Biochemical Markers Of Liver Disease Research Articles

CLINICAL PROFILE AND TREATMENT RESPONSE TO SOFOSBUVIR-VELPATASVIR REGIMEN AND ITS IMPACT ON THE QUALITY OF LIFE IN CHRONIC HEPATITIS C PATIENTS

Objective: Chronic Hepatitis C infection is one of the major global contributors to liver-related morbidity and mortality. Successful antiviral therapy with the direct-acting antiviral combination sofosbuvir-velpatasvir has shown to improve survival, liver-related outcomes, all-cause mortality, and even reverse fibrosis. We evaluated the treatment response of this regimen in terms of its impact on the Quality of life of patients during and after the therapy. Methods: This is an Observational, prospective, descriptive study of serologic HCV RNA-positive cases. Data on change in clinical, biochemical profile, and quality of life using 2 standardized questionnaires SF-36 and CLDQ was analyzed at baseline, 12 w from baseline, and 24 w after therapy cessation. Results: 62 out of the 87 patients registered during the study completed the desired study duration. 95% achieved sustained virological response (SVR) at 12 w and 100% at 24 w from baseline. Improved clinical profile with symptom resolution and change in the biochemical parameters and quality-of-life scores was statistically significant (P value-<0.001 and 0.005) at 12 w from baseline and 24 w after therapy cessation, respectively. Conclusion: Patients achieving SVR with sofosbuvir-velpatasvir have been shown to improve clinical profile with normalization in biochemical markers of liver disease, which is reflected in all the quality-of-life domains of SF-36 and CLDQ-HCV. However, long-term follow-up with larger sample size is required for improved study validity and to improve long-term liver-related outcomes.

SERUM LEVEL OF IL-6, TNF-α, IL-4, IL-10 IN PATIENTS WITH CIRRHOSIS DUE TO CHRONIC HEPATITIS B

Objectives: This study was conducted to evaluate the serum level of interleukin - 6 (IL - 6), tumor necrosis factor α (TNF - α), interleukin - 4 (IL - 4) and interleukin - 10 (IL - 10) in a sample of patients affected by chronic HBV infection in various stage of liver cirrhosis to evaluate differences of the aforementioned cytokines between Child - Pugh classes, as well as between chronic hepatitis B (CHB)patients and healthy controls.Patients and methods: 78 chronic hepatitis B patients who were divided into three groups according to the Child - Pugh scoring system: group A comprised 24 patients with Child Pugh class A; group B comprised 39 patients with Child Pugh class B; and group C comprised 15 patients with Child Pugh class C. The study also included 10 healthy controls for comparing. Biochemical markers of liver disease were measured by clinical routine methods approved by IFCC. Serum concentrations of IL - 6, TNF - α, IL - 4, and IL - 10 were measured with the Human Cytokine/Chemokine ELISA Kit, Arigo Biolaboratories Corporation, Taiwan.Results: CHB patients showed statistically significant difference in TNF - α (p < 0.001), IL - 4 (p <0.01) and IL - 10 (p < 0.01) levels versus healthy controls. Non-cirrhosis patients (Group A) showed statistically significant difference in TNF - α (p < 0.001), IL - 10 (p < 0.05) levels versus cirrhosis patients (Group B and C). Serum IL - 4 levels were significantly different between group B and group C patients (p < 0.05). There was not any correlation between cytokines and biochemical markers of livercirrhosis.Conclusions: This study evaluated the serum cytokine levels (IL - 6, TNF - α, IL - 10, and IL - 4) of chronic hepatitis B patients, as well as the differences in such levels between patients and healthy controls. Although no correlations of cytokine levels with biochemical markers of liver disease were observed, serum levels of TNF - α, IL - 4, IL - 10 increase significantly in chronic hepatitis B patient, especially elevating in cirrhosis group (TNF - α, IL - 10); IL - 4 only increased in severe cirrhosis group (group C). TNF - α, IL - 4, IL - 10 but not IL - 6 may be a possible mediator in the pathogenesis of liver fibrosis.

IL-18 in Blood Serum of Hepatitis C Patients Might be of Predictive Value for Individual Outcomes.

Pro- inflammatory cytokines including Interleukin (IL)-18 have been shown to be involved in the clearance of Hepatitis C virus (HCV) infection. However, changes in the balance of pro- and anti-inflammatory cytokines production during the immune response, can elicit a variety of liver damages. Therefore, it is of interest to study IL-18 serum levels in hepatitis patients and its correlation with HCV infection. Twenty-nine newly diagnosed HCV+ patients with no history of antiviral therapy, and 17 healthy controls, were enrolled in our study. Biochemical markers of liver disease were evaluated by biochemistry assay kits. Serum concentrations of IL-18 were determined with the ELISA method before and after treatment with pangenotypic direct-acting antivirals (DAAs) treatment. Our results showed statistically significant difference in serum levels of IL-18 in HCV+ patients (692.261 ± 48.76) compared to healthy controls (520.00 ± 44.73) (P=0.021). However, there was no significant difference in IL-18 serum levels between the treated group compared to untreated patients (P=0.74). No significant correlations were detected between the level of IL-18 and liver enzyme levels. According to our study, IL-18 might be a disease marker associated with HCV infection; however, this conclusion requires further investigation.

The dynamics of liver tests in pregnant women with non-infectious hepatitis in the case of ­prescription of ademetionine

Aim. To study the effect of ademetionine on the dynamics of biochemical markers of liver disease in pregnant women with non-infectious hepatitis.
 Methods. The study included 19 pregnant with non-infectious hepatitis (5 alcoholic, 7 drug, 7 alimentary) etiologies. For groups comparison it was used the history of previous pregnancies in these same women. To monitor the functional state of the liver in the blood of women, the content of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin was determined using HUMAN reagent kits on a BIOSKREM MS 2000 microanalyzer (USA). Examination of pregnant women was carried out immediately after registration, at the end of the first and second trimesters of pregnancy.
 Results. In pregnant women with a high content of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin in the blood, cases of pathological development of the fetus were recorded more often. The use of drugs based on ademetionine contributed to the positive dynamics of liver tests in drug and alimentary (caused by nutrition) hepatitis; no evidence of the positive dynamics in alcoholic hepatitis was obtained.
 Conclusion. Prescribing of ademetionine to pregnant women with liver damage by non-infectious etiology can positively affect both the biochemical parameters of the liver and, possibly, the formation of the fetus.

IN CHILDREN WITH FONTAN PHYSIOLOGY, LIVER STIFFNESS IS CORRELATED WITH AGE, TIME SINCE FONTAN COMPLETION AND BIOCHEMICAL MARKERS OF LIVER DISEASE

Liver disease is of growing concern in children and young adults with Fontan physiology. The natural history of liver disease is this patient population is not presently well defined, largely because a definitive diagnosis is reliant on invasive liver biopsy. Non-invasive investigations to detect liver pathology in Fontan patients have not yet been validated. Transient elastography (TE), to assess liver stiffness, is a validated measurement of liver fibrosis in patients a number of chronic liver diseases. This modality may represent a non-invasive method to assess liver fibrosis in pediatric Fontan patients. We hypothesized that TE values would be associated with age and biochemical markers of liver disease in children with Fontan physiology. We prospectively enrolled 60 patients with Fontan physiology at British Columbia Children’s Hospital. All patients underwent comprehensive liver evaluation including liver enzymes (ALT, AST, GGT, ALP), albumin, bilirubin, INR, CBC, abdominal ultrasound, and TE measurement. The AST to platelet ratio index (APRI) was calculated from the laboratory results. Trained personnel obtained TE measurements of liver stiffness using age-specific probes. A total of 86 TE measurements were performed on 60 unique patients with a median age of 11.3 years (interquartile range 7.7-14.7 years, 55% male). There was a significant correlation between liver stiffness and both the time since Fontan completion (rho=0.45, p < 0.001) and age at the time of TE measurement (rho=0.48, p < 0.001). In addition, there was a significant correlation between liver stiffness and laboratory measures of liver health including APRI (rho=0.39, p=0.01), AST (rho=-0.50, p < 0.01), and INR (rho=0.3128, p=0.05). Findings on ultrasound imaging of the liver and spleen did not correlate with liver stiffness. This represents the largest reported cohort of pediatric Fontan patients to undergo TE as part of a comprehensive liver assessment. While liver stiffness is elevated in the early post Fontan period, we found that TE measurements of liver stiffness increased with both age and time from Fontan completion. Furthermore, the rise in liver stiffness over time was also associated with worsening biochemical markers of liver disease. Our results support the notion that liver disease begins in childhood in this population, and that TE measurement of liver stiffness may be a non-invasive method to identify and monitor the progress of liver disease in pediatric Fontan patients.

Long‐Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure–Associated Liver Disease

Fish oil lipid emulsion (FOLE) and multidisciplinary care for infants with intestinal failure (IF) have been associated with reduced morbidity and mortality due to IF-associated liver disease (IFALD). With increased survival, a greater proportion of infants with IF are now able to remain on parenteral nutrition (PN) in the long term. The purpose of this study was to examine outcomes in children with IFALD who have required long-term PN and FOLE therapy due to chronic IF. A review of prospectively collected data was performed for children with IFALD who required at least 3 years of PN and FOLE therapy due to chronic IF. Outcomes examined include the incidence of death, transplantation, and essential fatty acid deficiency (EFAD), as well as growth parameters and the biochemical markers of liver disease. Of 215 patients with IFALD treated from 2004-2015, 30 required PN and FOLE therapy for at least 3 years (median, 4.6 years). To date, no patients have died, required transplantation, or developed EFAD. Biochemical markers of liver disease normalized within the first year of therapy with no recurrent elevations in the long term. Weight-for age and length-for-age z scores improved and PN dependence decreased in the first year of therapy, with a stable rate of growth in the long term. Children with IFALD who required long-term PN and FOLE for chronic IF had no mortality, need for transplantation, EFAD, or recurrence of liver disease in the long term, allowing for continued intestinal rehabilitation.

Evaluation of serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 in patients with chronic hepatitis

BackgroundChanges in various cytokine activities have been reported during both HBV and HCV infections, while an imbalance of pro-inflammatory and anti-inflammatory cytokine production influences their immunopathogenesis. The aims of the present study are (a) to measure serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-2 (IL-2) and interleukin-4 (IL-4) in a sample of patients affected either by chronic HBV infection or by chronic HCV infection and in healthy controls (b) to correlate serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 with biochemical markers of liver disease and (c) to evaluate differences of the aforementioned cytokines between HBV and HCV patients, as well as between patients and healthy controls. MethodsThe study population consisted of 50 patients with chronic hepatitis B, 40 patients with chronic hepatitis C and 30 healthy controls aged between 28 and 75 years. Biochemical markers of liver disease were evaluated by routine methods approved by IFCC. Serum concentrations of IL-6, TNF-α, IL-10, IL-2 and IL-4 were determined with the Human Cytokine/Chemokine Panel I Merck Millipore. ResultsHBV patients showed statistically significant difference in TNF-α and IL-2 levels, versus healthy controls. HCV patients showed statistically significant difference in TNF-α, IL-10 and IL-2 levels versus healthy controls. IL10 and IL-2 levels were significantly different between HBV and HCV patients. ConclusionsThis study evaluated the serum cytokine levels (IL-6, TNF-α, IL-10, IL-2 and IL-4) of chronic hepatitis B or C patients, as well as the differences in such levels between patients and healthy controls. Correlations of cytokine levels with biochemical markers of liver disease were also observed, reflecting the degree of activity of the inflammatory process in the liver.

Prognostic Implications of Elevated Serum IgE Levels in Primary Sclerosing Cholangitis

Purpose: Primary sclerosing cholangitis (PSC) is a prominent risk factor for cholangiocarcinoma (CCA), but reliable clinical biomarkers for predicting the risk of developing CCA are lacking. Recently, low serum IgE was found to be associated with CCA in a Japanese cohort of PSC patients. Our aim was to determine whether serum IgE levels predict the development of CCA and/or other adverse clinical outcomes in a United States-based cohort of PSC patients. Methods: Medical records of adult patients with well-defined PSC were retrospectively queried for serum IgE levels as well as other pertinent data, including age, sex, date of PSC diagnosis, IBD and immunosuppression status, biochemical markers of liver disease and other clinical variables and outcomes. The primary endpoint was time to developing adverse clinical endpoints including CCA, liver transplantation or death. Patients with low and high IgE (defined by sample median) were compared with respect to clinical characteristics using Mann-Whitney U and Fisher's exact test. Time to the development of adverse clinical endpoints in the low and high IgE groups was compared with Kaplan-Meier curves. The adjusted association between IgE and the primary outcome was assessed with multivariate proportional-hazards models. Results: Among the 38 patients included, the median age at PSC diagnosis was 41 years, 68% were male, 95% were non-Hispanic White and 89% had IBD. The median serum IgE was 47.6 kU/L, and median time from PSC diagnosis to IgE measurement was two weeks. The low and high IgE groups differed significantly only with respect to serum IgG levels and IgG1, IgG2 and IgG4 subclasses, all of which were higher in the high IgE group (all p<0.05). There was no significant difference in composite clinical endpoint-free (p=0.83, Figure) or CCA-free survival (p=0.20) between the low and high IgE groups. In multivariate analysis, only Mayo PSC risk score and MELD score were significant predictors of outcome (both p<0.05).Figure: Kaplan-Meier curves reveal no significant difference in the time to death, cholangiocarcinoma, or liver transplantation between the low and high IgE group (p=0.83).Conclusion: Serum IgE levels are associated with several serum IgG subclass levels, but do not appear to influence the time to development of CCA, LT or death in PSC patients from a United States-based cohort.

Hepatitis C treatment outcomes in Australian clinics

To determine hepatitis C (HCV) treatment effectiveness and predictors of response in the "real-world" Australian clinic setting. Patients with chronic HCV, who were HCV-treatment-naive at enrolment, and were then treated with standard therapy (pegylated interferon-α plus ribavirin), were recruited prospectively through a national network of 24 HCV clinics between April 2008 and December 2009. Patients were interviewed and a medical record review was conducted at enrolment and at routine follow-up clinic visits. Proportion of patients achieving a sustained virological response (SVR), predictors of SVR, and impact of treatment on biochemical markers of liver disease (alanine aminotransferase levels and aspartate aminotransferase-to-platelet ratio index scores). The SVR by intention to treat was 60% (327/550). Infection with HCV genotype 2 or 3 (compared with genotype 1) was an independent predictor of SVR (odds ratio [OR], 2.45; 95% CI, 1.70-3.52), while HIV coinfection (OR, 0.28; 95% CI, 0.10-0.82), cirrhosis (OR, 0.38; 95% CI, 0.18-0.81), and increased body mass index for ≥ 30 kg/m(2) v ≤ 25 kg/m(2) (OR, 0.58; 95% CI, 0.35-0.96) were independently associated with lower SVR. There was a significant improvement in biochemical markers of liver disease following SVR (P< 0.001). Our findings are similar to those seen in clinical trials, despite the inclusion of patients with a broad range of comorbid conditions such as injecting drug and alcohol use and psychiatric illness. They suggest that, with appropriate patient and infrastructure support, expansion of treatment services to the broader HCV-infected community is warranted.

Markedly Elevated Serum Transaminases in Glycogen Storage Disease Type III

Glycogen storage disease type III (GSD III) is an autosomal recessive metabolic disorder that is caused by the deficiency of the glycogen-debranching enzyme. Presenting problems often include hepatomegaly, elevated transaminases, hyperlipidemia, mild hypoglycemia, and failure to thrive. We describe a patient who developed marked elevation in serum transaminases (alanine aminotransferase [ALT] > 2000 IU/L), without evidence of significant hepatocellular necrosis or liver dysfunction. A 17-month-old girl presented to our emergency department with acute vomiting and diarrhea. Physical examination revealed hepatosplenomegaly (liver and spleen 6 and 2 cm below the costal margins, respectively). Her weight and height were at the 75th percentile. Laboratory tests showed elevated transaminases: ALT 408 IU/L (reference range <40 IU/L), aspartate aminotransferase (AST) 328 IU/L (reference range <40 IU/L), gamma-glutamyl transpeptidase (gGTP) 53 IU/L (reference range 8–78 IU/L), and total bilirubin 0.3 mg/dL (reference range <1.0 mg/dL). Initial workup revealed unremarkable acetaminophen level, creatine phosphokinase (CPK), coagulation studies, hepatitis virus panel, thyroid function tests, ceruloplasmin, α-1 antitrypsin phenotype, auto-immune studies, and liver ultrasound. Although the symptoms of acute gastroenteritis improved, her transaminases remained elevated. Additional history revealed that the patient had episodes of shakiness, crankiness, and vomiting in the morning before eating breakfast. Fasting laboratory studies revealed hypoglycemia (glucose 55 mg/dL [reference range 70–110 mg/dL] and hyperlipidemia (triglyceride 316 mg/dL [reference range 28–153 mg/dL] and cholesterol 188 mg/dL [reference range 75–200]). Given the clinical picture, a suspicion for GSD III arose, so genetic studies of peripheral blood DNA were undertaken. Although genetic studies were pending, the patient experienced a sudden spike in transaminases on routine testing (ALT 2104 IU/L, AST 1441 IU/L) without any signs of illness or other laboratory abnormalities (total bilirubin 0.5 mg/dL, direct bilirubin 0.2 mg/dL (0.1–0.4), gGTP 142 IU/L, prothrombin time 12.6 seconds (11.5–16.1 seconds), albumin 4.2 g/dL (3.8–5.4 g/dL), and CPK 71 IU/L (29–168 IU/L). A liver biopsy was performed to exclude other etiologies aside from GSD III for this elevation of transaminases. The biopsy revealed enlarged hepatocytes with abundant glycogen-rich material (Fig. 1), and enzymatic analysis of liver tissue revealed absent debranching enzyme activity (0 μmol/min/g tissue [control 0.31 ± 0.1 μmol/min/g tissue]), supporting the diagnosis of GSD III. Of note, there was minimal evidence of hepatocellular injury or inflammation. Subsequently, genetic studies revealed heterozygous mutations in the amylo-1,6-glucosidase (AGL) gene, including a nonsense mutation, c.2590C>T (R864X), previously reported to be causative for GSD type III (1–3), and a potentially pathological missense mutation in a highly conserved tyrosine residue, c.1484A>G (Y495C), not previously associated with GSD type III. During the ensuing 2 years, her serum transaminase levels remained elevated between 300 and 500 IU/L (Fig. 2). Her other biochemical markers of liver disease have remained unremarkable, and she has not developed any clinical stigmata of advanced liver disease. FIGURE 1 Microscopic appearance of GSD III. Left, The hepatocytes are plant-like with clear cytoplasm and prominent cell membranes. The nuclei are small and uniform. Scattered glycogenated nuclei are seen. No cholestasis or significant inflammation is present ... FIGURE 2 Clinical course of GSD III. Serum transaminase levels over time are shown.

Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and economic evaluation

To assess the clinical effectiveness and cost-effectiveness of pegylated interferon alpha (PEG) and non-pegylated interferon alpha (IFN) and ribavirin (RBV) for the treatment of adults with histologically mild chronic hepatitis C (HCV) infection. Electronic bibliographic databases were searched up to July 2005. A systematic review and an economic evaluation were carried out. A Markov state transition model was developed to estimate the cost-effectiveness of treatment strategies for adults with mild chronic HCV. Among the included studies, eight randomised controlled trials (RCTs) of antiviral treatment in mild HCV were identified and included. In general these RCTs were of good quality. The results suggested that effectiveness, particularly with respect to sustained virological response was similar in patients with mild disease to the results obtained in patients with moderate/severe disease. This finding was supported by RCTs reporting the results for mild HCV sub-groups. The authors' cost-effectiveness analysis showed that early treatment compared with watchful waiting is associated with quality-adjusted life-year (QALY) gains but with increased treatment costs. The base-case incremental costs per QALY for 48 weeks of treatment are: watchful waiting with IFN + RBV versus best supportive care = pound 3097-6585; early treatment with IFN + RBV versus watchful waiting with IFN + RBV = pound 5043-8092; watchful waiting with PEG 2a + RBV versus best supportive care = pound 3052; early treatment with PEG 2a + RBV versus watchful waiting with PEG 2a + RBV = pound 5900; watchful waiting with PEG 2b + RBV versus best supportive care = pound 2534; and early treatment with PEG 2b + RBV versus watchful waiting with PEG 2b + RBV = pound 5774. These results were consistent with previous assessments of cost-effectiveness. This systematic review and economic evaluation show that patients with histologically mild HCV can be successfully treated with both pegylated and non-pegylated interferon alpha. Early treatment and watchful waiting strategies are associated with acceptable cost-per-QALY estimates. Research needs to be directed towards newer, potentially more effective interventions, particularly those that improve treatment response in patients with genotype 1, with minimal adverse effects. Further research is required into the natural history of HCV to estimate better the rate of liver disease progression, and also into the effectiveness of non-invasive biochemical markers of liver disease, as an alternative to liver biopsy.

Cirrhosis in hepatitis C virus-infected patients can be excluded using an index of standard biochemical serum markers

ObjectiveAssessment of liver histology is pivotal in prognostication and decision-making regarding therapeutic intervention in patients with chronic hepatitis C virus (HCV). Being an invasive procedure, the liver biopsy is associated with complications, and a non-invasive alternative would be preferable.Material and methodsSera samples from 179 patients with chronic HCV infection collected at the time of liver biopsy were analyzed using routinely available biochemical markers of liver disease, and liver histology was evaluated using the Ishak protocol. The relationship between the serum biochemical markers and cirrhosis (Ishak stage ≥ 5) as well as bridging fibrosis (Ishak stage ≥ 3) was examined.ResultsConclusionsA strong association was found in the multivariate logistic regression analysis between fibrosis stage and aspartate aminotransferase (AST), platelet count and prothrombin-INR (international normalized ratio). An index (the Göteborg University Cirrhosis Index (GUCI)) was calculated using these variables: normalized AST×prothrombin-INR×100/platelet count (×109/l). Using a cut-off value of 1.0, the sensitivity was 80% and the specificity 78% for diagnosis of cirrhosis, and the negative predictive values (NPV) and positive predictive values (PPV) were 97% and 31%, respectively. The GUCI score proved slightly superior for sensitivity, specificity, NPV, PPV, and the area under the receiver operating characteristic (ROC) curve for prediction of cirrhosis and bridging fibrosis compared with the AST to platelet ratio index (APRI), which has been reported as a predictor of significant fibrosis and cirrhosis. An index using routinely available biochemical markers can with a high degree of accuracy discriminate patients with from those without hepatitis C-related cirrhosis.

Natural history of liver disease in cystic fibrosis.

The median age of the population with cystic fibrosis (CF) has increased worldwide, which has led to the suggestion that the prevalence of liver disease would increase. The aim of this study was to evaluate the natural history of CF-associated liver disease over a 15-year period in a well-controlled population of patients with CF. During the years 1976 through 1993, 124 patients were followed up by yearly liver function tests (LFTs). Fifteen patients were followed up with liver biopsies throughout the whole study period. More than 50% of the patients had pathological LFTs in infancy, later being normalized. Approximately 25% of children 4 years of age or older had biochemical markers of liver disease during the study period. In about 10% of the patients, cirrhosis or advanced fibrosis was confirmed at biopsy and 4% of patients had cirrhosis with clinical liver disease. Severe liver disease developed mainly during prepuberty and puberty. Of the 15 patients prospectively followed up with liver biopsies, only 3 had progressive fibrosis. No specific risk factor was identified, but deficiency of essential fatty acids was found more often in patients with marked steatosis (P <.05). No patient developed clinical liver disease in adulthood and the histological changes in the liver biopsies were usually not progressive. Liver disease was no more frequent at the end of the study period although the median age of the patient population had increased. Modern treatment might positively influence liver disease because it seemed less common, less progressive, and less serious than previously reported.

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.

Biochemical markers of liver disease

Biochemical markers of liver disease