摘要:

AbstractThe formation of intracellular lumina with apical differentiation is observed in several cancerous epithelial cell lines including human hepatocarcinoma. This disorder of cell polarization can be induced by the inhibition of cell‐cell communication, a known factor of carcinogenesis.This work was designed to study the effects of ethanol on the differentiation of hepatocytes in short‐term culture. Isolated hepatocytes were plated on plastic culture dishes that were 35 mm in diameter (106cells/dish). Three hours after plating, the hepatocytes were incubated in the presence of 20 mmol/L ethanol for 1 hr. Treated cells were compared with controls using morphometric methods after conventional treatment for ultramicroscopy and by measuring cellular dye coupling by the fluorescent Lucifer Yellow CH transfer method.Bile canaliculi formation decreased in alcoholtreated cells (6.5% vs. 9.9%, 2p<0.05), whereas intracellular lumina incidence increased (3.1% vs. 0.5%, 2p<0.01). In parallel, the dye‐coupling capacity decreased significantly when hepatocytes were treated with alcohol (2p<0.01).This work shows that short‐term ethanol treatment induces significant disturbances of cell polarization and inhibits the reestablishment of cell‐cell communication in cultured hepatocytes. These disorders could, at least in part, explain the carcinogenic effects of ethanol. (HEPATOLOGY1992;15

ISSN:0270-9139    

DOI:10.1002/hep.1840150502

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractA gene region encoding a segment of the major surface protein, HBsAg, of hepatitis B virus was analyzed from serum samples after orthotopic liver transplantation of three hepatitis B virus chronic carrier patients treated with a human anti—hepatitis B virus monoclonal antibody (SDZ OST 577). Each of these three patients became HBsAg negative after transplantation and therapy with the human anti—hepatitis B virus monoclonal antibody but returned to HBsAg positivity (first detected 143,251 and 252 days after the transplantation). Polymerase chain reaction DNA amplification was performed on DNA from serum samples showing low levels of recurrent HBsAg and reduced antigen reactivity with SDZ OST 577 antibody. Polymerase chain reaction DNA included a 230‐bp highly conserved, major S gene region that was cloned into M13 bacteriophage; analysis of this DNA segment provided a consensus of DNA sequences for the serum samples exhibiting altered reactivity with the therapeutic monoclonal. Analysis of independent DNA clones from serum samples of patients exhibiting low but detectable recurrent serum levels of posttherapy HBsAg revealed the presence of S protein variant sequences when compared with polymerase chain reaction DNA derived from the original infected liver or pretherapy serum HBsAg. Genetic variation was predominant in a highly conserved peptide domain that has previously been implicated in antibody binding and neutralizing antibody epitopes. In independent patients infected with eitheradworaywhepatitis B virus subtypes, single nucleotide changes resulted in one to two amino acid differences for each variant allele (residues 124, 129, 131, 137, 140 and/or 145) when compared with pretherapy viral DNA. Administration of serum containing one of these variant viruses to a single hepatitis B—naive chimpanzee resulted in subclinical hepatitis and detectable levels of circulating anti‐HBs and anti‐HBc antibodies 49 and 70 days after virus administration, respectively. Hepatitis B virus DNA was recovered on liver biopsy between 6 and 8 wk after inoculation, although the animal remained persistently seronegative for HBsAg. DNA sequence analysis of both primate and patient liver hepatitis B virus confirmed the presence of the DNA encoding the S protein variant and associates this DNA with the predominant hepatotropic virus in liver infection. (HEPATOLOGY1992;

ISSN:0270-9139    

DOI:10.1002/hep.1840150503

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTo assess the efficacy of interferon‐α in acute hepatitis C, 28 patients with acute posttransfusion hepatitis were randomized to receive 3 million units of recombinant interferon‐α three times weekly for 12 wk or no treatment. Biochemical, histological and serological parameters were monitored during 1 yr of follow‐up. Serum ALT levels were normal at the end of therapy in 73% of treated patients and only in 38% of control patients (p = 0.06); these differences disappeared at 6 and 12 mo of follow‐up. Anti–hepatitis C virus seroconversion occurred later and at a lower rate in the group of patients who received interferon‐α. Treated patients had a trend toward less severe hepatic lesions with lower histological activity as compared with the control group, but no statistical differences were observed. No severe side effects of interferon‐α were detected during the study. In summary, a 3‐mo course of interferon‐α in acute hepatitis C is safe and might have some effect in diminishing disease activity only during the treatment period; however, and probably because of a small sample size, no benefit of interferon‐α in the long‐term outcome of this disease was demonstrated.

ISSN:0270-9139    

DOI:10.1002/hep.1840150504

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractCellular immunity to HBcAg was studied in hepatitis B virus carrier children and neonates born to hepatitis B virus carrier mothers. A significant proliferative response of peripheral blood mononuclear cells to HBcAg was found in 5 of 10 children with elevated ALT levels but in none of the nine HBeAg‐positive children with normal ALT levels. HBeAg but not HBsAg was detected in cord blood of 9 of 10 neonates born to HBeAg‐positive carrier mothers, suggesting exposure of these neonates to HBeAgin utero.However, cord mononuclear cells from neonates born to HBeAg‐positive carrier mothers did not show a significant change in the proportion of suppressor and helper T‐cell subsets or proliferative response to HBcAg. Nor did they produce interleukin‐2 receptor after being cocultured with HBcAg. The unresponsiveness of peripheral‐blood mononuclear cells or cord mononuclear cells to HBeAg was not reversed by CD8+cell depletion. Although cord blood mononuclear cells from neonates born to carrier mothers positive for antibody to HBeAg also did not respond to HBcAg, we encountered an infant, born to a carrier mother positive for antibody to HBeAg, who contracted acute hepatitis B at 2.5 mo of age. The baby's peripheral‐blood mononuclear cells showed a significant proliferative response to HBcAg. These results support the view that transplacental maternal HBeAg probably induces a specific unresponsiveness of helper T cells to HBcAg and HBeAg in the neonates born to HBeAg‐positive carrier mothers. This specific helper T cell tolerance could be maintained throughout the early replicative phase of carrier state but might break someday with the appearance of raised ALT level. (HEPATOLOGY1

ISSN:0270-9139    

DOI:10.1002/hep.1840150505

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTo study the role of hepatitis C virus in non‐A, non‐B chronic hepatitis, 49 liver biopsy samples from 40 patients with non‐A, non‐B chronic hepatitis and 9 control patients were analyzed by complementary DNA/polymerase chain reaction. Two segments of the HCV genome, one in the nonstructural region and the other in the noncoding region, were amplified by two sets of primer pairs. With use of the nonstructural region primers, hepatitis C virus RNA was detected in 24 (60%) of 40 patients with non‐A, non‐B chronic hepatitis. Of these 40 patients, RNA was detected in 19 (70%) of 27 patients positive for antibody to hepatitis C virus and in 5 (38%) of 13 patients negative for antibody to hepatitis C virus. However, with the noncoding region primers, hepatitis C virus RNA was detected in 38 (95%) of 40 patients with non‐A, non‐B chronic hepatitis. Of these patients, the RNA was detected in 26 (96%) of 27 patients positive for antibody to hepatitis C virus and also in 12 (92%) of 13 patients positive for antibody to hepatitis C virus. Hepatitis C virus RNA was not detected in any of the control patients. Sequence analysis showed homology between our samples and the prototype to be only 66% to 77% in the nonstructural region but 99% to 100% in the noncoding region.We conclude that almost all patients with non‐A, non‐B chronic hepatitis in Japan are currently infected with hepatitis C virus, regardless of the presence or absence of antibody to hepatitis C virus. This assay appears useful for the diagnosis, treatment and prevention of hepatitis C virus infection. (HEPATOL

ISSN:0270-9139    

DOI:10.1002/hep.1840150506

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractMany clinicians subjectively feel that cirrhotic patients frequently have clinical signs of hypermetabolism. However, it is unknown whether hypermetabolism is a constant feature of chronic liver disease, corresponds to liver destruction and repair or is of prognostic value. This article is about resting energy expenditure and substrate oxidation rates in 123 patients with biopsy‐proven cirrhosis differing with respect to cause, duration of the disease, biochemical parameters of parenchymal cell damage, cholestasis, liver function, number of complications, clinical staging and nutritional state.Resting energy expenditure varied between 1,090 and 2,300 kcal/day and differed from the predicted values in 70% of the patients. Resting energy expenditure was closely related to fat‐free mass, and 52% of the variability could be explained by fat‐free mass, age and sex. Of all the patients, 18% were hypermetabolic and 31% were hypometabolic. Hypermetabolism showed no strict association with the cause of cirrhosis, the duration of the disease, liver function, cholestasis, cell damage, clinical staging, blood hemoglobin, plasma thyroid hormone levels or human leukocyte antigens. An increased resting energy expenditure was associated with significant losses of muscle, body cell mass and extracellular mass at unchanged body fat, whereas fat and fat‐free mass were increased in hypometabolic patients when compared with normometabolic patients. Lipid oxidation was increased, but glucose oxidation was reduced in nearly all patients with cirrhosis. This was most pronounced at advanced stages of liver disease.Although similar with respect to liver function and clinical staging, 76.2% of hypermetabolic patients had transplants within the observation period, compared with only 16.7% and 8.1% in the normometabolic group and hypometabolic group, respectively. Posttransplantation mortality was independent of pretransplantation resting energy expenditure, but it increased significantly in patients with losses in body cell mass.In conclusion, hypermetabolism is not a constant feature of cirrhosis and results more from extrahepatic than from hepatic factors. It may cause malnutrition and contributes to the clinical outcome of patients with chronic liver disease. (HEPATOLOGY1992;15:7

ISSN:0270-9139    

DOI:10.1002/hep.1840150507

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractGallbladder stasis may be an important factor in the pathogenesis of cholesterol‐gallstone formation in some individuals. We investigated gallbladder function in a group of nondieting, gallstone‐free, healthy subjects with normal (22 ± 1 kg/m2) and high (36 ± 1 kg/m2) body mass indexes. Fasting gallbladder volume (28.2 ± 4.4 ml) and residual volume after maximal emptying (8.4 ± 2.3 ml) in high–body‐mass index subjects were not significantly different from those of normal–body‐mass index subjects (20.5 ± 2.5 ml and 4.2 ± 1.3 ml, respectively). The percentage of gallbladder emptying (71% ± 5%) and the rate of gallbladder emptying (‐1.9 ± 0.3 × 10−2min−1) in high–body‐mass index subjects in response to a maximal emptying stimulus was similar to the percentage of emptying (78% ± 6%) and rate of emptying (−2.3 ± 0.6 × 10−2min−1) in normal–body‐mass index subjects. A liquid meal containing less than 1 gm fat, 14 gm protein and 6 gm carbohydrate resulted in both a decreased rate of gallbladder emptying and an increased residual gallbladder emptying and an increased residual gallbladder volume in both groups. The addition of 10 or 20 gm (but not 4 gm) of fat to the liquid meal restored gallbladder emptying to the maximal‐stimulus level. These results demonstrate that gallbladder emptying in response to a single liquid meal stimulus is not altered in obesity and that dose‐response relationships to fat are similar in obese and normal‐weight individuals. Furthermore, these findings suggest that a threshold quantity of fat–no more than 10 gm–included in a liquid‐meal stimulus might be able to restore gallbladder emptying to normal. It does not appear that an intrinsic defect in gallbladder contractility is responsible for the increased incidenc

ISSN:0270-9139    

DOI:10.1002/hep.1840150508

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe prevalence and prognostic significance of spontaneous bacterial peritonitis were prospectively studied in a series of 82 acute hepatitis patients decompensated with ascites. The in‐hospital prevalence of spontaneous bacterial peritonitis was 31.7% (26 of 82 patients). Twenty cases were culture positive, including one with multiple isolates, and six cases were culture negative.E. coliandKlebsiella pneumoniaewere the most common pathogens, accounting for 71.4% (15 of 21) of the total isolates, whereas only 9.5% were gram‐positive organisms. No significant difference in the age, sex, cause of acute hepatitis, liver biochemistry, prothrombin time and ascites fluid concentration of total protein was noted between patients with spontaneous bacterial peritonitis and those without spontaneous bacterial peritonitis, except that bacteremia was recognized significantly more frequently in the former (57.7% or 15 of 26 patients) than in the latter (25.0% or 14 of 56 patients, p<0.005). In addition, patients with spontaneous bacterial peritonitis, when compared with those without spontaneous bacterial peritonitis, were more likely to have kidney failure (57.7% vs. 30.4%, p<0.05) and gastrointestinal hemorrhage (53.8% vs. 30.4%, p0.01). Among patients without spontaneous bacterial peritonitis, the prevalence of kidney failure and gastrointestinal hemorrhage and the mortality rate in patients with bacteremia (57.1%, 64.3% and 71.4%, respectively) were significantly higher than in those without bacteremia (21.4%, 19.0% and 28.6%, respectively; p<0.05, p<0.01 and p<0.01, respectively). In conclusion, 31.7% of severe acute hepatitis patients with ascites were recognized as having spontaneous bacterial peritonitis; the other 17.1% had bacteremia. Patients with spontaneous bacterial peritonitis, bacteremia or both had high morbidity and mortality rates. Whether prophylactic antimicrobial therapy might be justified in patients with severe acute hepatitis awaits further study. (HEPATOLOGY1992;15:799

ISSN:0270-9139    

DOI:10.1002/hep.1840150509

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractPatients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined.The cholesterol nucleation time was significantly (p<0.01) longer in the bile from patients with solitary stones (<1 to 16 days, median = 2.0 days) than in the bile from patients with multiple stones (4 days) nucleation time.However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 ± 0.65 vs. 1.54 ± 0.59, mean ± S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones. (HEPATOLOGY1992;15:804‐

ISSN:0270-9139    

DOI:10.1002/hep.1840150510

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractAlthough arterial vasodilation is a well‐known feature in patients with cirrhosis, the venous system remains unexplored. To measure total effective vascular compliance, a reflection of the properties of the venous system, rapid volume expansion (300 ml of a gelatin solution in 3 min) was performed in 23 patients. Eleven patients had compensated cirrhosis (Child‐Pugh grade A or B), and eight had decompensated cirrhosis (Child‐Pugh grade C). Four control patients had mild chronic hepatitis, normal hepatic venous pressure and normal liver architecture. Cardiac index, hepatic venous pressures, hepatic and azygos blood flow and renal plasma flow were measured before and immediately after volume expansion. Right atrial pressure was recorded during volume expansion. This allowed the calculation of total effective vascular compliance, which was higher in patients with decompensated cirrhosis than in those with compensated cirrhosis (4.65 ± 4.21 vs. 1.34 ± 0.63 ml ± mm Hg−1· kg−1; p<0.05). In response to volume expansion, renal vascular resistance decreased significantly in patients with compensated cirrhosis, but not in those with decompensated cirrhosis (−30% ± 33% vs. +2% ± 23%; p<0.05). No change was seen in glomerular filtration rate. Systemic oxygen consumption increased in patients with compensated cirrhosis, but not in those patients with decompensated cirrhosis (25% ± 33% vs. −4% ± 9%; p<0.05). Although in all patients with cirrhosis volume expansion increased central venous pressures, azygos blood flow and the hepatic venous pressure gradient did not change. We conclude that in patients with cirrhosis and severe liver failure, total vascular compliance is elevated and probably accounts for blunted systemic and renal effects of volume expansion. (HEPATO

ISSN:0270-9139    

DOI:10.1002/hep.1840150511

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY