Normal Aspartate Aminotransferase Research Articles

Improving the End Point of Corticosteroid Therapy in Type 1 Autoimmune Hepatitis to Reduce the Frequency of Relapse

Relapse of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to corticosteroid withdrawal, and liver tissue examination prior to the termination of therapy may be insufficient to predict subsequent course. Our goal was to refine treatment end point criteria so as to reduce the frequency of relapse after drug withdrawal. One hundred thirty-two patients with definite type 1 autoimmune hepatitis who fulfilled clinical, laboratory, and histological criteria for remission were evaluated. The degree of laboratory improvement at the termination of treatment was correlated with subsequent clinical course in patients who had improved to normal or near-normal histological findings during corticosteroid therapy. Serum aspartate aminotransferase (AST) levels at the end of treatment were higher in patients who subsequently relapsed than in those who sustained remission (32 +/- 2 U/L vs 25 +/- 2 U/L, P= 0.04). Serum gamma-globulin (1.4 +/- 0.1 g/dL vs 1.2 +/- 0.1 g/dL, P=0.03) and immunoglobulin G (IgG) (1,416 +/- 55 mg/dL vs 1,079 +/- 57 mg/dL, P=0.001) levels were also higher in these patients prior to termination of therapy. The frequencies of abnormal serum AST (40%vs 13%, P=0.008), gamma-globulin (25%vs 3%, P=0.009), and IgG levels (36%vs 4%, P=0.001) at treatment withdrawal were also greater in the patients who subsequently relapsed. Patients who are treated to normal serum AST, gamma-globulin, and IgG levels have a lower frequency of relapse than others despite comparable histological findings.

Interferon lowers tumor recurrence rate after surgical resection or ablation of hepatocellular carcinoma: a pilot study of patients with hepatitis B virus-related cirrhosis

Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) often recurs after surgical or medical treatment. Eighty consecutive patients with HBV-positive cirrhosis and HCC who underwent potentially curative ablation for HCC were analyzed. Eleven patients received long-term interferon (IFN) therapy. HBV DNA was quantified at the time of HCC treatment. A DNA value of <6.0 log copies/ml was considered low. Initial DNA was low in 39 and high in 41 patients. HCC recurrence rates in the low DNA group and high DNA group were 46.9% and 82.6% at the fifth year, and 73.5% and 91.3% at the tenth year, respectively (P = 0.0103). Similarly, recurrence rates after treatment of HCC in the normal aspartate aminotransferase (AST) group (<38 IU/l, n = 42) and abnormal AST group (n = 38) were 50.6% and 84.0% at the fifth year, and 71.3% and 100% at the tenth year, respectively (P = 0.0003). Six of the 38 patients with abnormal AST, and 5 of 42 patients with normal AST, received IFN after confirmation of tumor ablation. In the subgroup of abnormal AST, tumor recurrence rates in the IFN and untreated groups were 16.7% and 37.9% at the end of the first year, 16.7% and 60.1% at the second year, and 16.7% and 83.4% at the third year, respectively (P = 0.0139). Multivariate analysis revealed that IFN significantly reduced the recurrence rate (hazard ratio = 0.21, P = 0.037) even after adjusting for background characteristics. IFN was inferred to decrease tumor recurrence after treatment of HCC in patients with HBV-related cirrhosis, especially in the subgroup with high AST.

Mild Ingestion of Used Frying Oil Damages Hepatic and Renal Cells in Wistar Rats

Male Wistar rats were fed ad libitum a powdered diet (AIN93G; no fat) containing 7 wt% of fresh oil (control) or used frying oil recovered from Japanese food manufacturing companies (recovered oil) for 12 weeks and subjected to anthropometric measurements, hematological analyses, and observations of the liver and kidneys. All of the rats grew well, and no gross symptoms attributable to recovered oil were observed. There was a tendency toward higher consumption of the diet in the experimental group as compared to the control group. In the serum of the experimental group, no difference was detected in the levels of glucose, triacylglycerol, and phospholipids. But many dark-red patches, necrosis, and bleeding were found in the livers of 75% of the experimental rats; these rats had extremely high aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values. Average AST and ALT values of the experimental group were significantly higher than those of the controls. The renal cells were also obviously damaged. These results raise the concern that frying oil contained in ready-made foods, snacks, etc., if deteriorated to an extent equal to or greater than that of the recovered oil, may be able to change human serum AST/ALT levels and damage the liver and kidneys.

Study of IgG Subclass Profiles of Anti-HBs in Populations With Different HBV Infection Status

To study IgG-specific subclasses of hepatitis B virus (HBV) surface antigen (anti-HBs), in different populations in Taiwan, a comparison was made between 104 chronic carriers (60 male and 44 female) and 439 recovered individuals (247 male and 192 female). Biochemical analyses of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also performed. Among the 104 chronic carriers, 21 patients had abnormal ALT and AST levels (> 25 IU/ml). When comparing the patients with abnormal ALT and AST levels to chronic carriers with normal ALT and AST levels, no statistical difference was observed for anti-HBs levels (p > 0.05). The IgG subclass pattern of the relative anti-HBs IgG subclass titers was IgG1 > IgG3 = IgG4 in both chronic carriers and recovered individuals (p < 0.05). IgG1 is the predominant anti-HBs antibody after HBV infection, in either chronic carriers or in HBV-cured individuals. This finding is partly inconsistent with data reported from other group who suggested in individuals naturally infected, the anti-HBs IgG consists mainly of IgG3 and IgG1. In contrast to that of our previous studies of anti-HBe and anti-HBc, the mean OD values of anti-HBs total IgG, and all IgG subclasses except for IgG2, of either males or females, were significantly higher in recovered individuals than in chronic carriers, while the mean OD values of anti-HBe and anti-HBc were significantly higher in chronic carriers than in recovered individuals (P < 0.05). The IgG subclass profile of anti-HBs in chronic carriers was not changed with liver inflammation and was independent of sex and age, except in individuals with abnormal ALT and AST for whom anti-HBs IgG1 was not significantly higher than IgG3 (p > 0.05), in spite of that whose mean O.D. value is higher.

Safety and Effectiveness of Rosiglitazone in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease

Background/PurposeNonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients and to improve the histologic markers of nonalcoholic steatohepatitis. This study aims to determine the safety and effectiveness of rosiglitazone in inadequately controlled type 2 diabetes patients with NAFLD.MethodsTaiwanese type 2 diabetes patients with inadequate control on insulin secretagogues and metformin, with no history of significant alcohol ingestion, with mildly elevated serum aspartate amino-transferase (AST) and/or alanine aminotransferase (ALT) and a diagnosis of fatty liver determined by ultrasonography were enrolled. Patients were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints were change in AST and ALT levels from baseline and reduction in A1C < 6.5%.ResultsOut of a total of 68 patients, 60 (88.2%) completed the study treatment without serious adverse events. Treatment in two (2.9%) patients was discontinued due to elevated AST or ALT levels to more than three times the upper limit of normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60 patients who completed the study treatment, mean fasting plasma glucose, A1C, fasting plasma insulin, mean ALT and homeostasis model assessment for insulin resistance were all significantly reduced. Normal AST and ALT levels were achieved and maintained for at least three consecutive measurements and through to the end of the study period in 20 (33.3%) patients. Weight increased by a mean of 2.6 ± 2.4 kg (p<0.001).ConclusionRosiglitazone was reasonably well tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One-third of patients showed improved liver function after treatment.

Inactive Hepatitis B Surface Antigen Carrier State and Hepatotoxicity During Antituberculosis Chemotherapy

<h3>Study objectives</h3> <i>:</i> To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide <h3>Design</h3> <i>:</i> Retrospective case-control study <h3>Setting</h3> <i>:</i> Tertiary university medical center <h3>Patients</h3> <i>:</i> One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10⁵ copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects <h3>Results</h3> <i>:</i> The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of ≥ 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p=0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects) <h3>Conclusions</h3> <i>:</i> Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed

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To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide. Retrospective case-control study. Tertiary university medical center. One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects. The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects). Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.

Is liver function testing necessary prior to methotrexate treatment for ectopic pregnancy?

Study objectives: Methotrexate is used extensively for the nonsurgical management of ectopic pregnancy. Hepatic function testing, specifically aminotransferase testing, was part of the initial methotrexate safety profile and continues to be routinely required before treatment with methotrexate. We seek to determine the incidence of abnormal aminotransferase values among emergency department (ED) patients with ectopic pregnancy. We examine risk factors for liver disease (eg, history of hepatitis, alcohol abuse) among patients with abnormal aminotransferase values and the time spent waiting for aminotransferase testing before methotrexate treatment. Methods: ED medical records were examined over a 4-year period for all patients with an International Classification of Diseases, Ninth Revision diagnosis of ectopic pregnancy. Patients with ectopic pregnancy were included if aminotransferase testing was performed during the ED visit. The medical record was reviewed for risk factors for liver disease if aminotransferase values were elevated. If a patient was treated with methotrexate, the time between orders for aminotransferase and methotrexate was recorded. Results: Over a 4-year period, 205 patients were diagnosed with ectopic pregnancy. Of these patients, the study group consisted of 121 patients who also had serum aminotransferase testing. In the study group, 42 patients were treated with methotrexate, and 79 were treated surgically. Two of the 121 (1.2%) patients had abnormal aminotransferase values. One patient had a normal aspartate aminotransferase (AST) level and an alanine aminotransferase (ALT) level of 43 U/L (reference range 15 to 40 U/L). This patient had a history of hepatitis C. The second patient had a normal ALT level and an AST level of 81 U/L (reference range 15 to 65 U/L). This patient had a history of alcohol abuse. Of the 42 patients treated with methotrexate, the mean time between orders for aminotransferase testing and methotrexate administration was 102 minutes (95% confidence interval 94 to 109 minutes). Conclusion: Among patients with ectopic pregnancy being considered for methotrexate treatment, the incidence of aminotransferase abnormalities is low. Aminotransferase testing significantly prolonged ED treatment time among patients receiving methotrexate. Further prospective study may identify a majority of patients who may be treated with methotrexate without previous aminotransferase testing.

Plasma Pyridoxal 5′-Phosphate Concentration Is Correlated with Functional Vitamin B-6 Indices in Patients with Rheumatoid Arthritis and Marginal Vitamin B-6 Status

Many patients with rheumatoid arthritis (RA) have low plasma pyridoxal-phosphate (PLP) but a normal erythrocyte aspartate aminotransferase activity coefficient (alpha EAST), a measure of vitamin B-6 status in the erythrocytes, compared with healthy subjects. The goal of the present study was to examine the correlations of PLP levels in these two compartments (plasma and erythrocytes) with other established indices of vitamin B-6 status, and to determine which indicator better reflects functional status of vitamin B-6 in patients with RA. Multiple indices of vitamin B-6 status were measured in 33 patients with RA. Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (DeltatHcy) and net increase in urinary xanthurenic acid after a tryptophan load (DeltaXA) were log-transformed to reach normality for statistical analyses. We found that log-plasma PLP levels were inversely correlated with both log-DeltatHcy (r = -0.368, P = 0.035) and log-DeltaXA (r = -0.333, P = 0.05). Plasma PLP was not correlated with alpha EAST or urinary 4-PA excretion. In contrast, erythrocyte PLP was inversely correlated with alpha EAST (r = -0.431, P = 0.012) and positively correlated with log-4-PA (r = 0.475, P = 0.005), but erythrocyte PLP was not correlated with the outcomes of a methionine or tryptophan load test. Erythrocyte PLP and log-4-PA, but not plasma PLP, were correlated with dietary intake of vitamin B-6 after adjusting for protein intake (r = 0.420, P = 0.015 and r = 0.333, P = 0.05, respectively). We suggest that in patients with RA, plasma PLP levels are a better diagnostic indicator of functional vitamin B-6 status than erythrocyte PLP levels.

Ultrasound Evaluation of Liver Disease in Cystic Fibrosis as Part of an Annual Assessment Clinic: A 9-year Review

AIM: To review 9 years of annual assessment data in cystic fibrosis (CF) and evaluate the frequency of hepatobiliary abnormalities and the correlation between ultrasound and biochemical findings. MATERIALS AND METHODS: Over a 9-year period (1990–99), 168 children (age range 1–18 years) with CF have undergone an annual assessment which has included clinical, biochemical and ultrasonographic evaluation of the hepatobiliary system. We have retrospectively reviewed the sequential ultrasound reports and correlated them with the contemporaneous biochemical results. RESULTS: A total of 725 ultrasound examinations were performed over the review period. Sixty patients had at least one examination showing an abnormality of liver echo texture and in 39 patients this was a persisting finding. Seven patients (4.2%) developed frank cirrhotic change on ultrasound criteria, while 15 patients (8.9%) had evidence of persistent splenomegaly. Gall-bladder calculi were present in 4.8%. In 176 examinations (24%) there was disparity between the ultrasound findings and aspartate aminotransferase (AST) levels. In 3.0% of cases (five patients) there were persisting abnormalities of liver echo texure and persisting splenomegaly with a normal range AST value. CONCLUSION: No perfect method of assessing hepatobiliary involvement in CF is currently available. Ultrasonographic and biochemical assessment may reflect different aspects of disease progression. Routine use of ultrasound in annual assessment allows identification of a minority of patients with liver changes but with normal biochemistry. Williams, S. M. et al. (2002) Clinical Radiology57, 365–370.

Retrospective Evaluation of the Effect of Valproate Therapy on Transaminase Elevations in Patients with Hepatitis C

To evaluate whether a relationship exists between valproate treatment and transaminase elevations in patients who are positive for hepatitis C virus (HCV). Retrospective medical record review. Veterans affairs medical center. A total of 214 HCV-positive patients; 28 were treated with valproate (study group), 186 were not (control group). Demographic characteristics; valproate treatment histories; plasma concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), albumin, and bilirubin; and exposure to other potentially hepatotoxic drugs, including probable alcohol abuse, were evaluated. Hepatotoxicity was staged by comparing maximum ALT and AST values against upper limits of normal or patients' mean elevated baseline ALT and AST values. Data were analyzed using a logistic regression model. Control patients and those with longer durations of HCV were more likely (p<0.0171 and p<0.0142, respectively) to exhibit higher stages of hepatotoxicity. More valproate-treated patients were exposed to other potential hepatotoxins at the time of peak transaminase elevations (50% vs 39%, p<0.005), whereas more control patients received two or more potential hepatotoxins (13% vs 4%, p<0.00005). Valproate treatment, either alone or in the presence of other potential hepatotoxins, does not appear to be related to increased transaminase elevations in patients with HCV

Serum collagen type VI and XIV and hyaluronic acid as early indicators for altered connective tissue turnover in alcoholic liver disease.

Hepatic fibrosis in alcoholic liver disease often heralds progression to cirrhosis and, therefore, noninvasive parameters are required for early diagnosis and follow-up. Collagens VI and XIV, procollagen-III-N-propeptide, hyaluronic acid, and active transforming growth factor-beta1 (TGF-beta1) were measured in healthy volunteers, patients with alcoholic cirrhosis, and heavy drinkers without cirrhosis. Noncirrhotic alcoholics were assigned to two groups with either normal aspartate aminotransferase or levels > or = 2 normal. Collagens VI and XIV were elevated in all alcoholic patients compared to controls (P < 0.0001, all instances). Procollagen-III-N-propeptide and hyaluronic acid levels were higher in alcoholic patients with elevated liver enzymes and in cirrhotics as compared to controls. Procollagen-III-N-propeptide revealed a significant correlation with serum levels of TGF-beta1 (P < 0.0001). Collagens VI, and XIV, procollagen-III-N-propeptide, and hyaluronic acid appear to be sensitive markers indicating fibrotic transformation in alcoholics. The correlation between procollagen-III-N-propeptide and TGF-beta1 emphasizes its role in hepatic fibrogenesis.

Biological Markers of Alcoholism With Respect to Genotypes of Low‐Km Aldehyde Dehydrogenase (ALDH2) in Japanese Subjects

Although the mutant low-Km acetaldehyde dehydrogenase (ALDH2) allele (ALDH2(2)) with reduced capacity to metabolize acetaldehyde offers biological protection against alcoholism and subsequent alcohol-induced organ damage in many individuals, a significant proportion of individuals with heterozygote of the normal and mutant ALDH2 gene (ALDH2(1)/2(2)) consume excessive amounts of alcohol. Indeed, it has been postulated that habitual drinkers with ALDH2(1)/2(2) may be at a higher risk for alcoholic liver disease than those with ALDH2(1)/2(1). In this study, we determined how representative biological markers of alcoholism (gamma-glutamyltransferase [GGT], carbohydrate-deficient transferrin [CDT], and the mean corpuscular volume of erythrocytes [MCV]) differ with respect to the ALDH2 genotypes in Japanese habitual drinkers. We obtained genomic DNA samples from 227 Japanese men with various drinking habits. ALDH2 genotypes were determined by allele-specific polymerase chain reaction. GGT, CDT, and MCV were determined and compared between ALDH2(1)/2(1) and ALDH2(1)/2(2) habitual drinkers who consumed more than 66 g of alcohol per day for more than 5 years. We measured CDT by anion-exchange chromatography followed by turbidity immunoassay by using a commercially available assay kit (Axis %CDT TIA). CDT levels were comparable between the two groups. GGT activities were significantly greater in ALDH2(1)/2(1) than in ALDH2(1)/2(2) habitual drinkers (81 +/- 85 vs. 53 +/- 40 IU/liters, p < 0.02). MCV values, on the other hand, were significantly larger in ALDH2(1)/2(2) than in ALDH2(1)/2(1) subjects (98.2 +/- 5.8 vs. 95.8 +/- 4.2 fl, p = 0.02). When we used elevation of either CDT or GGT to detect habitual drinking in ALDH2(1)/2(1) and 2(1)/2(2) subjects, the sensitivities were 57% and 46%, respectively. CDT levels were similar between habitual drinkers with normal aspartate aminotransferase levels and those with elevated levels. GGT and MCV, but not CDT, differ with respect to the ALDH2 genotypes in Japanese male habitual drinkers. ALDH2 genotypes should be considered when interpreting data on biological markers of alcoholism.

Computerized reminders to monitor liver function to improve the use of etretinate

Objective: to determine whether computerized reminders during the process of prescribing can improve the use of drugs requiring prior laboratory testing according to the indications listed in the Drug Package Insert. Measures: Change in proportion of appropriate prescribing and frequency of severe hepatotoxicity between pre- and post-intervention. Methods: etretinate, a medication indicated for psoriasis, was selected as a monitored drug because it was the most prescribed of all the identified drugs that require specific prior laboratory tests. Computerized reminders are designed to alert a physician who is about to prescribe etretinate either without the alanine aminotranceferase (ALT) test or the aspartate aminotransferase (AST) test within 3 months or despite abnormality in ALT or AST. Data on alerts were gathered by using electronic mail whenever alerts occurred. Results: prescriptions of etretinate with normal ALT or AST results within the previous three months increased suddenly from 25.9% (127/491) in the pre-intervention period to 66.2% (353/533) in the post-intervention period ( P<0.0001). Moreover, three patients who used etretinate had markedly abnormal tests in the pre-intervention period, but none of the patients were classified in this way in the post-intervention period. Conclusions: the computerized reminders appear to improve physicians’ use of a drug requiring specific prior laboratory tests.

Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis

Background & Aims: The diagnosis of hemochromatosis is now possible for C282Y homozygous patients using noninvasive molecular genetic tests. The aim of this study was to define noninvasive factors predictive of severe fibrosis (bridging fibrosis or cirrhosis) to avoid unnecessary liver biopsies in such patients. Methods: Clinical and biological data were recorded at the time of diagnosis in 197 French C282Y homozygous patients, 52 (26%) of whom had severe fibrosis. Variables significantly linked to severe fibrosis using univariate analysis were entered into a multivariate stepwise analysis. These variables were combined to obtain a simple index allowing for prediction of severe fibrosis. Results: Serum ferritin, hepatomegaly, and serum aspartate aminotransferase were selected using multivariate analysis. Their combination applied to the 96 patients with ferritin level of ≤1000 μg/L, normal aspartate aminotransferase values, and absence of hepatomegaly showed that no severe fibrosis was encountered in this subgroup of patients. The results were validated in 113 C282Y homozygous patients in Canada with a good reproducibility of negative prediction but a poor reproducibility of the positive prediction of severe fibrosis. Conclusions: In C282Y homozygous patients, the diagnosis of severe fibrosis relies on liver biopsy, but absence of severe fibrosis can be accurately predicted in most patients on the basis of simple clinical and biochemical variables. GASTROENTEROLOGY 1998;115:929-936

High Prevalence of Hepatitis G Virus in Bone Marrow Transplant Recipients and Patients Treated for Acute Leukemia

Hepatitis G virus (HGV) is a newly described virus that has been implicated in transfusion-associated hepatitis. The prevalence of HGV in a group of multitransfused patients with hematological malignancy was studied using a reverse transcription polymerase chain reaction technique. Transfusion histories and serum aspartate aminotransferase (AST) levels were recorded. HGV was detected in 29 of 60 (48%) patients. There was no difference in HGV positivity rates between those with normal AST levels and those with raised AST levels. Analysis of patients by treatment type showed that 20 of 33 (61%) patients who received a bone marrow transplantation procedure were HGV positive compared with 9 of 27 (33%) treated with conventional combination chemotherapy (P = .036) despite similar transfusion histories. There was no significant difference in HGV positivity between patients treated before the introduction of United Kingdom blood donor screening for hepatitis C virus antibody:18 of 39 (46%) and those treated after the introduction of screening 11 of 21 (52%). HGV infection appears to be extremely common in these patients; however, the clinical significance of these findings with respect to liver dysfunction is not yet clear.

High Prevalence of Hepatitis G Virus in Bone Marrow Transplant Recipients and Patients Treated for Acute Leukemia

AbstractHepatitis G virus (HGV) is a newly described virus that has been implicated in transfusion-associated hepatitis. The prevalence of HGV in a group of multitransfused patients with hematological malignancy was studied using a reverse transcription polymerase chain reaction technique. Transfusion histories and serum aspartate aminotransferase (AST) levels were recorded. HGV was detected in 29 of 60 (48%) patients. There was no difference in HGV positivity rates between those with normal AST levels and those with raised AST levels. Analysis of patients by treatment type showed that 20 of 33 (61%) patients who received a bone marrow transplantation procedure were HGV positive compared with 9 of 27 (33%) treated with conventional combination chemotherapy (P = .036) despite similar transfusion histories. There was no significant difference in HGV positivity between patients treated before the introduction of United Kingdom blood donor screening for hepatitis C virus antibody:18 of 39 (46%) and those treated after the introduction of screening 11 of 21 (52%). HGV infection appears to be extremely common in these patients; however, the clinical significance of these findings with respect to liver dysfunction is not yet clear.

Role of non-transferrin bound iron in iron overload and liver dysfunction in long term survivors of acute leukaemia and bone marrow transplantation.

To determine whether nontransferrin bound iron is present in the serum of long term survivors of acute leukaemia and bone marrow transplantation who have liver dysfunction as indicated by consistently raised serum aspartate aminotransferase (AST) activities. Thirty eight patients, who were at least three years from the end of treatment, were studied. Serum samples were analysed for hepatitis C, hepatitis B, AST, ferritin, and non-transferrin bound iron. A bleomycin based assay was used to detect non-transferrin bound iron. Patient and blood bank records were examined to determine the number of units of transfused blood received by each patient. Ten patients had consistently raised serum AST activities. Of these, two had evidence of hepatitis C infection, one had chronic hepatitis B infection and one had chronic graft versus host disease affecting the liver. None of these four patients had detectable non-transferrin bound iron. The remaining six patients had no obvious reason for raised AST activities, but four had non-transferrin bound iron detectable in their serum as compared with only two out of 28 patients with normal AST activities. Patients with abnormal AST activities had higher serum ferritin concentrations than those with normal AST, though serum ferritin was raised in 21 of 28 patients without liver dysfunction. Non-transferrin bound iron may be found in this group of patients, suggesting that iron overload is the cause of the observed liver dysfunction. Non-transferrin bound iron may also be a more specific indicator of iron overload than the serum ferritin concentrations.

Hepatic Injury during Propylthiouracil Therapy in Patients with Hyperthyroidism: A Cohort Study

To evaluate the incidence, severity, and course of propylthiouracil-induced hepatic injury in patients with hyperthyroidism. Cohort study. Outpatient clinic of a university-based hospital. Fifty-four patients with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values and a definite diagnosis of hyperthyroidism. Treatment with propylthiouracil, 300 mg/d for 2 months followed by 100 to 150 mg/d for 3 months and a subsequent maintenance dose of 100 mg/d. Liver biochemical tests were studied before therapy and 2 months and 5 months after starting propylthiouracil therapy. The patients were monitored with clinical evaluation and weekly liver biochemical tests after AST or ALT levels became abnormal. Serologic markers of hepatitis A, B, C, and delta virus infection were also studied when appropriate. Fifteen (28%; 95% CI, 16% to 42%) of the 54 patients showed ALT elevations 2 months after propylthiouracil therapy. The mean peak ALT level for these patients was 1.35 mu kat/L (range, 0.65 3.85 mu kat/L). None of these patients had symptoms or hyperbilirubinemia. Liver biopsy in three patients showed mild perivenular focal necrosis or ill-defined granuloma composed of foamy histiocytes with ceroid pigment and mild fatty metamorphosis. Despite continued propylthiouracil therapy at a reduced dose, ALT levels returned to normal in 13 of 15 patients in the following 3 months. None of these ALT elevations resulted from hepatitis A, B, C, or delta virus infection. No statistical difference was seen in the pretreatment characteristics between patients with and those without ALT elevation, except that the former had a higher pretreatment T4 level (270 +/- 12.9 compared with 237 +/- 7.72 nmol/L, P = 0.027) and T3 level (7.22 +/- 0.72 compared with 5.85 +/- 0.39 nmol/L, P = 0.048). Propylthiouracil-induced subclinical liver injury is common and is usually transient and asymptomatic. Therapy with propylthiouracil may be continued with caution in the absence of symptoms and hyperbilirubinemia.

A clinical and biochemical study on tissue polypeptide antigen (TPA) in non-malignant hepatic disorders

The behaviour of the tumour marker TPA was studied in 160 patients with benign diffuse liver diseases which underwent a thorough clinical and biochemical evaluation. Abnormal serum levels were found in 71.9% of the 160 patients, 87.2% of the 86 cirrhotics, and 98.4% of the 61 cirrhotics with elevated aspartate aminotransferase (ASAT) levels. TPA correlated with numerous clinical and biochemical markers of liver disease, serum ASAT being the most significant one (r = 0.63, p < 0.00001). TPA values were higher in cirrhotics than in non-cirrhotics (p < 0.0001) and in the patients with increased ASAT as compared with those with normal ASAT (p < 0.0001). In liver disease the cut-off level had to be raised five-fold to allow 10% abnormal values. This fact severely limits the usefulness of TPA in oncologic patients who also have liver disease. Cytolysis and/or liver regeneration appear to play an important role in the increase of TPA in these patients although other mechanisms such as impaired metabolism due to hepatocellular insufficiency also may be involved.