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Increased lung uptake on technetium-99m-sulfur colloid liver-spleen scans in patients with hepatic venoocclusive disease following bone marrow transplantation.

Three patients who developed signs and symptoms of liver dysfunction following autologous bone marrow transplantation showed varying degrees of increased lung uptake on technetium-99m-sulfur colloid (99mTc-SC) liver-spleen-scans and were subsequently demonstrated to have hepatic venoocclusive disease (VOD) at autopsy. Although increased lung uptake of labeled colloid has been noted in solid organ and bone marrow transplant patients, an association between this phenomenon and VOD has not been previously reported.

Adult↗

Liver transplantation for hereditary tyrosinemia: the Quebec experience.

Sixteen tyrosinemic patients were evaluated in our institution for a possible liver transplantation. All patients showed biochemical and/or radiological evidence of liver dysfunction. Renal involvement was found to be more abnormal than expected. Seven patients have been transplanted, with two patients receiving a combined liver-kidney transplant. Hepatocarcinoma was detected in two of eight patients in whom the whole liver was examined. Six (37.5%) of the initial 16 patients have died since evaluation, one of the six dying after combined liver-kidney transplantation. Posttransplantation survival was 86%, with normal liver function, normal growth, and no recurrence of neurological crises on a normal diet.

Adolescent↗

Treatment of malignant endocrine pancreatic tumors with human leukocyte interferon.

Twelve patients with malignant endocrine pancreatic tumors refractory to cytotoxic treatment were treated with human leukocyte interferon im at daily doses of 3 X 10(6)-6 X 10(6) IU. Ten of 12 patients showed an objective response with a mean duration of 15.2 months, median, 11 months (range, 2-36+). All ten patients had a decrease in tumor markers and an objective reduction in tumor size was also noted in four. Improvement of clinical manifestations was seen in all cases with an objective response. Adverse effects, including influenza-like syndrome, reduction of blood cells, and chemical signs of liver dysfunction occurred, but were reversible or could be circumvented by dose reduction. One patient developed hypothyreosis on an autoimmune basis; another patient developed liver steatosis. Although the number of patients is small, the results are promising. Interferon therapy seems to be as potent as cytotoxic treatment but with far less side effects. This study indicates that further trials with interferon in patients with less advanced stages of malignant endocrine pancreatic tumor should be performed.

Adult↗

Liver and thyroid function and autoimmunity during interferon-beta 1b treatment for MS.

BACKGROUND: The occurrence or recurrence of autoimmune diseases or of autoantibodies (autoAb) has been reported during type I interferon (IFN) treatment. OBJECTIVE: To define the frequency of thyroid and liver dysfunction and of autoimmunity during IFN-beta 1b (IFNB) treatment of MS. METHODS: Prospective 1-year multicenter follow-up of 156 patients with MS recruited by 18 centers was conducted. Thyroid-stimulating hormone and anti-thyroid autoAb were measured by an immunoradiometric method, thyroid hormones by chromatographic assay, and non-organ-specific autoAb by indirect immunofluorescence. Tests were repeated every 3 months. The probability of having liver, thyroid, or autoAb alterations was analyzed longitudinally with the generalized estimating equations (GEE) method. RESULTS: Thyroid dysfunction was observed in 5.3% of cases at baseline and 8.3% de novo during IFNB treatment. GEE analysis showed that the probability of having thyroid alteration did not change significantly during treatment compared with baseline. Liver alteration was observed in 4.6% of cases at baseline and 37.5% de novo during IFNB treatment (p < 0.0001). GEE analysis showed that the probability of having liver alteration was higher (p < 0.002) at months 3 and 6 compared with baseline, returning to values similar to baseline by month 9. AutoAb were detected in 16.1% of patients at baseline and in 20% during IFNB. GEE analysis showed that the probability of having autoAb did not change significantly during treatment compared with baseline. Thyroid or liver alteration or autoAb occurring de novo during IFNB were usually transient. CONCLUSIONS: Differently from the frequency of liver function alteration (which significantly increased during the first months of IFNB treatment, suggesting a probable causal relationship with IFNB), the frequency of thyroid dysfunction or of autoimmunity showed random and insignificant changes over time, probably not related to IFNB treatment.

Adjuvants, Immunologic↗

The use of plasma levels for FK 506 dosing in liver-grafted patients.

FK 506 plasma levels were analyzed in 89 liver-grafted patients under FK 506-based immunosuppression. Plasma levels were found to be influenced by the patients' liver function: compared to patients without major liver dysfunction, those with cholestasis had higher plasma levels and these plasma levels were able to differentiate between rejection and toxicity. In patients with stable liver function, no clear difference was observed with regard to the plasma levels detectable during toxicity or rejection. We conclude that plasma levels can be used to determine the FK 506 dose but only in patients with cholestasis (i.e., during the early post-transplant course, or in patients with cholestatic rejection). In patients with stable liver function, plasma levels are only of limited clinical relevance.

Cholestasis↗

CNS tryptamine metabolism in hepatic coma.

Lumbar CSF indoleacetic acid (IAA) was higher in patients with cirrhosis of the liver than in controls. It was also higher in CSF of patients in coma than in those with hepatic cirrhosis but not in coma. There was a strong correlation (r = 0.89, p less than 0.01) between the grade of hepatic coma and CSF IAA. These data indicate that there is an association between elevated CNS tryptamine metabolism and hepatic coma. How far changes in the metabolism of tryptamine and other trace amines are relevant to the induction of hepatic coma or are simply a reflection of advanced liver dysfunction is unclear.

Adult↗

Pharmacokinetic studies of cimetidine in patients with liver disease.

The tolerability and metabolism of cimetidine administered for over 7 days were studied in 30 patients with liver diseases and 19 control subjects who had peptic ulcers. Cimetidine was well tolerated by these patients without any side effects. The cimetidine in the serum and urine was determined by high-performance liquid chromatography. The serum cimetidine levels and pharmacokinetic parameters of the patient group did not significantly differ from those of the control group after oral administration. Following intravenous administration, the half-life of cimetidine increased and cimetidine clearance decreased in the liver disease group. These differences seem to be totally explicable by the impaired renal function associated with the liver disease. Furthermore, accumulation of cimetidine in serum did not occur following continuous treatment with cimetidine in these patients. It was concluded that a reduction of cimetidine dosage is not necessary in patients with liver disease as far as their renal function is not disturbed, since the metabolism of cimetidine was not affected by the liver dysfunction itself.

Administration, Oral↗

Inhibition of biotransformation by nitric oxide (NO) overproduction and toxic consequences.

Hepatic nitric oxide (NO) biosynthesis is induced by local or systemic inflammation. The highly reactive NO radical binds to prosthetic iron groups such as heme or iron-sulfur clusters leading to either activation or inhibition of enzymes such as guanylate cyclase, cyclooxygenase and aconitase. It has been known for years that NO also binds to the heme moiety of cytochrome P450s (CYP) with high affinity. However, it was demonstrated recently that binding of NO to CYPs also inhibits their enzymatic activity. This is true for exogenously applied as well as for endogenously synthesized NO. Suppression of CYP-dependent metabolism, which is a major problem of inflammatory liver diseases, can be significantly reversed by inhibition of NO synthesis in vivo under experimental conditions. We investigated whether these findings are applicable as a novel therapeutic principle in severe inflammatory liver dysfunction.

Animals↗

Another observation with VATER association and a complex IV respiratory chain deficiency.

The VATER association of vertebral anomalies (V), anal atresia (A), esophageal atresia and/or tracheo-esophageal fistula (TE), radial and renal anomalies (R) is a common congenital association of unknown origin with probably heterogeneous causes. Here, we report on a girl presenting with pre- and postnatal growth retardation, esophageal atresia, vertebral and costal anomalies and a unilateral radial defect, consistent with the diagnosis of VATER association. In the first month of life, she presented with failure to thrive, severe episodes of hypoglycemia, liver dysfunction and high levels of lactate, which prompted us to perform metabolic screening. A complex IV respiratory chain deficiency (RCD) was diagnosed on a liver biopsy. The respiratory chain defect was not observed in skin fibroblasts. No mtDNA point mutation or deletion was identified. The girl is now 9 years old and has a normal mental development but persistent feeding difficulties and moderate hyperlactatemia. To our knowledge, this is the second report of VATER association with mitochondrial disorder. In a previous report, a VACTERL association was observed in a girl with the mitochondrial A3243G point mutation. The association of VATER phenotype with a mitochondrial disorder may be coincidental but could also suggest that the presence of multiple malformations is the result of the antenatal expression of RCD.

Abnormalities, Multiple↗

Surgery in the patient with liver disease.

Management of the surgical patient with liver disease begins with a careful preoperative assessment (Fig. 1). Any clues to liver disease on history and physical examination should be investigated to ascertain the cause of the clinical finding. More data on surgical patients with unexpected liver disease are now available. Patients undergoing emergent surgery are at significant risk of developing liver dysfunction. Child's class still correlates strongly to postoperative complications. Cornerstones of perioperative management in these patients are medical treatment of complications of chronic liver disease, such as ascites; coagulopathy; prevention of encephalopathy; and rapid treatment of dangerous postoperative complications, such as acute acalculous cholecystitis. Evolving knowledge of the effects of anesthesia, improving surgical techniques, and use of better diagnostic tests will help in the reduction of perioperative complications in these patients.

Biliary Tract Surgical Procedures↗

Signal intensity of the liver parenchyma in microbubble contrast agent in the late liver phase reflects advanced fibrosis of the liver.

BACKGROUND: Microbubble of Levovist accumulates in liver parenchyma, and the phenomenon has been reported as late liver-specific parenchymal. The aim of the present study was to compare the parenchymal enhancement effect of Levovist with the degree of liver dysfunction. PATIENTS AND METHODS: Sixty consecutive patients who consented to be treated were enrolled in this study. Pulse-inversion ultrasonography (US) in the liver parenchymal phase of enhancement with Levovist was performed in a preoperative examination. The mechanical index of pulse-inversion US was set at 1.3. The gray-scale intensity of the non-tumor area of the liver parenchyma at the level of the focal zone was measured. The hepatic fibrosis index was measured in each liver by morphometric analysis. The correlation between the gray-scale intensity of the non-tumor area of the liver parenchyma and the hepatic fibrosis index was assessed. RESULTS: There was a significant inverse correlation between the gray scale of the liver parenchyma and the hepatic fibrosis index (r = -0.809, P < 0.01). The average signal intensity of the liver parenchyma was 144.5 in a normal liver, 133.6 in chronic hepatitis, and 102.6 in liver cirrhosis, demonstrating a significant difference between a normal and cirrhotic liver (P < 0.01). CONCLUSIONS: The signal intensity of a microbubble disruption of the liver parenchyma in the late phase of enhancement with Levovist was considered to reflect the degree of hepatic fibrosis.

Adult↗

Molecular adsorbents recirculating system dialysis for liver insufficiency and sepsis following right ventricular assist device after cardiac surgery.

We report a case of right heart failure (RHF) and sepsis with liver insufficiency in a 70-year-old patient after coronary artery bypass graft surgery. Three hours after surgery the patient suddenly developed therapy refractory cardiac arrest caused by RHF. He had to have emergency surgery, under which the graft to the right coronary artery was revised and a right ventricular assist device was implanted. Heart function recovered and the assist device was explanted on day 1 after surgery. Thoracic closure was performed on day 5 after surgery. The patient went into septic shock on day 11. Liver dysfunction developed postoperatively and worsened the course of sepsis. Therefore, MARS (molecular adsorbents recirculating system) dialysis was performed once on day 20 after surgery. Liver function improved after MARS therapy and the patient recovered from sepsis. On day 46 the patient was transferred from the ICU of another hospital to one of the peripheral wards, to be finally discharged on day 67.

Aged↗

Histological changes in the thyroid in cirrhosis of the liver.

The thyroid has been examined histologically in 77 cases of cirrhosis of the liver and in an equal number of control cases. Contrary to expectation, no difference was found between the incidence or the severity of lymphocytic infiltration of the thyroid in the two groups. A conspicuous fibrosis or ;cirrhosis' of the thyroid, not related to lymphocytic infiltration, was associated with cirrhosis of the liver, especially in elderly women. The significance of this lesion is not clear but its origin is probably to be sought in liver dysfunction rather than in auto-immunization.

Aged↗

Development of hepatocellular carcinoma in a woman with HBV- and HCV-negative autoimmune hepatitis with unsatisfactory response to Corticosteroid.

A 57-year-old woman was admitted due to a hemorrhage from esophageal varices. Laboratory tests showed liver dysfunction, elevated immunoglobulin G levels and positivity for anti-nuclear antibodies. Serum hepatitis B virus and hepatitis C virus markers were negative. The liver biopsy specimen was compatible with autoimmune hepatitis, and low-dose prednisolone was started. During the follow-up, her serum alanine aminotransferase levels continued to fluctuate between 40 and 60 IU/l. Nine years later, hepatocellular carcinoma 20 mm in diameter was detected. This case suggests that hepatocellular carcinoma develops even if serum alanine aminotransferase levels are maintained at less than twice the upper normal limit.

Adrenal Cortex Hormones↗

[Differential diagnosis of hepatitis: development of new laboratory tests for autoimmune hepatitis and progress in pathophysiology].

Liver dysfunction has been found in 8.1% of postpartum women in the general population. This dysfunction was speculated to be developed by postpartum aggravation of subclinical autoimmune hepatitis. Therefore, we developed two methods for detection of autoantibodies to liver-specific antigens: an ELISA for anti-liver-specific arginase antibodies, and a highly sensitive radioligand assay for anti-CYP2D6 antibodies. Basic examinations of dilution curve, inhibition study and reproducibility were satisfactory for clinical application in both assays. Anti-arginase antibodies and anti-CYP2D6 antibodies were found in 28.6% and 42.6% of patients with autoimmune hepatitis, respectively. There was no correlation between the two autoantibodies and thus, combined use of these antibodies detects 55.3% of autoimmune hepatitis. Autoimmune hepatitis exists frequently when we include mild cases.

Arginase↗

Reanastomosis after jejunoileal bypass.

One hundred and one patients underwent jejunoileal bypass after careful preoperative evaluation. These patients were re-evaluated after operation on a frequent basis, and 23% have required restoration of intestinal continuity (reanastomosis) by a mean postoperative time of 44 months. The most frequent reasons for reanastomosis were liver dysfunction (5% of the entire series), severe malnutrition or weakness (5%), and late electrolyte imbalance (4%). Two patients did not survive reanastomosis, both having liver failure. Of the patients who did survive, weight gain (approaching prebypass weight) and improvement in liver function tests, electrolyte balance, serum vitamin levels, and diarrhea have been the rule. Of the entire series of 101 patients who underwent bypass, 58% either had life-threatening complications, had to be reanastomosed, or died. These morbidity and mortality rates raise the important question of whether jejunoileal bypass is an appropriate procedure for the treatment of morbid obesity.

Body Weight↗

[Cyclic adenosine monophosphate in the cerebrospinal fluid of patients with liver disease (author's transl)].

The concentration of adenosine 3':5'-cyclic monophosphate in the spinal fluid of ten patients with liver dysfunction was analyzed. Ages of the patients ranged from 31 to 75 years. The state of consciousness varied between normality and stupor. After a liver biopsy the diagnoses were as follows: cirrhosis in six cases, porphyria cutanea tarda in one case, hepatic metastases in two cases and Wilson's disease in one case. Mean values in these patients (22.91 +/- 4.18 pM/ml) have been significantly greater (p less than 0.0005) than those in ten control individuals (15.55n control individuals (15.44 +/- 3.66 pM/ml). Values corresponding to two patients in coma were still higher (52.62 and 36.50 pM/ml respectively). A previous lumbar puncture carried out in one of these patients when he was conscious showed a figure of 23 pM/ml. These results suggest a progressive rise of cyclic adenosine monophosphate in the spinal fluid in relation to clinical impairment, and may indicate a similar behaviour for this nucleotide to that of tryptophan, as reported by other authors. These findings point toward the role of the alteration of neurotransmitters in the pathogenesis of hepatic coma.

Adenosine Monophosphate↗

Personal experience of right anterior segmentectomy (segments V and VIII) for hepatic malignancies.

BACKGROUND: Right anterior segmentectomy is the most difficult type of hepatic resection to perform and is reported only rarely. For patients with tumors limited to the anterior segment but complicated by mild liver dysfunction, this is the only type of hepatectomy that can be tolerated. This article described personal experience with this operation in 17 patients with liver malignancies. METHODS: Fourteen patients had hepatocellular carcinoma, one had cholangiocellular carcinoma, and two had metastases, one from rectal and the other from gastric carcinoma. Except in one case of dense adhesion of the hepatoduodenal ligament, hemihepatic vascular occlusion was used. Both the right and middle hepatic veins were fully exposed in 14 patients. RESULTS: The average operation time was 412 minutes and the average blood loss was 1482 ml. There was one operative death as a result of pneumonia and liver failure. Another patient had prolonged bile leakage with right pleural effusion and bleeding gastric erosions. The cumulative 1- and 5-year survival rates were 88% and 47%, respectively. CONCLUSIONS: The results of this experience indicate that in selected patients with hepatic malignancies this procedure is safe and compatible with improved survival. This may be the first report to describe the clinical features and operative technique in a series of patients treated by right anterior segmentectomy.

Aged↗