thrombin III Simian Virus 40 T transgenic mice. We show that a unique population of small heterogenous epithelial cells, which probably corresponds to oval and/or transitional cells according to their morphological features, consistently appears at approximately the 10th week after birth and proliferates thereafter. This oval cell–like population stained positively for A6 and G7 monoclonal antibodies. Furthermore, different subpopulations usually recognized as possible precursors of carcinoma cells including hyperplastic foci and neoplastic nodules as well as carcinoma cells, were also positive for A6 but not G7 monoclonal antibodies. Stimulation of cell proliferation by partial hepatectomy performed at the time of emergence of the oval–like cells resulted in a rapid increase in the number of oval/transitional A6–positive cells. Our findings support the view that a common mechanism may be involved in the development of carcinomas that are induced by chemical carcinogens and in transgenic mice expressing a potent oncogene under the control of a hepatic specific promoter. In addition, our findings demonstrate a specific precursor–product relationship between the appearance of the oval/transitional cells and the development of neoplastic hepatocytes in this transgenic model.
Liver transplantation and alcohol: Who should get transplants?
Authors: Krom Ruud A. F.
Published: March 2007

Medical selection criteria should be the same for all patients with end-stage liver disease and should aim for an acceptable outcome of the liver transplant procedure in matter of survival and quality of life, taking the scarce resources into account. The psychiatric selection criteria should aim at avoidance of recidivism of alcohol use in alcoholic patients. At least 6 mo of sobriety should be required. The patient must have a stable and supportive environment and should participate in an alcohol counseling program. A multicentered trial using uniform scoring criteria such as the Alcohol Prognosis Scale is needed to better define the selection of patients with alcoholic liver disease and long-term outcome of alcoholism after transplantation. (Hepatology 1994;20:28S-32S.)
Sequential treatment of biliary atresia with kasai portoenterostomy and liver transplantation: A review†
Authors: Otte Jean-Bernard , De Ville De Goyet Jean , Reding Raymond , Hausleithner Victoria , Sokal Etienne , Chardot Christophe , Debande Benoit
Published: March 2007

Biliary atresia is the most frequent cause of chronic cholestasis in infants. When left untreated, this condition leads to death from liver insufficiency within the first 2 yr of life. The modern therapeutic approach consists of a sequential strategy with Kasai portoenterostomy as a first step and, in case of failure, liver transplantation. After portoenterostomy, no more than 20% to 30% of patients will live jaundice-free into adulthood. Illness in another third will be palliated, and these patients have extended survival, delaying liver transplantation to later childhood (2 to 15 yr). The remaining 30% to 40% will not benefit from the Kasai operation and will die of liver failure in infancy. The annual need of liver transplantation for biliary atresia is one case per million people. This indication represents 35% to 67% of the reported series of pediatric liver transplantation and between 5% and 10% of the indications for liver transplantation, all ages included. Approximately four of five children transplanted for biliary atresia will become long-term survivors with good physical and mental development; recurrence of the disease after transplantation has not been observed. Because most candidates are young children (<3 yr) of small size (>10 kg), there is a shortage of size-matched donors (which has been alleviated by the use of innovative techniques such as reduced and split livers). The resulting redistribution of the adult donor liver pool is ethically justified by the equal quality of the results after transplantation of a full-size or partial graft. (Hepatology 1994;20:41S-48S.)
Disease gravity and urgency of need as guidelines for liver allocation
Authors: Eghtesad Bijan , Bronsther Oscar , Irish William , Casavilla Adrian , Abu-Elmagd Kareem , Van Thiel David , Tzakis Andreas , Fung John J. , Starzl Thomas E.
Published: March 2007

One thousand one hundred and twenty-eight candidates for liver transplantation were stratified into five urgency-of-need categories by the United Network for Organ Sharing (UNOS) criteria. Most patients of low-risk UNOS 1 status remained alive after 1 yr without transplantation; the mortality while waiting was 3% after a median of 229.5 days. In contrast, only 3% of those entered at the highest risk UNOS 5 category survived without transplantation; 28% died while waiting, the deaths occurring at a median of 5.5 days. The UNOS categories in between showed the expected gradations, in which at each higher level fewer patients remained as candidates throughout the 1-yr duration of study while progressively more died at earlier and earlier times while waiting for an organ. In a separate study of posttransplantation survival during the same time period, the best postoperative results were in the lowest-risk UNOS 1 and 2 patients (88% combined), and the worst results were those in UNOS 5 (71%). However, a relative risk cross-analysis showed that a negative benefit of transplantation may have been the result in terms of 1-yr survival for the low-risk elective patients, but that a gain in life extension was achieved in the potentially lethal UNOS categories 3, 4 and 5 (greatest for UNOS 3). These findings and conclusions are discussed in terms of total care of patients with liver disease, and in the context of organ allocation policies of the United States and Europe. (Hepatology 1994;20:56S-62S.)
Selective transmission of variant genomes from mother to infant in neonatal fulminant hepatitis B
Authors: Weizsäcker Fritz Von , Pult Irmgard , Geiss Katja , Wirth Stefan , Blum Hubert E.
Published: March 2007

Hepatitis B virus (HBV) nucleotide sequences isolated from mother/child pairs were analyzed in three cases of neonatal fulminant hepatitis B (FHB). Heterogeneous HBV sequences consistent with both adw2 and ayw subtype were found in all three mothers. In one case, in which the child survived, both subtypes were transmited. By contrast, only the ayw subtype was present in the two other children with a fatal course of FHB. In one fatal case, studied in greater detail, multiple HBV variants (viral quasi-species) were identified in both mother and child. A direct sequence comparison showed that only a subfraction of the virus pool from the mother was transmitted and that multiple new mutations emerged in the child. These data suggest that a minor HBV subpopulation from the mother may prevail as the dominant species in the child and that neonatal FHB is associated with the selection of mutant strains. (Hepatology 1995;21:8-13).
Determination of hepatitis delta virus RNA by polymerase chain reaction in acute and chronic delta infection
Authors: Jardi Rosendo , Buti Maria , Cotrina Montserrat , Rodriguez Francisco , Allende Helena , Esteban Rafael , Guardia Jaime
Published: March 2007

The objective of this study was to evaluate the usefulness of hepatitis delta virus (HDV) RNA detection by polymerase chain reaction (PCR) in acute and chronic D hepatitis and to correlate with HDV-RNA detection by dot blot and hepatic delta antigen. Serum samples from 33 patients with acute hepatitis B surface antigen (HBsAg)-positive hepatitis (15 with hepatitis B and D coinfection, 8 with HDV superinfection, and 10 with acute hepatitis B), 85 patients with chronic HBsAg-positive hepatitis (73 with chronic D hepatitis and 12 with chronic B hepatitis), and consecutive serum samples from nine patients with chronic D hepatitis treated with interferon alfa-2b were studied. HDV-RNA was detected by PCR in 93% of the patients with hepatitis B and D coinfection, in 100% of the patients with of the patients with hepatitis D superinfection, and in 1 of the 10 patients with acute hepatitis B who subsequently seroconverted to total antibody to hepatitis delta antigen (HDAg), whereas HDV-RNA was found by dot blot technique in 60% of the hepatitis B and D coinfection cases, in 62.5% of the patients with hepatitis D superinfection, and in none of the acute hepatitis B cases. In chronic D hepatitis, HDV-RNA tested positive by PCR assay in 97% of patients with intrahepatic HDAg, in one patient with undetectable hepatic HDAg, and in none of the patients with chronic hepatitis B. In the treated patients, HDV-RNA was observed to become negative by PCR only in the three patients who had a persistent response to interferon. The results of this study show that HDV-RNA determination by PCR assay is a reliable tool for the diagnosis of delta infection and a clear improvement over other methods for the evaluation of HDV replication and response to antiviral therapy. (Hepatology 1995;21:25-29).
Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation
Authors: Sheiner Patricia A. , Schwartz Myron E. , Mor Eytan , Schluger Leona K. , Theise Neil , Kishikawa Keiji , Kolesnikov Vadim , Bodenheimer Henry , Emre Sukru , Miller Charles M.
Published: March 2007

Recurrent hepatitis C causes significant morbidity after liver transplantation. Because immunosuppression is associated with enhanced viral replication, we postulated that clinical recurrence of the disease may be associated with augmented immunosuppression for rejection. In 96 patients with hepatitis C who received liver transplants, we recorded the interval from transplantation to recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the number of rejection episodes, and the use of OKT3 induction. Recurrence was diagnosed based on elevated transaminases and characteristic histology. Hepatitis C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously had SRR hadrecurrence, versus 28 of 75 patients (37.3%) who either had no SRR (72 patients) or had it after recurrence was diagnosed (3 patients) (P <.01). Mean time to recurrence was 127 ± 31 days in the 15 patients who had had SRR versus 246 ± 42 days in the other 28 patients (P = 0.02). Recurrence and number of rejection episodes were clearly associated: 6 of 33 patients (18.2%) with no rejection had recurrence (P<.05), versus 11 of 26 patients (42.3%) with one rejection episode (P<.05) and 26 of 37 (70.2%) with more than 1 episode (P<.05). OKT3 induction was used in 15 patients; 9 of 15 patients had recurrence (ns) at 337 ± 95 days. Of 72 patients who initially received triple immunosuppression, 30 patients had recurrence at 186 ± 25 days (P = 0.05). Nine patients received primary FK506; 4 had recurrence at 68 ± 14 days. SRR requiring OKT3 is associated with a higher incidence and earlier presentation of recurrent hepatitis C. Multiple rejection episodes are also associated with a higher recurrence rate. Induction immunotherapy, by reducing the rate of early rejection, may delay the clinical recurrence of hepatitis C. (Hepatology 1995;21:30-34).
Plasma levels of substance p in liver cirrhosis: Relationship to the activation of vasopressor systems and urinary sodium excretion
Authors: Fernández-Rodriguez Conrado M. , Prieto Jesús , Quiroga Jorge , Zozoya José Manuel , Andrade Amalia , Núñez Marina , Sangro Bruno , Penas José
Published: March 2007

The mediators of the hyperdynamic circulation of liver cirrhosis are not well characterized. Substance P is a potent vasodilatory peptide produced by the enteric nervous system and partly cleared by the liver. In this work we have investigated the plasma levels of substance P and their relationship to the hemodynamic, neurohormonal, and renal function changes occurring in patients with cirrhosis. Seven healthy subjects (control group), 7 cirrhotic patients without ascites (group I), and 24 cirrhotic patients with ascites (group II) were studied. Cardiac output (CO), femoral blood flow (FBF), blood volume (BV), femoral arteriovenous difference of oxygen content (Ca-v O2), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma norepinephrine (NE) were determined. Five patients underwent trans-jugular intrahepatic porto-systemic stent shunt (TIPSS) because of refractory ascites. Immunoreactive substance P (irSP) was measured by radioimmunoassay after plasma extraction. irSP was higher in ascitic patients than in healthy controls (P<.01) and directly correlated with PRA, PAC, plasma NE, and Pugh's score and was inversely correlated with urinary sodium excretion, glomerular filtration rate, and Ca-v O2. No differences were observed between portal and peripheral vein irSP concentration. TIPSS placement induced a decrease in portal pressure and an increase in CO but circulating irSP remained unchanged. Our data show that circulating irSP is increased in decompensated cirrhotic patients and may be involved in the pathogenesis of the hemodynamic changes of cirrhosis. Alleviation of portal hypertension did not result in decreased plasma levels of this vasodilatory substance. (Hepatology 1995;21:35-40).
Long-term effects of cholecystectomy on bile acid metabolism
Authors: Kullak-Ublick Gerd-Achim , Paumgartner Gustav , Berr Frieder
Published: March 2007

Comparative studies between different patient groups have suggested that cholecystectomy enhances bacterial dehydroxylation of the primary bile acid cholic acid (CA) to the secondary bile acid deoxycholic acid (DCA). DCA may exert a cocarcinogenic effect on the colonic mucosa. In a short-term follow-up study on nine female patients we found no alterations of the CA or DCA pools after cholecystectomy. However, in the long term, cholecystectomy could promote changes of the intestinal bacterial flora and thereby lead to enhanced conversion of CA to DCA, causing an expansion of the DCA pool size and a reduction of the CA pool size. To test this hypothesis, pool sizes, fractional turnover rates (FTR), and synthesis or input rates of CA, chenodeoxycholic acid (CDCA) and DCA were determined in 12 female patients before and again 5 to 8 years after cholecystectomy. In the long term, pool size and synthesis rate of CA had not changed and DCA pool size had expanded by only 7.5% (not significant [NS]). DCA input increased by 32% (NS) but was balanced by an increase in FTR of 36%. Pool size (-17%) and synthesis rate (-5%) of CDCA were not significantly diminshed. Overall, the sizes of the total bile acid pool (-6%, NS; 50 ± 8 vs. 53 ± 13 μmol/kg) and the pool fractions of CA (44.7 ± 10.3% vs. 42.8 ± 7.6%) and DCA (25.5 ± 14.1% vs. 23.6 ± 9.3%) remained similar. In conclusion, cholecystectomy causes no changes in bile acid pool composition and thus has no adverse effects on bile acid metabolism in the long term. (Hepatology 1995;21:41-45).
Anti-liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease
Authors: Han Shuhua , Tredger Micheal , Gregorio Germana V. , Mieli-Vergani Giorgina , Vergani Diego
Published: March 2007

Antibodies to liver cytosol antigen type 1 (anti-LC1), which recognize a 60-kd peptide contained in the liver cytosolic fraction, have been reported to define a subset of autoimmune hepatitis (AIH) either negative for other autoantibodies or positive for anti-liver kidney microsomal antibody type 1 (LKM-1) and to be best detected in immunodiffusion. To analyze the prevalence of anti-LC1 in childhood liver disease, we have tested the sera of 95 patients using immunoblot, indirect immunofluorescence, and immunodiffusion. Fifteen children had smooth muscle antibody (SMA) and/or anti-nuclear antibody (ANA)-positive AIH, 13 had anti-LKM-1-positive AIH, 14 had autoimmune sclerosing cholangitis (ASC) (all SMA and/or ANA positive), and 53 had non-autoimmune liver disease (10 had α1-anti-trypsin deficiency [α1-ATD], 11 had Wilson's disease [WD], 14 had Alagille's syndrome, and 18 had chronic hepatitis B virus [HBV] infection). Twenty healthy children were studied as controls. Anti-LC1 positivity in immunodiffusion and strong reactivity in immunoblot were found in 4 LKM-1- and 2 SMA/ANA-positive patients with AIH and in 1 patient with ASC, but in none of the patients with other liver diseases nor in controls. A weak 60-kd band was detected by immunoblot in 6 more patients with AIH (2 were LKM-1- and 4 were SMA/ANA-positive) and 6 patients with ASC, all anti-LC1-negative by immunofluorescence and immunodiffusion. No distinct clinical features characterized the anti-LC1-positive patients. Our data show that, in pediatric age, LC1 reactivity, although associated with autoimmune liver disease, does not identify a distinct disease, subset and that immunoblot is the most sensitive technique to detect anti-LC1. (Hepatology 1995;21:58-62).
Early cellular rejection after orthotopic liver transplantation correlates with low concentrations of FK506 in hepatic tissue
Authors: Sandborn William J. , Lawson George M. , Cody Timothy J. , Porayko Michael K. , Hay Eileen J. , Gores Gregory J. , Steers Jeffery L. , Krom Ruud A. F. , Wiesner Russell H.
Published: March 2007

We have previously reported that low hepatic tissue cyclosporine levels correlate with early cellular rejectionafter liver transplantation. The aim of this study is to determine whether there is a similar relationship in patients treated with FK506. Twenty-five liver biopsies were performed in 10 patients immunosuppressed with FK506 without cellular rejection: day 7 = 10; day 14 = 3; day 21 = 9; day 28 = 1; day 35 = 1; and day 42 = 1. These 10 patients without cellular rejection were compared with 7 patients immunosuppressed with FK506 with cellular rejection who underwent a total of 23 liver biopsies, including 9 biopsies that showed rejection: day 7 = 4; day 14 = 2; day 21 = 1; day 28 = 1; and day 49 = 1. There was no significant difference between the nonrejection and current rejection groups in the median plasma concentration of FK506, 0.9 ng/mL versus 0.9 ng/mL (P = 0.50). In contrast, the median hepatic tissue concentration of FK506 was significantly higher in the nonrejection group than it was in the current rejection group, 144 ng/g versus 48 ng/g (P = 0.02). In the current rejection group, 7 of 9 hepatic tissue concentrations of FK506 were <100 ng/g, and in the nonrejection group, 18 of 25 hepatic tissue concentrations were >100 ng/g. Low hepatic tissue concentrations of FK506 correlate with the occurrence of early cellular rejection after liver transplantation, in contrast to plasma concentrations of FK506. A hepatic tissue concentration of FK506 <100 ng/g is 78% sensitive and 72% specific for cellular rejection. These findings support the hypothesis that low hepatic tissue concentrations of immunosuppressives may lead to cellular rejection after liver transplantation. (Hepatology 1995;21:70-76).
Noninvasive measurement of femoral blood flow and portal pressure response to propranolol in patients with cirrhosis
Authors: Luca Angelo , Garí-Pagán Juan Carlos , Feu Faust , Lopez-Talavera Juan Carlos , Fernández Mercedes , Bru Concepció , Bosch Jaime , Rodés Juan
Published: March 2007

This study investigated the correlation between changes in hepatic and systemic hemodynamics and femoral blood flow (FBF), measured by dual-beam pulsed wave Doppler, in 58 portal hypertensive patients receiving propranolol (0.15 mg/Kg intravenously; n = 44) or placebo (n = 14) under double-blind conditions. Placebo administration had no effects. Propranolol caused significant reductions (P <.0001) in hepatic venous pressure gradient (HVPG; from 19.1 ± 4.1 to 16.2 ± 4.2 mm Hg), azygos blood flow (from 563 ± 204 to 387 ± 176 mL/ min), cardiac index (CI; from 4.4 ± 1.0 to 3.3 ± 0.8 L/m2/min), and FBF (from 237 ± 79 to 176 ± 58 mL/m2/min). In 17 patients HVPG decreased below 12 mm Hg and/or more than 20% of the baseline value (good response; mean change, -26 ± 8%); in the remaining 27 patients (poor response) the mean change in HVPG was less: -9 ± 6%. Patients with a good response had bled less often from varices, had significantly higher FBF (272 ± 73 vs. 215 ± 76 mL/m2/min) and lower baseline HVPG (16.8 ± 3.9 vs. 20.6 ± 3.6 mm Hg) than those with poor response in HVPG. The good response was also associated with greater decreases in FBF (-33 ± 12 vs. -19 ± 13% in poor responders), CI (-30 ± 9 vs. -19 ± 12%), and heart rate (-19 ± 5 vs. -16 ± 6%). A decrease in FBF of >20% predicted a good response in 16 of 28 patients (positive predictive value, 57%). A negative test (decrease in femoral blood flow of <20%) predicted a lack of response in HVPG in 15 of 16 patients (negative predictive value, 94%). This study suggests that the noninvasive measurements of FBF allow the identification of patients with a poor response of HVPG to propranolol. However, measurements of HVPG would still be needed for patients whose FBF decreased >20%, half of whom have an insufficient decrease in HVPG. (Hepatology 1995;21:83-88).
Metabolism of cholesterol and low- and high-density lipoproteins in primary biliary cirrhosis: Cholesterol absorption and synthesis related to lipoprotein levels and their kinetics
Authors: Gylling Helena , Färkkilä Martti , Vuoristo Matti , Miettinen Tatu A.
Published: March 2007

Cholesterol absorption, elimination, and synthesis, and low-density lipoprotein (LDL) and high density lipoprotein (HDL) kinetics were studied in patients with mild to severe primary biliary cirrhosis (PBC) (n = 16) to show how this cholestatic disease modified cholesterol and lipoprotein metabolism as compared with healthy controls (n = 50). Serum total and lipoprotein cholesterol and triglyceride levels were similar in the two groups, but in PBC, especially in severe forms, very low density lipoprotein (VLDL) was rich in apoprotein (apo) B and cholesterol and low in triglycerides, whereas LDL was rich in triglycerides and low in triglycerides and low in esterified cholesterol, and HDL was enriched by surface lipids, phospholipids, and free cholesterol. In severe PBC, the fractional catabolic rate (FCR) for LDL apo B was reduced. The transport rate (TR) for LDL apo B was unaffected and it tended to correlate with the LDL apo B and LDL cholesterol levels in PBC, whereas in the controls the LDL apo B concentration was regulated by both the FCR and TR, and LDL cholesterol was regulated only by FCR. FCR for apo A-I in HDL was unaltered in PBC, but TR for apo A-I was reduced in the severe cases. Cholesterol absorption efficiency was significantly reduced in PBC (14.5 ± 3.0% in severe PBC and 34.0 ± 2.5% in mild PBC vs. 47.4 ± 1.4% in the controls, respectively). Bile acid synthesis and cholesterol transport were significantly diminished in PBC, but, even in a case with severe PBC and low basal absorption efficiency and synthesis of cholesterol, lowering of LDL cholesterol by combined inhibition of hydroxymethyl-glutaryl-coenzyme A reductase and cholesterol absorption, removal of LDL apo B could still be upregulated. The significant interrelations between the LDL apo B level, cholesterol absorption efficiency and synthesis, and LDL apo B kinetics, observed in the controls, were lacking in PBC, suggesting that cholestasis and hepatic parenchymal cell dysfunction modified the relationship between cholesterol and lipoprotein metabolism so that treatment of hypercholesterolemia and bile acid-related itching might not be constantly successful. (Hepatology 1995;21:89-95).