bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual color fluorescence analysis of peripheral T cell subsets in hepatitis B virus-induced liver disease
Authors: Hasegawa Kiyoshi , Yamauchi Katsumi , Furukawa Takaji , Obata Hiroshi
Published: March 2007

By using dual color fluorescence analysis, peripheral T cells can be divided into four different subsets, Leu-2a+, Leu-2a+15−, Leu-3a+8+ and Leu-3a+8− cells. The ratio of these T cell subsets in hepatitis B virus-induced hepatitis patients was studied and compared with that of controls. No significant difference was found in acute hepatitis and chronic hepatitis, but an elevation of Leu-2a+15− (29.5 ± 2.8% vs. 18.8 ± 4.1%, p < 0.05) as well as a reduction of Leu-2a+15+ cells (3.2 ± 0.7% vs. 10.4 ± 3.2%, p < 0.05) were found in fulminant hepatitis patients. In addition, serial studies of two fulminant hepatitis patients revealed that the imbalance of these two Leu-2a cells was only found in the acute phase, but not in the recovery phase. These results indicate that the imbalance of these two Leu-2a cells is associated with the clinical status of patients with fulminant hepatitis.
The demise and resurrection of large paracenteses
Authors: Rodés Joan
Published: March 2007

To investigate the usefulness of paracentesis as an alternative treatment for ascites, 41 cirrhotic patients with ‘tense’ ascites were randomly assigned to treatment with either repeated paracenteses plus i.v. albumin infusion (n=20) or diuretics (n=21). Satisfactory mobilization of ascites was obtained with paracentesis in all but one case and with diuretics in all but two cases. Ascites disappeared within 3 or 4 days with paracentesis, but only after 15 days with diuretics. The rate of reaccumulation of ascites following paracentesis, without diuretic administration, exceeded 300 g/day in only 5 patients. The incidence of complications and the mortality rate were similar in both groups of patients during hospital stay and during follow-up. This was corroborated by the evidence that no negative changes were induced in clinical and laboratory parameters of hemodynamic, hepatic and renal function after evacuation of the ascites. These results confirm that repeated paracenteses combined with human albumin replacement are safe and effective for treating ‘tense’ ascites, and more rapid than traditional diuretic therapy.
A rat strain that spontaneously develops severe hepatic necrosis and later hepatocellular carcinoma
Authors: Okuda Kunio
Published: March 2007

A new mutant causing hereditary hepatitis associated with severe jaundice has been discovered in the LEC strain of rats. Hepatitis appears suddenly in adult rats three to four months after birth. The clinical signs of hepatitis are characterized by severe jaundice, subcutaneous bleeding, oliguria, and loss of body weight. The affected rats showed a high lethality and histological changes of the liver with focal necrosis of enlarged hepatocytes without inflammatory cell response. Genetic tests indicate that at least a single autosomal recessive gene is responsible for the major cause of hepatitis. Furthermore, liver cancer appears in long survived rats after recovery from jaundice as well as a few asymptomatic rats without jaundice. The LEC rats thus provide an animal model useful for the basic and clinical studies of hepatitis and liver cancer, including their pathogenesis, prevention, and treatment.
Acupuncture in epidemic HBV hepatitis: In china too?
Authors: Conn Harold O.
Published: March 2007

An epidemiologic investigation of an acupuncturist’s practice in Rhode Island identified 35 patients who were infected with hepatitis B virus during 1984. Of 366 patients seen by the acupuncturist during 1984,316 (86%) completed questionnaires and submitted serum for hepatitis B serology. Use of tests for immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) identified 17 case-patients who otherwise may have gone undetected. Thirty-four of the 35 case-patients were treated in only one of the two clinics run by the acupuncturist. Patients who received a greater number of acupuncture needles during their treatment course were more likely to have been infected; the attack rate for patients who received <150 needles was 9%, compared with 33% for patients who received ≥450 needles (p < 0.001). Attack rates were higher during a one-month period when the index case-patient was more likely to have been viremic than during any other period in 1984 (relative risk = 4.1, 95% confidence interval = 2.3-7.3). While observing the acupuncturist’s technique, the investigators noted several potential mechanisms for needle contamination. This study highlights the potential for transmission of hepatitis B in situations of repeated needle use.
Three-dimensional view of the vascular structure of the lower esophagus in clinical portal hypertension
Authors: Hashizume Makoto , Kitano Seigo , Sugimachi Keizo , Sueishi Katsuo
Published: March 2007

The venous anatomy of the lower esophagus and upper stomach was studied in nine patients with portal hypertension and in five without, following infusion of a silicon rubber compound into vessels of the excised organs within whole tissues made transparent with methyl salicylate. Four venous channels were identified in normal tissues: intraepithelial, subepithelial superficial, deep submucosal and adventitial veins. In portal hypertensive patients, giant esophageal varices formed 2 to 3 cm above the esophagogastric junction fused with numerous superficial and deep submucosal veins. Gastric varices were present in the submucosa where the left gastric venous branch penetrated the gastric wall 2 cm below the esophagogastric junction. The lower esophageal varices were classified into two types of vascular structure: palisading type in five and bar type in four. The palisading type had dilated intraepithelial channels and numerous small superficial collateral veins extending in a longitudinal arrangement. The bar type had triply dilated subepithelial superficial veins and deep submucosal veins which eroded the epithelium, and the gastric varices were present in the latter type. Our study provides evidence of the three-dimensional vascular structure of the lower esophageal varices without the necessity for tissue dissection.
Microvascular abnormalities of the portal hypertensive gastric mucosa
Authors: Tarnawski Andrzej S. , Sarfeh James I. , Stachura Jerzy , Hajduczek Andrew , Bui Hai X. , Dabros Wojciech , Gergely Hella
Published: March 2007

Compared with normotensive mucosa, the portal hypertensive gastric mucosa has increased susceptibility to injury by noxious agents such as alcohol and aspirin, but the mechanism of this phenomenon is unclear. Since the microvasculature of the normal gastric mucosa is an important target of injury by these agents, we studied the histologic and ultrastructural features of gastric vasculature and mucosal microvasculature in rats with portal hypertension (produced by staged portal vein ligation) and in sham-operated rats. In portal hypertensive rats, the gastric mucosa was swollen and hyperemic and the endothelial cells of mucosal microvessels had very prominent enlarged cytoplasm obstructing capillary lumina. Quantitative analysis of transmission electron micrographs demonstrated that in portal hypertensive rats the gastric mucosal capillary endothelium had significantly increased cytoplasmic area (236%), increased pinocytic vesicular area (416%) and increased capillary basement membrane thickness (143%) compared to respective parameters in sham-operated control rats. Arterioles in the muscularis mucosae and in submucosa were thickened, and submucosal veins demonstrated features of arterialization. All these findings indicate that portal hypertension produces definite microvascular changes in the gastric mucosa resulting in compromise of the capillary lumina. These changes may be the basis for the observed morphologic and functional abnormalities of the portal hypertensive mucosa and its increased predisposition to injury.
Prophylactic sclerotherapy of high-risk esophageal varices: Results of a multicentric prospective controlled trial
Authors: Piai Guido , Cipolletta Livio , Claar Max , Marone Giampiero , Bianco Maria Antonietta , Forte Giovanni , Iodice Giuseppe , Mattera Daniele , Minieri Mauro , Rocco Pietro , Santoro Lorenzo Michele , Mazzacca Gabriele
Published: March 2007

In this prospective, multicenter trial, 140 cirrhotic patients with no previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage were randomized to receive either sclerotherapy or conservative treatment for the prevention of first variceal bleeding. The end-points of the study were bleeding and death. Life table curves showed that prophylactic sclerotherapy significantly diminished the incidence of variceal hemorrhage (p < 0.001) and overall mortality (p < 0.01). Two-year cumulative bleeding rate was 18% in the sclerosis group (95% confidence interval = 10 and 31) and 57% (95% confidence interval = 40 and 72) in the control group. Two-year cumulative mortality rate was 30% (95% confidence interval = 19 and 45) in the sclerotherapy group and 56% (95% confidence interval = 39 and 72) in the controls. One patient died after hemorrhage from an ulcer secondary to sclerotherapy. Analysis by the Cox model of the factors potentially confounding or interacting with the effect of sclerotherapy suggested that sclerotherapy was more efficient in preventing first bleeding in patients with decompensated disease (Child B and C) than in those in good condition (Child A). However, the 2-year cumulative bleeding rate of untreated Child A patients was only 19%, showing how in this group the endoscopic findings were unreliable in selecting high-risk varices and explaining why after a 2-year follow-up prophylactic sclerosis did not show any benefit in such patients.

We conclude that sclerotherapy can decrease the incidence of first variceal bleeding and death for a period of 2 years in cirrhotic patients with high-risk varices.
Glucagon selectively increases splanchnic blood flow in patients with well-compensated cirrhosis
Authors: Lee Samuel S. , Moreau Richard , Hadengue Antoine , Cerini Raimondo , Koshy Abraham , Lebrec Didier
Published: March 2007

To delineate the circulatory effects of glucagon in cirrhosis, we infused two moderately supraphysiological doses of this hormone into 19 patients with cirrhosis and determined hemodynamic responses. Patients were divided into a group with good liver function (Pugh Class A, n = 8) and poorer function (Pugh Class B and C, n = 11). All patients received glucagon at 10 ng per kg per min for 20 min, then 20 ng per kg per min for a further 20 min. These doses raised serum glucagon levels to a similar degree in both groups of patients. Serum glucose levels also rose in both groups but to a lesser degree in Class BC patients. Serum noradrenaline and adrenaline remained unchanged in both groups. Heart rate, mean arterial pressure, cardiac index, systemic vascular resistance, hepatic venous pressure gradient and hepatic blood flow were measured basally and during the second glucagon infusion. None of these measurements significantly changed in either group of patients. Azygos and renal venous blood flow were measured basally and during the first and second infusions. Azygos flow increased significantly only in Group A patients: basal, 0.32 ± 0.03 liter per min; first infusion, 0.40 ± 0.06 liter per min; second infusion, 0.49 ± 0.07 liter per min. Corresponding values in Group BC patients were: 0.54 ± 0.08, 0.54 ± 0.08 and 0.52 ± 0.08 liter per min. Renal blood flow did not change significantly. One patient with a portacaval shunt increased superior mesenteric venous flow from 0.78 liter per min to 0.95 liter per min with glucagon. These results, showing a selective increase in superior portocollateral flow in well-compensated patients, suggest that glucagon can act as a splanchnic vasodilator. However, since progression of liver disease was associated with attenuation of this response, we suggest that glucagon may mediate splanchnic hyperemia only in the early stages of cirrhosis.
Heterogeneous acinar localization of the asialoglycoprotein internalization system in rat hepatocytes
Authors: Sluijs Peter Van Der , Braakman Ineke , Meijer Dirk K. F. , Groothuis Geny M. M.
Published: March 2007

Desialylated glycoprotein is rapidly cleared from plasma by a receptor-mediated endocytic mechanism located on hepatocytes. We studied the hepatic acinar distribution of this asialoglycoprotein transport system with the ligand 125I-asialoorosomucoid using rat liver perfused in either antegrade or retrograde direction in combination with quantitative light microscopic autoradiography. Grain distribution along the acinus appeared dependent on the perfusion direction. A rather shallow zone 1 to zone 3 gradient was observed if livers were perfused in the normal direction. However, a statistically significantly steeper zone 3 to zone 1 gradient was detected in retrograde perfusions. Kinetic analysis of perfusate clearance profiles yielded a hepatic clearance of 21.6 ± 1.3 ml per min in antegradely perfused liver. Hepatic extraction was calculated to be 60.1 ± 7.4%. Biliary secretion of radioactivity amounted to 1.89 ± 0.18% of the dose within 1 hr after injection and consisted of intact material (1.39 ± 0.25%) and radioactive low-molecular-weight degradation products (0.52 ± 0.08%), of which more than 90% could be accounted for by 125I−. Apart from a minor difference regarding biliary secretion of an unidentified glycopeptide (less than 0.1% of the injected dose), transport data for the retrogradely perfused livers were identical to those obtained with livers perfused in antegrade direction, emphasizing the functional equivalence of both groups of livers. The autoradiographic data indicate that zone 3 hepatocytes take up 125I-asialoorosomucoid more avidly than zone 1 cells. The kinetic and biochemical data indicate that further processing in the hepatocytes is virtually similar in the two zones. The functional significance of this higher uptake in zone 3 is presently unknown. A possible role in the mechanism of removal of senescent plasma proteins is discussed.
S-Phase cells in diseased human liver determined by an in Vitro BrdU-anti-BrdU method
Authors: Shimizu Akio , Tarao Kazuo , Takemiya Shouji , Harada Masaoki , Inoue Tohru , Ono Tetsuo
Published: March 2007

Using a monoclonal antibody to bromodeoxyuridine, we studied the cell kinetics of human hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis. Specimens were taken either by biopsy or surgery and immediately incubated with 0.1% bromodeoxyuridine solution at 37°C for 45 min. After in vitro labeling, the bromodeoxyuridine taken up by the nuclei of S-phase cells was determined by the avidinbiotin-peroxidase complex method, using an anti-bromodeoxyuridine monoclonal antibody as the first antibody. The number of positive nuclei in 1,000 hepatic cells was counted, and the bromodeoxyuridine labeling index was expressed per thousand.

The mean bromodeoxyuridine labeling index ± S.D. of the cancerous portion of hepatocellular carcinoma, the noncancerous portion of hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis were 64.1 ± 31.3, 33.6 ± 14.4, 23.2 ± 20.8, 9.1 ± 6.1 and 21.6 ± 13.0, respectively. The mean bromodeoxyuridine labeling index of the hepatocellular carcinoma cancerous portion was statistically higher than that of any other group. There was no statistical difference by the t test or the Wilcoxon test between the noncancerous portion of hepatocellular carcinoma and liver cirrhosis, and these two groups were proved interdependent by χ2 test (Fisher’s exact test), whether they were subdivided by bromodeoxyuridine labeling index ±10 or not.

Bromodeoxyuridine labeling index was not significantly correlated with the usual biochemical parameters such as serum AST, ALT, γ-GTP, alkaline phosphatase, lactate dehydrogenase, cholinesterase, albumin, and α-fetoprotein.

These results suggest that the bromodeoxyuridine labeling index of biopsied or resected specimens could give valuable information on cell kinetics when analyzing liver diseases and could be especially useful in distinguishing hepatocarcinogenesis from hepatic cirrhosis.
The autologous mixed lymphocyte reaction in primary biliary cirrhosis: Analysis of activation and blastogenesis of autoreactive T lymphocytes
Authors: Lindor Keith D. , Wiesner Russell H. , Dickson Rolland E. , Homburger Henry A.
Published: March 2007

Blastogenesis of autoreactive T lymphocytes in the autologous mixed lymphocyte reaction has been shown to be decreased in patients with primary biliary cirrhosis, but the mechanisms underlying this abnormality are not known. To investigate further the abnormal autologous mixed lymphocyte reaction in primary biliary cirrhosis, we measured the activation of autoreactive helper/inducer and suppressor/cytotoxic T lymphocytes concurrently with blastogenesis in 35 patients with primary biliary cirrhosis and 18 healthy controls. Blastogenesis was diminished in autologous mixed lymphocyte reaction cultures from primary biliary cirrhosis patients compared to the control subjects (25,273 ± 20,259 dpm vs. 36,004 ± 14,951 dpm, p < 0.02), but cultures from patients with primary biliary cirrhosis contained significantly increased percentages of activated helper/inducer and suppressor/cytotoxic T lymphocytes: 20.6 ± 7.9 vs. 15.5 ± 5.3%, p < 0.008, and 9.8 ± 7.8 vs. 5.4 ± 3.0%, p < 0.02, respectively. These findings were not related to the histologic stage of liver disease or to the serum bilirubin concentration and were not associated with abnormalities of lymphocyte subsets in fresh peripheral blood specimens. We conclude that the percentage of autoreactive T lymphocytes in autologous mixed lymphocyte reaction cultures from peripheral blood is increased in patients with primary biliary cirrhosis and diminished blastogenesis in autologous mixed lymphocyte reaction cultures is not due to the loss of autoreactive T lymphocytes from peripheral blood. Diminished blastogenesis reflects a diminished proliferative response of activated, autoreactive T lymphocytes in primary biliary cirrhosis. Possible mechanisms that may account for the paradoxical findings of decreased blastogenesis and increased activation of autoreactive T lymphocytes in primary biliary cirrhosis are discussed.
Phospholipase activity in human bile
Authors: Nakano Toru , Yanagisawa Jiro , Nakayama Fumio
Published: March 2007

To investigate the importance of bacterial infection in the formation of free fatty acids found in brown pigment gallstones, free fatty acids and phospholipase activity in hepatic bile, with or without the presence of bacterial infection, were compared. The concentration of free fatty acids in bile with bacterial infection [0.467 ± 0.447 mg per ml (mean ± S.D.)] was significantly higher than when bacterial infection was absent (0.073 ± 0.041 mg per ml; p < 0.01). However, there was no significant difference in the composition of free fatty acids in hepatic bile when bacterial infection was present. Biliary phospholipase activity was determined by counting [14C] palmitic acid released from [14C]dipalmitoyl phosphatidylcholine that was incubated with native bile. The biliary phospholipase activity was significantly higher when bacterial infection was present. Furthermore, a positive correlation (p < 0.001) was found between the activity of biliary phospholipases and the concentration of free fatty acids in hepatic bile. Most bacterial strains isolated from bile were shown to have both phospholipase A1 and A2 activity. On the other hand, human pancreatic juice and human gallbladder epithelial cells contained mainly phospholipase A2. Since fatty acids in the gallstone are mainly palmitic acid and must have been cleaved from first position in the biliary phosphatidylcholine molecule, bacterial phospholipase A1 seems to play an important role in the formation of calcium palmitate found in brown pigment gallstones.
The relationship between insulin sensitivity and skeletal muscle enzyme activities in hepatic cirrhosis
Authors: Kruszynska Yolanta , Williams Nicholas , Perry Michael , Home Philip
Published: March 2007

We have examined the hypothesis that insulin insensitivity in hepatic cirrhosis is related to abnormalities of glycogen deposition and skeletal muscle enzyme activities. Otherwise well patients with biopsy-proven hepatic cirrhosis secondary to previous excess alcohol intake were studied. Prior to study, in basal state, patients had identical blood glucose concentrations but raised serum insulin concentrations (cirrhotic: 8.5 ± 0.8 mU per liter; matched control subjects: 5.7 ± 0.5 mU per liter, p < 0.01). Muscle glycogen content, glycogen synthase activity and pyruvate dehydrogenase activity were normal in the basal state. The cirrhotic patients required less glucose to maintain the clamp in response to 0.1 unit per kg per hr insulin (6.7 ± 0.5 vs. control 8.3 ± 0.4 mg per kg per min, p < 0.05) and deposited less glycogen in muscle during the clamp (8.6 ± 0.5 vs. 12.0 ± 1.4 mg per gm protein, p < 0.05). Glycogen deposition correlated with clamp glucose requirement in the cirrhotic patients (r = 0.78, p < 0.05). The expressed activity of glycogen synthase activity was significantly lower in cirrhotic patients at the end of the clamp (26.5 ± 1.1% vs. 30.9 ± 1.6%) and again correlated with clamp glucose requirement (r = 0.82, p < 0.05). Skeletal muscle pyruvate dehydrogenase activity was not different in patients and control subjects. Insulin insensitivity in hepatic cirrhosis appears to be related to abnormalities of glucose deposition as glycogen in skeletal muscle.
Polycystic liver disease: Quantitation of parenchymal and cyst volumes from computed tomography images and clinical correlates of hepatic cysts
Authors: Everson Gregory T. , Scherzinger Ann , Berger-Leff Nancy , Reichen Juerg , Lezotte Dennis , Manco-Johnson Michael , Gabow Patricia
Published: March 2007

Polycystic liver disease is a common manifestation of autosomal dominant polycystic kidney disease. However, factors that regulate hepatic cystogenesis have not been defined, and the effect of cyst formation on hepatic parenchymal mass has not been studied. We validated computed tomographic methods for measuring volumes from computed tomographic images using plastic-agar models and demonstrated that measured volumes were within 10% of actual volumes. The validated methods were used to measure hepatic parenchymal, hepatic cyst and kidney volumes in 25 subjects with polycystic liver disease and nine controls without autosomal dominant polycystic kidney disease. Hepatic cyst volume varied considerably in the 25 subjects with polycystic liver disease (20 to 7,148 ml), but hepatic parenchymal volume was not altered by hepatic cysts and was similar to that of controls (polycystic liver disease vs. controls: 1,357 ± 185 vs. 1,319 + 340 ml). Total liver volume increased linearly as cyst volume increased (slope = 1.02 ± 0.05, r = 0.994). Nine of 18 women with polycystic liver disease had massive hepatic cysts (cyst:paren-chymal volume >1; range of cyst volumes from 1,354 to 7,148 ml), and the other nine had cyst volumes (20 to 399 ml) similar to men with polycystic liver disease (25 to 1,107 ml). Total kidney volume, a measure of renal cystic disease, did not correlate with either total liver volume or the volume of hepatic cysts. The data indicate that hepatic parenchymal volume is preserved in polycystic liver disease despite massive cystic involvement and that women are uniquely susceptible to massive hepatic cystic disease.
Evidence for expression in human liver of halothane-induced neoantigens recognized by antibodies in sera from patients with halothane hepatitis
Authors: Kenna Gerald J. , Neuberger James , Williams Roger
Published: March 2007

Previous investigations have shown that antibodies in sera from patients with halothane hepatitis recognize neoantigens, expressed in livers of halothane-exposed rabbits and rats, which consist of a halothane metabolite bound covalently to specific microsomal proteins. These studies have suggested that the patients’ antibodies may play a role in the pathogenesis of the hepatitis. In the present investigation, human liver biopsy samples were analyzed using an immunoblotting method to seek evidence for expression of halothane-induced neoantigens in humans. Sera from four patients with halothane hepatitis, which recognized halothane-induced rabbit liver neoantigens of 100, 76 and 57 kD, reacted strongly with antigens of very similar molecular weights that were expressed in livers from two patients who had died of cardiac failure following recent anesthesia with halothane. The antigens were not expressed in normal human liver or in livers from three patients who died of cardiac failure following anesthesia with agents other than halothane. The human antigens were not recognized by antibodies present in various control sera. Recognition of the 100- and 76-kD human antigens by the patients’ antibodies was greatly reduced by absorption of sera with liver microsomes from halothane-exposed rabbits, but not by absorption of sera with control rabbit microsomes. These results indicate that humans exposed to halothane express liver neoantigens which are analogous to the halothane metabolite-protein neoantigens characterized previously in halothane-exposed animals.
Relative risks of death due to liver disease among Japanese male adults having various statuses for hepatitis B s and e antigen/antibody in serum: A prospective study
Authors: Sakuma Koshi , Saitoh Nobuteru , Kasai Misako , Jitsukawa Hiroshi , Yoshino Izumi , Yamaguchi Momoko , Nobutomo Kouichi , Yamumi Makoto , Tsuda Fumio , Komazawa Tsutomu , Nakamura Tetsuo , Yoshida Yasuo , Okuda Kunio
Published: March 2007

Taking advantage of the compulsory annual medical check-up at the Central Institute of Health, Japan National Railways, hepatitis B seromarkers were tested in male employees at work and their “dead and alive” status was followed for more than 6 years for their prognostic significance. Two prospective studies were carried out. In the first study, two groups (cohorts) of males age 40 to 55 years were tested in 1973 and 1978, respectively, for HBsAg and anti-HBs. The relative risk of dying from primary liver cancer in HBsAg-positive carriers (n = 126) as compared to the controls who were negative for both HBsAg and anti-HBs (n = 5,322) was 30.03 and significantly high, whereas those positive for anti-HBs (n = 1,470) had no increased risk of dying from primary liver cancer or from other liver diseases. The follow-up period ranged from 6.5 to 11.5 years, averaging 8.5 years.

In the second study, three male cohorts of the same ages were tested for HBsAg and HBeAg/anti-HBe (micro-Ouchterlony method) in 1977, 1978 and 1979, respectively. There were 513 HBsAg-positive carriers among 25,547 examinees, who were followed for an average of 7.3 (6 to 8) years. Among these HBsAg carriers, those who were positive for HBeAg on entry had the highest risk of dying from primary liver cancer (relative risk, 50.25) and from other liver diseases (78.06), followed by those negative for both (28.95 and 21.78, respectively) and those positive for anti-HBe (9.47 and 6.43) when compared with 25,034 noncarriers. There was no significant increase in the risk of dying from nonhepatic diseases among these three e-oriented carrier groups.
Long-term immunogenicity and efficacy of hepatitis B vaccine in infants born to HBeAg-positive HBsAg-carrier mothers
Authors: Lo Kwang-Juei , Lee Shou-Dong , Tsai Yang-Te , Wu Tzee-Chung , Chan Cho-Yu , Chen Gran-Hum , Yeh Ching-Lan
Published: March 2007

In an attempt to evaluate the long-term immunogenicity and efficacy of plasma-derived hepatitis B vaccine in preventing hepatitis B virus infection, 199 infants born to hepatitis B e antigen-positive hepatitis B surface antigen-carrier mothers were found to be antibody to HBsAg-positive (± 10 mIU per ml) 2 months after the first booster of hepatitis B vaccination at age 1, and their serum HBsAg and anti-HBs were rechecked annually to ages 3 to 5. Of the nine infants whose initial anti-HBs were low (10 to 100 mIU per ml) in concentration, four (44%) were found to be anti-HBs seronegative at age 3, while none of the 127 vaccine responders with high anti-HBs levels (> 1,000 mlU per ml) lost their anti-HBs during the 4-year follow-up period. Also, in 63 infants whose initial anti-HBs titers were around 101 to 1,000 mIU per ml, only two lost their anti-HBs at age 4, and another two at age 5, respectively. Whether the vaccine responders lost their anti-HBs or not, no hepatitis B virus infection occurred in these vaccinees during the follow-up period. Thus, in the first 5 years of life, the protective efficacy in the high-risk infants who responded to plasma-derived hepatitis B vaccine was 100%. Because of the diversity of anti-HBs response in individuals, we suggest testing anti-HBs titer in all vaccinated infants after the first booster vaccination in order to calculate the time of next booster before the minimal protective level is reached.
Long-term follow-up of anti-HBe-positive chronic active hepatitis B
Authors: Fattovich Giovanna , Brollo Lucio , Alberti Alfredo , Pontisso Patrizia , Giustina Giuliano , Realdi Giuseppe
Published: March 2007

Twenty-eight patients with chronic active hepatitis without cirrhosis who were positive for hepatitis B surface antigen and antibody to hepatitis B e antigen were followed for 1 to 15 years (mean 6.6 years) and underwent follow-up biopsy. At presentation, 12 of the 28 patients (43%) had hepatitis B virus DNA in serum, 10 (36%) had serologic evidence of hepatitis delta virus infection and 6 (21%) had no serologic markers of either hepatitis B virus replication or hepatitis delta virus infection. During follow-up, 15 (54%) patients developed active cirrhosis, including eight patients with hepatitis delta virus infection and five with hepatitis B virus DNA in serum. In seven (47%) of the 15 patients, cirrhosis developed within the first 2 years; all seven patients had bridging necrosis in the first liver biopsy, and five of these were infected with hepatitis delta virus. The remaining 13 (46%) patients did not develop cirrhosis during follow-up and showed either unchanged features of chronic active hepatitis (seven cases) or histologic improvement to chronic persistent hepatitis (five cases) or to normal liver (one case). In conclusion, the prognosis of anti-HBe-positive patients with chronic hepatitis B is poor, as 54% of the cases developed cirrhosis during a mean histologic follow-up period of 4.5 years, mainly in association with hepatitis delta virus infection or continuing hepatitis B virus replication.
Serial passage of hepatitis delta virus in chronic hepatitis B virus carrier chimpanzees
Authors: Ponzetto Antonio , Negro Francesco , Popper Hans , Bonino Ferruccio , Engle Ronald , Rizzetto Mario , Purcell Robert H. , Gerin John L.
Published: March 2007

Five consecutive passages of hepatitis delta virus in hepatitis B virus carrier chimpanzees were performed in order to further characterize the infectious and pathogenic nature of this naturally occurring defective virus. Three animals received identical inocula at fourth passage in order to assess individual animal variation as a factor in the course of infection and disease. Acute hepatitis delta virus infection occurred in all hepatitis B virus carrier chimpanzees as demonstrated by coincident intrahepatic hepatitis delta antigen, serum hepatitis delta antigen and serum hepatitis delta virus RNA followed by seroconversion to antibody to hepatitis delta antigen. In all animals, acute hepatitis was temporally associated with hepatitis delta virus infection and was self-limited. The incubation period to hepatitis shortened with passage, whereas biochemical and histologic evidence of liver diseases increased. The marked increase in liver disease with passage was not associated with increasing markers of hepatitis delta virus replication or expression, thus indicating that adaptation to the chimpanzee by serial passage resulted in increased hepatitis delta virus virulence. The duration of hepatitis due to hepatitis delta virus infection in three chimpanzees which received the same inoculum varied from 1 to 8 months. The observations of passage adaptation and individual host variation in this experimental model of hepatitis delta virus disease parallel known pathogenic variations in human hepatitis delta virus infection.
Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2
Authors: Martini Eric , Abuaf Nisen , Cavalli Florence , Durand VÉRonique , Johanet Catherine , Homberg Jean-Claude
Published: March 2007

A new autoantibody was detected by immunoprecipitation in the serum of 21 patients with chronic active hepatitis. The antibody reacted against a soluble cytosolic antigen in liver. The antibody was organ specific but not species specific and was therefore called antiliver cytosol antibody Type 1 (anti-LC1). In seven of 21 cases, no other autoantibody was found; the remaining 14 cases had anti-liver/kidney microsome antibody Type 1 (anti-LKM1). With indirect immunofluorescence, a distinctive staining pattern was observed with the seven sera with anti-LC1 and without anti-LKM1. The antibody stained the cytoplasm of hepatocytes from four different animal species and spared the cellular layer around the central veins of mouse and rat liver that we have called juxtavenous hepatocytes. The immunofluorescence pattern disappeared after absorption of sera by a liver cytosol fraction. The 14 sera with both antibodies displayed anti-LC1 immunofluorescent pattern after absorption of anti-LKM1 by the liver micro-somal fraction. The anti-LC1 was found in the serum only in patients with chronic active hepatitis of unknown cause. Anti-LC1 antibody was not found in sera from 100 patients with chronic active hepatitis associated with anti-actin antibody classic chronic active hepatitis Type 1, 100 patients with primary biliary cirrhosis, 157 patients with drug-induced hepatitis and a large number of patients with liver and nonliver diseases. This new antibody was considered a second marker of chronic active hepatitis associated with anti-LKM1 (anti-LKM1 chronic active hepatitis) or autoimmune chronic active hepatitis Type 2.
Characterization of a new monoclonal antibody to rat macrophages and Kupffer cells
Authors: Bodenheimer Henry C. , Faris Ronald A. , Charland Colette , Hixson Douglas C.
Published: March 2007

We have characterized the cell and tissue binding specificity of a newly generated monoclonal antibody, Mab Ku-1, which shows selective reactivity with rat macrophages and Kupffer cells. The hybridoma secreting Mab Ku-1 was constructed by fusion of 8653 myeloma cells with spleen cells isolated from a mouse immunized with nonparenchymal liver cells coated with antihepatocyte antibodies. When binding was assessed by indirect immunofluorescence on frozen sections from normal liver tissue, Mab Ku-1 showed strong reactivity with Kupffer cells but was unreactive with hepatocytes, endothelial cells, bile ducts or lymphocytes. Both resident and activated macrophages bound Mab Ku-1. Reactivity in other tissues was compatible with specificity for macrophages. In the gut, scattered cells in the lamina propria were positive, whereas epithelial cells were negative. Individual cells in the lung were reactive. In the spleen, cells in the red pulp peripheral to germinal centers bound antibody. Reactivity of Mab Ku-1 to isolated Kupffer cells correlated with endogenous peroxidase activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of components immunoprecipitated by Mab Ku-1 from detergent lysates of Kupffer cells biosynthetically labeled with 35S-cysteine and 35S-methionine demonstrated that the reactive antigen was a peptide with an apparent molecular weight of 107 kD. This rat macrophage-reactive monoclonal antibody is a useful marker for identification of macrophage populations in tissue as well as in isolated cell populations.
Alterations in the functional expression of receptors on cirrhotic rat hepatocytes
Authors: d’Arville Carolyn N. , Le Mysan , Kloppel Thomas M. , Simon Francis R.
Published: March 2007

Reduced hepatic uptake and clearance of macromolecules in liver cirrhosis is due to two major factors: increased diffusional barriers, resulting primarily from the deposition of excessive connective tissue in the space of Disse, and hepatocellular dysfunction, manifested by receptor and/or postreceptor defects.

To probe the mechanisms underlying hepatocellular dysfunction in liver cirrhosis, we have investigated receptor-ligand interactions for asialoorosomucoid, insulin and epidermal growth factor in hepatocytes isolated from the livers of rats chronically exposed to phenobarbital and carbon tetrachloride for up to 12 weeks. Viable cells were allowed to attach at 37°C and the high-affinity cell surface binding sites for each ligand were assessed at 4°C in the presence of [125I]-ligand. In parallel incubations, digitonin (0.055%) was added to the binding medium to assess total cellular binding sites.

Results demonstrated that chronic treatment of rats with phenobarbital increased hepatocyte asialoorosomucoid surface receptor affinity (p < 0.05) but had no affect on the number of asialoglycoprotein binding sites. Treatment with CCl4 and phenobarbital significantly reduced the number of surface binding sites for asialoorosomucoid (p < 0.05) and epidermal growth factor (p < 0.02), although this treatment had no effect on either the binding affinity or the number of binding sites for insulin. The decrease in cell surface binding sites for asialoorosomucoid and epidermal growth factor was not due to a redistribution of the surface sites to intracellular locations, since the total number of cellular binding sites also was reduced. These results indicate that cirrhosis induced by phenobarbital and CCl4 results in a differential effect on one parameter of hepatocellular function: receptor-ligand interaction.
Differential location of hemopoietic colonies within liver acini of postnatal and phenylhydrazine-treated adult mice
Authors: Barberá-Guillem Emilio , Ayala Ricardo , Vidal-Vanaclocha Fernando
Published: March 2007

We have measured the location of embryonic and adult hemopoietic foci in the liver tissue of postnatal and adult phenylhydrazine-treated mice. Differentiation of acinar domains in liver tissue was made possible by carrying out succinate dehydrogenase histochemical reactions on liver cryostat sections. To determine the position of hemopoietic foci within the lobular gradient of the hepatocyte succinate dehydrogenase activity, this enzyme was measured in hepatocytes surrounding both portal and central veins and hemopoietic foci. Then, assuming the periportal succinate dehydrogenase activity value to be 1.00 ± 0.2, succinate dehydrogenase activity around postnatal hemopoietic foci was 0.65 ± 0.19, around phenylhydrazine-induced hemopoietic foci 0.83 ± 0.24 and around central veins 0.44 ± 0.11. Scaling the portal to central vein distance and taking 1 as the portal vein point and 0 as the central vein point, the relative position of hemopoietic foci, indirectly calculated from succinate dehydrogenase activity values, was 0.35 ± 0.13 in postnatal livers and 0.73 ± 0.12 in phenylhydrazine-treated adult livers. Hemopoietic foci frequencies varied according to both the origin and the liver acinar domain: in postnatal liver acini, it was 37.1% in zone 1, 22.8% in zone 2 and 40% in zone 3; in phenylhydrazine-treated adult acini, it was 89.4% in zone 1 and 10.6% in zone 2. Postnatal hemopoietic foci mainly occurred extrasinu-soidally, between hepatocytes and reticular-like cells, whereas adult hemopoietic foci were mostly intrasinu-soidal and closely associated to macrophage-like cells. Adult hemopoietic colonies specifically developed in the periportal microenvironment of liver acini, which contrasts with the random distribution of residual hemo-poiesis in postnatal mice. The biological conditions underlying phenylhydrazine-induced adult hemopoiesis are in the periportal regions of liver tissue.
Reactivity of primary biliary cirrhosis sera with a human fetal liver cDNA clone of branched-chain α-keto acid dehydrogenase dihydrolipoamide acyltransferase, the 52 kD mitochondrial autoantigen
Authors: Surh Charles D. , Danner Dean J. , Ahmed Aftab , Coppel Ross L. , Mackay Ian R. , Dickson Rolland E. , Gershwin Eric M.
Published: March 2007

Antimitochondrial autoantibodies recognizing 68 to 74 and 50 to 52 kD inner membrane mitochondrial antigens are characteristically present in sera of patients with primary biliary cirrhosis. The biochemical identification of the antigens, however, has remained elusive. We report herein that the 52 kD antigen is the dihydrolipoamide acyltransferase of the branched-chain α-keto acid dehydrogenase complex. This was demonstrated by three experiments through the use of recombinant fusion protein expressed in Escherichia coli from a cDNA insert encoding the human autoantigen. First, 36 of 37 primary biliary cirrhosis patients exhibiting reactivity toward the 50 to 52 kD mitochondrial antigen by immunoblotting also showed reactivity toward the recombinant fusion protein. Second, absorption of primary biliary cirrhosis sera with recombinant fusion protein, but not with an irrelevant recombinant clone, the F-specific rat liver antigen, was effective in absorbing out reactivity against the 50 to 52 kD mitochondrial antigen but not the 68 to 74 kD antigen. Third, complete removal of reactivity toward all four different isoelectric point polypeptides at 50 to 52 kD was observed in two-dimensional gel analysis. Furthermore, primary biliary cirrhosis sera were analyzed with mitochondria from three sources, rat liver, human placenta and bovine heart, in order to compare reactivity patterns and to determine precisely the comparative molecular weights of the autoantigens in the three species. The availability of recombinant autoantigens will provide improved diagnostic tests and, more importantly, will allow definite issues in primary biliary cirrhosis to be studied, including identification of immunodominant epitopes, the significance of autoantigen recognition and the establishment of autoreactive T cell clones.
Hepatitis B-associated polyarteritis nodosa in alaskan eskimos: Clinical and epidemiologic features and long-term follow-up
Authors: McMahon Brian J. , Heyward William L. , Templin David W. , Clement David , Lanier Anne P.
Published: March 2007

We analyzed the demographic, clinical, laboratory and histologic features of 13 patients who were diagnosed as having polyarteritis nodosa associated with hepatitis B virus infection over a 12-year period, 1974 to 1985. All 13 patients were Yupik Eskimos and resided in southwest Alaska, an area hyperendemic for hepatitis B virus infection. The annual incidence of hepatitis B virus-associated polyarteritis nodosa for this population is 7.7 cases per 100,000 population. All patients presented with multisystem disease, and all had biopsy or angiographic findings consistent with polyarteritis nodosa. All 13 were positive for hepatitis B surface antigen and hepatitis B e antigen at diagnosis. Two untreated patients and two of five patients who received corticosteroids died, vs. none of six who received corticosteroids plus cyclophosphamide. None of the patients who survived the initial bout of polyarteritis nodosa has relapsed after a mean follow-up of 55 months, but all have become chronic HBsAg carriers. In eight patients, clinical or serologic evidence indicated that polyarteritis nodosa followed recent hepatitis B virus infection. We concluded that hepatitis B virus-associated polyarteritis nodosa is a serious, life-threatening complication that occurs early in the course of hepatitis B virus infection, is ameliorated by immunosuppressive therapy and can be prevented by hepatitis B vaccine.
α-fetoprotein monitoring in chinese patients with chronic hepatitis B virus infection: Role in the early detection of hepatocellular carcinoma
Authors: Lok Anna S. F. , Lai Ching-Lung
Published: March 2007

Two hundred ninety patients (203 men, 87 women), age 7 to 74 years (mean: 39.1 years), with chronic hepatitis B virus infection, were prospectively followed for a period of 1 to 4 years to determine the value of α-fetoprotein monitoring in the early detection of hepatocellular carcinoma. At presentation, 66% of the patients were asymptomatic, 19% had chronic hepatitis and 15% had established cirrhosis.

Forty-four (15%) patients had elevated α-fetoprotein levels on one or more occasions during the study period. Twenty patients with normal α-fetoprotein levels at presentation developed elevated α-fetoprotein levels during the course of follow-up, whereas 24 patients had elevated α-fetoprotein levels at presentation. Six (14%) of these 44 patients (five men and one woman), age 23 to 66 years, had persistent or progressive increase in α-fetoprotein levels and were confirmed to have hepatocellular carcinoma. In four patients, the α-fetoprotein levels were below 500 ng per ml at the time of tumor localization. Only three patients had resectable tumors. All six patients would have been missed if α-fetoprotein screening was restricted to men above the age of 40 with cirrhosis and anti-HBe. Of the remaining 38 patients, elevation in α-fetoprotein levels in 18 patients was associated with exacerbations of the underlying liver disease and/or significant changes in level of hepatitis B virus replication, but in 20 patients, no apparent cause could be identified. The elevation in AFP levels exceeded 200 ng per ml in 26% and persisted beyond 6 months in 15% of these patients.

We observed that elevation in α-fetoprotein levels occurred quite frequently in patients with chronic hepatitis B virus infection. The differentiation between benign and malignant causes of α-fetoprotein elevation was at times difficult. Thus, α-fetoprotein monitoring alone is not a satisfactory tool in the early diagnosis of hepatocellular carcinoma.
Treatment of post-shunt portal-systemic encephalopathy by embolization of the shunt
Authors: Henderson Michael J.
Published: March 2007

Operative ligation of portosystemic shunts is effective in controlling chronic portosystemic encephalopathy (CPSE) but is associated with significant mortality. Review of the records of five paients with CPSE treated with radiologic occlusion procedures showed that these are suitable alternatives to surgery. Three patients had alcoholic cirrhosis, one had hepatic fibrosis from schistosomiasis, and one had post-necrotic cirrhosis. All had CPSE with progressive, severe cerebral impairment refractory to clinical treatment. Four patients had a spontaneous splenorenal shunt, and one had a surgically created mesocaval shunt (MCS). Partial splenic embolization was performed in two patients, direct shunt embolization was performed via percutaneous transhepatic portography in two other patients, and an MCS embolization was performed in one patient through the inferior vena cava. In four patients embolization controlled the CPSE. In the remaining patient it could not be evaluated because of his premature death from intraabdominal bleeding, a late complication of the procedure. Interventional radiologic procedures are effective in the control of CPSE in selected patients.
Prostatic hypertrophy in the elderly cirrhotic patient: An estrogenic or androgenic response?
Authors: Van Thiel David H. , Gavaler Judith S.
Published: March 2007

In elderly males hormonal changes occur that are believed to cause benign prostatic hyperplasia (BPH). These are decreased testosterone production, an increased testosterone SHBG and a slightly increased estradiol production. Liver cirrhosis in males causes similar endocrine changes. We carried out a post mortem study evaluating the prostates of 51 men who died with liver cirrhosis compared with a similar group without any hepatic disease. The occurrence of BPH in cirrhotic subjects was diminished and delayed compared to total population. Furthermore in cirrhotic men BPH is more common as early nodular hyperplasia (early stage) or stromal hyperplasia (suggesting estrogenic prevalence), while in the general population stromal and epithelial hyperplasia (androgenic stimulation), were almost equally present.