bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of chronic type B hepatitis with recombinant α-interferon induces autoantibodies not specific for autoimmune chronic hepatitis
Authors: Mayet Werner-J. , Hess Georg , Gerken Guido , Rossol Siegbert , Voth Rita , Manns Michael , ZumBüschenfelde Karl-Hermann Meyer 
Published: March 2007

Recombinant human α-interferon is now under intensive investigation as therapy for chronic Type B hepatitis. Recent reports have suggested that prolonged α-interferon therapy may induce autoimmune reactions. We have evaluated the problem of autoimmunity related to α-interferon therapy by testing for 15 different antibodies in the sera of 31 patients treated with α-interferon. No patient had autoantibodies before treatment; 27 (87%) of 31 patients developed at least one autoantibody. Eleven patients had antinuclear antibodies and 21 had smooth muscle antibodies, both of which usually developed during α-interferon therapy. In contrast, antibodies to endocrine organs such as thyroid microsomal, thyroglobulin and parietal cell antibodies arose in 12 patients, but usually several months after α-interferon treatment. The appearance of these autoantibodies did not correlate with disease activity or response to α-interferon. No patient developed autoantibodies specifically associated with autoimmune liver diseases such as liver kidney microsomal antibodies, autoantibodies to soluble liver antigen and the primary billiary cirrhosis-specific subtypes of antimitochondrial antibodies.
These results suggest that prolonged α-interferon therapy can induce autoantibody production and, in susceptible patients, may lead to autoimmune disorders.
Prolonged duck hepatitis B virus replication in duck hepatocytes cocultivated with rat epithelial cells: A useful system for antiviral testing
Authors: Fourel Isabelle , Gripon Philippe , Hantz Oliver , Cova Lucyna , Lambert Véronique , Jacquet Chantal , Watanabe Kyoichi , Fox Jack , Guillouzo Christiane , Trepo Christian 
Published: March 2007

Duck cultured hepatocytes from Pekin ducks naturally infected by duck hepatitis B virus can remain functional twice longer if a coculture system with rat liver epithelial cells is used instead of ordinary primary culture. The use of a selective medium in which ornithine and lactate replaced arginine and glucose, respectively, allowed viral replication initiated in vivo to be maintained in the coculture for 2 months.
Several antiviral compounds including the pyrophosphate analog (phosphonoformic acid) or nucleoside analogs (9β-arabinofuranosyl AMP, 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodocytosine, 1,2′-deoxy-2′-fluoro-β-D-arabinofuranosyl-5-ethyluracil and 1,2′-deoxy-2′-fluoro-β-D-arabinofuranosyl thymine were studied in both culture systems for their ability to inhibit duck hepatitis B virus replication. Hepatocytes were treated for 7 days with 1,2′-deoxy-2′-fluoro-β-D-arabinofuranosyl-5-ethyluracil (10 μM) and 1,2′-deoxy-2′-fluoro-β-D-arabinofuranosyl thymine (0.5 μM) or for 14 days with 9β-arabinofuranosyl AMP (90 μM), phosphonoformic acid (100 μM) and 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodocytosine (6 μM). The effects of the drugs on viral replication were monitored by testing for duck hepatitis B virus DNA in the culture supernatant and in the cells by molecular hybridization. All the above-mentioned drugs demonstrated an inhibitory activity in both types of cultures which at the quite distinct doses used was greater for phosphonoformic acid and 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodocytosine than for 9β-arabinofuranosyl AMP, 1,2′-deoxy-2′-fluoro-β-D-arabinofuranosyl-5-ethyluracil or 1,2′-deoxy-2′-fluoro-β-D-arabinofuranosyl thymine. Viral replication, however, resumed following discontinuation of treatment.
More studies are needed to further confirm the relevance of this tissue culture system for the screening of new potential anti-hepatitis B virus agents.
Hepatitis during measles in young adults: Possible role of antipyretic drugs
Authors: Ackerman Zvi , Flugelman Moshe Y. , Wax Yohanan , Shouval Daniel , Levy Micha 
Published: March 2007

Fifty-six per cent of 118 young adults observed during a recent measles epidemic had some disturbance on liver function tests. Five per cent developed overt jaundice. Patients treated for fever with paracetamol were found to have significantly higher rates of transaminase impairment compared to those treated with dipyrone. Sixty-five and 58% of patients given paracetamol had elevated ALT and AST levels, respectively. Only 15% of patients given dipyrone had elevated levels of these two enzymes (p < 0.01 for ALT and p < 0.02 for AST).
The mean levels of transaminases and bilirubin in the paracetamol-treated patients were significantly higher than those found in the dipyrone-treated patients [92 ± 86 vs. 42 ± 49 IU (p < 0.02) for AST and 12 ± 6.0 vs. 7.0 ± 2.0 μmoles per liter (p < 0.01) for bilirubin]. The cumulative dose of paracetamol in those who had impaired liver function was higher than that ingested by patients who did not develop liver damage, although still within the usual therapeutic range [11.6 ± 5.8 vs. 7.6 ± 4.2 gm (p = 0.02)]. The possible ways in which measles infection and paracetamol in combination can lead to hepatic damage are discussed.
Effects of propylthiouracil and methimazole on splanchnic hemodynamics in awake and unrestrained rats
Authors: Kawasaki Tsunehisa , Carmichael Frederick J. , Giles Gwynne , Saldivia Victor , Israel Yedy , Orrego Hector 
Published: March 2007

The treatment of alcoholic liver disease with propylthiouracil is based on its effect of suppressing the ethanol-induced increase in hepatic oxygen consumption. It has been postulated that liver necrosis ensues when the increase in oxygen demand by the liver exceeds oxygen delivery to this organ. Data are now presented which show that propylthiouracil also increases portal blood flow in awake, unrestrained rats.
Liver blood flow was determined using the labeled microsphere technique in rats at various intervals (0.25, 0.5, 1.0, 3.0, 6.0 and 24 hr) after oral propylthiouracil (50 mg per kg). Administration of propylthiouracil (dose range: 6.25 to 100.0 mg per kg) produced a dose-dependent increase in portal blood flow when given either orally or intraarterially. Maximal flows were obtained with 50 mg per kg (controls = 37.8 ± 1.5, oral propylthiouracil = 50.7 ± 2.2 ml ± kg−1-min−1). This increase in portal blood flow was accompanied by a decrease in preportal vascular resistance (controls = 2.61 ± 0.16; propylthiouracil, 50 mg per kg = 1.79 ± 0.09 mmHg per ml ± kg−1 ± min−1). These effects were correlated with the plasma concentrations of propylthiouracil (r = 0.67, n = 68, p ≤ 0.001). The effect of oral propylthiouracil (50 mg per kg) on portal blood flow started at 0.5 hr and lasted for 6 hr after administration, whereas total liver blood flow was increased for 3 hr. Oral propylthiouracil (50 mg per kg) for 5 days resulted in a 53% increase in thyroid weight, an 85% reduction in 125I thyroid uptake and a 74% decrease in serum thyroxine concentration. This treatment, however, did not modify portal blood flow, nor the response to acute propylthiouracil. Oral administration of equipotent doses of another antithyroid drug, methimazole (10 and 20 mg per kg), had no effect on portal blood flow. Because of the rapid increase in portal blood flow following a single oral or parenteral dose of propylthiouracil and the lack of effect of methimazole, it is concluded that this response of propylthiouracil is independent of its effect on the thyroid gland and of intestinal absorption. The increase in portal blood flow can contribute to the protective effect of propylthiouracil against alcohol-induced liver necrosis by increasing oxygen delivery to the liver.
Hepatitis delta virus infection in French male HBsAg-positive homosexuals
Authors: Pol Stanislas , Dubois Frédéric , Roingeard Philippe , Zignego Linda , Housset Chantal , Brechot Christian , Goudeau Alain , Berthelot Pierre 
Published: March 2007

The prevalence and serological features of hepatitis delta virus infections were studied in a French population of chronic, non-drug addict, hepatitis B surface antigen carriers: 42 male homosexual patients were compared to 30 nonhomosexuals (20 who evidently had not been exposed to any of the usual hepatitis B virus-hepatitis delta virus risk factors and 10 hemodialyzed patients or kidney allograft recipients).
Six of the 42 male homosexuals (14.3%) had at least one serological marker of hepatitis delta virus infection (hepatitis delta antigen, total and/or IgM anti-hepatitis delta antibodies). Serological follow-up was obtained for five of these patients over several months and confirmed the chronicity of the delta infection in at least four of the five subjects. Hepatitis delta antigen and hepatitis delta virus RNA were found in the liver and in the serum, respectively, of four of the five tested patients.
Hepatitis B virus DNA was negative in the serum of five of the six hepatitis delta virus-positive homosexuals vs. only eight of 35 hepatitis delta virus-negative homosexuals (p < 0.02). Human immunodeficiency virus was negative in all of the nonhomosexuals; its prevalence did not differ between the hepatitis delta virus-positive and -negative homosexuals: three were human immunodeficiency virus-positive among the six former vs. 15 among the 36 latter. Human immunodeficiency virus positivity was without obvious influence on hepatitis B virus replication, since among 35 hepatitis delta virus-negative homosexuals hepatitis B virus DNA was found in 80% of the human immunodeficiency virus-positive individuals and 70% of those who were human immunodeficiency virus-negative.
Our results provide evidence for the following: French homosexual hepatitis B surface antigen chronic carriers are at particular risk of hepatitis delta virus infection, most often chronic, quite probably related to sexual transmission and characterized by a wide range of serological hepatitis delta virus profiles.
Effect of d-tryptophan-6-luteinizing hormone-releasing hormone on the tumoral growth and plasma sex steroid levels in cirrhotic patients with hepatocellular carcinoma
Authors: Guéchot Jérôme , Peigney Nicolas , Ballet François , Vaubourdolle Michel , Giboudeau Jacqueline , Poupon Raoul 
Published: March 2007

Certain evidence suggests androgen dependence of hepatocellular carcinoma in cirrhotic patients. Consequently, it was postulated that antiandrogen therapy might be effective in the treatment of hepatocellular carcinoma. d-Tryptophan-6-luteinizing hormone-releasing hormone is a potent agonist analog of luteinizing hormone-releasing hormone which, when chronically administered, inhibits the pituitary gonadal axis and testicular androgen secretion in man. We studied the effects of d-tryptophan-6-luteinizing hormone-releasing hormone on tumoral growth in 17 male cirrhotic patients with hepatocellular carcinoma. After 3 to 6 months of therapy, no tumoral response was observed. Furthermore, measurements of plasma levels of testosterone, dihydrotestosterone, androstenedione, estradiol, estrone and sex hormone-binding globulin were performed before and 3 months after initiation of the antiandrogenic treatment. Before treatment, hypoandrogenism and hyperestrogenism were present; d-tryptophan-6-luteinizing hormone-releasing hormone induced a fall in plasma testosterone and dihydrotestosterone levels. Only a moderate decrease in estradiol and no modification of plasma estrone and sex hormone-binding globulin were found, indicating that the hyperestrogenemia of cirrhotic patients could be attributed to an increase in peripheral aromatization of androgens of adrenal origin.
The inability of d-tryptophan-6-luteinizing hormone-releasing hormone to reduce the growth of hepatocellular carcinoma is not totally in disagreement with the concept of androgen dependence of hepatocellular carcinoma since d-tryptophan-6-luteinizing hormone-releasing hormone does not inhibit the production of androgens of adrenal origin.
Uptake of Bile Acids by Perfused Rat Liver: Evidence of A Structure–Activity Relationship
Authors: Aldini Rita , Roda Aldo , Simoni Patrizia , Lenzi Pierluigi , Roda Enrico 
Published: March 2007

The hepatic extraction of unconjugated and taurineconjugated bile acids, provided with different hydrophilicity values, has been measured in the perfused rat liver, in order to evaluate the role of the bile acid structure and bile acid hydrophilicity on their uptake by the liver. Ursocholic, cholic, ursodeoxycholic and chenodeoxycholic acids, free and taurine–conjugated, were injected into the portal vein in dose response studies, using a nonrecirculating perfusion system.
For all of the bile acids, the uptake process showed saturation.
In addition, a nonsaturable component was apparent in bile acids provided with the lowest hydrophilicity values, as expressed by the lowest values of the water to octanol partition coefficient. The maximum uptake velocity increased with increasing values of the partition coefficient, which in turn were associated with 7–OH α to β epimerization, the presence of 12–OH in α position and taurine conjugation. The ratio of maximum uptake velocity to Km (Km being the half–saturation constant) appeared to be markedly increased by taurine conjugation and by 7–OH α to β epimerization, whereas it was reduced by the presence of 12–OH in α position.
Reduction of Intrapulmonary Shunt and Resolution of Digital Clubbing Associated With Primary Biliary Cirrhosis After Liver Transplantation
Authors: Stoller James K. , Moodie Douglas , Schiavone William A. , Vogt David , Broughan Thomas , Winkelman Eugene , Rehm Patrice K. , Carey William D. 
Published: March 2007

This report describes a patient with marked hypoxemia caused by intrapulmonary shunt associated with primary biliary cirrhosis. Liver transplantation resulted in resolution of digital clubbing and reduction of intrapulmonary shunt as demonstrated by normalization of room air arterial blood gases, reduction in shunt fraction and normalization of the indocyanin–enhanced echocardiogram and perfusion lung scan.
This patient's course challenges the conventional notion that intrapulmonary shunting associated with chronic liver disease does not reverse after liver transplantation. (HEPATOLOGY 1990; 11: 54-58.)
In Vivo Hepatic Energy Metabolism During the Progression of Alcoholic Liver Disease: A Noninvasive 31P Nuclear Magnetic Resonance Study in Rats
Authors: Takahashi Hisao , Geoffrion Yves , Butler Keith W. , French Samuel W. 
Published: March 2007

We investigated serially in vivo the rations of phorylated metabolites and the intracellular PH in the livers of rats fed ethanol chronically to evaluate the relation between changes in energy metabolism and the progression of alcoholic liver disease with 31P nuclear magnetic resonance spectroscopy.

31P nuclear magnetic resonance spectra of the liver were acquired noninvasively from rats pair–fed a nutritionally adequate liquid diet containing ethanol or an isocaloric amount of dextrose with an implanted intragastric cannula of dextrose with an implanted intragastric cannula for up to 24 wk. A high blood alcohol level was constantly maintained. The spectra were obtained using a surface coil combined with a ferrite screen to eliminate nuclear magnetic resonance signals derived from the superficial muscles. Contaminating 31P nuclear magnetic resonance signals. Contaminating 31P nuclear magnetic resonance signals arising from abdominal tissues other than the liver were climinated from the spectra by digital subtraction.
Throughout the study the inorganic phosphate/β– ATP peak area ratio observed in alcohol–fed rats was found to be consistently elevated in comparison with the control rats ( at 3 to 5 wk alcohol–fed rats = 1.20 ± 0.10, control rats = 0.78 ± 0.04, p < 0.05,; at 22 to 24 wk alcohol–fed rats = 1.23 ± 0.10, control rats = 0.81 ± 0.06, p < 0.05.; mean ± S. E.). The phosphomonoesters/β–ATP ratio tended to be higher in alcohol–fed rats when compared with control rats. The intracellular pH measured by the chemical shift of the inorganic phosphate peak showed no significant differences between alcohol–fed rats and control rats. Steatosis, necrosis, inflammation and fibrosis were observed to be progressively more severe in the monthly liver biopsy speciments from alcohol–fed rats, so that the pathological score significantly increased with the duration of feeding (r = 0.623, p <0.001). The inorganic phosphate / β–ATP ratio was not significantly correlated with the changing pathological score, since the increased inorganci phosphate/β –ATP ratios remained constant over the duration of feeding.
This observation suggests that the increase in the inorganic phosphate/β–ATP rations is a primary effect of chronic ethanol feeding rather than a result of the workesening morphological changes observed in the liver. This low energy state in the liver may contribute to the pathogenesis of alcoholic liver disease. (HEPATOLOGY 1990; 11: 65-73.)
The Natural History of Nonalcoholic Steatohepatitis: A Follow–Up Study of Forty–Two Patients for Up to 21 Years
Authors: Powell Elizabeth E. , Cooksley Graham W.E. , Hanson Reginald , Searle Jeffrey , Halliday June W. , Powell Lawrie W. 
Published: March 2007

Forty–two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obeser; 35 o f42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Inital liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked and in another two subjects liver biopsy showed marked fibrosis with distured architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5–yr observation period, and in the patients with extensive fibrosis the the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis.
We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol–induced liver disease but usually slowly progressive and of low–grade severity. However, the disorder may ultimatley result in cirrhosis, Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of “cryptogenic cirrhosis.” (HEPATOLOGY 1990; 11: 74-80.)
Graft–Vs.–Host Disease After Liver Transplantation
Authors: Alexander Graeme , Portmann Bernard 
Published: March 2007

Clinically evident, generalized graft–vs.–host disease is not thought to occur as a consequence of transplantation of most solid organs. The large inoculum of donor lymphoid cells required and the inability of the recipient to destroy these passenger cells are apparently rarely produced by solid–organ transplantation. However, there is a risk of graft–vs.–host disease when normal spleens are included in vascularized pancreas transplants.
We report on a case of severe, generalized acute graft–vs.–host disease in a recipient of a liver tranplant, involving documented transient chimerism of donor origin. This life–threatening complication was treated successfully with increase in the corticosteroid dosage and administration of anti–thymocyte globulin.
A Controlled Trial of Oral Propranolol Compared With Injection Sclerotherapy for the Long–Term Magnagement of Variceal Bleeding
Authors: Westaby David , Polson Rex J. , Gimson Alexander E.S. , Hayes Peter C. , Hayllar Karen , Williams Roger 
Published: March 2007

This trial was carried out to assess the value of propranolo for the prevtion of recurrent variceal bleeding in patinets with well–compensated cirrhosis. We also compared porpranolol therapy to long–term injection sclerotherapy. One hundred and eight patients, in whom the orginal variceal hemorrhage stopped spontaneousley (before diagnostic endocopy) and without sclerotherpay or surgical intervention were included. All were pugh grade A or B; 55% had alcoholic cirrohosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long–term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long–term sclerothrapy. Follow –up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long–term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (P < 0.20). On an intetion–to–treat basis, the risk of bleedings expressed per patient–month of follow–up was similar for the two groups, at 0.05 and 0.037, respectitively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p <0.40). Stepwise regression analysis of possible factors prediciting further bleeding in patients taking propranolo selected only two variables — the pretreatment pulse rate and the extent of pulse–rate reduction in response to propranolol.
These data support propranolol as an alternative first–line measure to long–term injection for the management of variceal bleeding. The pretreatment pulse rate and subsequent response to propranolo may provide means of selecting those most likely to benefit. (Hepatology 1990;11:353-359.)