Laboratory Evidence Of Liver Disease Research Articles

Could serum nitrate and nitrite levels possibly predict hepatorenal syndrome in hepatitis C virus-related liver cirrhosis?

This study aimed to determine whether serum levels of nitric oxide metabolites (nitrates and nitrites) correlate with renal dysfunction in patients with liver cirrhosis and, moreover, to assess nitric oxide metabolite (NOx) power for predicting hepatorenal syndrome (HRS) in such patients. Among patients admitted to the Tropical Medicine Department, Ain Shams University Hospital, a total of 60 patients with chronic hepatitis C-related liver cirrhosis were included in this study. Patients were divided into three groups. Group I included 20 patients with compensated liver cirrhosis (CLC). Group II included 20 patients with decompensated liver cirrhosis (DLC). Group III included 20 patients with decompensated liver cirrhosis and HRS. Twenty healthy subjects with no clinical or laboratory evidence of liver disease were enrolled as a control group (group IV). Patients with HRS had a higher mean nitrite levels followed by DLC, then CLC, and then controls. The sensitivity and specificity of NO metabolites (nitrites) were 100 % and 93.3 %, respectively, with accuracy of 95 % at cutoff value of 387 μmol/L for diagnosing patients with HRS. There was a highly significant statistical difference between patients positive and negative for nitrites as regards renal profile (p = 0.000). A strong relation between nitrite cutoff value and renal dysfunction in liver cirrhosis has been found. Also, patients with HRS had higher mean serum nitrite levels than decompensated liver cirrhosis or compensated liver cirrhosis, raising the possibility of using nitrate and nitrite levels as a predictor for HRS in HCV-related liver cirrhosis.

Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C

Before the introduction of hepatitis C virus (HCV) screening for blood donors, the risk of acquiring HCV infection as a result of a transfusion was about 10%. The aim of this study was to assess the frequency and rate of progression to cirrhosis in patients with transfusion-associated chronic HCV infection and identify possibly negative prognostic factors. Of 2477 consecutive patients with clinical or laboratory evidence of liver disease, 392 (16%) were anti-HCV- and HCV-RNA-positive, had anamnestic evidence of a single and precisely dated transfusion event, and showed no other causes of chronic liver disease; 268 (68%) underwent ultrasound-guided liver biopsy and were enrolled in the study. After a mean interval of 18.4 years, 54 patients (20.1%) had cirrhosis, which multivariate analysis showed to be independently associated with the duration of follow-up, age at infection and at the time of liver biopsy, and serum alanine aminotransferase levels at biopsy. The time necessary to have a 50% probability of developing cirrhosis in patients aged 21-30, 31-40, and more than 40 years was 33, 23, and 16 years, respectively. In comparison with those aged 20 years or less at infection, the risk ratio of developing cirrhosis over a period of 30 years for patients aged 21-30 and at least 31 years at infection was, respectively, 4.51 (95% confidence interval, 1.03-19.76) and 12.29 (95% confidence interval, 3.06-49.40). In patients with transfusion-associated chronic hepatitis C, the risk of cirrhosis is related to age at infection and disease activity. Our findings suggest that an aggressive therapeutic approach should be adopted in patients infected by HCV at an older age to prevent the progression to end-stage liver disease.

40-Year-Old Man With Anemia, Chronic Low Back Pain, and Hypoalbuminemia

40-Year-Old Man With Anemia, Chronic Low Back Pain, and Hypoalbuminemia

Prevention of vitamin K deficiency bleeding in newborns.

Newborn babies are born vitamin K deficient; however, the deficiency is not sufficiently severe to cause a vitamin K deficiency coagulopathy and haemorrhagic disease of the newborn (HDN). Severe vitamin K deficiency can develop quickly in breast-fed newborns and can result in the appearance of classic HDN during the first week of life or late HDN during the first 2 months of life. Both forms of the disease can be severe, causing brain damage and death. Classic and late HDN are prevented by the intramuscular administration of vitamin K at birth. Oral prophylaxis prevents classic HDN but is ineffective in preventing late HDN. Despite proven effectiveness of intramuscular vitamin K prophylaxis there have been concerns about the need for, and safety of, this therapy. This review provides evidence that there is need for intramuscular vitamin K prophylaxis for all babies in order to eradicate haemorrhagic disease of the newborn and concludes that there is no evidence that this therapy is harmful.

Predictors of GBV-C infection among patients referred for renal transplantation

The etiology of liver disease remains unknown in about 4 to 23% of dialysis patients and 10 to 16% of renal transplant recipients. A search for other causative agents of liver disease led to the discovery of the GB group of viruses. We studied the association between the presence of GB virus C (GBV-C) infection, known risk factors for parenterally-transmitted infections and history or laboratory evidence of liver disease among end-stage renal disease (ESRD) patients referred for renal transplantation to the New England Organ Bank, MA. Stored sera from patients on the renal transplantation waiting list between November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV). Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV positive cohort and 286 randomly selected anti-HCV negative patients formed the anti-HCV negative cohort (573 patients overall). Additional sera were available for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%. The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not significantly different from that among anti-HCV negative patients (29%; P = 0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P = 0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03), and a higher proportion of patients with history of transfusions (OR 4.58, P = 0.01). Serum GBV-C RNA was not associated with a significantly increased OR for history of liver disease or non-A, non-B hepatitis, or elevated serum alanine aminotransferase levels. In a step-wise multivariate regression analysis, a younger age (OR 0.98 per year of age, P = 0.03), and history of blood transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR 1.07, P = 0.77). The results of this study support the fact that GBV-C is a parenterally transmitted virus and shed light on the modes of transmission of GBV-C among ESRD patients. However, the association with liver disease remains to be established.

Screening for Wilson's disease in patients with liver diseases by serum ceruloplasmin

Background/Aims: A low serum ceruloplasmin level is considered a diagnostic test for Wilson's disease. To examine whether it is useful to detect presymptomatic patients with Wilson's disease, serum ceruloplasmin was determined by radial immunodiffusion (normal: 20–60 mg/dl) in all patients ( n=2867) admitted for evaluation of a liver disease in 1993 and 1994. Methods: Patients with levels lower than 20 mg/dl were further evaluated by determination of serum copper concentration, urine copper excretion and ophthalmological examination. If possible, a liver biopsy was performed and the hepatic copper content was determined by flame atomic absorption spectroscopy. Results: Seventeen patients had serum ceruloplasmin levels <20 mg/dl. One had asymptomatic Wilson's disease (no Kayser-Fleischer rings or neurological symptoms). In the other 16 patients Wilson's disease was excluded. Based on elevated hepatic copper concentration, three were considered as heterozygous carriers of the WD gene. The remaining patients had various liver diseases (acute viral hepatitis in three, chronic hepatitis in two, drug-induced liver disease in three, alcoholic induced liver disease in two) or malabsorption ( n=3). Conclusions: The positive predictive value of low serum ceruloplasmin was only 5.9%. Although helpful for identifying presymptomatic Wilson's disease, screening by determining of serum ceruloplasmin in unselected patients with clinical or laboratory evidence of liver disease in neither feasible nor cost effective.

Current Thoughts on the Use of Methotrexate in Patients with Psoriasis

Background: There are many problems associated with the use of methotrexate in the treatment of psoriasis. Objective: We will attempt to assist the clinician in resolving some of these problems. Methods: This article is a summary of a Round Table Discussion on methotrexate held at the Canadian Dermatology Association meeting at Whistler, BC, July 1995; of a Continuing Medical Education meeting on methotrexate at Langdon Hall, Cambridge, ON, May 1996; and our review of the pertinent literature. Results: We recommend routine folic acid supplementation in patients receiving methotrexate. A baseline pretreatment liver biopsy is probably not indicated in patients without clinical or laboratory evidence of liver disease; and patients on 15 mg or less of methotrexate per week with normal liver function may not need liver biopsy. Conclusion: Liver biopsy of patients on methotrexate for psoriasis may not be necessary.

Cirrhosis and muscle cramps: Evidence of a causal relationship

The aim of the study was to define the features, prevalence, and pathophysiology of therapy for muscle cramps in cirrhotic patients. The first protocol study included 294 cirrhotic patients and 194 age- and sex-matched controls. Controls were defined as inpatients or outpatients without any clinical and laboratory evidence of liver disease. Features and prevalence of muscle cramps were defined on the basis of a standard questionnaire. As far as the pathophysiological associations of muscle cramps were concerned, the following parameters were evaluated: mean arterial pressure (MAP), nutritional status, liver function tests, plasma volume (PV), plasma renin activity (PRA), and electrolyte, mineral, and acid-base status. The prevalence of cramps was higher in cirrhotic patients than in controls, and it was related to the duration of recognized cirrhosis and to the severity of liver function impairment. At a multiple regression analysis, the presence of ascites, low values of MAP, and high values of PRA were the independent predictive factors for the occurrence of cramps in cirrhosis. In the second protocol study, the effects of a sustained expansion of the effective circulating volume induced by intravenous infusion of human albumin were compared with those of a placebo in 12 cirrhotic patients with more than three cramp crises a week. Compared with the placebo, albumin reduced the cramp frequency (P < .01). In conclusion, an increased prevalence of true muscle cramps occurs in patients with cirrhosis. Our data indicate that the pathophysiological link between cirrhosis and cramps may be represented by the reduction of the effective circulating volume. They also indicate that weekly infusion of human albumin may be an effective treatment for cramps in cirrhosis. (Hepatology 1996 Feb;23(2):264-73)

142 SCREENING FOR ALPHA-1 ANTITRYPSIN DEFICIENCY IN NEWBORN INFANTS IN SPAIN

Alpha-1 antitrypsin (AAT) deficiency is an hereditary metabolic disorder which predisposes affected individuals to juvenile liver disease and to pulmonary emphysema towards the third or fourth decade of life. Since prevention and treatment of this pulmonary complication is at present perfectly feasible, we have carried out a pilot study of neonatal screening for AAT deficiency in order to determine the incidence of this deficiency in Spain and to evaluate the parents' reactions on being told of this metabolic disorder. Fifteen thousand four hundred spanish newborn infants were screened for AAT deficiency. The study was carried out using the eluate from dried blood samples provided by the Cantabria University and the Basque Country Health Service Units for the detection of metabolic disorders. The screening test was based on a semiquantitative electroimmunoassay for AAT together with transferrin. For all cases suspected of AAT deficiency, the Pi phenotype was determined. With the screening test, 58 suspect cases were detected. Of these, the phenotype study showed 32 AAT deficient cases (8 Pi Z and 24 Pi SZ) representing a global incidence of 2.08±0.72 per thousand. In 4 Pi Z cases there was clinical and laboratory evidence of liver disease. The parents of the AAT-deficient children were informed of the potencially harmfull effect of tobacco smoke on the child. Their reaction towards this information was positive. Bearing in mind the high incidence of AAT-deficiency, and the existing preventive and therapeutic measures for pulmonary emphysema in AAT-deficient cases, mass-screening for this deficiency may be advisable. This screening could be considerably facilitated by recently developed genome analysis techniques.

Hepatic failure in dairy cattle following mastitis or metritis.

Hepatic failure developed following mastitis or metritis in five adult cows. In all five cases, cows initially showed clinical signs compatible with endotoxemia, which resolved with appropriate therapy for the mastitis or metritis. Subsequently, signs of liver failure developed including profound anorexia, weight loss, cessation of milk production, and in one case, photosensitization. Four cows had laboratory evidence of liver disease and failure (abnormally prolonged sulfobromophthalein [BSP] clearance half-life and abnormally high serum liver enzyme activity). Hepatocellular necrosis or vacuolization was seen on histopathologic examination of liver specimens from all five cows. The hepatocellular necrosis, in some cases, was thought to be due to the direct or indirect effects of endotoxin on the liver. Three of the cows responded to symptomatic therapy. One cow failed to respond and one was not treated.

Left lateral view in liver scans.

The left lateral view (LLV) in liver scans is not a routine view in many institutions and has not been thoroughly described in the literature. To determine the limits of normal in the LLV, the authors examined this view in liver scans of 56 patients whose six-month follow-up showed no clinical or laboratory evidence of liver disease. The distribution of normal shapes and axis angles is described. Neither of these descriptors showed significant correlation with age, sex, weight, height, or body surface area, except for a slight correlation between axis angle and sex. The authors conclude that the appearance of the left lobe of the liver on LLV is not related to body habitus. The role of the LLV in routine liver scanning is yet to be defined.

Reye Syndrome Without Initial Hepatic Involvement

We report Reye syndrome in an 11-year-old boy whose first symptoms were generalized convulsions and coma without clinical or laboratory evidence of liver disease. Serum glutamic oxaloacetic transaminase and lactate dehydrogenase (LDH) values increased strikingly on the third day after the onset of coma. These enzymatic changes were associated with prolongation of prothrombin time. A rise in blood ammonia concentrations began on the fourth day of coma. The diagnosis of Reye syndrome was confirmed by a liver biopsy and at autopsy. This case demonstrates that encephalopathy in Reye syndrome can develop prior to detectable hepatic involvement, and suggests that factors unrelated to generalized liver damage may occasionally play a role in the pathogenesis of this obscure disorder.

Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants.

We prosepctively studied 200,000 newborns to determine the frequency and clinical characteristics of alpha1-antitrypsin deficiency. One hundred and twenty Pi Z, 48 Pi SZ, two PI Z-and one Pi S-infants were identified and followed to the age of six months. Fourteen of 120 Pi Z infants had prolonged obstructive jaundice, nine with severe clinical and laboratory evidence of liver disease. Five had only laboratory evidence of liver disease. Eight other Pi Z infants had minimal abnormalities in serum bilirubin and hepatic enzyme activity and variable hepatosplenomegaly. All 22 Pi Z infants with hepatic abnormalities, two thirds of whom were made, appeared healthy at six months of age. Ninety-eight Pi Z infants did not have clinical liver disease, but liver-function tests gave abnormal results in 44 of 84 at three months, and in 36 of 60 at six months of age. The number of small-for-gestational-age infants was greater (P less than 0.001) among those with clinical liver disease. None of the 48 Pi SZ infants had clinical liver disease, but 10 of 42 at three months and one of 22 at six months of age had abnormal liver function. The Pi Z and Pi SZ phenotypes are associated with covert or readily apparent hepatic dysfunction in the first three months of life.

Persistent increased immunoglobulin M in treated narcotic addiction: Association with liver disease and continuing heroin use

The increased serum IgM in treated narcotic addiction was studied using quantitative radial diffusion techniques. Seventy per cent of 68 untreated heroin addicts had serum IgM levels above 880 mg. per deciliter, the upper limit of normal. Only 7 per cent of 15 abstinent patients had high serum IgM, while 36 or 33 per cent of 109 patients maintained on methadone for at least one year had high serum IgM levels. Fourteen of these 36 had known heroin use and 10 others abused other drugs including alcohol, whereas only 2 of the 73 methadone-maintained patients with normal serum IgM had known drug abuse. The association between positive urine spots for morphine and elevated serum IgM levels was significant (p < 0.01). There was a significant relationship between laboratory evidence of liver disease and increased serum IgM levels. Increased serum alkaline phosphatase correlated better (p < 0.01) than the serum glutamic oxaloacetic transaminase (SGOT) (p < 0.05) with high serum IgM levels in methadone-maintained patients. High serum IgM levels in treated addicts are associated with continuing drug abuse and/or with laboratory evidence of continuing mild liver disease.

Neonatal jaundice associated with cystic fibrosis.

Jaundice caused by cystic fibrosis is rare in the neonatal period. The reported child had jaundice, possibly due to cystic fibrosis, at 3½ weeks of age. This was followed by hepatomegaly, hyperbilirubinemia and abnormal levels of hepatic enzymes at 6 weeks of age. Complete resolution of clinical and laboratory evidence of liver disease occurred at 10 weeks of age, which suggests that temporary plugging may have caused the jaundice. Treatment with choleretics may be indicated.

Normal sulfobromophthalein retention in established liver disease.

The aim of this investigation was to quantify individual indices of sulfobromophthalein (BSP) transport and metabolism in patients with documented liver disease and normal results of the standard BSP retention tests. With the use of bolus-injection and constant-infusion technics, the kinetics of BSP removal were elucidated by determinations reflecting the hepatic functions of uptake, conjugation, storage, and transport maximum (Tm) for biliary excretion. The results in 5 patients with hemochromatosis, 9 with Wilson's disease, and 6 with portal cirrhosis, all with normal BSP retention, were compared with results in 12 cirrhosis patients with abnomal BSP retention and 29 control subjects without clinical or laboratory evidence of liver disease. Among the patients with normal BSP retention, fractional clearance and storage were significantly decreased (p<0.02), whereas Tm and conjugation were normal. Normal results of standard BSP retention tests in established liver disease are sometimes explained as being caused by the dilution effect of an expanded plasma volume, as previously reported. The present investigation has delineated another mechanism, wherein the hepatic injury is such that, with mild impairment of uptake and storage, maintenance of normal Tm was sufficient for the efficient removal of BSP.

The relationship of the serum alkaline phosphatase to urinary hydroxyproline excretion in liver and bone diseases

A close correlation was observed between the urinary hydroxyproline excreti and the serum alkaline phosphatase in patients with various bone diseases known to be associated with increased enzyme levels. Patients with elevated serum alkaline phosphatase activities due to hepatobiliary disease exhibited normal urinary hydroxyproline outputs. Differentiation of the two groups of patients by determination of the urinary hydroxyproline agreed with that established by electrophoresis of the serum alkaline phosphatase in 8 out of 9 patients studied by both methods. The exceptional patient, in whom clinical and laboratory evidence of liver disease and radiologic evidence of localized Paget's disease was found, had an elevated serum alkaline phosphatase suggested by electrophoresis to be of osseous origin, but had a normal urinary hydroxyproline.

The use of indocyanine green for the evaluation of hepatic function and blood flow in man.

This study was performed to evaluate the use of single intravenous injections of Indocyanine Green in evaluating liver function and estimating hepatic blood flow. Thirty-three subjects were studied, 23 of whom had no clinical or laboratory evidence of liver disease and 10 who had proven hepatic dysfunction of varying etiology. Nine of the normal subjects had hepatic vein catheterization performed in order to determine extraction ratios and to estimate hepatic blood flow. Half-life of disappearance, decay slopes, and plasma clearances of the dye are reported for both groups. A comparison of the difference in means of these parameters for the two groups shows a high degree of statistical significance. This difference is ascribed to the impairment of dye removal in the liver dysfunction group. The values for estimated hepatic blood flow in the normal group were found to be slightly lower than values previously reported for studies using bromsulphalein. A lower value for hepatic blood flow is to be expected if Indocyanine Green has a hepatic to extrahepatic clearance ratio larger than bromsulphalein. It is concluded that because of the properties of rapid exponential loss from the circulation and a large hepatic to extrahepatic extraction ratio of the dye, this method provides an excellent and relatively simple means of assessing liver function.