bluuebunny/crossref_metadata_2025 huggingface dataset:
Technetium-99m-iminodiacetic acid organic anions: Review of biokinetics and clinical application in hepatology
Authors: Krishnamurthy Shakuntala , Krishnamurthy Gerbail T.
Published: March 2007

Technetium-99m-labeled iminodiacetic acid analogs are a new class of organic anions, taken up and secreted by hepatocyte into hepatic bile by a carrier-mediated organic anion pathway. They provide a new dimension in the assessment of pathophysiology and morphology of the hepatobiliary system. The amount of uptake and the rapidity of its elimination from the liver is dependent upon the structural configuration of the agent as well as the functional integrity of the hepatocyte and the patency of the biliary system. The clinical areas for application are wide and include most of the hepatobiliary diseases. Technetium-99m-iminodiacetic acid, an agent well suited for both planar and single photon tomographic scintigraphy, is ideal for early diagnosis prior to anatomical changes in the hepatobiliary system. The data collection directly from the liver provides quantitation of both regional and global liver diseases. The count-based method for measuring gallbladder emptying overcomes the theoretical disadvantages of geometric tests. Biokinetics and current clinical application of six of the 99mTc-iminodiacetic acid agents are reviewed, and the potential future clinical and research areas of application are indicated.
Primary lymphoma of the liver: A more optimistic point of view
Authors: Anthony Peter P.
Published: March 2007

Nine adult white men ranging in age from 27 to 76 (mean, 55 years) were treated for primary hepatic lymphoma between 1972 and 1986 at the Memorial Sloan-Kettering Cancer Center. Six patients presented with right upper quadrant or epigastric pain or discomfort, and three patients complained of fatigue and lethargy. Fever and night sweats were evident in two, and two patients had lost weight. One patient was asymptomatic; the liver mass was detected during the work-up for cancer of the prostate. Seven patients on whom computerized tomography was performed all had solitary masses in the liver although in three of them tumor had extended into both lobes as noticed at surgery. One had additional porta hepatic lymph node metastasis. Eight patients underwent an exploratory laparotomy; four had hepatic resection, and four had wedge biopsies of unresectable liver tumor. One patient had a percutaneous needle biopsy of the liver. Eight patients received combination chemotherapy. Six patients are alive, five of whom are in initial complete remission. All three patients who died had persistent or recurrent disease in the liver. The results of therapy and surgery to date in these and in other cases in the literature are encouraging.
Biochemical aspects of α-l-fucosidase in hepatocellular carcinoma
Authors: Leray Geneviève , Deugnier Yves , Jouanolle Anne-Marie , Lehry Dominique , Bretagne Jean-François , Campion Jean-Plerre , Brissot Pierre , Treut André Le
Published: March 2007

Biochemical characteristics of α-l-fucosidase (α-L-fu-coside hydrolase, EC 3.2.1.51) were studied in tumorous and nontumorous human hepatocellular carcinoma (n=14). Five parameters were studied: (i) specific activity, (ii) thermostability, (iii) enzyme affinity for an artificial substrate (Km), (iv) isoenzyme patterns of the glycosi-dase before and after neuraminidase treatment and (v) pH influence on enzyme activity. The specific activity of α-l-fucosidase was significantly decreased in tumoral liver when compared to nontumoral liver. The curve of pH activity constantly showed a broad optimum centered near pH 5, whereas two optima were always observed in nontumoral areas. In contrast, there was no modification of the thermostability, the substrate affinity and the isoenzyme patterns of α-l-fucosidase in hepatocellular carcinoma.
Morphological and histological features of resected hepatocellular carcinoma in cirrhotic patients in the west
Authors: Kemeny François , Vadrot Jacqueline , Wu Andrew , Smadja Claude , Meakins Jonathan L. , Franco Dominique
Published: March 2007

The pathological findings of 26 consecutive resections for hepatocellular carcinomas developing in cirrhotic patients were analyzed morphologically with a special interest in the presence of a capsule, vascular extension and satellite nodules. Tumor sizes varied from 2 to 11 cm. There were 20 expanding (76.9%) and six infiltrating tumors. Infiltrating tumors were significantly larger than expanding tumors (p<0.01). Histologically, the most common subgroups were the trabeculated pattern (65.4%) and the Edmonson-Steiner Type II (53.9%). Of the 20 expanding tumors, only six had direct spread in the liver parenchyma adjacent to the tumor (p<0.02). There was a significant relationship between the presence of a tumor extension in the distal portal branches and the presence of satellite nodules around the tumor (p<0.01). Survival at 6 months was significantly lower in patients with infiltrating (16.7%) than in those with expanding tumors (75%), (p<0.05).

The present results indicate that pathological features of hepatocellular carcinomas in cirrhotic patients in Western countries are similar to those encountered in the East: (a) tumors are frequently encapsulated; (b) the propensity for the tumor to spread is closely related to the presence of a tumor capsule. This study suggests that a thorough preoperative search for the capsule should be made whenever resection of a hepatocellular carcinoma in a cirrhotic patient is contemplated.
Serotonin blockade in conscious, unrestrained cirrhotic dogs with portal hypertension†
Authors: Mastaï Ricardo , Rocheleau Bernard , Huet -Michel P.
Published: March 2007

It has recently been reported that the administration of ketanserin, a serotonin antagonist, was associated with a significant reduction in portal pressure both in portal hypertensive rats and cirrhotic patients. However, this beneficial effect on splanchnic hemodynamics was accompanied by a significant reduction in arterial pressure. Using conscious dogs, we investigated the effect of the chronic oral administration of a new specific antiserotonergic drug, ritanserin (10 mg per day for 5 days), on portal pressure and systemic hemodynamics. Eleven dogs with secondary biliary cirrhosis and portal hypertension due to chronic bile duct ligation were evaluated. One week prior to study, heparinized catheters were placed in the portal vein and brought subcutaneously to the dorsal cervical area. Measurements were made under baseline conditions, following ritanserin administration and 72 hr after the last dose. Ritanserin administration caused a significant reduction in portal pressure (from 17.3 ± 3.1 mmHg to 13.6 ± 4.5 mmHg; mean decrease: 23.1%; p<0.001). Maximal effects on portal pressure were reached on the fourth day. During the recovery period, hemodynamic parameters returned to baseline values. In six of the 11 cirrhotic dogs with successful chronic catheterization of the inferior vena cava and aorta, ritanserin administration did not cause significant changes in the mean arterial pressure, heart rate, cardiac output and peripheral vascular resistance. These data indicate that chronic implantation of venous and arterial catheters in dogs with secondary biliary cirrhosis is a useful experimental model for pharmacological studies of portal hypertension in conscious animals. The selective effect of ritanserin on portal pressure of portal hypertensive dogs indicates that this drug may be of value in the medical treatment of portal hypertension.
Controlled clinical trial of injection sclerotherapy for active variceal bleeding
Authors: Westaby David , Hayes Peter C. , Gimson Alexander E. S. , Polson Rex J. , Williams Roger
Published: March 2007

In a prospective, randomized clinical trial, immediate injection sclerotherapy was compared with treatment by a combined infusion of vasopressin (0.4 unit per min) and nitroglycerin (40 to 400 μg per min) in 50 consecutive patients with 64 episodes of endoscopy-proven active variceal hemorrhage. Control of bleeding was assessed over a 12-hr period following entry into the trial. Patients in the vasopressin + nitroglycerin group were then treated by sclerotherapy, as were those in the sclerotherapy group who continued to bleed.

At 12 hr, bleeding was controlled in 29 (88%) of the 33 episodes treated by sclerotherapy compared with 20 (65%) of 3 episodes treated by vasopressin + nitroglycerin (p<0.05). Recurrence of variceal bleeding occurred at the same frequency (31%). Although admission mortality was less in those initially treated by sclerotherapy compared to those managed by vasopressin + nitroglycerin, this did not reach statistical significance (27 and 39%, respectively, p>0.20). Sclerotherapy carried out as the first treatment of the active variceal hemorrhage proved both safe and effective, even in the presence of major hemorrhage, and as compared to combined vasopressin and nitroglycerin it proved superior.
Alteration of hepatic tissue spaces by platelet-activating factor and phenylephrine
Authors: Lapointe David S. , Olson Merle S.
Published: March 2007

Mean transit times for the movement of extracellular and intracellular reference compounds through isolated perfused rat livers were determined during exposure of livers to platelet-activating factor (AGEPC; 1-0-hexa-decyl-2-acetyl-sn-glycero-3-phosphocholine) and the α-adrenergic agonist phenylephrine, using the multiple indicator dilution technique. From the outflow profiles of rapid bolus injections of 3H-sucrose and 14C-urea given to the liver, the estimated intracellular volume of distribution of small freely permeant substances, Vi, and Θ′, the ratio of intracellular to extracellular space, were computed. Exposure of the liver to AGEPC decreased Vi and Θ′ by 32 and 34%, respectively, from control values, whereas infusion of phenylephrine increased Vi by 16% and Θ′ by 33%. The results indicate that the hemodynamic effects of AGEPC in perfused rat liver cause the apparent loss of tissue space accessible to small permeant compounds. Phenylephrine, although increasing hepatic vascular resistance, measured at the portal vein, by the same magnitude as AGEPC, led to an increase in the apparent tissue space accessible to this same species.
Compact organization of the hepatitis B virus genome
Authors: Miller Roger H. , Kaneko Shuichi , Chung Cathie T. , Girones Rosina , Purcell Robert H.
Published: March 2007

The genome of hepatitis B virus (HBV) is a circular DNA molecule approximately 3,200 base pairs (bp) in length. Relative to other double-stranded DNA viruses capable of independent replication, HBV possesses the smallest genome of any virus known to infect man. Therefore, it is not surprising that HBV utilizes its genetic material economically. This is accomplished by two rare genetic arrangements: proteins are encoded from overlapping translation frames, and all regulatory signal sequences reside within protein-encoding sequences. Thus, HBV obtains multiple use from many regions of its genome, which underscores the sophistication of this virus from an evolutionary standpoint.
Relapsing or reinfectious lyme hepatitis
Authors: Schoen Robert T.
Published: March 2007

Lyme disease, a multi-system disorder caused by the tick-borne spirochete, Borrelia burgdorferi, is characterized by malaise, fever, headache, arthralgia, myalgia, stiff neck, lymphadenopathy, paresthesias, and a distinctive rash, erythema chronicum migrans (ECM) in its early phase. Neurologic, cardiac, and joint abnormalities may follow within weeks to months. A patient is described in whom acute recurrent Lyme disease occurred and in which spirochetes were identified in the skin and liver histologically.
Laser-assisted angioplasty of inferior vena caval obstructions: What’s good for the artery is good for the vein
Authors: Deckelbaum Lawrence I.
Published: March 2007

Three cases of hepatic inferior vena cava (IVC) obstruction (two segmental and one membranous) associated with Budd-Chiari syndrome were successfully treated with percutaneous transluminal angioplasty (PTA) with use of an Nd-YAG (neodymium-yttrium, aluminum, garnet) laser. The occluded portions were canalized by advancing a ceramic-capped delivery system and delivering intermittent laser emissions. The canal was widened by simultaneous inflation of three or four Gruentzig balloon catheters. In two of the three cases, this procedure was done after unsuccessful canalization of the occluded portions by conventional means. Postoperatively, all patients showed disappearance of Budd-Chiari syndrome. One patient also showed marked regression of a huge intraluminal thrombus. There were no serious complications during and after the procedures. Use of the Nd-YAG laser seems to be of value in PTA for the treatment of hepatic IVC obstructions as well as in treatment of arteriosclerotic lesions.
Suppressive effects of cyclosporin a in murine schistosomiasis
Authors: Dunn Michael A.
Published: March 2007

Cyclosporin A (CsA), administered subcutaneously as 5 daily injections of 50 mg·kg−1, reduced the numbers of Schistosoma mansoni perfused from MF1 mice at 7 weeks post-infection. The timing of drug administration revealed that the antischistosomal effects were greater when CsA treatment coincided with or was within a few days of infection with a parasite. CsA exerted a clear prophylactic effect, which decreased with time and was virtually abolished by 4 months pre-infection. Adult worms treated in vivo were partially susceptible to CsA. In addition to its antiparasite action, CsA reduced hepatosplenomegaly due to schistosomiasis and diminished the granulomatous inflammatory response of mice to parasite eggs in the liver. The mode of action of CsA is not understood but evidence is presented that supports the proposition that the anti-parasite effects are perhaps host-mediated.
Digoxin-like immunoreactive substances in chronic liver disease
Authors: Yang Sien-Sing , Korula Jacob , Sundheimer James E. , Keyser Anthony J.
Published: March 2007

Digoxin-like immunoreactive substances, which cross-react with digoxin antibody, have been found to have natriuretic effect and Na+,K+-ATPase inhibitory effect. The role of digoxin-like immunoreactive substances in chronic liver disease was studied by radioimmunoassay in 63 serum and 60 urine samples from 58 patients with chronic liver disease and compared with 16 controls. Although the mean serum digoxin-like immunoreactive substances level of compensated chronic liver disease patients (0.06 ± 0.05 ng per ml, p < 0.01) was higher than that of controls (0.02 ± 0.03 ng per ml), only four patients had serum digoxin-like immunoreactive substances higher than 0.10 ng per ml. Mean serum digoxin-like immunoreactive substances level was much higher in patients with decompensated chronic liver disease who had ascites (0.32 ± 0.17 ng per ml, p < 0.001), hepatorenal syndrome (0.57 ± 0.20 ng per ml, p < 0.001) and hepatic encephalopathy (0.43 ± 0.20 ng per ml, p < 0.001). Five patients with recent variceal hemorrhage requiring transfusions and saline infusion had significantly increased serum digoxin-like immunoreactive substances (mean: 0.16 ± 0.06 ng per ml, p < 0.001) before the development of clinically detectable ascites. The serum digoxin-like immunoreactive substances level was positively correlated with serum total bilirubin (r = 0.581, p < 0.001), AST (r = 0.454, p < 0.001), serum creatinine (r = 0.539, p < 0.001), urine digoxin-like immunoreactive substances (ng of urine digoxin-like immunoreactive substances per gm of urine creatinine, r = 0.578, p < 0.001) and negatively correlated with serum albumin (r=−0.604, p < 0.001), prothrombin activity (r=−0.589, p < 0.001), serum sodium (r=−0.685, p < 0.001) and urine sodium (mEq of urine sodium per gm of urine creatinine; r=−0.476, p < 0.001). The present study shows increased serum digoxin-like immunoreactive substances in decompensated chronic liver disease. The negative correlation between serum digoxin-like immunoreactive substances and urine sodium suggests that digoxin-like immunoreactive substances level is higher in patients having low urinary sodium output. This finding may be explained by a possible renal insensitivity to digoxin-like immunoreactive substances in decompensated chronic liver disease.
Hepatic metabolism of colloidal gold-low-density lipoprotein complexes in the rat: Evidence for bulk excretion of lysosomal contents into bile
Authors: Renaud Guy , Hamilton Robert L. , Havel Richard J.
Published: March 2007

Rats were treated with 17α-ethinyl estradiol to induce high levels of low-density lipoprotein receptors in hepatocytes. When these rats were given intravenous injections of low-density lipoprotein-colloidal gold complexes, most of the gold (labeled with 195Au) appeared to be taken up by Kupffer cells, as were complexes of colloidal gold with albumin or polyvinylpyrrolidone. However, when these rats were also administered gadolinium chloride, which blocks Kupffer cell activity, most of the low-density lipoprotein-gold (but not gold complexed with albumin or polyvinylpyrrolidone) was taken up into hepatocytes by receptor-mediated endocytosis and concentrated in peribiliary lysosomes, as determined by electron microscopy. Colloidal gold taken up as a complex with low-density lipoprotein was excreted into the feces via the common bile duct at a maximal rate of about 5% daily, 4 to 12 days after injection. Thereafter, the rate of gold excretion fell off until reaching a plateau after 3 weeks. At this late time, most of the colloidal gold was shown by electron microscopy to be in Kupffer cells, whereas earlier (6 days after injection) it was contained mainly in older hepatocytic lysosomes, identified by lipofuscin granules. It is concluded that, in rats, hepatocytic lysosomes empty most of their contents into bile every week or two, apparently by exocytosis.
Immunization of experimental animals with dihydrolipoamide acetyltransferase, as a purified recombinant polypeptide, generates mitochondrial antibodies but not primary biliary cirrhosis
Authors: Krams Sheri M. , Surh Charles D. , Coppel Ross L. , Ansari Aftab , Ruebner Boris , Gershwin Eric M.
Published: March 2007

The availability of recombinant mitochondrial autoantigens may permit the experimental study of the pathophysiology of primary biliary cirrhosis. Previously, we demonstrated that high-titer antibodies to the 74 kD mitochondrial autoantigen dihydrolipoamide acetyltransferase could be generated when BALB/c mice were immunized with purified recombinant protein. Based on these data, we attempted an 8-month study to induce antibodies and liver dysfunction by immunizing AKR/J, C3H/J and CBA/HeJ mice as well as rats, guinea pigs, rabbits and rhesus monkeys with purified recombinant human dihydrolipoamide acetyltransferase. Antibodies to dihydrolipoamide acetyltransferase were readily induced and detected in all species of experimental animals with species and strain differences in the titer of the responses. Of particular interest, rabbits and guinea pigs produced antibodies which were specifically reactive with the functional site of dihydrolipoamide acetyltransferase, whereas the other strains and species produced antibodies to other epitopes on the molecule. Finally, similar to data on humans with primary biliary cirrhosis, the pyruvate dehydrogenase enzyme pathway was inhibited in the presence of immunized animal sera. These data imply that features other than simply an antibody response to mitochondrial enzymes are required for the development of primary biliary cirrhosis. Further studies will be necessary to determine the mechanisms by which mitochondrial proteins elicit an immune response.
Polymorphonuclear cell count response and duration of antibiotic therapy in spontaneous bacterial peritonitis†
Authors: Fong Tse-Ling , Akriviadis Evangelos A. , Runyon Bruce A. , Reynolds Telfer B.
Published: March 2007

The purposes of this study were (a) to measure serially ascitic fluid polymorphonuclear cell response in treated spontaneous bacterial peritonitis and (b) to determine whether an ascitic fluid polymorphonuclear cell count of less than 250 per mm3 on serial paracenteses was a satisfactory endpoint for antibiotic therapy. Thirty of 33 patients showed an exponential fall in ascitic fluid polymorphonuclear cell count after 48 hr of antibiotic therapy; the magnitude of decrease correlated with survival (p<0.01). Among the patients whose antibiotic therapy was discontinued when the ascitic fluid polymorphonuclear cell count reached 250 per mm3 or less, the duration of therapy was considerably shorter than for the patients who received “conventional” therapy (p<0.01). Recurrence of spontaneous bacterial peritonitis was similar in the two groups. Mortality correlated with the severity of underlying liver disease but not with duration of antibiotic therapy.
Propranolol does not alter cerebral blood flow and functions in cirrhotic patients without previous hepatic encephalopathy
Authors: Calès Paul , Pierre-Nicolas Max , Guell Antonio , Mauroux Jean-Louis , Franco-Sempe Anne , Vinel Jean-Pierre , Geraud Gilles , Pascal Jean-Pierre
Published: March 2007

Since it has been suggested that propranolol could lead to hepatic encephalopathy, we undertook a study to assess the effects of propranolol on cerebral blood flow and cerebral functions. Sixteen patients with alcoholic cirrhosis and large esophageal varices and without major hepatic dysfunction (Child-Pugh score <14) or previous hepatic encephalopathy were randomized to receive either propranolol or placebo. The following measurements weré performed before and 15 min after single intravenous administration of 15 mg propranolol or placebo and again 1 week after chronic oral administration of propranolol 160 mg per day or placebo: cerebral blood flow by the xenon-133 inhalation technique, quantitative electroencephalogram, psychometric test (number connection test), arterial ammonia, pH and pCO2, resting and exercise heart rates (after single administration, electroencephalogram, number connection test and biochemical measurements were not performed). Cerebral blood flow was not significantly modified by treatment (propranolol group: 80 ± 23 vs. 76 ± 11 and 83 ± 9; placebo group: 73 ± 10 vs. 75 ± 11 and 81 ± 18 ml per 100 gm per min, respectively, before and after single and repeated administration). Likewise, neither of the two treatments significantly altered number connection test, quantitative electroencephalogram index, arterial ammonia, pH and pCO2. We conclude that, in this population of cirrhotic patients, propranolol did not alter cerebral blood flow or neuropsychological functions. As a consequence, hemodynamic alterations cannot be considered as causes of possible cerebral side effects of propranolol in cirrhotic patients without severe hepatic dysfunction and previous hepatic encephalopathy.
Nodular regenerative hyperplasia of the liver following bone marrow transplantation†
Authors: Snover Dale C. , Weisdorf Sally , Bloomer Joseph , McGlave Philip , Weisdorf Daniel
Published: March 2007

Liver disease in the early period following bone marrow transplantation may be due to a number of causes, including pretransplant cytoreduction with chemotherapy and irradiation. Although the relationship of veno-occlusive disease to these agents has been well established, another process, nodular regenerative hyperplasia, may also occur.

In this retrospective study, we evaluated the incidence and clinical signs of these two processes as defined by histological criteria. In 103 patients studied, nine (8.8%) had venoocclusive disease and 23 (22.5%) had nodular regenerative hyperplasia. Venoocclusive disease was significantly associated with transplantation for malignancy other than acute or chronic leukemia and use of busulfan as a cytoreductive agent and occurred in younger patients. Nodular regenerative hyperplasia did not differ from the general transplant population in terms of underlying disease, cytoreductive regimen, graft vs. host disease prophylaxis or age. Both venoocclusive disease and nodular regenerative hyperplasia were associated with ascites. Venoocclusive disease had a poor prognosis, with eight of nine cases dying of or with venoocclusive disease, whereas no case of nodular regenerative hyperplasia died of liver disease and only 5 of 23 died with nodular regenerative hyperplasia. Using retrospective data, five of 11 patients fulfilling clinical criteria for the diagnosis of venoocclusive disease actually had nodular regenerative hyperplasia, as did all of nine patients fulfilling the criteria for “possible” venoocclusive disease.

These results indicate that nodular regenerative hyperplasia is a process which occurs commonly following bone marrow transplantation and which may be clinically misdiagnosed as venoocclusive disease.
Prospective assessment of donor blood screening for antibody to hepatitis B core antigen as a means of preventing posttransfusion non-A, non-B, hepatitis
Authors: Hoyos Melchor , Sarrión José V. , Pérez-Castellanos Teresa , Prieto Martín , Marty María L. , Garrigues Vicente , Berenguer Joaquín
Published: March 2007

The relationship between donor status for antibody to hepatitis B core antigen and the occurrence of non-A, non-B posttransfusion hepatitis in the recipient was prospectively studied in 112 patients undergoing open-heart surgery who were followed for 6.5 months after surgery. Non-A, non-B posttransfusion hepatitis occurred in five (7.93%) of 63 patients who had received at least one anti-HBc-positive blood unit compared to seven (14.28%) of 49 patients who received anti-HBc-negative blood only. Statistical analysis revealed that the incidence of non-A, non-B posttransfusion hepatitis was independent of the use of blood positive for anti-HBc. Based upon these results and the high prevalence (17.3%) of anti-HBc among our blood donor population, the exclusion of anti-HBc-positive blood does not seem appropriate to achieve a reduction in the incidence of non-A, non-B posttransfusion hepatitis.
The etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers
Authors: Chu Chia-Ming , Liaw Yun-Fan , Pao Chia C. , Huang Miau-Ju
Published: March 2007

To study the etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers, paired sera were collected in acute and convalescence phases for measurement of HBeAg, anti-HBe, hepatitis B virus DNA and anti-delta from 76 adult patients with acute hepatitis who were HBsAg positive but IgM anti-HBc negative or positive only at low titer. None of them were IgM anti-hepatitis A virus positive on admission. Of the 34 patients who were HBeAg positive initially, two (5.9%) were diagnosed as having delta superinfection, and another two (5.9%) were suspected to have non-A, non-B virus superinfection because of a transient decrease of serum hepatitis B virus DNA. The remaining 30 (88.2%) cases were hepatitis B virus DNA negative with or without anti-HBe seroconversion on follow-up. The episodes of acute hepatitis in these cases may represent “immune clearance of HBeAg” or “immune clearance of hepatitis B virus with delayed anti-HBe seroconversion,” respectively, in the natural course of chronic hepatitis B virus infection. Of the patients who were anti-HBe positive initially, 23 (54.8%) were diagnosed as having delta superinfection, including eight with de novo seroconversion of anti-delta and 15 with a rising titer of anti-delta; 10 (23.8%) were positive for hepatitis B virus DNA and were considered as reactivation of hepatitis B virus, and the other nine (21.4%) were suspected as having non-A, non-B virus superinfection. We conclude that the vast majority of episodes of acute hepatitis in HBeAg carriers may represent immune clearance of hepatitis B virus in the natural history of chronic hepatitis B virus infection, and, by contrast, in anti-HBe carriers they are usually the result of superinfection with other non-B viruses, the majority of which are due to delta superinfection.
Does hypophosphatemia play a role in acute liver failure?
Authors: Knochel James P.
Published: March 2007

This is the first record of hypophosphataemia in acute liver failure induced by paracetamol; it occurred in most of the patients and was severe (<0.3 mmol/l) in more than one third. At this level hypophosphataemia produces impaired oxygen transport and tissue hypoxia, abnormal leucocyte function, depressed platelet numbers and function, generalised muscle weakness, and disorder of the central nervous system; these are frequent complications of acute liver failure. The similarity of the effects of liver failure and hypophosphataemia on the central nervous system (irritability, muscle weakness, dysarthria, confusion, and coma) suggests that phosphate depletion may be important in hepatic encephalopathy, and a progressive defect of phosphate metabolism in brain tissue of patients with chronic liver disease was shown recently by nuclear magnetic resonance spectroscopy.

The cause of hypophosphataemia in acute liver failure remains unclear. None of the recognised causes of moderate (0.3-0.7 mmol/l) hypophosphataemia correlated with the phosphate concentrations in our patients. The reduced maximum tubular reabsorption of phosphate in two patients suggests an increased loss of renal phosphate, perhaps due to a direct effect of paracetamol, although the correlation between plasma phosphate and creatinine concentrations suggests that renal failure may protect against hypophosphataemia. Because of the serious clinical implications of phosphate imbalance in acute liver failure the homoeostatic mechanisms of bone and renal phosphate reabsorption in this condition need to be studied urgently. Plasma phosphate concentrations should be monitored carefully during infusion of glucose in patients with liver failure.
Androgen receptor analysis on needle biopsy of the liver: A step closer in determining whether hepatocellular carcinomas are sex hormone-sensitive
Authors: Mishkin Seymour , Mishkin Shaindel Y. , Erdstein Julius
Published: March 2007

The liver is a steroid-responsive organ and contains high levels of androgen receptors (AR). The present study investigated cytosolic AR concentrations in diseased human liver obtained by needle biopsy. Insufficient tissue was available for full Scatchard analysis. Previous studies have shown the binding affinity of the liver AR to be sufficiently constant to allow the use of a single saturating dose analysis, using 3H-mibolerone as the active ligand, for the estimation of binding sites. Thirteen samples were studied and compared to normal liver. AR was identified in all samples and the level negatively correlated to the degree of liver damage. A role for AR in hepatocellular carcinoma has been postulated and anti-androgens used in treatment. This study shows AR can be measured in needle-biopsy specimens and, if hepatocellular carcinoma is proven to be hormone sensitive, then this technique may help in the assessment of such tumours.
Benign recurrent intrahepatic cholestasis: A long-term follow-up study of two patients
Authors: Bijleveld Charles M. A. , Vonk Roel J. , Kuipers Folkert , Havinga Rick , Fernandes John
Published: March 2007

Two brothers with benign recurrent intrahepatic cholestasis were studied over a period of 6 years. During this period, 11 episodes of cholestasis were observed, with a mean duration of 2.6 months (range: 2 weeks to 6 months). Once, both brothers developed cholestasis simultaneously. There was a prevalence for episodes of cholestasis in wintertime. The postprandial rise in serum sulfated glycolithocholic acid was increased in the patients, and the bile acid pool was enriched with secondary bile acids. In periods prior to cholestasis, the urinary 3αOH-bile acid concentration was often elevated (>50 μmoles per liter) without a clear correlation with the clinical prodromata. However, it could not be used as a predictor of cholestasis. In contrast, the postprandial rise in serum 3αOH-bile acids was always grossly elevated in periods just before cholestasis. An increase both in fecal bile acid excretion as well as secondary bile acids in the bile acid pool indicated an increased spillover of bile acids into the large bowel. Cholestyramine administered directly after the first signs of cholestasis appeared to shorten an episode of cholestasis. On the other hand, withdrawal of cholestyramine in a cholestasis-free period may have resulted in an episode of cholestasis. Neither taurine supplementation for 3 and 7 weeks nor calcium phosphate, which binds sulfated bile acids in vitro, for 3 weeks could prevent an episode of cholestasis, although the latter normalized the bile acid pool composition. There is a rationale for a fat-restricted diet and cholestyramine therapy only as maintenance treatment. However, unpredictable patient compliance in permanent cholestyramine therapy entails an increased risk for cholestasis due to reduced bile acid pool.
Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile†
Authors: Schriever Carolin Erika , Jüngst Dieter
Published: March 2007

Rapid aggregation of cholesterol-phospholipid vesicles in gallbladder bile seems to be the first event in the production of cholesterol crystals, a prerequisite for cholesterol gallstone formation. We examined the amount of these vesicles in 33 human gallbladder biles in relation to biliary lipid composition and to the presence of cholesterol crystals. Biliary microscopy detected cholesterol crystals in all 19 biles from patients with cholesterol gallstones but in none of 14 biles from patients with pigment stones. Gel chromatography was used to separate vesicles and micelles in the native bile with an eluting buffer containing 10 mM sodium cholate to prevent disruption of micellar lipids. Cholesterol, phospholipid and bile salt concentrations were measured in every fraction collected. Bile acid, phospholipid, cholesterol and total lipid concentrations were not significantly different in samples with and without cholesterol crystals. The cholesterol saturation index (1.4 ± 0.11 vs. 1.0 ± 0.08) was significantly (p < 0.01) higher in biles with crystals than without crystals. Gel filtration revealed a vesicular peak in addition to micellar fraction in 18 (23.1 ± 3.2% of total cholesterol) of the 19 biles with crystals but only in three (15.7 ± 2.4% of total cholesterol) of 14 biles without crystals. There was no relation between biliary lipid concentration or the cholesterol saturation index and the percentage of vesicular cholesterol in biles with or without crystals. The close association of vesicles and crystals in human gallbladder bile supports the contention that vesicles are important in the initial nucleation of cholesterol monohydrate crystals.
Studies on the regulation of cholesterol metabolism by low-and high-density lipoproteins in HepG2 cellsx
Authors: Ranganathan Subramanian , Kottke Bruce A.
Published: March 2007

The uptake and degradation of low-density lipoproteins and the esterification and synthesis of cholesterol were poorly down-regulated by low-density lipoproteins in HepG2 cells. Addition of low-density lipoproteins to the cells increased the free and esterified cholesterol in the cells. The heavier fraction of high-density lipoproteins enhanced the degradation of low-density lipoproteins and cholesterol synthesis and decreased acyl CoA:cholesterol acyltransferase activity. Addition of the heavier fraction of high-density lipoproteins also caused a net efflux of cholesterol from HepG2 cells. The lighter fraction did not have any significant effect on cholesterol metabolism or cellular cholesterol level. Neither the lighter nor the heavier fractions of high-density lipoproteins were found to have any specific binding properties to HepG2 cells.
Modulation of hepatic ferrochelatase activity by dietary manipulation of mitochondrial phospholipid fatty acyl groups†
Authors: Kools Ann M. , Straka James G. , Hill Hazel D. , Whitmer Dorothy I. , Holman Ralph T. , Bloomer Joseph R.
Published: March 2007

Ferrochelatase is an enzyme bound to the inner mitochondrial membrane, which is important in heme biosynthesis. Activity of purified ferrochelatase is affected by the presence of certain fatty acids. In the present study, we examined whether the activity of ferrochelatase is altered by dietary manipulation of the composition of mitochondrial membrane phospholipid fatty acylgroups.

Rats were fed diets containing triolein, safflower or menhaden oil as 5% (w/w) of the diet. After 3 weeks, the animals were killed and liver mitochondria were isolated. Phospholipid fatty acid composition and ferrochelatase activity were assayed in the isolated mitochondria. Marked differences were seen. The proportion of oleic acid was highest in the triolein oil-fed group, that of linoleic and arachidonic acid was highest in the safflower oil-fed group and the proportion of eicosapentaenoic acid was highest in the menhaden oil-fed group. Ferrochelatase activity was greatest in the triolein oilfed group and lowest in the menhaden oil-fed group regardless of whether the mitochondria were intact, sonicated or sonicated and treated with Tween 20. Mixing of mitochondria from menhaden oil-fed rats with triolein oil resulted in a significant increase in ferrochelatase activity. Membrane fluidity and activities of the mitochondrial membrane enzymes succinic dehydrogenase and cytochrome oxidase did not differ among the groups.

We conclude that dietary manipulation of mitochondrial membrane phospholipid fatty acyl group composition can directly modulate hepatic ferrochelatase activity. This has potential application in the treatment of protoporphyria, the genetic disorder in which ferrochelatase activity is deficient.
Changes in liver and spleen volume in alcoholic liver fibrosis of man
Authors: Tarao Kazuo , Hoshino Hiroshi , Motohashi Ikuko , Iimori Kazuto , Tamai Setsuo , Ito Yoshihiko , Takagi Seiichi , Oikawa Yubo , Unayama Shiro , Fujiwara Takuya , Odagiri Kunio , Ikeda Toshio , Hayashi Kazuhiro , Sakurai Akira , Uchikoshi Toshiyuki
Published: March 2007

Alcoholic liver fibrosis is a relatively common form of alcoholic liver disease in Japan. It is regarded by some investigators as a prodromal stage of alcoholic liver cirrhosis, but little is known about the volumes of the liver and spleen in this disease state. Therefore, liver and spleen volumes were measured by computed tomography in 32 patients with alcoholic liver fibrosis in comparison with 10 healthy volunteers. Patients with alcoholic liver fibrosis were divided into three subgroups (13 of Grade 1, 9 of Grade 2 and 10 of Grade 3) according to the severity of fibrosis. The volume was calculated from the sum of the area measurements of successive transverse sections of the two organs. The liver volume (mean ± S.D.) in Grade 2 alcoholic liver fibrosis (1,281 ± 112 cm3) was significantly (p < 0.01) larger than in healthy volunteers (1,017 ± 73 cm3) and in Grade 1 (1,090 ± 157 cm3), and the liver volume in Grade 3 (1,490 ± 132 cm3) was larger than in Grade 2 (p < 0.01). The mean volume of hepatocytes estimated by a two-dimensional image analysis system was significantly (p < 0.05) larger in Grade 3 than in Grade 2, and that in Grade 2 was larger than in Grade 1. The spleen volume in Grade 3 (151 ± 40 cm3) was significantly (p < 0.01) larger than in healthy volunteers (86 ± 26 cm3), Grade 1 (89 ± 38 cm3) and Grade 2 (68 ± 19 cm3). The presumed reason for hepatic volume increase would be the ballooning of hepatocytes along with increased fibrotic component.
The effect of several sex steroid hormones on the growth rate of three morris hepatoma tumor lines
Authors: Erdstein Julius , Wisebord Steven , Mishkin Shaindel Y. , Mishkin Seymour
Published: March 2007

Morris hepatoma 44, whose growth is sensitive to thyroid hormones and prolactin, contains specific receptors for these hormones. In the present experiments, male Buffalo rats bearing Morris hepatoma 7787 were studied to determine the effects of several sex steroid hormones. Castration 1 week postimplantation inhibited tumor growth relative to controls (-53%). Replacement with testosterone propionate (1 mg per day s.c. injection) restored tumor growth to control levels, whereas administration of testosterone (2 mg per day s.c. injection) to castrated controls resulted in significant stimulation. Testosterone administered to control animals at a dose of 1 mg per day stimulated tumor growth (62%), whereas 2 mg per day failed to do so. Progesterone (4-pregnon-3,20-dione) at doses of 125 or 250 μg per day (Silastic implants) had no effect on tumor growth, whereas 500 μg per day stimulated tumor growth relative to controls. Estrogen (17β-estradiol) at doses of 6, 12, 04 24 μg per day (Silastic implants) did not influence tumor growth. Cytoplasmic testosterone receptors have been demonstrated in tumors (2.2 ± 0.8 fmoles per mg cytoplasm), although specific cytoplasmic estrogen and progesterone receptors could not be identified in this model. In female rats bearing either Morris hepatoma 44, 7787 or 5123-D, testosterone markedly stimulated tumor growth (226, 328 and 58%, respectively, relative to controls).

In conclusion, although Morris hepatoma 7787 appears to be androgen (testosterone) dependent and contains cytoplastic androgen receptors, it lacks specific cytoplasmic receptors for estrogen and progesterone and is not influenced by these hormones except at very high doses of progesterone.
Impaired sulfoxidation in patients with primary biliary cirrhosis
Authors: Scharschmidt Bruce F. , Lake John R.
Published: March 2007

An impaired sulfoxidation pathway has been implicated in the pathogenesis of chlorpromazine-induced hepatotoxicity. Since some patients with chronic chlorpromazine-induced cholestasis may have features of primary biliary cirrhosis, we studied the ability to sulfoxidate the amino acid analogue S-carboxymethyl-cysteine in 44 patients with primary biliary cirrhosis and in two control groups—one without liver disease and one with a variety of liver diseases other than primary biliary cirrhosis.

Poor sulfoxidation was observed in 84 percent of the patients with primary biliary cirrhosis, as compared with 24 percent of patients with other liver diseases and 22 percent of normal controls (P < 0.0005 for both comparisons). Poor sulfoxidation did not correlate with the degree of hyperbilirubinemia or histologic severity of liver disease in any of the groups studied. There was an inverse correlation with age only in the patients with primary biliary cirrhosis (r = −0.44, P < 0.001). Liver transplantation was performed in six of the patients and improved sulfoxidation in five; in the four with primary biliary cirrhosis, sulfoxidation improved from poor to good or intermediate.
Targeted therapy for hepatic cancer: Good in theory, problematic in practice
Authors: Wright Teresa L.
Published: March 2007

We present evidence that normal hepatocytes can be specifically protected from galactosamine toxicity in vitro by targeting an antagonist to these cells via receptor-mediated endocytosis. The strategy is based upon the following principles: 1) galactosamine is a highly selective hepatotoxin that causes a dose-dependent depletion of uridine intermediates; 2) galactosamine toxicity can be antagonized by supplemental administration of uridine; 3) normal hepatocytes possess unique cell-surface receptors that can internalize galactose terminal (asialo-) glycoproteins with subsequent degradation of the glycoprotein ligand.

Based on these facts, we hypothesized that chemical coupling of a galactosamine antagonist to an asialoglycoprotein could result in cell-specific delivery and protection of normal hepatocytes by targeting the antagonist via asialoglycoprotein receptors. Using a model system consisting of freshly isolated rat hepatocytes (receptor(+)) and Morris 7777 rat hepatoma (receptor (−)) cells, sensitivity to galactosamine in vitro was determined and found to be similar for both types of cells. A targetable antagonist was synthesized by coupling uridine monophosphate to asialoorosomucoid in a molar ratio of 5 to 1. Exposure of Morris 7777 cells to the targetable antagonist in the presence of a toxic concentration of galactosamine did not protect these cells as evidenced by a steady decline in the number of viable cells in a fashion identical to cells treated with galactosamine alone. However, normal hepatocytes that received the conjugate in the presence of galactosamine were protected as their viable cell number remained the same as control (untreated) cells. Competition by an excess of asialoglycoprotein inhibited the protective effect of the conjugate, supporting the concept that the asialoglycoprotein component of the conjugate was responsible for the specific delivery of the antagonist to the target cells.
Sexual behavior in women with nonalcoholic liver disease
Authors: Bach Nancy , Schaffner Fenton , Kapelman Barbara
Published: March 2007

Sexual behavior in women with liver disease was examined in 150 women to determine whether liver disease influenced sexual desire, frequency or performance. The average age of women studied was 53 years (range: 26 to 76 years), and a wide variety of liver diseases were represented. Sexual desire was reduced in 33%. Difficulty in becoming sexually aroused was noted by 18%. Orgasm during intercourse was not experienced by 25%. The frequency of sexual intercourse decreased since onset of disease in 27%. Dyspareunia was a complaint by 21%, most often attributed to decreased vaginal lubrication. Liver disease was considered a significant factor interfering with sexual function in 17%. No statistical difference was found between sexual desire or function in our study and in large studies of sexual behavior in women. Each category was subdivided by presence or absence of cirrhosis, pre- or postmenopausal state, laboratory values and duration of disease. Except for a greater number of postmenopausal women with complaints of painful intercourse, no statistical differences or trends were found. Nonalcoholic liver disease does not affect sexual desire, function or performance. Variables other than liver disease influence sexuality. Women with liver disease can thus be reassured that they can maintain normal sexual relations.
Hepatic aldehyde dehydrogenase activity in liver diseases, with particular emphasis on alcoholic liver disease
Authors: Takase Shujiro , Takada Akira , Yasuhara Minoru , Tsutsumi Mikihiro
Published: March 2007

Hepatic aldehyde dehydrogenase isozyme activity was measured in 51 patients with various types of liver diseases, including 24 patients with alcoholic liver disease, to elucidate the relationship between hepatic aldehyde dehydrogenase activity and liver disease, especially alcoholic liver disease. The levels of low-Km and total aldehyde dehydrogenase activity in the liver decreased both in alcoholic and nonalcoholic liver disease patients, who showed an isoelectric focusing pattern of the usual type. There was no significant difference in the aldehyde dehydrogenase activity between alcoholic and nonalcoholic liver disease. In alcoholic liver disease, the decrease in the activity was significantly correlated with the progression of liver histology. The activity in liver cirrhosis was significantly lower than that in the other types of alcoholic liver disease. In nonalcoholic liver disease patients, the unusual type of hepatic aldehyde dehydrogenase activity observed was not different from the unusual type observed in nonhepatobiliary disease patients. These results indicate that the reduction of hepatic low-Km aldehyde dehydrogenase activity is a change that occurs subsequent to liver damage. Genetic abnormality in aldehyde dehydrogenase may not be important in the pathogenesis of alcoholic liver injury.