bluuebunny/crossref_metadata_2025 huggingface dataset:
Portal hemodynamics during nitroglycerin administration in cirrhotic patients
Authors: Garcia-Tsao Guadalupe , Groszmann Roberto J.
Published: March 2007

Nitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 ± 6.5 mm Hg (mean ± S.D.) to 15.1 ± 5.1 mm Hg (p < 0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 ± 10 mm Hg to a peak decrease of 76 ± 18 mm Hg (p < 0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p < 0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 ± 15 to 83 ± 15 beats per min, p < 0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal-pressure-reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal-collateral vasodilatation.
Prevention of recurrence of esophageal varices after endoscopic injection sclerotherapy with ethanolamine oleate
Authors: Kitano Seigo , Koyanagi Nobuhiro , Iso Yasunori , Higashi Hidefumi , Sugimachi Keizo
Published: March 2007

Endoscopic injection sclerotherapy was given to 155 patients with esophageal varices mainly related to non-alcoholic liver cirrhosis. The formation of a superficial ulcer in the lower esophagus was achieved in 141 (91.0%) of the 155 patients, with an average of 4.1 sessions of endoscopic injection sclerotherapy during an average time of 4.9 weeks. The average volume of 5% ethanolamine oleate sclerosant used was 24.8, 19.2, 12.3 and 6.5 ml for the initial to fourth sessions of endoscopic injection sclerotherapy, respectively.

For 14 patients, a sufficient number of sessions of endoscopic injection sclerotherapy could not be given: 10 early deaths (5 hepatoma, 4 liver failure and 1 gastric bleeding), and 4 refused further sessions.

When the esophageal mucosa had been eliminated and a superficial ulcer had formed, episodes of recurrent bleeding or recurrence of esophageal varices were nil over a median follow-up of 14.6 months, with a range of 1 to 27 months. In seven patients, bleeding recurred before elimination of the mucosa could be achieved, but these bleeding episodes were well controlled with an additional session of endoscopic injection sclerotherapy.

At the time of analysis, there were 36 deaths (20 hepatoma, 14 liver failure and 2 gastric bleeding) among these 155 patients. Thus, the mean follow-up was 16.3 months (range: 7 to 27 months) in the 119 survivors, with no recurrence of the varices.

We propose that removal of the esophageal mucosa may well be the endpoint of repeated endoscopic injection sclerotherapy in the management of patients on injection sclerotherapy.
Fatty acid-binding protein: A major contributor to the ethanol-induced increase in liver cytosolic proteins in the rat
Authors: Pignon Jean-Pierre , Bailey Naila C. , Baraona Enrique , Lieber Charles S.
Published: March 2007

To study the acute and chronic effects of ethanol on hepatic fatty acid-binding protein, rats were pair-fed with liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 4 to 5 weeks. Animals were killed 90 min after intragastric administration of diets with or without ethanol. Alcohol feeding markedly increased liver triglycerides, with a modest rise in nonesterified fatty acids. Alcohol-fed rats developed hepatomegaly, with a 48% increase in hepatic cytosolic proteins. Fatty acid binding was first assessed by the kinetics of [14C]palmitate binding to cytosolic proteins. The maximal binding capacity more than doubled in the cytosol of the ethanol-fed rats compared to pair-fed controls, whereas the dissociation constant increased by 64%. Acute ethanol administration (3 gm per kg body weight) either to ethanol-fed or control rats did not have a significant effect. To identify the fatty acid-binding protein, labeled cytosolic proteins were fractionated by gel filtration: most of the cytosolic fatty acids eluted as a single peak in the 12,000 to 18,000 molecular weight region corresponding to the hepatic fatty acid-binding protein. The increase in this protein, confirmed by radial immunodiffusion (27.0 ± 1.4 mg per 100 gm body weight vs. 11.2 ± 1.6, in controls; p < 0.01), accounted for 22% of the total rise in cytosolic protein induced by chronic ethanol feeding.
Enhanced autoreactivity of T-lymphocytes in primary sclerosing cholangitis
Authors: Lindor Keith D. , Wiesner Russell H. , Larusso Nicholas F. , Homburger Henry A.
Published: March 2007

Primary sclerosing cholangitis is a chronic, cholestatic liver disease in which immune mechanisms are thought to play a role in the pathogenesis. We have determined the frequencies and functional phenotypes of autoreactive T-lymphocytes in peripheral blood specimens from patients with primary sclerosing cholangitis and healthy adults as an indicator of autoreactivity in primary sclerosing cholangitis. We found a significant increase in the percentage of autoreactive suppressor/cytotoxic T-lymphocytes that become activated in the T-, non-T-autologous mixed lymphocyte reaction in primary sclerosing cholangitis patients (p < 0.002). Blastogenesis in autologous mixed lymphocyte reaction cultures from primary sclerosing cholangitis patients was significantly decreased (p < 0.02), and the magnitude of the decrease correlated directly with the percentage of activated suppressor/cytotoxic T-lymphocytes (r = 0.56, p < 0.01). The percentage of autoreactive, suppressor T-lymphocytes was increased in autologous mixed lymphocyte reaction cultures from primary sclerosing cholangitis patients (p < 0.0001); and suppression of mitogen-induced blastogenesis by autologous concanavalin A-treated mononuclear cells was significantly enhanced. These results, which were unrelated to the histologic stage of liver disease and the presence or absence of active colitis, document the presence of an expanded population of T-lymphocytes in the peripheral blood of patients with primary sclerosing cholangitis that became activated on exposure to autologous major histo-compatibility antigens in the autologous mixed lymphocyte reaction. We hypothesize that these autoreactive cells may be a marker or may participate as effector cells in cell-mediated autoimmunity in primary sclerosing cholangitis.
Bile salt shift from albumin to high-density lipoprotein in cholestasis†
Authors: Buscher Hans-Peter , Beger Mathias , Sauerbier Hella , Gerok Wolfgang
Published: March 2007

The distribution of [3H]taurocholate between albumin and the lipoproteins of serum of patients with various diseases in which lipoprotein metabolism and/or bile salt concentrations were altered and of healthy control subjects was investigated by means of the density gradient centrifugation method.
A population study on the prevalence of gallstone disease: The sirmione study
Authors: Barbara Luigi , Sama Claudia , Labate Antonio Maria Morselli , Taroni Francesco , Rusticali Anna Giulia , Festi Davide , Sapio Carlo , Roda Enrico , Banterle Claudio , Puci Armando , Formentini Franco , Colasanti Silvia , Nardin Francesco
Published: March 2007

The prevalence of gallstone disease (cholelithiasis and previous cholecystectomy for gallstones) in the population of the town of Sirmione, Italy, examined by ultrasonography, was 6.7% in men and 14.6% in women, ranging from 18 to 65 yr of age (overall prevalence = 11%). The prevalence of cholelithiasis in the same age span was 6.9% (4.5% in men and 8.9% in women). Prevalence of cholelithiasis increased with age in both sexes.

Twenty-two percent of gallstone subjects suffered from biliary pain vs. 2% of subjects without gallstones. No difference was observed in the frequency of nonspecific symptoms between subjects with and without gallstones. Of the 132 gallstone subjects, 108 (82%) were not aware of having gallstones prior to the study.

Prevalence of gallstone disease was found to be higher in obese and hypertriglyceridemic subjects and to increase with the number of pregnancies.
Hepatitis B vaccination of newborn infants: Clinical study of new vaccine formulation and dose regimen
Authors: Lee Keun Soo , Lee Hahng , Moon Soo Jee , Choi Kyu Jong , Kim Ki Hong , Kim Chun Won , Chung Wha Soon , Choi Tae Yael
Published: March 2007

To investigate the efficacy in anti-HBsAg response with half the recommended adult dose in a standard vaccination schedule or with a full dose in reduced number of vaccination schedule, 201 healthy newborn infants were randomized to receive either 2.5 μg Hevac B vaccine at birth [1, 2 and 14 months in Group I (101)] or 5 μg at birth [2 and 14 months in Group II (100)]. Anti-HBsAg responses in the two groups were compared. Passively acquired anti-HBsAg positivity rates at birth were 51.5 and 45.0% in Groups I and II, respectively. Cumulative anti-HBsAg seroconversion rates in Group I were 12.2, 76.6, 82.6 and 86.4% at 2, 4, 14 and 16 months, while the rates in Group II were 2.5, 62.5, 73.7 and 91.0%, showing no significant difference (p > 0.05). Significant difference in seroconversion rates at the 2-month follow-up stage between passively acquired anti-HBsAg-negative and -positive groups was observed (11.9 vs. 2.6%). Significant rise in anti-HBsAg titer at 16 months following the booster at 14 months was noted: 36.4 mIU per ml before, 546.4 mIU per ml after in Group I and 25.3 mIU per ml before, 782.6 mIU per ml after in Group II. The booster, 12 months after the primary vaccination series, is therefore considered imperative for maximum effectiveness of hepatitis B active immunization. Although the present programs of unselective vaccination with modified dose schedules were ineffective for lowering the number of persistent HBsAg carriers for the high-risk newborn infants exposed to HBsAg- and HBeAg-positive mothers, and the high-risk group infants were not excluded in this study, the over-all effectiveness of these programs is considered comparable to that of the currently recommended standard dose schedule for immunization of low-risk newborn infants.
Liver cell dysplasia and hepatocellular carcinoma: Non-A, non-B hepatitis, too?
Authors: Cohen Cynthia
Published: March 2007

Liver cell dysplasia (LCD) is a premalignant cytologic change of hepatocytes that has been statistically linked to cirrhosis, hepatocellular carcinoma (HCC), and chronic liver disease related to hepatitis B virus. The relationship of LCD to non-A, non-B (NANB) hepatitis is currently unknown. We studied liver biopsy and surgical resection specimens from 36 patients with NANB hepatitis, and identified LCD in 17 (42.5%) of 40 specimens, most often associated with cirrhosis. Dysplasia was present in individual hepatocytes, in clusters, and in a distinctive “spreading” pattern of hepatocytes about central veins. Three patients had HCC with a predominant giant cell pattern, as well as LCD. These findings suggest that LCD and HCC should be included among the potential pathologic sequelae of NANB hepatitis.
Hepatitis B virus infection and liver transplantation
Authors: Snover Dale C.
Published: March 2007

The histologic findings in the original liver obtained from 9 liver allograft patients with active B virus hepatitis were compared with 28 post-transplant pathology specimens. All specimens were studied with the use of light and immunohistochemical microscopy in conjunction with pertinent clinical data. Eight of the 9 patients had chronic active hepatitis B (HB) with cirrhosis, prior to transplant, one of which had coexistent hepatocellular carcinoma. The ninth patient had fulminant hepatic necrosis secondary to acute HB prior to transplantation. In all of the patients with chronic HB prior to transplantation who survived more than 2 months after transplantation, recurrent infection of the graft developed despite perioperative HB immunoglobulin therapy. The patient with acute fulminant hepatitis B pretransplant has done well postoperatively and has evidence of HB virus immunity (positive anti-HBs) 15 months after transplantation. Examination of tissue specimens obtained during episodes of allograft dysfunction in these 9 patients indicates that pathologic alterations of active HB infection of the allograft are associated with a preferential lobular insult, whereas those occurring in rejection preferentially involve portal tract structures. Serologic data combined with biopsy histopathologic data are essential in distinguishing between the two quite different events.
Comparing bacterial infections in portacaval and distal splenorenal shunts
Authors: Moussa Ousama E. , Conn Harold O.
Published: March 2007

Since 1976, we have compared the end-to-side portacaval shunt (PCS) with the distal splenorenal shunt (DSRS) in patients with alcoholic liver disease and recurrent variceal bleeding. Fifty-four patients were randomly assigned to receive either shunt procedure. There were 27 patients in each group and both groups were highly comparable in clinical and laboratory characteristics. Median follow-up was 31 mo in each group. Postoperative complications and operative mortality (7% after PCS, 12% after DSRS) were comparable. Spontaneous portasystemic encephalopathy developed in 32% of the patients at risk after PCS and in 39% after DSRS. Rebleeding from varices occurred in 4% of the patients after PCS and in 27% after DSRS. Cumulative survival was not significantly different between groups (5-yr survival: 31% after PCS, 43% after DSRS). We have failed to demonstrate superiority of DSRS in our patients with alcoholic liver disease with respect to postoperative encephalopathy or survival, and have experienced an unusually high rate of variceal rebleeding after DSRS.
Hepatic carbonic anhydrase inhibition by diuretic drugs
Authors: Maren Thomas H.
Published: March 2007

1. In isolated perfused rat liver, urea synthesis is rapid and reversibly inhibited not only by the well-known carbonic anhydrase inhibitors acetazolamide, methazolamide and ethoxzolamide, but also by diuretics, like xipamide, mefruside, chlortalidone, and chlorothiazide. Furosemide was without effect.

2. Similar to findings with isolated perfused rat liver, acetazolamide inhibits urea synthesis from ammonium ions in normal and cirrhotic human liver slices.

3. Inhibition of urea synthesis by xipamide and acetazolamide is accompanied by a 70% decrease of the cellular citrulline content and the tissue levels of 2-oxoglutarate and citrate, suggesting a block of urea synthesis at a step prior to citrulline formation.

4. At a constant extracellular pH (7.4), inhibition of urea synthesis by xipamide, mefruside and acetazolamide was overcome by increasing the extracellular concentrations of HCO3
− and CO2 to above twice the normal values. This shows that inhibition of urea synthesis by these diuretics is not due to an unspecific inhibition of one of the urea cycle enzymes but is due to an inhibition of mitochondrial carbonic anhydrase and therefore due to an impaired HCO3
− provision for mitochondrial carbamoylphosphate synthesis.

5. It is concluded that the activity of mitochondrial carbonic anhydrase is required for urea synthesis also in human liver and that several diuretics impair urea synthesis by inhibition of mitochondrial carbonic anhydrase. The pathophysiological significance of these data is discussed with respect to the development of diuretics-induced hyperammonemia and alkalosis in liver disease.
Mallory bodies and intermediate filaments: Of mice and men
Authors: Denk Helmut
Published: March 2007

Livers from 12 mice fed griseofulvin for 4 to 6 months were perfused in situ with a detergent solution to extract lipid membranes leaving the cytoskeleton intact. Seven control mice were similarly studied. After 30 to 120 minutes perfusion, liver samples were examined by scanning electron microscopy and transmission electron microscopy. By light microscopy, Mallory bodies (MBs) were observed in pericentral hepatocytes. These were confirmed by transmission electron microscopy. Intermediate filaments (IFs) were observed in close apposition to MBs. Numerous IFs were seen throughout the cytoplasm. The 3-dimensional organization of the cytoskeleton and MBs were clearly visualized by scanning electron microscopy. The IFs were disorganized in the hepatocytes and formed small MBs in griseofulvin- treated mice. In the case of hepatocytes containing large MBs, there was an apparent decrease in the concentration of IFs. Transition forms of dense networks of IFs between the normal cytoskeleton and the MBs were noted in the cytoplasm between small MBs and the nucleus and also at the cell border. The IFs connected to the nucleus and invaded the MBs. The MBs appeared to form as a result of condensation or collapse of the IFs.

Evidence has been accumulating that Mallory body (MB) is a heritable phenotype of hepatocellular carcinoma (HCC) and is closely related to hepatocarcinogenesis in some carcinogen-fed animals. This prompted us to try to evaluate the MB phenomenon in human HCCs, in which its significance remains unclear to date. Whole liver slices were obtained from 28 autopsied livers in which MB-positive HCC was found, and distribution of MBs within the HCC was examined. There were three distribution patterns: clustering, diffuse, and sparse types. The clustering type was the most frequent and was found in 21 of the 28 cases. In this type, there was a formation of groups of the MB-containing cells within the HCC, and the cluster of MB-positive cells was variable in number, size, and shape. There was often a sharp border line between MB-positive clusters and the surrounding MB-negative HCC cell areas where a collision line could occasionally be seen. Some of the MB-containing HCC cells were positive for γ-glutamyl transpeptidase and α-fetoprotein. These data led the authors to speculate that MB-positive HCC cells in human livers are capable of proliferation to form the clusters and that therefore, MBs are expressed as a kind of heritable phenotype in such clusters.
The protective effects of prostaglandin E1 in an experimental massive hepatic cell necrosis model
Authors: Mizoguchi Yasuhiro , Tsutsui Hiroko , Miyajima Keiji , Sakagami Yoshihide , Seki Shuichi , Kobayashi Kenzo , Yamamoto Sukeo , Morisawa Seiji
Published: March 2007

When a small amount of Gram-negative lipopolysaccharide was intravenously injected into mice which had been injected with heat-killed Propionibacterium acnes 7 days before, massive hepatic cell necrosis was induced and most of the mice died 24 hr later. However, when prostaglandin E1 was administered with lipopolysaccharide, remarkable improvements in the survival rate and in the histological changes of the liver were observed. In order to find out how prostaglandin E1 suppressed the induction of massive hepatic cell necrosis in this experimental model, we studied the effects of prostaglandin E1 on the activation of liver adherent cells, from which the cytotoxic factor is released, and on the protection of hepatocytes from the cytotoxic factor. As a result, prostaglandin E1 not only inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor, but it also directly affected the hepatocytes and protected them from the cytotoxic factor.
Metabolic effects of enteral formula feeding in alcoholic hepatitis
Authors: Soberon Santos , Pauley Mary P. , Duplantier Richard , Fan Angelita , Halsted Charles H.
Published: March 2007

The etiology of malnutrition and the metabolic effect of aggressive nutritional support by enteral feeding were evaluated in patients with moderately severe alcoholic hepatitis. Among 21 patients presenting with jaundice, ascites, coagulopathy and low grade encephalopathy, the mean digestibilities (intake - fecal excretion/intake × 100) of total energy and fat were subnormal at 74.6 ± 2.9 and 64.5 ± 4.4%, respectively, and nitrogen balance was negative in half the patients with a mean value of +0.74 gm per day ± 1.2. Based on initial ad libitum intake of hospital diet, patients were grouped as six patients with adequate caloric intake who underwent a repeated 3-day balance study to assess the effect of hospitalization (Group I) and eight anorectic patients who underwent a repeat balance study during constant nasoduodenal infusion of the liquid formula Isocal-HCN in an amount sufficient to provide 35 kcal per kg ideal body weight (Group II). During the initial phase of hospital tray diet, the mean digestibilities of energy, fat, protein and carbohydrate, and the mean nitrogen balance were similar in each group. The digestibilities of each diet constituent and nitrogen balance were similar in both phases of hospital tray diet in patients in Group I. On the other hand, the infusion of Isocal-HCN to patients in Group II resulted in significant increases over their baseline values in intakes of energy and protein and in digestibilities of energy, fat and protein, and in a 5-fold increase in nitrogen balance. Provision of essential nutrients by enteric infusion had no effect on fluid balance or degree of encephalopathy. These short-term studies provide a metabolic basis for enteric formula feeding in improving the intestinal absorption and nitrogen balance of anorectic patients with alcoholic hepatitis.
Antibodies against acetaldehyde-modified protein epitopes in human alcoholics
Authors: Niemelä Onni , Klajner Felix , Orrego Hector , Vidins Eva , Blendis Laurence , Israel Yedy
Published: March 2007

Acetaldehyde, the primary metabolite of ethanol, binds covalently to proteins forming condensation products which have been recently shown to be immunogenic. To assess whether an antibody response against acetaldehyde-modified protein epitopes is associated with alcoholic liver disease, the serum immunoreactivity against proteins modified in vitro by acetaldehyde and against the corresponding unmodified proteins was measured by an enzyme-linked immunosorbent assay in 58 alcoholics with varying degrees of liver damage. Alcoholics showed significantly higher titers against protein-acetaldehyde conjugates than against the unmodified protein, independent of the nature of the carrier protein. The highest titers occurred in alcoholic hepatitis patients. Sera of patients with chronic hepatitis of nonalcoholic origin and of healthy controls also reacted with acetaldehyde conjugates, but their titers were significantly lower than those in alcoholic hepatitis patients. Our data support the idea that binding of acetaldehyde to proteins in humans generates antigenic determinants which trigger a corresponding immune response against such epitopes and suggest that this humoral immune response may be implicated in autoantibody formation and liver damage associated with excessive alcohol consumption.
Serum type III procollagen and basement membrane proteins as noninvasive markers of hepatic pathology in Indian childhood cirrhosis
Authors: Trivedi Premila , Risteli Juha , Risteli Leila , Tanner Stuart M. , Bhave Sheila , Pandit Anand N. , Mowat Alex P.
Published: March 2007

While serum concentrations of antigens of the aminopropeptide of type III procollagen have been considered as indicators of hepatic pathology in adults, the high concentrations normally found in children during growth may preclude their use in pediatric liver disease. To clarify this and to determine the role of other circulating connective tissue-related substances in children, we have measured serum concentrations of antigens related to aminopropeptide of type III procollagen, the 7S domain of type IV collagen and the P1 fragment of laminin in healthy subjects aged 1 month to 4 yeers and in children with Indian childhood cirrhosis, a particularly aggressive form of liver disease. In healthy subjects, there was a considerable age variation in serum aminopropeptide of type III procollagen but not in 7S collagen or laminin P1. In Indian childhood cirrhosis, all three serum antigens were increased (p < 0.001) above the upper limit of normal for age. Both the serum 7S collagen and laminin P1 concentrations showed a significant correlation with the degree of intralobular fibrosis and also with the severity of necrosis and cellular infiltration, suggesting that these serum antigens may be a noninvasive means of assessing and monitoring events associated with hepatic fibrosis in Indian childhood cirrhosis. The raised serum aminopropeptide of type III procollagen in Indian childhood cirrhosis did not correlate with any histological parameter assessed. Gel filtration of serum showed that, in healthy subjects, the predominant antigenic form of aminopropeptide of type III procollagen was a degradation peptide smaller than authentic aminopropeptide of type III procollagen; while in Indian childhood cirrhosis the authentic peptide and a larger degradation peptide predominated. These findings suggest that, in Indian childhood cirrhosis, serum aminopropeptide of type III procollagen raised above the normally high levels found in children reflect, at least in part, the very rapid hepatic type III collagen synthesis which occurs in this condition.
Mucus hypersecretion in the gallbladder epithelium of ground squirrels fed a lithogenic diet for the induction of cholesterol gallstones
Authors: Pemsingh Ramjeet S. , Macpherson Brian R. , Scott Gerald W.
Published: March 2007

This study identified mucus granules, determined mode of release and quantified their volume in the gallbladder epithelium of Richardson's ground squirrels (Spermophilus richardsonii) fed a lithogenic diet of 2% cholesterol to experimentally induce gallstone formation. Tissue was examined using light microscopy histochemistry, scanning and transmission electron microscopy, as well as autoradiography and morphometry at the electron microscopic level. Autoradiography demonstrated incorporation of a glycoprotein precursor, [3H]galactose, within the membrane-bound granules localized in the supranuclear region of the epithelial cells. Exocytosis of granule contents was by merocrine secretion. Morphometry indicated a significant increase in the amount of intracellular mucin granules as early as 18 hr on the lithogenic diet, a feature that continued throughout the experimental period of 20 weeks. Mucus synthesis/secretion rates returned to control values within 3 weeks after removal from the diet. Scanning electron microscopy observations revealed a thick sludge-like layer overlying the epithelium at a time in the chronology of the cholelithiasic model that correlated well with the initial phases of stone formation. Histochemistry showed this layer to be a mixture of acidic mucins. Neutral mucins were not observed. The hypersecretion of mucus and formation of this sludge-like layer appear to be critical nucleating factors in the formation of cholesterol gallstones.
Prognosis of hepatocellular carcinoma smaller than 5 cm in relation to treatment: Study of 100 patients
Authors: Ohnishi Kunihiko , Tanabe Yuichi , Ryu Munemasa , Isono Kaichi , Yamamoto Yoshikazu , Usui Sadahito , Hiyama Yoshiaki , Goto Nobuaki , Iwama Shosuke , Sugita Shujiro , Nomura Fumio , Okuda Kunio
Published: March 2007

A total of 100 patients with small hepatocellular carcinoma, ≤5 cm in diameter, seen during the last 8 years were analyzed retrospectively for survival time in relation to treatment and Child's grading. When analyzed with respect to major treatment modalities without considering stage, the median survival was 35.0 months for 34 patients treated by surgery, 28.8 months for 20 patients treated by transcatheter arterial embolization, 10.6 months for 25 patients treated by intraarterial chemotherapy and 9.7 months for 17 patients who received no specific treatment. When patients were divided into three stages without considering treatment, the median survival was 37.1 months for 37 Child's A patients, 16.2 months for 36 Child's B patients and 1.6 months for 27 Child's C patients. These results suggest that the prognosis depended on treatment given and the Child's grade. The effects of major therapeutic modalities on survival were analyzed with regard to Child's grading. Among Child's A patients, the actuarial survival rate for surgery was better than that for transcatheter arterial embolization and for arterial chemotherapy. Among Child's B patients, the survival rate for transcatheter arterial embolization was better than for other treatments. Among Child's C patients, there was no significant difference in survival rate regardless of treatment and its modality. These results suggest that surgery may be indicated as a first choice in Child's A patients, transcatheter arterial embolization in Child's B patients, and there is no effective treatment in Child's C patients. The major cause of death was hepatic failure irrespective of treatment.
Characteristics of a cell line (tong/HCC) established from a human hepatocellular carcinoma
Authors: Stevenson Douglas , Lin Jiing-Huey , Tong Myron J. , Marshall June G.
Published: March 2007

A continuous adherent cell line was established from a hepatocellular carcinoma of an HBsAg-positive Italian male. This cell line, designated Tong/HCC, has been grown in a hormone-supplemented medium for more than 18 months. The cell line secretes HBsAg, α-fetoprotein, albumin and α1-antitrypsin. α-Fetoprotein production is enhanced by the addition of hydrocortisone and appears to be glucocorticoid concentration-dependent. The concentrates of the supernatant from the cell cultures and cell lysates were negative when tested for HBeAg. The cell culture medium was negative for hepatitis B virus DNA when tested by dot-blot hybridization. However, hepatitis B virus DNA was found to be integrated in the chromosomal DNA by Southern blot analysis. At least five different integration sites were identified, and no free hepatitis B virus DNA was observed.

The modal chromosome number was 64, and a translocation on Chromosome 15 was consistently noted. HLA typing revealed sites for A3, Aw24, Bw34 and Cw1.
HLA Class i antigen display on hepatocyte membrane in chronic hepatitis B virus infection: Its role in the pathogenesis of chronic type B hepatitis
Authors: Chu Chia-Ming , Shyu Wei-Chue , Kuo Ruey-Wen , Liaw Yun-Fan
Published: March 2007

It has been suggested that cytotoxic T cells are involved in the recognition and lysis of the infected hepatocytes in chronic hepatitis B virus infection, and that the target antigen is probably HBcAg which is displayed on the hepatocyte membrane during active viral replication. However, studies in other viral infection have demonstrated that cytotoxic T cells recognize viral antigen on the infected cells only in the context of HLA class I antigens. To test whether this mechanism is also operative in chronic hepatitis B virus infection, we studied the expression of HLA class I antigens in livers from 35 patients with chronic hepatitis B virus infection by indirect immunofluorescence using monoclonal antibody against HLA class I antigens. The blocking effect of monoclonal antibody against HLA class I antigens on the in vitro T cell cytotoxicity to autologous hepatocytes was also studied. The results revealed that HLA class I antigen was undetectable on the hepatocyte membrane in all of 10 HBeAg-positive carriers with minor hepatitic activity, whereas it was demonstrated in 15 (88%) of the 17 HBeAg-positive patients with chronic active liver disease and in 7 (87%) of the 8 anti-HBe-positive “normal” carriers. The in vitro T cell cytotoxicity to autologous hepatocytes in six HBeAg-positive patients with chronic active liver disease was significantly inhibited by preincubation of hepatocytes with monoclonal antibody (10 to 40 μg per ml) against HLA class I antigen, but not by monoclonal antibody against HLA class II antigens and non-HLA-associated surface molecules (Leu 11). These findings suggested that HLA class I antigens became detectable on hepatocyte membrane while significant histological activity developed in chronic hepatitis B virus infection, and that the effector cytotoxic T cells required HLA class I antigen as target structure(s).
Immunoelectron microscopic observations on the inflammatory infiltrates and HLA antigens in hepatitis B and non-A, Non-B
Authors: Dienes Hans P. , Hütteroth Thomas , Hess Georg , Meuer Stefan C.
Published: March 2007

The present knowledge of the inflammatory reaction occurring in situ during hepatitis B favors a T cell-dependent MHC-restricted immune response. However, the reports in the literature are primarily based on the application of monoclonal antibodies directed at different lymphocyte subsets which discern only lymphocytic phenotypes and do not reflect the actual situation adequately. Therefore, we investigated the liver biopsies of patients with hepatitis B (28 patients) and non-A, non-B (21 patients) by immunoelectron microscopy with monoclonal antibodies directed at lymphocyte subtypes (pan-B, pan-T, T8, T4 and NKH1) and at activation epitopes (IL-2 receptor, TA1 and T11/3) as well, in order to determine the phenotype in association with the activation status of the lymphocytes that are in close contact with hepatocytes; thus, establishing an effector-target cell relationship on the ultrastructural level.

We were able to confirm the central role of T8 lymphocytes being the predominant type of lymphocytes in close contact with liver cells in the space of Disse. A certain percentage of these cells expressed “activation” markers as IL-2 receptor, TA1 and T11/3. In acute hepatitis, the NK lymphocytes made up a fifth of all lymphocytes, whereas their number dropped below 10% in the chronic stage. There was a vague correlation between the inflammatory activity of the disease and the expression of HLA antigens (both classes I and II) on inflammatory cells and also on hepatocytes. The results did not show significant differences between hepatitis B and non-A, non-B.

Our findings underline the significance of a T lymphocyte-dependent, MHC-restricted immune response in chronic hepatitis B and non-A, non-B as the decisive mechanism which seems to be flanked by NK cell activity in the acute phase. The expression of the T11/3 antigen on many lymphocytes indicates that a certain proportion of the T lymphocytes may be activated by an antigen-independent alternative pathway.
Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: A second type of “autoimmune” hepatitis
Authors: Homberg Jean-Claude , Abuaf Nisen , Bernard Olivier , Islam Shamsul , Alvarez Fernando , Khalil Samir H. , Poupon Raoul , Darnis François , Lévy Victor-Georges , Grippon Patrick , Opolon Pierre , Bernuau Jacques , Benhamou Jean-Pierre , Alagille Daniel
Published: March 2007

Sixty-five patients with histologically proven chronic active hepatitis of unknown cause but associated with the antiliver/kidney microsome antibody type 1, confirmed by immunofluorescence and immunoprecipitation, were selected as forming a special entity.

This disease was found to be rare with a prevalence of 5/1,000,000. The female to male ratio was 8:1. The condition occurred at all ages but was most common between the ages of 2 and 14 years. In 22 of the 65 cases, the hepatitis was associated with an autoimmune disease, most commonly insulin-dependent diabetes, autoimmune thyroid disease and vitiligo. The same autoimmune diseases were present in first-degree relatives from seven families. In 36 cases, the onset of disease resembled acute viral hepatitis. Serum biochemical tests showed marked elevation in aminotransaminases and hypergammaglobulinemia. Paradoxically, serum and salivary IgA levels were often normal or low. Histologic findings were multifocal hepatic necrosis with bridging in the acute stage, and aggressive hepatitis with mono-nuclear cell infiltration or macronodular cirrhosis in the late stages. Serologically, apart from the presence of antiliver/kidney microsome antibody type 1, the disease was characterized by the absence of antiactin, antimitochondria and antinucleus antibodies; however, organ-specific autoantibodies were often present. The clinical course was usually severe: six patients in the acute stage presented with fulminant hepatitis, and all, except two, other patients progressed to cirrhosis, Prolonged treatment with corticosteroids and immunosuppressants was usually effective in rendering the cirrhosis inactive. The cumulative survival rate was 51% at 14 years.
The epidemiology and clinical outcome of hepatitis D virus (delta) infection in Jordan
Authors: Toukan Ala U. , Abu-El-Rub Omayma A. , Abu-Laban Salwa A. , Tarawneh Musleh S. , Kamal Feisal M. , Hadler Stephen C. , Krawczynski Krzysztof , Margolis Harold S. , Maynard James E.
Published: March 2007

The epidemiology and clinical outcome of hepatitis D viral infection in HBsAg-positive acute hepatitis, chronic liver disease, primary hepatocellular carcinoma and the symptomless carrier state was studied in Jordan. The prevalence of hepatitis D viral infection was significantly higher in patients with chronic liver disease (18/79, 23%) and acute hepatitis (17/108, 16%) than in symptomless HBsAg carriers (2/136, 2%). The highest prevalence of hepatitis D viral infection was found in patients with primary hepatocellular carcinoma (10/15, 67%) who were also significantly older than such patients without hepatitis D viral infection. Antihepatitis D virus IgM was detected persistently in 83% of patients with antihepatitis D virus-positive chronic liver disease and transiently in 41% of patients with acute hepatitis. A trend to increased mortality was observed in acute hepatitis D viral superinfection (25%) compared to hepatitis D viral coinfection (0%) and to antihepatitis D virus-negative HBsAg-positive acute hepatitis (4%). In patients with established chronic liver disease, however, neither survival nor histological parameters of disease activity were significantly different in the antihepatitis D virus-positive and antihepatitis D virus-negative groups. While the early stage of hepatitis D viral super-infection is associated with increased mortality, it appears that in patients with late-stage chronic liver disease, severe histological activity subsides, and survival is no longer influenced by the factor of hepatitis D viral infection. However, primary hepatocellular carcinoma appears to complicate the course of those antihepatitis D virus-positive patients surviving beyond this stage.
FM ultrasonography: A revolution?
Authors: Burns Peter N. , Hammers Lynwood
Published: March 2007

FM sonography—a signal-processing technique that uses frequency and phase information as well as amplitude data—shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsyproved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalitites. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.
Graft-versus-host-induced cirrhosis: Possible mechanisms
Authors: Shulman Howard M.
Published: March 2007

A 28-yr-old woman with severe idiopathic aplastic anemia received an HLA-identical mixed lymphocyte culture nonreactive bone marrow transplant from her brother. In the months after successful engraftment, she developed cutaneous and hepatic graft-versus-host disease, associated with marked cholestatic jaundice. Despite a series of therapeutic maneuvers, cholestasis persisted but remained relative stable over the enuing 10 yr. However, serial liver biopsies revealed progressive biliary-type firbrosis culminating in cirrhosis. Subsequently, her clinical course deteriorated and she developed signs of hepatic failure, and ultimately died 10.5 yr after bone marrow transplantation. The evolution of chronic graftversus-host disease to cirrhosis may be a limiting factor in the long-term survival of this group of bone marrow transplant recipients. The lack of correlation between the stable clinical or biochemical indices and the progressive hepatic disease underscores the need for sequential liver biopsies in patients with sustained liver function abnormalities after bone marrow transplantation.
Hepadnaviruses and retroviruses share genome homology and features of replication
Authors: Robinson William S. , Miller Roger H. , Marion Patricia L.
Published: March 2007

The hepadnavirus (1-3) family includes hepatitis B virus (HBV), woodchuck hepatitis virus (WHV) (4), ground squirrel hepatitis virus (GSHV) (5) and duck hepatitis B virus (DHBV) (6). These viruses share unique ultrastructural, molecular and biological features. HBV has great medical importance in many parts of the world. More important numerically than acute hepatitis B in high prevalence geographic regions is the liver disease associated with chronic infection. There appear to be more than 200 million chronically infected humans in the world (7), and these HBV infections appear to be the single most common cause of chronic liver disease and liver cancer in man (7, 8). All hepadnaviruses share the propensity for silent infection in early life leading to persistence of the virus, and hepatocellular carcinoma (HCC) is clearly associated with longstanding persistent infection in man (7, 8), woodchucks (1, 9, 10) and ground squirrels (10a). Although the viral DNA has been found to be integrated in cellular DNA of many HCC in man (11), woodchucks (9, 10) and ground squirrels (10a), the precise role of the virus in tumor formation has not been defined.

Hepadna viruses have an interesting molecular structure and mechanisms of replication, and they appear to share certain important features with retroviruses as reviewed here. It is of interest to define similarities and differences between hepadnaviruses and retroviruses in order to understand their evolutionary relationship and to determine whether they share a common oncogenic mechanism, since infection with members of both virus families is associated with neoplastic disease.
Lack of vasopressin action on splanchnic hemodynamics during bleeding: A study in conscious, portal hypertensive rats
Authors: Valla Dominique , Girod Catherine , Lee Samuel S. , Braillon Alain , Lebrec Didier
Published: March 2007

Due to the marked effects of hemorrhage on cardiac output and splanchnic hemodynamics, the circulatory actions of vasopressin may differ during bleeding as opposed to stable conditions. We evaluated this hypothesis in conscious rats with portal hypertension due to chronic portal vein stenosis, by comparing the effects of a vasopressin infusion (0.02 IU per kg per min) to those of a control saline infusion, during and after a hypoten-sive hemorrhage (25 ml per kg). We also studied unbled portal hypertensive rats receiving an identical infusion of vasopressin or saline. During and after hemorrhage, vasopressin induced significant changes in systemic hemodynamics but had no effect on portal pressure, portal tributary blood flow and nonhepatic splanchnic arteriolar resistance. In unbled animals, by contrast, vasopressin decreased portal pressure and portal tributary blood flow and increased nonhepatic splanchnic arteriolar resistance. Our data further indicate that hemorrhage alone caused an early vasoconstriction in the portal tributaries and a delayed vasoconstriction in the nonsplanchnic vascular bed while vasopressin during hemorrhage induced an early and sustained vasoconstriction in the nonsplanchnic vascular bed as well as in the portal tributaries. The results show that, during and after severe bleeding, vasopressin exerts little influence on portal hemodynamics. Although these data do not allow firm conclusions concerning the therapeutic efficacy of vasopressin in bleeding esophageal varices, they demonstrate that the splanchnic actions of vasoac-tive substances cannot be readily extrapolated from stable conditions to hemorrhage.
Recurrence of spontaneous bacterial peritonitis in cirrhosis: Frequency and predictive factors
Authors: Titó Llúcia , Rimola Antoni , Ginès Pere , Llach Josep , Arroyo Vicente , Rodés Joan
Published: March 2007

We investigated whether spontaneous bacterial peritonitis in cirrhosis is a recurrent process and attempted to identify possible predictors of recurrence in 75 consecutive cirrhotics who had recovered from a first episode of spontaneous bacterial peritonitis between January, 1981 and December, 1984 and who were followed closely throughout their illness (follow-up period 10 ± 13 months; mean ± S.D.). Thirty-eight patients (51%) developed one or more episodes of spontaneous bacterial peritonitis during follow-up, the probability of recurrence (Kaplan-Meier’s method) being 43% at 6 months, 69% at 1 year and 74% at 2 years. Twenty-three variables (age, sex, etiology of cirrhosis, standard liver and renal function tests and characteristics of the first spontaneous bacterial peritonitis) were analyzed as possible predictors of recurrence of spontaneous bacterial peritonitis. In univariate analysis (curves of Kaplan-Meier compared with Mantel-Cox’s method), serum bilirubin >4 mg per dl, prothrombin ≤45% and protein concentration in ascitic fluid ≤1 gm per dl were significantly (p < 0.05) associated with a high risk or recurrence of spontaneous bacterial peritonitis. In multivariate analysis (Cox multiple regression model), only ascitic fluid protein concentration (p = 0.005) and prothrombin activity (p = 0.009) were found to be independent predictors of recurrence of spontaneous bacterial peritonitis. Fifty-nine patients (79%) died during follow-up, 18 of them (31%) secondary to spontaneous bacterial peritonitis. The 1-year survival probability in the whole series of patients was 38%. We conclude that spontaneous bacterial peritonitis frequently recurs in cirrhosis, particularly in patients with severe liver failure or low protein concentration in ascitic fluid, and that the survival of cirrhotics who recover from a first episode of spontaneous bacterial peritonitis is very short, the cause of death being the recurrence of spontaneous bacterial peritonitis in many cases.
Hepatic encephalopathy and orotic aciduria associated with hepatocellular carcinoma in a noncirrhotic liver
Authors: Jeffers Lennox J. , Dubow Richard A. , Zieve Leslie , Reddy Rajender K. , Livingstone Alan S. , Neimark Sidney , Viamonte Manuel , Schiff Eugene R.
Published: March 2007

A 40-yr-old man presented with encephalopathy and was found to have hepatocellular carcinoma without cirrhosis. A large vascular hepatic mass was defined by CT scan and angiography; laparoscopy with biopsy confirmed the absence of chronic liver disease. A definitive tissue diagnosis of hepatocellular carcinoma was made at laparotomy; the tumor was unresectable. Peripheral arterial and selective portal and hepatic venous ammonia levels were high, and this finding suggested that the encephalopathy was nitrogenous and hepatic in origin. The proposed mechanisms of the encephalopathy are generation of ammonia from tumor breakdown and por-tosystemic shunting, a result of partial tumor occlusion of the hepatic veins. An unusually high urinary excretion of orotic acid was found similar to that seen in hereditary orotic aciduria.