bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc Supplementation Reduces Blood Ammonia and Increases Liver Ornithine Transcarbamylase Activity in Experimental Cirrhosis
Authors: Riggio Oliviero , Merli Manuela , Capocaccia Livio , Caschera Massimo , Zullo Angelo , Pinto Giorgio , Gaudio Eugenio , Franchitto Antonio , Spagnoli Roberta , D'aquilino Elvira , Seri Siro , Moretti Renzo , Cantafora Alfredo 
Published: March 2007

Zinc deficiency is common in cirrhosis and may be involved in the alteration of ammonia metabolism. Rats with carbon tetrachloride-induced cirrhosis have high plasma ammonia and low serum and tissue zinc levels. We used this model to examine the effects of oral zinc supplementation on activities of plasma ammonia and liver ornithine transcarbamylase (a key enzyme in the urea cycle). These parameters were examined in two consecutive experiments. Each experiment included two groups of rats treated with carbon tetrachloride; one group received zinc in the drinking water during the induction of cirrhosis, and another served as a control group. Regardless of zinc supplementation, all carbon tetrachloride-treated rats exhibited similar micronodular cirrhosis, with similar histological appearance and liver function impairment.
Cirrhotic rats without zinc supplementation showed high plasma ammonia and low serum and hepatic zinc levels and reduced liver ornithine transcarbamylase activity. Serum, hepatic zinc and liver ornithine transcarbamylase activity increased significantly in the zinc–supplemented group, and these rats' plasma ammonia levels became normal. Plasma ammonia level was significantly inversely correlated with liver ornithine transcarbamylase activity and positively correlated with serum and hepatic zinc content. Our results suggest that zinc deficiency may modify hepatic ornithine transcarbamylase activity and, therefore, ammonia disposal. (Hepatology 1992;16:785-789.)
Aflatoxin and Hepatocellular Carcinoma: A Useful Paradigm for Environmentally Induced Carcinogenesis
Authors: Kolars Joseph C. 
Published: March 2007

Aflatoxin is believed to be a major causative agent in the high incidence of primary liver cancer seen in certain regions of the world. In Fujian Province, an aflatoxin–endemic region of China, we compared the cigarette smoking habits of 200 primary hepatoma patients with those of 200 matched nonhepatoma controls. We excluded from our study all individuals with evidence of hepatitis B virus serum antigen and/or alcoholic cirrhosis. Interestingly, two groups of hepatoma patients could be discerned. In patients more than 50 years of age, a significantly higher number of cases of primary hepatoma was found among nonsmokers than smokers (odds ratio = 2.06; 95% confidence interval = 1.32-3.20). In patients less than 50 years of age, this difference was not seen. Previous studies in the rat, mouse and duck had suggested that agents present in cigarette smoke might induce a cytochrome P450–mediated detoxication pathway, leading to protection against aflatoxin–induced primary liver cancer. Our clinical data in the present study are therefore consistent with the previous laboratory animal experiments.
Mutations of the p53 gene are found in hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Specific mutations might reflect exposure to specific carcinogens and we have screened HCC samples from patients in 14 different countries to determine the frequency of a hotspot mutation at codon 249 of the tumour suppressor p53 gene.
We detected mutations in 17% of tumours (12/72) from four countries in south Africa and the southeast coast of Asia. There was no codon 249 mutation in 95 specimens of HCC from other geographical locations including North America, Europe, Middle East, and Japan. Worldwide, the presence of the codon 249 mutation in HCCs correlated with high risk of exposure to aflatoxins and the hepatitis B virus (HBV). Further studies were completed in two groups of HBV–infected patients at different risks of exposure to aflatoxins. 53% of patients (8/15) from Mozambique at high risk of aflatoxin exposure had a tumour with a codon 249 mutation, in contrast with 8% of patients from Transkei (1/12) who were at low risk.
HCC is an endemic disease in Mozambique and accounts for up to two thirds of all tumours in men. A codon 249 mutation of the p53 gene identifies an endemic form of HCC strongly associated with dietary aflatoxin intake.
Elsewhere Reviews. Nitric Oxide and Hyperdynamic Circulation in Portal Hypertension
Authors: Häussinger Dieter 
Published: March 2007

ABSTRACT

1 The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG–monomethyl–L–arginine (L–NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine.
2 Portal hypertension was induced by partial portal vein ligation, 2 weeks prior to study. This procedure induced a reduction in systemic arterial blood pressure (MAP), an increase in cardiac output as measured by radiolabelled microspheres, a reduction in peripheral and splanchnic vascular resistance and an increased portal venous inflow (PVI) and portal pressure, as compared to control non–ligated rats.
3 l–NMAA (6.25 and 50 mg kg-1, i.v.) dosedependently increased MAP, reduced cardiac output and PVI, and increased peripheral and splanchnic vascular resistance. With l–NMMA (50 mg kg-1), PVI and the vascular resistances returned to values comparable to those determined in control non–ligated anaesthetized rats under resting conditions.
4 Porto–collateral resistance was also increased by these doses of l–NMMA, whereas portal pressure was unchanged. The increase in renal blood flow and decrease in renal vascular resistance also seen in portal–hypertensive rats was reversed by l–NMMA (50 mg kg-1).
5 These effects of l–NMMA (50 mg kg-1) were inhibited by prior administration of l–arginine (300 mg kg-1, i.v.).
6 These findings indicate that the chronic hyperdynamic circulatory characteristics following portal vein stenosis can be attenuated by l–NMMA. Thus, the excessive formation of endogenous NO may be implicated in the pathogenesis of the haemodynamic disturbances and splanchnic vasodilatation associated with chronic portal hypertension.
Hepatology Elsewhere: Twenty Years After!
Authors: Blendis Laurence M. 
Published: March 2007

ABSTRACT

Background.
Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta–analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease.

Methods.
We conducted a randomized, double–blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsyproved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant–function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time — control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty–seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months.

Results .
One patient was lost to follow–up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [± SE] survival, 46 ± 8 percent), as compared with 4 of 32 preduieolone recipients (survival, 88 ± 5 percent) (log–rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional–hazards model.

Conclusions .
Treatment with prednisolone improves the short–term survival of patients with severe biopsyproved alcoholic hepatitis.
Cholangitis and Endoscopic Drainage
Authors: Barnett Jeffrey L. 
Published: March 2007

ABSTRACT

Background.
Emergency surgery for patients with severe acute cholangitis due to choledocholithiasis is associated with substantial morbidity and mortality. Because recent results suggested that emergency endoscopic drainage could improve the outcome of such patients, we undertook a prospective study to determine the role of this procedure as initial treatment.

Methods.
During a 43–month period, 82 patients with severe acute cholangitis due to choledocholithiasis were randomly assigned to undergo surgical decompression of the biliary tract (41 patients) or endoscopic biliary drainage (41 patients), followed by definitive treatment. Hospital mortality was analyzed with respect to the use of endoscopic biliary drainage and other clinical and laboratory findings. Prognostic determinants were studied by linear discriminant analysis.

Results.
Complications related to biliary tract decompression and subsequent definitive treatment developed in 14 patients treated with endoscopic biliary drainage and 27 treated with surgery (34 vs. 66 percent, P > 0.05). The time required for normalization of temperature and stabilization of blood pressure was similar in the two groups, but more patients in the surgery group required ventilatory support. The hospital mortality rate was significantly lower for the patients who underwent endoscopy (4 deaths) than for those treated surgically (13 deaths) (10 vs. 32 percent, P < 0.03). The presence of concomitant medical problems, a low platelet count, a high serum urea nitrogen concentration, and a low serum albumin concentration before biliary decompression were the other independent determinants of mortality in both groups.

Conclusions.
Endoscopic biliary drainage is a safe and effective measure for the initial control of severe acute cholangitis due to choledocholithiasis and to reduce the mortality associated with the condition.
Chronic Graft–Vs.–Host Disease of the Liver: Another Indication of Ursodeoxycholic Acid?
Authors: Erlinger Serge 
Published: March 2007

ABSTRACT

Objective:
To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft–versus–host disease (GVHD) of the liver.

Design:
Open–label study in which each patient served as his or her own control.

Setting:
Private practice and a university bone marrow transplant center.

Patients:
Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation.

Interventions:
After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks.

Measurements:
Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotrasferase (AST), alkaline phosphatase, gamma–glutamyltransferase (GGT), total serum bilirubin, prothrombin time.(Text missing).
Role of Mesenchymal Cell Populations in Porcine Serum–Induced Rat Liver Fibrosis
Authors: Bhunchet Ekapot , Wake Kenjiro 
Published: March 2007

The role of liver mesenchymal cell populations in porcine serum–induced rat liver fibrosis were studied morphologically and immunohistochemically. Fiveweek–old rats were intraperitoneally injected with porcine serum twice a week and examined at various intervals between 3 and 24 wk after the initial injection. At an early phase, numbers of fibroblasts and extracellular matrix increased in the walls of central veins and in portal and capsular connective tissues. In the walls of central veins, the number of “second–layer cells” (i.e., the fibroblasts located at the second layer of the wall) increased. Connective tissue septa, accompanying some fibroblasts, extended from these interstitial tissues into the hepatic parenchyma, and their foremost edges came into direct contact with the perisinusoidal stellate cells. The sinusoids adjacent to the newly formed septa collapsed and later disappeared; this process resulted in the formation of hepatic limiting plates along the septa. At a more advanced stage, the interstitial fibroblasts and septal cells–which were derived from interstitial fibroblasts and the stellate cells – increased and became multilayered, constructing three–dimensional cell networks. These networks, together with increased collagen fibrils and elastic fibers, constitute the fibrotic dense connective tissue.
In the control rat, smooth muscle cells were positive on vimentin, desmin and smooth muscle–α–actin staining. The stellate cells, second–layer cells, capsular and portal fibroblasts were shown to be vimentin and desmin positive and smooth muscle–α–actin negative. In the fibrotic liver, septal(fibroblastic) cells were vimentin and desmin positive and smooth muscle–α–actin negative.
We conclude that not only the perisinusoidal stellate cells but also the interstitial fibroblasts, including the second–layer cells, play substantial role in the development of porcine serum–induced septal fibrosis in rat liver.
Transmission of Hepatitis C: Sexual, Vertical or Exclusively Blood–Borne?
Authors: Bach Nancy , Bodenheimer Henry C. 
Published: March 2007

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother–to–child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti–HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti–HCV–positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti–HCV antibodies during follow–up. This loss of antibodies was also observed in PCR–negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.
Body fluids from 14 patients with chronic hepatitis C were analyzed for the presence of hepatitis C viral RNA using the polymerase chain reaction. Nucleic acids were extracted from serum, saliva, and semen in guanidinium thiocyanate, subjected to reverse transcription, and then amplified by a double polymerase chain reaction technique using “nested” primers from the highly conserved 5′ noncoding region of the hepatitis C virus genome. Hepatitis C viral RNA was found in the serum of all patients in titers ranging between 10-1 and 10-3. The hepatitis C viral genome was not detected in any saliva or semen sample. These findings suggest that body fluids of patients with chronic hepatitis C are rarely, if ever, contaminated with the hepatitis C virus. This may help to explain the infrequent transmission of this disease by sexual or close physical contact.
Persistence of Hepatitis B and Hepatitis C Viral Genomes in Primary Liver Cancers from HBsAg-Negative Patients: A Study of a Low-endemic Area
Authors: Paterlini Patrizia , Driss Françoise , Nalpas Bertrand , Pisi Emilio , Franco Dominique , Berthelot Pierre , Bréchot Christian 
Published: March 2007

The role of HBV and HCV in the course of primary liver cancer in patients who are negative for HBsAg has been debated. Using a combination of serological and polymerase chain reaction assays, we investigated the association between HCV and HBV infections and primary liver cancer in 24 HBsAg-negative patients living in France. The presence of HCV RNA and HBV DNA sequences was tested for in serum and in tumorous and nontumorous liver samples. Twelve patients had anti-HCV, and 11 patients had anti-HBs and/or anti-HBc. HCV RNA sequences were found in the serum samples of all anti-HCV-positive patients and none of the patients who were negative. Patients with HCV viremia had HCV RNA genomic sequences and presumed replicative intermediates in both tumorous and nontumorous specimens. Sequence analysis of a hypervariable region in the E2/NS1 gene of HCV showed significant variations between the viral molecules isolated from the nontumorous, tumorous and serum samples. This eliminated the hypothesis of the contamination of the tumor by nontumorous cells and serum particles and assessed that liver tumor cells did contain HCV RNA genomes.
Eleven of 22 patients tested had HBV DNA in the serum; 5 patients were anti-HBc positive and anti-HBs positive. Patients with HBV viremia had HBV DNA sequences in both tumorous and nontumorous liver specimens. Selective loss of part of the HBV genome in the tumorous tissue of two of these patients suggested HBV DNA persistence in clonally expanded malignant cells. Only 4 of the 22 patients were negative for both viruses. Our results show that HBsAg-negative hepatocellular cancer in France is associated with chronic HBV or HCV infection and, in some cases, both; these findings are consistent with an etiological role for HBV and HCV in HCC that develops in cirrhotic patients living in areas of low prevalence. (Hepatology 1993;17:20-29.)
Mixed chimerism after transplantation: Mechanism or marker of specific tolerance?
Authors: Judge Thomas 
Published: March 2007

We have previously reported data from clinical and laboratory animal observations which suggest that organ tolerance after transplantation depends on a state of balanced lymphodendritic cell chimerism between the host and donor graft. We have sought further evidence to support this hypothesis by investigating HLA-mismatched liver allograft recipients.
Nine of nine female recipients of livers from male donors had chimerism in their allografts and extrahepatic tissues, according to in-situ hybridisation and molecular techniques 10 to 19 years post-transplantation. In 8 women with good graft function, evidence of the Y chromosome was found in the blood (6/8), skin (8/8), and lymph nodes (7/8). A ninth patient whose transplant failed after 12 years from recurrent chronic viral hepatitis had chimerism in her lymph nodes, skin, jejunum, and aorta at the time of retransplantation.
Although cell migration is thought to take place after all types of transplantation, the large population of migratory cells in, and the extent of their seeding from, hepatic grafts may explain the privileged tolerogenicity of the liver compared with other organs.
Hepatitis B vaccine: Should we give it a shot?
Authors: Dickinson Chris J. , Olson Alan 
Published: March 2007

Objective:
To determine clinical and economic consequences of alternative vaccination strategies for preventing hepatitis B virus infection (HBV).

Methods:
Decision analysis was used to evaluate costs, outcomes, and cost-effectiveness of three HBV management strategies (“no vaccination,” “universal vaccination,” and “screen and vaccinate”) in four populations (newborns, 10-year-old adolescents, a high-risk adult population, and the general adult U.S. population). Information on HBV incidence and prevalence, clinical course, and management of acute illness and chronic sequelae was obtained from the literature and a panel of experts. Actual payments (costs) were obtained from Blue Cross/Blue Shield and local pharmacies. Incremental cost-effectiveness was calculated from the perspective of the payer of medical care and subjected to sensitivity analysis.

Results:
Vaccination (with or without screening) prevents more disease at somewhat increased cost than no vaccination for the neonatal, adolescent, and adult populations. Vaccination (with or without screening) is a dominant strategy in adult high-risk populations (lower cost and greater benefit than no vaccination). Optimal cost-effectiveness, with nonmonetary benefits not discounted, results if all pregnant women are screened for active HBV infection, and HBV vaccine and hepatitis B immune globulin are administered to babies born to mothers with positive screening tests. Then HBV vaccine is administered to all children at age 10 and again 10 years later (incremental cost-per-year-of-life-saved relative to the “no vaccination” strategy is $375). A strategy of universal newborn vaccination alone leads to an incremental cost-per-year-of-life saved of $3332. If adolescents are vaccinated at age 10, incremental cost-per-year-of-life saved is $13,938; for the general adult population, the incremental cost-per-year-of-life saved of universal vaccination is $54,524. Discounting benefits will increase cost-per-year-of-life saved 7 to 12 times for all strategies.

Conclusions:
HBV vaccine is most cost-effective when a strategy of screening newborns is combined with routine administration to 10-year-old children. The means to achieve substantial improvements in the health of the public in a cost-effective fashion are now available and should be pursued aggressively.
Cryoglobulinemia and hepatatrophic viruses
Authors: Baker Alfred L. 
Published: March 2007

Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis. This report presents four cases of cryoglobulinemia with vasculitis associated with chronic hepatitis related to hepatitis C virus infection. Hepatitis C virus infection was ascertained in the four patients by both the presence in the serum of anti-HCV antibodies detected by the fourantigen recombinant immunoblot assay and of HCV RNA detected by polymerase chain reaction. In two patients tested, anti-HCV antibodies were not detected after centrifugation in the purified cryoglobulin but were detected in the supernatant. HCV RNA was detected in the purified cryoglobulin in all four patients and was detected in the supernatant in three patients. In one patient receiving recombinant interferon alfa, serum aminotransferases normalized and cryoglobulin disappeared; in another patient receiving recombinant interferon alfa, serum aminotransferases remained high and the cryoglobulin persisted. The presence of HCV RNA in the cryoglobulin and the parallelism of the changes of the cryoglobulinemia and of the serum aminotransferases during recombinant interferon alfa administration suggest that HCV infection is responsible for the production of cryoglobulinemia and vasculitis. It is proposed that HCV infection is a cause of cryoglobulinemia associated with chronic hepatitis.

Background.
Type II cryoglobulinemia is a vasculitis characterized by cryoglobulins consisting of complexes of polyclonal IgG and monoclonal IgM rheumatoid factors. The cause of these immune complexes is unknown, though both the hepatitis B (HBV) and C (HCV) viruses have been suspected.

Methods.
We studied 19 patients with Type II cryoglobulinemia for markers of HCV and HBV infection. Quantitative HCV antibody and RNA studies were performed on whole serum, cryoprecipitates, and supernatants.

Results.
Eight patients (42 percent) had HCV antibodies, and 16 (84 percent) had HCV RNA. Of the 19 patients, 5 (26 percent) had HBV markers, but only 1 had evidence of active HBV infection. Control serum samples from nine patients with Type I cryoglobulinemia were negative for HCV antibody and HCVRNA. There was a close, although not exclusive, association of one type of rheumatoid factor (WA) with HCV RNA. HCV antibody and HCV RNA were concentrated approximately 10-fold and 1000-fold, respectively, in the Type II cryoglobulins examined.

Conclusions.
Type II cryoglobulinemia is strongly associated with concomitant HCV infection and a high rate of false negative serologic tests. HCV virions and HCV antigen-antibody complexes are concentrated in the cryoprecipitates, most commonly in association with the WA type of rheumatoid factor, suggesting a role for HCV in the pathogenesis of mixed cryoglobulinemia.