Liver function assessment with three (13)C breath tests by two-point measurements.

In this study, we performed three breath tests - l-[1-(13)C ]phenylalanine breath test (PBT), l-[1-(13)C ] methionine breath test, and [(13)C]methacetin breath test (MethaBT) - in patients with chronic liver disease to determine the optimal timing of expired air collection for diagnosing chronic liver disease and evaluating the grade of fibrosis. The subjects were 61 adults with normal livers, 98 chronic hepatitis patients, and 91 liver cirrhosis patients. We investigated the relationships of breath test results with routine biochemical tests and the Child-Pugh score, as well as the diagnostic capacities of the breath tests for liver dysfunction/cirrhosis and grade of liver fibrosis. For the diagnosis of liver cirrhosis and correlations with liver fibrosis, the accuracy of the PBT at 30 min (PBT30) was similar to that of the MethaBT at 15 min (Metha15). For liver function assessment by two-point measurement with (13)C breath tests, we recommend the PBT30 and the Metha15.

Assessment of chronic hepatitis and fibrosis: comparison of MR elastography and diffusion-weighted imaging.

OBJECTIVE: The purpose of our study was to compare the utility of MR elastography (MRE) and diffusion-weighted imaging (DWI) in characterizing fibrosis and chronic hepatitis in patients with chronic liver diseases. SUBJECTS AND METHODS: Seventy-six patients with chronic liver disease underwent abdominal MRI, MRE, and DWI. Severities of liver fibrosis and chronic hepatitis were graded by histopathologic analysis according to standard disease-specific classifications. The overall predictive ability of MRE and DWI in assessment of fibrosis was compared by constructing a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) on the basis of histopathologic analysis. RESULTS: Using ROC analysis, MRE showed greater capability than DWI in discriminating stage 2 or greater (≥ F2), stage 3 or greater (≥ F3), and cirrhosis (≥ F4), shown as significant differences in AUC (p = 0.003, p = 0.001, and p = 0.001, respectively). Higher sensitivity and specificity were shown by MRE in predicting fibrosis scores ≥ F2 (91% and 97%), scores ≥ F3 (92% and 95%), and scores F4 (95% and 87%) compared with DWI (84% and 82%, 88% and 76%, and 85% and 68%, respectively). Although MRE had higher ability in identification of liver with fibrosis scores ≥ F1 than DWI, a significant difference was not seen (p = 0.398). Stiffness values on MRE increased in relation to increasing severity of fibrosis confirmed by histopathology scores; however, a consistent relationship between apparent diffusion coefficient (ADC) values and stage of fibrosis was not shown. In addition, liver tissue with chronic hepatitis preceding fibrosis may account for mild elevation of liver stiffness. CONCLUSION: MRE had greater predictive ability in distinguishing the stages of liver fibrosis than DWI.

Assessment of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma in Middle Eastern patients.

BACKGROUND: Alpha-fetoprotein (AFP) levels for the diagnosis of hepatocellular carcinoma (HCC) may vary by geographical region and racial background. No data exists for this test in the Middle Eastern population. In addition, there is limited data on the impact of virological status on AFP levels. METHODS: In a multicenter, case-control study involving 206 cases, 199 cirrhotic and 197 chronic hepatitis controls, we assessed the utility of AFP in the diagnosis of HCC (sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and positive likelihood ratios (LR). PPV and NPV were evaluated for three additional HCC prevalence rates (5, 10, and 20%). RESULTS: The best discriminating AFP value was 11.7 ng/ml. The sensitivity ranged from 32 to 79.5% at different AFP levels with the specificity increasing sequentially from 47.7 to 98.5%. Sensitivity of AFP at the best cut-off level for hepatitis C virus (HCV), hepatitis B virus (HBV) and non-viral etiology for HCC was 73.7, 65.6, and 59.5%, respectively. Specificity at this level for HCV, HBV, and non-viral etiology was 36.6, 30.1, and 29.4%, respectively. AFP cut-off levels of 102, 200, and 400 ng/ml showed similar sensitivity (39.8, 35.9, and 32%, respectively) and specificity (96, 98.5, and 98.5% respectively). Positive LR for AFP at >11.7, >20, >102, >200, >400 ng/ml were 2.8, 3.3, 9.9, 23.8, and 21.2, respectively. CONCLUSIONS: In cirrhotic patients, AFP has a poor screening and diagnostic value for HCC. Underlying viral etiology fails to influence the diagnostic accuracy of this test. An AFP level greater than 100 ng/ml has a high degree of specificity and may be used as a confirmatory test.

Assessment of liver function in children with acute lymphoblastic leukemia in remission.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common malignant neoplasm in children. Antineoplastic treatment alone or with coexisting chronic viral hepatitis may permanently impair liver function. The aim of this study was to examine the effect of ALL and chronic viral hepatitis on the pharmacokinetics of lidocaine and its metabolite MEGX. MATERIAL AND METHODS: We enrolled 17 children and young adults with ALL in remission. Mean remission time was 61 +/- 30 months. Eleven patients were also infected with chronic viral hepatitis type B and/or type C. The control group comprised 12 healthy children. Lidocaine and MEGX pharmacokinetics were studied after intravenous administration of 1 mg/kg lidocaine. Serum samples were obtained at 15, 30, 60, 120, 240, and 360 min. from drug administration and were processed for separation by high-performance liquid chromatography. Statistical analysis was performed with Student's t-test. RESULTS: Elevated serum concentrations of MEGX 30 min. after lidocaine administration were observed in patients with ALL and hepatitis. The remaining pharmacokinetic parameters of lidocaine and MEGX did not differ significantly between groups. Our results suggest that pharmacokinetics of lidocaine and MEGX remain essentialy unaltered in ALL with coexisting chronic hepatitis.

[Viral hepatitis. Insurance medicine observations]. / Die Virushepatitiden. Versicherungsmedizinische Betrachtungen.

The major cause of liver diseases world-wide are the infectious hepatitis A-E which are due for different viruses. Most of the cases are clinically asymptomatic and without jaundice with a high rate of cure. The diagnosis and the differentiation of the various clinical syndromes are based mainly on serological markers of the involved antigen-antibody-systems. For insurance purposes the chronic hepatitis B, C and D are of great importance. Where chronic persistent hepatitis has a nearly normal life expectancy, chronic active hepatitis which may develop into cirrhosis and/or hepatocellular carcinoma has an increased mortality.

Non-invasive assessment of diffuse liver disease by in vivo measurement of proton nuclear magnetic resonance relaxation times at 0.08 T.

44 patients with a range of parenchymal liver diseases diagnosed by biopsy or laboratory investigations underwent proton nuclear magnetic resonance (NMR) relaxometry of the liver at 0.08 T. T1 maps were produced using an interleaved saturation recovery and inversion recovery sequence and T2 maps using a four echo Carr-Purcell-Meiboom-Gill sequence. Significantly raised relaxation times compared with a previously studied group of 42 normal volunteers were found in groups of patients with alcoholic cirrhosis (p < 0.001 for T1 and T2), chronic active hepatitis (CAH) (p < 0.01 for T1 and T2) and minor liver abnormalities (p < 0.01, T2 only). T1 was significantly higher in cirrhotics than in patients with CAH (p < 0.002) and minor abnormalities (p < 0.001). This suggests a role for relaxometry in the confirmation of the presence of cirrhosis (sensitivity = 75%, specificity approximately 97%, taking T1 > 266 ms as a positivity criterion). Reduced T2 values were found in patients with liver iron overload prior to venesection (p < 0.001 versus normals, p < 0.02 versus venesected patients). Although this latter test has relatively low sensitivity and specificity, it may have a role in the monitoring of treatment for iron overload.

[The assessment of liver microsomal oxidative capacity via caffeine and antipyrine elimination in patients with chronic active hepatitis: preliminary results]. / Valoración de la capacidad microsomal oxidativa hepática mediante la eliminación de cafeína y antipirina en pacientes con hepatitis crónica activa: resultados preliminares.

The hepatic metabolism of drugs in patients with chronic active hepatitis has been studied in a few occasions, finding discordant results. In our preliminary study we pretend to appraise the microsomal oxidative hepatic metabolism in 10 chronic active hepatitis HBs Ag(+) outpatients without clinical symptoms. The concentrations of both substances were measured in saliva and the caffeine and antipyrine tests of these patients were compared to control group. The difference found in the caffeine and antipyrine elimination, between the chronic active hepatitis group and the control group, have been low, without statistics significance (p > 0.1). Although, the results are preliminaries and is necessary to follow this study in many patients, probably the caffeine and antipyrine elimination are not decreased in the chronic active hepatitis without clinical symptoms. In these patients, the microsomal oxidative hepatic metabolism is not altered.

Clinical assessment and incidence of hepatitis C RNA in 50 consecutive RIBA-positive volunteer blood donors.

OBJECTIVES: (i) To assess evidence of liver disease in 50 consecutive volunteer blood donors who were anti-hepatitis C virus (anti-HCV) antibody positive and who were referred to one hepatologist; (ii) to assay for viral RNA in serum in these patients. SETTING: Royal Prince Alfred Hospital, a teaching hospital of the University of Sydney. PATIENTS: Fifty people who were detected by the NSW Red Cross Blood Transfusion Service to be anti-HCV antibody positive and to have a positive result on recombinant immunoblot assay (RIBA) were assessed by one hepatologist for symptoms, signs and biochemical evidence of hepatic dysfunction. These patients were consecutive referrals from this source. Sixteen of these patients also consented to liver biopsy assessment. All patients had serum assayed for viral RNA by polymerase chain reaction with a combination of 3' and 5' primers. RESULTS: The 50 blood donors consisted of 28 men and 22 women, with a mean age of 34.5 years. Forty-six patients were asymptomatic. Only six had a past history of hepatitis while 14 had minor signs of chronic liver disease. In 28, injecting drug use was thought the most likely source of exposure to HCV. The minimal mean time since exposure to HCV in these patients was 8.8 +/- 5.2 years. Eight patients had received a blood transfusion at a mean time of 15.0 +/- 9.8 years from the time of consultation. The mean maximum level of alanine aminotransferase (ALT) in all 50 patients was 102.8 U/L. Five patients had persistently normal ALT levels; another 22 had at least one normal ALT level. Liver biopsies indicated chronic persistent hepatitis in 11 patients, mild chronic active hepatitis in three patients and more severe chronic active hepatitis in one. One patient had cirrhosis on biopsy. Forty-two patients had viral RNA detected in serum. CONCLUSION: Chronic infection with HCV in blood donors was invariably asymptomatic; 78% of patients had no signs of chronic liver disease and 68% had a maximum hepatic transaminase level of less than 100 U/L. Although severe liver disease was seen in two of 16 biopsies, the majority of these patients have mild liver disease despite a mean of about 10 years since exposure to the virus. Eighty-four per cent of patients had evidence of viral RNA in serum.

Assessment of liver function using a novel galactose single point method.

A novel, simple, clinically useful quantitative liver function test, called the galactose single point (GSP) method, was developed by measurement of galactose blood concentration 1 h after galactose was administered (0.5 g/kg). It was quickly infused intravenously in 55 normal healthy volunteers, 73 patients with chronic hepatitis (CH), 36 with cirrhosis and 41 with hepatocellular carcinoma (HCC). Patients with CH diagnosis were assessed by liver biopsy. Cirrhosis was diagnosed by histological examination or a chronic hepatitis history with esophageal varices or ascites, whereas HCC was diagnosed either histologically, or cytologically proved, or as implied in the 'one imagine study' being positive with AFP > 300 ng/dl. Highly significant galactose blood levels were observed between normal healthy volunteers and patients 50, 60 and 70 min after galactose was administered. Galactose elimination capacity (GEC), modified GEC (MGEC) and consecutive GSP tests were performed in 6 healthy volunteers for 2 days. 0.64-16.87% variation was observed for each subject. The significant differences (p < 0.001) in average GSP values were 247 +/- 18.1, 422 +/- 27.3, 629 +/- 42.8 and 579 +/- 43.6 micrograms/ml for normal healthy volunteers, CH, cirrhosis and HCC patients, respectively. Highly significant correlations (p < 0.001) were obtained among GSP, GEC and MGEC for all patients. Positive correlations were observed between GSP, GEC, MGEC and AST (serum aspartate aminotransferase), ALT (serum alanine aminotransferase), serum bilirubin, albumin, prothrombin time and r-globulin. According to results obtained from 202 normal healthy volunteers and patients, the GSP method may be a simple, clinically useful quantitative measurement of liver function for the determination of a patient's residual liver function, the prognosis of liver function for patients with cirrhosis, postoperational follow-up and, finally, the timing of a liver transplant.

Laboratory assessment of chronic hepatitis in Syrian hamsters.

Clinical chemistry studies in the diagnosis of hamster diseases have received little attention. Although normal values exist for serum constituents, the effects of disease on these values are not well documented. Chronic hepatitis is endemic in several Syrian hamster (Mesocricetus auratus) colonies and is reported mainly through routine histologic examination. We investigated whether any differences in serum clinical chemistries were present in animals with hepatobiliary disease versus unaffected hamsters. Only serum alanine aminotransferase (ALT) and bile acids were significantly elevated in hamsters with chronic hepatitis only. In hamsters that had both chronic hepatitis and biliary disease, the serum ALT, alkaline phosphatase, cholesterol, and bile acids were significantly elevated. The results of this study indicated that serum clinical chemistries may be a useful antemortem diagnostic test for chronic hepatobiliary disease in hamsters.