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Mechanism of liver mitochondrial dysfunction associated with bile duct obstruction.

To elucidate the mechanism of liver mitochondrial dysfunction induced by obstructive jaundice, the following experiments were performed. In vivo study: Using Wistar male rats, bile ducts were ligated, and serum levels of total bilirubin (T-Bil), GOT, GPT, mitochondrial GOT (mGOT) and total bile acids (TBA) were measured at 3 and 7 days after the ligation. Then, the liver was isolated to determine mitochondrial functions and to measure the content of fatty acids in mitochondrial phospholipids by high performance liquid chromatography. The levels of T-Bil, GOT, GPT, mGOT and TBA were elevated by the bile duct ligation. Mitochondrial functions were deteriorated, and contents of arachidonic acid, palmitic acid and stearic acid in mitochondrial phospholipids decreased. Pretreatment with coenzyme Q10 (E-0216, CoQ10), an antidetergent agent, prevented not only the development of mitochondrial dysfunction and the decrease in mitochondrial phospholipids but also the elevation of GOT, GPT, and mGOT although CoQ10 did not prevent the elevation of T-Bil and TBA levels. In vitro study: Using intact rat liver mitochondria, the effect of taurocholic acid (TCA), one of the physiological bile salts, on the mitochondrial function and on mitochondrial phospholipids was examined. Incubation of mitochondria with TCA induced a dose-dependent deterioration of mitochondrial function and the increase in the content of solubilized phospholipids. The protective effect of CoQ10 was also observed in the in vitro study. These results indicate that degradation of mitochondrial phospholipids by bile acids is responsible for the early phase of liver dysfunction induced by obstructive jaundice.

Alanine Transaminase↗

Duration of vecuronium-induced neuromuscular block as a predictor of liver allograft dysfunction.

The major causes of liver graft failure are acute rejection, technical failure, and primary nonfunction (PNF). This study was undertaken to determine whether delayed return of neuromuscular function correlates with allograft primary dysfunction in humans given vecuronium. Twenty-two adult patients undergoing orthotopic liver transplantation were given an initial dose of vecuronium, 0.1 mg/kg intravenously (i.v.). All patients recovered from vecuronium-induced neuromuscular block prior to explantation. No additional neuromuscular blocker was given until the liver graft was implanted and reperfused. Fifteen minutes after reperfusion another 0.1 mg/kg vecuronium was given IV and recovery time from attaining complete neuromuscular block to return of the fourth twitch of a train-of-four was recorded. Patients were divided into three groups according to postoperative liver function. Group I consisted of 17 patients with immediate normal liver graft function. Group II consisted of four patients with primary dysfunction (PDF) [peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2000 U/L, prothrombin time > 16 s, and poor quality and quantity of bile within 3 days postoperatively] which eventually recovered normal function. Group III consisted of one patient with PNF (uncorrectable coagulopathy, severe metabolic acidosis, rising AST and ALT, and minimal or no bile output), whose graft never recovered. Recovery time in Groups II and III was prolonged compared to Group I (P < 0.05). Recovery time in Group III was prolonged compared to Group II (P < 0.05). A test based on these results using a recovery time of > 135 min as a predictor of PDF has a sensitivity and specificity of 80% and 76%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fatal chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis.

We report a 22-year-old female who presented with pyrexia, pancytopenia and liver dysfunction. The patient showed mild liver dysfunction with low-grade fever and mild hepatosplenomegaly 6 years previously, and autoimmune hepatitis (AIH) was diagnosed based on the examination of the laboratory data and liver biopsy. On admission, both markers of Epstein-Barr virus (EBV) and in-situ hybridisation from a liver biopsy specimen indicated chronic active EBV infection (CAEBV). The patient was administered an immunosuppressive agent and antiviral drug added to steroid therapy, but ultimately died from liver failure and virus-associated haemophagocytosis 10 months after the definite diagnosis. Retrospective examination of the serum at the diagnosis of AIH revealed extremely high titres of antibody to EBV, and EBV-DNA was also detectable by polymerase chain reaction. These results suggest the possibility that the patient may already have suffered from CAEBV at the initial diagnosis. We presume that hepatic involvement of CAEBV should be considered as differential diagnosis in cases showing liver dysfunction with clinical and biochemical features observed in AIH.

Adult↗

Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Part I: Analysis of 1744 HBsAg carriers.

A total of 1744 HBsAg carriers were investigated to determine whether there are clinical differences among HBsAg subtypes or not. Although adr was more predominant than adw in 1078 asymptomatic carriers as well as in 666 carriers with liver dysfunction, the adr carriers had liver dysfunction more frequently than the adw carriers (p = 0.005). In addition, the adr carriers were more often positive for HBeAg and less often positive for anti-HBe than the adw carriers (p less than 0.001). Multivariate analyses indicated that the HBsAg subtypes were associated with liver dysfunction not directly but through the relationship between the HBsAg subtypes and HBeAg/anti-HBe status. HBeAg/anti-HBe status of each age bracket in the adr carriers and in the adw carriers suggested that adr carriers are seroconverted later than adw carriers. In conclusion, HBsAg subtypes may affect the development of chronic liver disease, through their association with HBeAg/anti-HBe status.

Adult↗

The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis.

In cirrhosis, intrahepatic endothelial dysfunction is one of the mechanisms involved in the increased resistance to portal blood flow and therefore in the development of portal hypertension. Endothelial nitric oxide synthase (eNOS) uncoupling due to deficiency of tetrahydrobiopterin (BH4) results in decreased production of NO and plays a major role in endothelial dysfunction in other conditions. We examined whether eNOS uncoupling is involved in the pathogenesis of endothelial dysfunction of livers with cirrhosis. Basal levels of tetrahydrobiopterin and guanosine triphosphate (GTP)-cyclohydrolase (BH4 rate-limiting enzyme) expression and activity were determined in liver homogenates of control and rats with CCl4 cirrhosis. Thereafter, rats were treated with tetrahydrobiopterin, and eNOS activity, NO bioavailability, assessed with a functional assay, and the vasodilator response to acetylcholine (endothelial function) were evaluated. Livers with cirrhosis showed reduced BH4 levels and decreased GTP-cyclohydrolase activity and expression, which were associated with impaired vasorelaxation to acetylcholine. Tetrahydrobiopterin supplementation increased BH4 hepatic levels and eNOS activity and significantly improved the vasodilator response to acetylcholine in rats with cirrhosis. In conclusion, the impaired response to acetylcholine of livers with cirrhosis is modulated by a reduced availability of the eNOS cofactor, tetrahydrobiopterin. Tetrahydrobiopterin supplementation improved the endothelial dysfunction of cirrhotic livers.

Animals↗

Lipid intolerance in newborns is associated with hepatic dysfunction but not infection.

OBJECTIVE: To examine the hypothesis that fat intolerance in newborns who receive intravenous lipid is related to both infection and liver dysfunction. DESIGN: Prospective survey. SETTING: Tertiary intensive care nursery. PATIENTS: All newborns who were admitted to the neonatal intensive care unit during a 20-month period and received parenteral lipid for 2 or more weeks were eligible for the study. Of 279 newborns who received parenteral nutrition, 162 met eligibility criteria and form the basis of this report. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Fat intolerance as defined by a serum triglyceride level of 1.69 mmol/L or greater (> or = 150 mg/dL). RESULTS: Triglyceride levels were similar in infected and noninfected patients. Newborns with hypertriglyceridemia were more likely to have liver dysfunction (P < .001) or growth retardation (P < .01), but not infections. Hypertriglyceridemia was approximately twice as likely (P < .05) in newborns with either growth retardation or liver dysfunction. CONCLUSIONS: Liver dysfunction and fetal growth retardation were associated with lipid intolerance in newborns who received intravenous fat. Infection does not appear to be independently associated with hypertriglyceridemia. In the absence of liver dysfunction or growth retardation, there is no a priori reason to limit intravenous lipid use in the presence of infection. Close monitoring of triglyceride levels with adjustments in lipid dose is warranted, especially in small, sick newborns who are at highest risk for hypertriglyceridemia.

Contraindications↗

Procedures of simultaneous radical resection indicated for primary synchronous esophageal and liver cancers--from the personal experience of three cases.

Primary double cancers of the liver and esophagus are extremely rare. Only 7 cases, both cancers resected, were reported. A 2 stage surgical procedure has been recommended for such a case. We experienced 3 consecutive patients who underwent successful simultaneous radical resection with a good outcome. Case 1 with an advanced esophageal cancer (EC) and hepatocellular carcinoma (HCC) without liver dysfunction received subtotal esophagectomy and posterior segmentectomy of the liver under a thoraco-laparotomy. Case 2, with an early stage EC and HCC with Child A cirrhosis, received the same surgical procedures as case 1 to complete stanching under good visibility for esophagectomy, because of his bleeding tendency due to liver dysfunction. But post operative bleeding from the thoracic cavity continued for 5 consecutive postoperative days. Case 3, with an early stage EC and cholangiocellular carcinoma (CCC), underwent transhiatal esophagectomy and right hepatic lobectomy under laparotomy. All cases received active enteral nutritional (EN) support from the early postoperative day with good outcomes. In conclusion, simultaneous radical resection for synchronous cancers of the esophagus and liver might be a possible indication for patients who have little or slight liver dysfunction. In the case with liver dysfunction, esophagectomy should be performed under thoracotomy, but transhiatal resection, for complete stanching, even in the early stage EC. Post-operative EN support is essential for these patients to obtain a good outcome.

Aged↗

Structural integrity and identification of causes of liver allograft dysfunction occurring more than 5 years after transplantation.

The clinicopathologic features of liver allograft dysfunction occurring in 51 symptomatic recipients after more than 5 years' survival (mean 7.1 years) with the same hepatic allograft were compared with those of a similar group of 14 asymptomatic patients (mean survival, 9.9 years) who underwent a nonclinically indicated protocol liver biopsy evaluation. Predictably, patients who had clinically indicated biopsies more frequently showed histopathologic alterations (76% versus 36%, p < 0.002). After detailed clinicopathologic correlation, the changes in the symptomatic patients were attributed primarily to definite or presumed viral hepatitis in 17 of 51 (33%) patients, 11 of whom had recurrent viral disease; seven of 51 (14%) had nonviral recurrent original disease, three (6%) had obstructive cholangiopathy, and 11 (22%) had acute and/or chronic rejection. In 13 of 51 (25%) of the symptomatic patients, the clinical and pathologic abnormalities were minimal. Long-term liver allograft survival in nine of 14 (64%) of the asymptomatic patients was associated with minimally abnormal histologic alterations. Two of the asymptomatic patients had obstructive cholangiopathy; two others has recurrence of the original disease and one has possible viral hepatitis. Viral hepatitis types B and C, alcoholic liver disease, autoimmune hepatitis, granulomatous hepatitis (not otherwise specified), and probably primary biliary cirrhosis and primary sclerosing cholangitis were shown to recur after hepatic transplantation. The histopathologic changes associated with acute and chronic rejection frequently overlapped with other syndromes causing late dysfunction, such as chronic viral or autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis; more than one insult could be identified in 15 cases, which made the differential diagnosis of causes of late liver allograft dysfunction much more difficult than early after hepatic transplantation. It is important to correlate the biopsy findings with the liver injury tests, the results of viral and autoimmune antibody serologic studies, and review of previous biopsies and to be aware of the original disease, recent changes in immunosuppression, and results of therapeutic intervention(s) to identify correctly the causes of liver allograft dysfunction in this patient population.

Adult↗

Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction: a preliminary report of the National Cancer Institute Organ Dysfunction Working Group.

Oxaliplatin, which was recently approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer, is often administered to patients with altered liver function caused by hepatic metastases. Because of the absence of data on the clearance of oxaliplatin in patients with liver dysfunction, and to develop dosing recommendations for the safe use of oxaliplatin in this clinical setting, the Organ Dysfunction Working Group of the National Cancer Institute performed a phase I and pharmacokinetic trial of this drug in patients displaying a wide range of liver function abnormalities. Sixty patients grouped into five classes of liver function were enrolled in this study, including a 12-patient control group with normal liver function, 15 patients with "mild," 16 patients with "moderate," and 16 with "severe" liver dysfunction, as well as one patient who had undergone liver transplantation. The patients had a median age of 62 years and a Eastern Cooperative Oncology Group performance status of 0. All patients had received prior systemic chemotherapy, and 70% had a diagnosis of a gastrointestinal malignancy. The control patients were treated with 130 mg/m(2) oxaliplatin intravenously every 21 days; the starting doses for patients with mild, moderate, or severe liver dysfunction or post-liver transplantation were 105, 80, or 60 mg/m(2), respectively. Cohorts of three or more patients were escalated from these starting doses to 130 mg/m(2) if dose-limiting toxicities were not observed, and pharmacokinetic evaluations were performed at each dose level for every category of liver dysfunction. We found that oxaliplatin was well tolerated at its recommended dose and schedule of 130 mg/m(2) every 21 days in patients with all levels of liver dysfunction, and that there was no apparent alteration in the clearance of either total or ultrafilterable platinum species from plasma, even in patients with severe hepatic functional abnormalities.

Antineoplastic Agents↗

Liver disease during the first post-transplant year in bone marrow transplantation recipients: retrospective study.

Liver dysfunction is a common problem in BMT recipients and it is important to determine the etiology in order to institute appropriate therapy. The purpose of this study was to evaluate the possible causes of liver dysfunction during the first post-transplant year in BMT recipients and to identify a possible relationship between pre-existing liver dysfunction and viral hepatitis with prognosis after BMT. We reviewed liver status before and after BMT in 130 consecutive patients at the Catholic Hematopoietic Stem Cell Transplantation Center. Liver dysfunction during the first post-transplant year occurred in 85 out of 101 (84. 2%) allogeneic BMT recipients and 13 out of 29 (44.8%) autologous BMT recipients. In allogeneic BMT, GVHD and drug hepatotoxicity were major causes. In autologous BMT, drug hepatotoxicity was the most common cause. Eighteen out of 130 patients (13.8%) had abnormal liver function tests before BMT. These patients did not have an increased risk of post-transplant liver dysfunction, GVHD, and death compared to patients who had normal liver function tests prior to BMT. Nine patients were hepatitis B antigen positive and three patients were anti-HCV positive prior to BMT. There was no significant increase in the incidence of post-transplant liver dysfunction, GVHD, and death in these patients.

Adult↗

ONO-5046, an elastase inhibitor, attenuates liver mitochondrial dysfunction after endotoxin.

OBJECTIVE: To investigate the effect of ONO-5046, an elastase inhibitor, on liver mitochondrial dysfunction after endotoxin administration. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male Hartley guinea pigs. INTERVENTIONS: Endotoxin shock was induced by intravenous infusion of Escherichia coli lipopolysaccharide endotoxin (50 mg/kg). Six guinea pigs were treated with endotoxin and saline. Twenty-four guinea pigs received 5, 10, and 30 mg/kg/hr of ONO-5046 after endotoxin administration. Six guinea pigs received only saline. MEASUREMENTS AND MAIN RESULTS: We measured oxygen uptake in state 3 (substrate and adenosine 5'-diphosphate [ADP]) and state 4 (excess substrate, no ADP), as well as the respiratory control ratio (state 3/state 4), adenosine 5'-diphosphate/oxygen ratio (ADP/O), and arterial ketone body ratio. ONO-5046 was dose dependently effective in liver mitochondrial oxidative phosphorylation, such as oxygen uptake in stage 4, respiratory control ratio, adenosine triphosphate synthesis, ADP/O, and arterial ketone body ratio when ONO-5046 was started 30 mins after endotoxin. The administration of 30 mg/kg/hr of ONO-5046 improved mean blood pressure, which had decreased after endotoxin. CONCLUSION: ONO-5046 attenuates the endotoxin-induced liver mitochondrial dysfunctions that may be related to increased liver blood flow.

Adenosine Diphosphate↗

Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil.

BACKGROUND: Renal dysfunction caused by treatment with the calcineurin inhibitors (CNI) is a major problem in the long-term course after liver transplantation. PATIENTS: In 22 liver graft recipients with renal dysfunction and stable graft function between 3 weeks and 12 years after transplantation, CNI were substituted by MMF at a final dose of 1.5-3 g/day between October 1996 and October 1998. METHODS: In a prospective non-randomized study, the development of renal function, the side effects of MMF medication, and the stability of liver function were analyzed for a mean follow-up of 15 months. Results. (1) MMF was withdrawn in four patients for major side effects between 1 and 7 months after study entry; eight patients had minor side effects. (2) Six months after study entry, renal function had improved in 17 of the 22 study patients; mean serum creatinine +/-SD (micromol/L) was 201+/-77 at entry and 153+/-65 after 3 months (P<0.001). (3) Improvement occurred in 11 of 15 patients with creatinine elevation > or =12 months and in 6 of 6 patients with creatinine elevation < or =6 months. (4) One patient developed transient liver dysfunction and a second required retransplantation for progressive cholestasis but without signs of rejection. CONCLUSIONS: In patients who undergo liver transplantation, substitution of CNI by MMF leads to improvement of acute as well as chronic renal dysfunction in most cases. Side effects of MMF may be limiting in some patients, and the immunological consequences remain to be studied.

Adult↗

Intraoperative continuous external bile drainage during pancreaticoduodenectomy.

PURPOSE: The common hepatic duct is usually divided during the early stage of pancreaticoduodenectomy. However, abrupt, complete, and prolonged closure of the proximal common duct stump can cause liver damage in the course of this long operation, resulting in postoperative liver dysfunction and associated complications. Here, we investigate this phenomenon further. METHODS: We performed intraoperative continuous external bile drainage (IBD) in 43 consecutive patients (drainage group) and compared postoperative liver enzyme levels, morbidity including liver dysfunction, and outcomes with those of a control group (n = 41). RESULTS: There were no complications associated with IBD catheter insertion in this series. The drainage group had significantly lower transaminase levels within the first 7 postoperative days (PODs) than the control group. Postoperative liver dysfunction was confirmed in six patients from the control group and in one patient from the drainage group (P = 0.04). However, there were no significant differences between these two groups in terms of postoperative morbidity (other than liver dysfunction), relaparotomy, and in-hospital mortality rates. CONCLUSION: Intraoperative continuous external bile drainage failed to improve the overall morbidity and mortality rates in this series. However, our findings showed that prolonged intraoperative complete closure of the common hepatic duct contributed to postoperative liver dysfunction in most patients and that IBD, which is easy and safe to perform, could reduce intra-operative liver damage and prevent postoperative liver dysfunction.

Aged↗

Differentially expressed genes in postperfusion biopsies predict early graft dysfunction after liver transplantation.

BACKGROUND: Preservation induced injury is a major contributing factor to early graft dysfunction in liver allograft recipients. We hypothesized that changes in gene expression represent the earliest indicator of ischemia/reperfusion-related injuries measurable in the graft and could be used as prognostic marker for the occurrence of graft-related complications. METHODS: We studied the expression of 67 genes, known to play a role in acute inflammatory processes by real-time polymerase chain reaction in 59 postperfusion biopsies. The level of expression was correlated with the occurrence of graft-related complications. RESULTS: We identified six genes that were significantly correlated with the occurrence of early graft dysfunction (Spearman test, two-tailed; P<0.05). High C-reactive protein (CRP) gene expression levels correlated significantly with the need of therapeutic interventions due to graft-related complications (P=0,011). Furthermore, five genes related to vascular endothelial cell physiology (CTGF, WWP2, CD274, VEGF. and its receptor FLT1) showed significantly reduced expression in the postperfusion biopsies of patients with need of therapeutic interventions due to graft-related complications in the first month (P<0.05). Using a risk score based on the expression of these five genes, complications could be predicted with 96% sensitivity (ROC analysis, specificity: 74%, positive predictive value: 72%, negative predictive value: 96%). CONCLUSION: Quantitative gene expression analysis in postperfusion biopsies may be a valuable tool to prospectively identify patients at risk for early clinical allograft dysfunction after liver transplantation.

Acute Disease↗

The influence of ethanol and liver disease on sex hormones and hepatic oestrogen receptors in women.

In contrast to the numerous studies of men, very few studies have been concerned with sex hormone disturbances in women with chronic alcoholic and non-alcoholic liver diseases. The aim of the study was, to evaluate the effect of ethanol and liver dysfunction on menstrual cycle, serum sex hormone concentrations and hepatic oestrogen receptors in women. In premenopausal female alcoholics ethanol consumption increase the frequency of menstrual disturbances, abortions, and miscarriages, while infertility is not frequent. Acute ethanol intoxication has only minor effects on pituitary-gonadal hormones in premenopausal women, while chronic ethanol abuse lead to reduced concentrations of sulphated steroids, and these changes may be seen before severe liver dysfunction has appeared. In women liver dysfunction lead to earlier occurrence of menopause in comparison with normal controls, while information is insufficient or lacking regarding the influence upon fertility, pregnancy outcome and sexual behavior in women. In postmenopausal women with alcoholic and non-alcoholic liver disease, the main disturbances of sex hormone metabolism consist of elevated oestrone and sex hormone binding globulin (SHBG) concentrations, while serum concentrations of steroid sulphates and 5 alpha-dihydrotestosterone (DHT) are reduced, and the degree of liver dysfunction is a major determinant for the observed disturbances. The presence of high affinity, low capacity, specific oestrogen receptors (ER) in the liver is confirmed using a ligand binding assay (DCC), specificity analyses, and sucrose gradient centrifugation. Furthermore, the sensitivity of an enzyme immunoassay has been improved enabling the quantitative measurement of hepatic ER in 102 small liver biopsies from patients with alcoholic and non-alcoholic liver diseases. The method is suitable for quantitative assessment and ER in small tissue samples, and can be applied to other tissues than the liver. Patients with chronic liver diseases have significantly lower hepatic ER concentrations, and this reduction is determined by the degree of liver dysfunction, while the degree of alcoholic hepatitis or active ethanol consumption are less important factors. The importance of this observation for hepatic physiology and pathophysiology remains to be determined.

Adult↗

[Acute relapsing sensory-dominant polyneuropathy associated with anti-GQ1b antibody and autoimmune hepatitis].

A 43-year-old male with 2 episodes of sensory impairments in four extremities and liver dysfunction, developed an acute exacerbation of both sensory impairments and liver dysfunction after administration of interferon-alpha. On admission, neurological examination revealed a mild distal weakness of four extremities, moderate impairment of superficial sensation in hands and severe impairment of deep sensation and areflexia in all extremities. Routine laboratory tests were normal except for a mild liver dysfunction. His serum was positive for antinuclear antibody, but negative for anti-DNA antibody and LE-test. Since he was seropositive for hepatitis B (HB) c antibody but seronegative for HBs antigen and antibody, HBe antigen and antibody, he was considered to be a seroconverted carrier of HB virus. Liver biopsy revealed chronic active hepatitis with marked lymphocytic infiltration. CSF examinations were within normal limits. Sensory conduction studies of median and sural nerves showed no response, but motor conduction studies of median and peroneal nerves were within normal limits. Light and electron microscopic examination of biopsied sural nerve disclosed a moderate decrease in large myelinated fibers, but not in either small myelinated or unmyelinated fibers. Thin-layer chromatography with immunostaining showed the presence of anti-GQ1b antibody in his serum. The anti-GQ1b antibody did not react with GT1a. Oral administration of prednisolone alleviated liver dysfunction, muscle weakness and superficial sensory impairment of four extremities, but not in deep sensation.

Acute Disease↗

Cytomegalovirus in liver biopsies of marrow transplant recipients: detection methods, clinical, histological and immunohistological features.

In a retrospective analysis liver biopsy specimens obtained from 44 marrow transplant recipients were studied to evaluate the frequency of local presence of human cytomegalovirus (CMV) and graft-versus-host disease (GvHD)-like histological and immunohistological alterations in patients with and without liver dysfunction following bone marrow transplantation (BMT). In 22 of 28 patients with marked liver dysfunction after BMT and histopathological alterations described as typical for acute GvHD CMV could be detected in the liver biopsy specimen. The polymerase chain reaction (PCR) technique revealed the highest sensitivity for CMV detection in liver biopsy samples, but in 20 of 22 PCR-positive specimens CMV infection could be confirmed by at least one additional technique. All the liver biopsies obtained from 16 patients with normal liver function lacking histopathological signs of GvHD were CMV negative. In all 3 patients with CMV-positive liver biopsy started on antiviral therapy liver function improved and no generalized CMV disease occurred. All the 4 patients without local presence of CMV started on severe immunosuppressive therapy showed an improvement of liver dysfunction without occurrence of CMV infection. Local CMV infection of the liver could not be differentiated from hepatic GvHD by clinical and histopathological features, nor by immunohistological analysis of the bile duct epithelium. In contrast, only in liver biopsy with local viral presence could an increase in HLA class II- and ICAM-1 expression be demonstrated on hepatocytes. Thus, especially the high negative predictive value of the PCR technique helps to manage the patient with liver dysfunction after BMT.

Adolescent↗

The significance of serum hepatocyte growth factor levels in planning follow-up of postoperative jaundice-free patients with biliary atresia.

PURPOSE: The aim of this study was to clarify the significance of serum hepatocyte growth factor (HGF), interleukin (IL)-6, and IL-1 receptor antagonist (ra) levels in the evaluation of disease status in jaundice-free survivors with biliary atresia after Kasai operation. PATIENTS AND METHODS: Serum concentrations of HGF, IL-6, and IL-ra were measured in 31 long-term jaundice-free patients with biliary atresia after Kasai operation and 29 controls. Patients were divided into 4 groups: group A (n = 8), normal liver function; group B (n = 9), mild liver dysfunction without portal hypertension; group C (n = 9), moderate liver dysfunction with controllable portal hypertension; and group D (n = 5), receiving liver transplantation. RESULTS: Serum IL-6 levels were significantly higher in patients than in controls. There was no difference in serum IL-6 levels among groups B, C, and D. Serum IL-1ra levels were elevated according to liver dysfunction. Serum HGF levels in group D were significantly higher than in controls and the other groups. Serum hyaluronic acid levels were positively correlated with serum levels of IL-1ra and HGF. CONCLUSIONS: Elevation of serum IL-1ra and HGF levels correlated with the progression of liver fibrosis and dysfunction. In particular, serum HGF levels could be used as a predictor for requiring liver transplantation.

Biliary Atresia↗