International Hepatology Communications最新文献

Of 112 patients with chronic hepatitis C, 12 (11%) tested positive for RNA of GB virus C (GBV-C) by reverse-transcription polymerase chain reaction with primers deduced from the 5′ untranslated region. RNAs of GBV-C and hepatitis C virus (HCV) were followed in the 12 patients before and after they received 19 trials of interferon (IFN) therapy. GBV-C RNA disappeared from serum in 11 (58%) trials on eight patients. However, it stayed negative at 6 months after IFN only in two patients. One of them regained GBV-C RNA at 12 months and kept it thereafter, while an additional patient who failed to clear it at the completion of IFN turned negative at 24 months after therapy. Thus, two patients (17%) became persistently negative for GBV-C RNA. HCV RNA disappeared from serum at the completion of ten trials (53%) on eight patients, and stayed negative in three patients (25%). Two of them did not lose GBV-C RNA but kept normal transaminase levels. These results indicate that GBV-C is susceptible to IFN with a sensitivity comparable to but independent of HCV, and that GBV-C by itself would not elevate transaminases in hepatitis C patients who respond to IFN.

Patients, 38, with decompensated cirrhosis were enrolled in a 3 year prospective follow-up to investigate the long-term prognostic value of free-water peritoneal clearance (FWPC) and intraabdominal pressure (IAP). All patients were ‘a priori’ divided into different subgroups, according to the basal values of FWPC (methylene-blue dilution method) and IAP (direct manometry). Arbitrarily chosen cut-off levels (90 ml/min for FWPC and 17 cm H₂O for IAP) were adopted. The cumulative 3 year mortality was significantly lower in the subgroup of patients with FWPC above 90 ml/min than in those with FWPC below 90 ml/min (P < 0.05, Kaplan Meier method and log-rank test). No significant difference was found between the cumulated survivals of the subgroups discriminated by means of the IAP cut-off. Our results suggest that FWPC has an intrinsic prognostic value in patients with decompensated cirrhosis. Therefore, FWPC may be helpfully considered in a multivariate prognostic model for the estimate of the individual survivals in ascitic patients.

A new mutation site has been found in a case of cholinesterase (ChE) deficiency diagnosed upon routine blood screening. Genomic DNA was sequenced and four point mutations were found: P1 (exon 2) nucleotide 298 (CCA-TCA), codon 100 (proline-serine), which is a novel mutation site; P4 (exon 2) nucleotide 1410 (CGT-CGG), codon 470 (arginine not changed); PS (exon 3) nucleotide 1543 (CGT-TGT), codon 515 (arginine-threonine); and P6 (exon 4) nucleotide 1615 (GCA-ACA), codon 539 (alanine-threonine). The patient had three (P1, P5, P6) heterozygous and one (P4) homozygous mutations. The three other family members studied had one (P1) or two (P5 and 6) heterozygous mutations in addition to a P4 homozygous mutation but their serum levels of ChE were normal or only slightly decreased. We concluded that three simultaneous mutations at codons 298, 1543 and 1615 are required to reduce serum ChE activity and that the single mutation at codon 298 or two mutations at codon 1543 and 1615 are not enough to reduce ChE activity.

Effects of interleukin-4 (IL-4) and interferon-γ (IFN-γ) on rat Kupffer cell (KC) functions were investigated. Lipopolysaccharide (LPS)-stimulated KCs pretreated with IL-4 produced much more prostaglandin E₂ than those pretreated with IFN-γ. In contrast, LPS-stimulated KCs pretreated with IFN-γ produced much more tumor necrosis factor-α, and nitrate and nitrite than those pretreated with IL-4. Different morphologic changes were induced after the culture with each cytokine; transformation of KCs into multinucleated giant cells with IL-4 was especially noted. These results suggest that IFN-γ and IL-4, produced by different subsets of T-helper lymphocytes, differently induce KC into specific morphology, and change KC response to endotoxins, possibly resulting in a modulation of hepatic inflammation.

Serum soluble HLA-class I and CD8 molecules were sequentially (pre, during, and post-therapy) measured by sandwich ELISA, in 20 interferon (IFN)-treated chronic hepatitis C (CHC) patients, who were judged as responders (n = 8) or non-responders (n = 12) with respect to the response to the therapy. Pretreatment levels of sHLA-I and sCD8 did not differ between responders and non-responders. Both values increased just after the start of therapy and peaked at 2–4 weeks. The IFN was discontinued at 24 weeks, when sHLA-I decreased to baseline levels in responders, whereas they remained at levels significantly higher than baseline levels even at 48 weeks in non-responders (P < 0.01). sCD8 decreased significantly under than baseline levels at 48 weeks in responders (P < 0.05), in contrast in non-responders, sCD8 did not decrease beyond baseline levels. In summary, serum levels of sHLA-I and sCD8 were elevated by the IFN treatment, and serial follow-up of these immunological parameters could provide additive information regarding the response to IFN therapy.

Lecithin-cholesterol acyltransferase (LCAT) is secreted by the liver into plasma where measurement of its catalytic activity is considered a sensitive serum test of hepatocyte synthetic capacity. The enzyme, a 68 kDa glycoprotein with a normal plasma concentration of ∼6 mg/l, contains four N-linked oligosaccharide chains which are reported to influence its activity. Because hepatic disease may result in serum glycoproteins with abnormal glycosylation patterns, we have developed a two-step procedure of immunoaffinity chromatography and high-performance liquid chomatography to isolate LCAT from plasma (1 ml) of individual subjects for subsequent characterization studies. Although patients infected with hepatosplenic schistosomiasis mansoni had half the normal plasma LCAT activity, the purified enzyme had a molecular mass indistinguishable from that of healthy subjects, as judged by SDS-PAGE and silver staining. However, in preliminary studies of microheterogeneity, isoelectric focusing revealed several acidic isoforms (pI 4.27–4.85) in patients which were reduced or absent in normal individuals. Whether such abnormal glycosylation of LCAT affects its catalytic activity and is a consistent feature of hepatosplenic schistosomiasis remains to be established.

Recent studies indicated that bile duct ligation down-regulates the expression of Na⁺/taurocholate cotransporting polypeptide and Na⁺-dependent taurocholate uptake by basolateral membrane vesicles in the rat. These findings suggest that hepatic taurocholate uptake in bile duct-ligated rats is mediated by the organic anion transporting polypeptide, a Na⁺-independent taurocholate uptake system which is common for sulfobromophthalein uptake. Therefore, the effect of sulfobromophthalein on biliary excretion of taurocholate and pravastatin in bile ductligated rats was studied. Although biliary excretion of pravastatin was markedly inhibited by sulfobromophthalein, biliary taurocholate excretion was not affected by sulfobromophthalein in bile duct-ligated rats. The excretory maximum of sulfobromophthalein in bile duct-ligated rats was reduced to one-fifth of control rats. These findings indicate that, in the bile duct-ligated rats, taurocholate uptake is mediated not by the multispecific organic anion transporter, but by other uptake system(s).

The purpose of this report is to evaluate the usefulness of serum hepatocyte growth factor (HGF) levels as a prognostic factor in hepatectomized patients with early postoperative hyperbilirubinemia (HB). The serum HGF levels of 14 patients with early postoperative HB (serum total bilirubin level above 5 mg/dl lasting at least 3 days), were measured perioperatively (prior to and 6 h, 1, 2, 3, 4, 7 and 14 days following surgery) and the relationship between changes in serum HGF levels and postoperative outcome was analyzed. The 14 patients were divided into two groups; 6 patients (Group A) ameliorated by conservative therapies within 7 days after surgery, and 8 patients (Group B) with prolonged HB more than 2 weeks after surgery. Five patients (83%) in Group A showed relatively low maximum serum HGF levels (<2.0 ng/ml), whereas 7 patients (88%) in Group B showed high serum HGF levels (>2.0 ng/ml). Six of the 7 patients in Group B developed hepatic failure and died. These results suggest that, in patients with HB or those in whom it is expected to occur soon after hepatectomy, the measurements of serum HGF levels would be beneficial for determining therapy and predicting postoperative outcomes.

Aim, clinical usefulness of a non radioactive HBV DNA measuring method was evaluated. Subjects and methods, the subjects were 8 anti-HBe positive chronic hepatitis B (CH-B) patients and five CH-B patients who were orally administered reverse transcriptase inhibitor (RTI). Serum HBV DNA and DNA-P were serially determined at 1.5–2 month intervals for 1 year in CH-B with anti-HBe positive patients and before, 2, 4, 8, and 12 weeks after RTI administration. Serum HBV DNA was determined by two different non radioactive method (Viraprobe HB Lumi, Quantiplex HBV DNA). Results, the HBV DNA levels measured with two methods were highly correlated (P < 0.0001). Generally, the results for serum HBV DNA and the DNA-P were also correlated (P < 0.01). While, among a total of 51 determinations in CH-B patients with anti-HBe positive, discrepancies between serum HBV DNA and DNA-P from different sensitivities were noted in 15 determinations, and in all cases the pattern was HBV DNA positive and DNA-P negative. From 2 to 12 weeks after RTI administration, the same pattern was observed in three cases. These results were thought to be mainly due to the high sensitivity of HBV DNA measurement. (Conclusion) The non radioactive methods of measuring of HBV DNA are useful for detecting low level HBV replication.

We detected the hepatitis GB virus C genome by reverse transcription-polymerase chain reaction in three Japanese patients with chronic liver diseases. Partial nucleotide sequences of 5′ noncoding, envelope and NS3 regions had 88.6–90.1, 86.388.0, and 78.6–79.6% nucleotide sequence homology compared with the prototype GBV-C genome. However, they showed higher homology with each other (96.197.1, 88.7–91.2, 84.0–87.0%, respectively), suggesting that they were a genotype of GBV-C. The domains that were highly conserved among all these genomes were present in the 5′ noncoding region. The frequency of detecting the genome by the polymerase chain reaction was higher when we used primers designed on these domains compared with primers designed on the core and NS3 region. The virus genome was detected in eight of 50 (16.0%) consecutive Japanese patients with hepatocellular carcinoma who had received more than ten units of blood transfusion, three of 60 (5.0%) patients with non-B, non-C liver disease and 12 of 35 (34.3%) Malaysian patients with non-B chronic liver disease. Since there are no reliable assays to detect hepatitis GB virus C at present, the detection of the genome by the polymerase chain reaction should be useful for diagnosis. Further nucleotide sequence analysis of the genomes is necessary for epidemiological survey studies and vaccine strategy.