Alanine Aminotransferase Threshold Research Articles

Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT

Introduction and ObjectivesEarly diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care. Materials and MethodsAll patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31–41 U/L, 42–54 U/L and ≥55 U/L were compared. Results16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31–41 U/L, 31 (18 %) had ALT 42–54 U/L and 116 (69 %) had ALT ≥55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31–41 U/L, 28 (19 %) had ALT 42–54 U/L and 97 (67 %) had ALT ≥55 U/L. Conclusions33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31–54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care.

Remdesivir Discontinuation Decisions Based on Thresholds of Aminotransferase in an Observational Registry.

Remdesivir is an antiviral approved by the US Food and Drug Administration (FDA) for treatment of coronavirus disease 2019 (COVID-19), and aminotransferase elevation is commonly reported. Thresholds to be considered for discontinuation due to alanine aminotransferase (ALT) elevation differ between the FDA and European Medicines Agency (EMA). The primary objective was to describe aminotransferase thresholds being used in real-world practice for discontinuation of remdesivir in patients with COVID-19, and compare them with labeled recommendations. This study used a descriptive design based on an ongoing national registry of adverse events, the FDA ACMT COVID-19 ToxIC (FACT) pharmacovigilance project, with 17 participating health systems in the USA. Cases were identified retrospectively for an 18-month period (23 November 2020-18 May 2022). Classification of discontinuation as premature and due to aminotransferases was based on chart documentation by the treating team. Of 1026 cases in the FACT registry, 116 cases were included with supplemental data forms completed for aminotransferase elevation with remdesivir, defined a priori for inclusion as ALT doubling or increasing by ≥ 50 U/L. ALT was elevated prior to remdesivir in 47% and increased above baseline during dosing by a median of 92 U/L [interquartile range (IQR) 51-164, max 8350]. Remdesivir was discontinued early in 37 (31.9%) patients due to elevated aminotransferases. The ALT threshold for premature discontinuation was median 200 U/L (IQR 145-396, range 92-5743). Among patients with premature discontinuation of remdesivir for aminotransferase elevation, only 21.6% met FDA criteria to consider discontinuation, and 40.5% met prior EMA criteria to consider discontinuation. In this descriptive study of real-world practice in the USA, clinicians are overall making more conservative treatment decisions than are recommended for consideration in approved drug labeling of discontinuation, with wide variation in the aminotransferase thresholds being used.

Prevalence of Elevated ALT in Adolescents in the US 2011-2018.

The objective of this study is to characterize suspected nonalcoholic fatty liver disease (NAFLD) using elevated alanine aminotransferase (ALT) in a diverse and nationally representative cohort of adolescents and to characterize higher ALT elevation in adolescents with obesity. Data from the National Health and Nutrition Examination Survey 2011-2018 were analyzed for adolescents 12-19 years. Participants with causes for elevated ALT other than NAFLD were excluded. Race and ethnicity, sex, body mass index (BMI), and ALT were examined. Elevated ALT was defined as >22 U/L (females) and >26 U/L (males) using the biologic upper normal limit (ULN). Elevated ALT thresholds up to 2X-ULN were examined among adolescents with obesity. Multivariable logistic regression was used to determine the association of race/ethnicity and elevated ALT, adjusting for age, sex, and BMI. Prevalence of elevated ALT in adolescents was 16.5% overall and 39.5% among those with obesity. For White, Hispanic, and Asian adolescents, prevalence was 15.8%, 21.8%, and 16.5% overall, 12.8%, 17.7%, and 27.0% in those with overweight, and 43.0%, 43.5%, and 43.1% in those with obesity, respectively. Prevalence was much lower in Black adolescents (10.7% overall, 8.4% for overweight, 20.7% for obesity). Prevalence of ALT at 2X-ULN was 6.6% in adolescents with obesity. Hispanic ethnicity, age, male sex, and higher BMI were independent predictors of elevated ALT. Prevalence of elevated ALT in U.S. adolescents is high, affecting 1 in 6 adolescents during 2011-2018. The risk is highest in Hispanic adolescents. Asian adolescents with elevated BMI may comprise an emerging risk group for elevated ALT.

Effect of the change in antiviral therapy indication on identifying significant liver injury among chronic hepatitis B virus infections in the grey zone.

In clinical practice, a substantial proportion of chronic hepatitis B virus (HBV) infections that do not fit into any of the usual immune states are considered to be in the "grey zone (GZ)". This study aimed to investigate the effect of the change in antiviral therapy indication on identifying significant hepatic injury among GZ patients. Patients with chronic HBV infections and a persistent normal alanine aminotransferase (ALT) level (PNALT) who underwent ultrasonography-guided percutaneous liver biopsy were examined retrospectively. Evidenced hepatic injury (EHI) was defined as an inflammation grade ≥2 (≥G2) and/or fibrosis stage ≥2 (≥F2). Complete clinical data, liver inflammation, and fibrosis grades were collected, and the levels of cytokines were detected by the Luminex technique, all of which were analysed to investigate the immune and histopathology states of the liver. A total of 347 patients with chronic HBV infections and PNALT were categorized into immune tolerant (IT, n = 108), inactive HBV surface antigen (HBsAg) carrier (IHC, n = 61), GZ-1 (HBeAg positive in GZ, n = 92), and GZ-2 (HBeAg negative in GZ, n = 68) phases. Among them, 51.3% were in the GZ phase, and 50.1% presented with EHI. The IL-6 levels were higher in the EHI group than in the non-EHI group (2.77 vs. 1.53 pg/ml, Z = -13.32, p = 0.028). The monocyte chemoattractant protein 1 (MCP-1) level was positively correlated with HBV DNA (R = 0.64, p < 0.001) and HBeAg (R = 0.5, p < 0.001) but negatively correlated with fibrosis grade (R = -0.26, p = 0.048). The ratio of EHI in the GZ phase was 60.55%, which was significantly higher than that in patients in the IT (39.8%) and IHC phases (37.7%) (χ2 = 10.4, p = 0.006). A total of 46.69% of all patients exceeded the new ALT antiviral treatment threshold (30 U/L for men and 19 U/L for women). The EHI values in the IT and IHC phases below the new ALT threshold were 32.6% and 37.8%, respectively, whereas higher EHI values of 67.4% and 68.4% were seen in GZ-1 and GZ-2 patients, respectively, exceeding the new ALT threshold, and the difference was statistically significant (χ2 = 11.13, p < 0.001; χ2 = 14.22, p = 0.002). The median age in our cohort was 38.91 years, and only 21.03% were less than 30 years old. The EHI values in the IT and IHC patients <30 years old were 32.4% and 35.8%, respectively, while the ratio of EHI increased to 43.2% once patients were older than 30 years but still in the IT and IHC stages. Setting 30 years old as a cut-off and lowering the ALT threshold could facilitate screening for the presence of significant liver injury, especially for GZ patients. IL-6 was a good indicator of EHI, and MCP-1 was significantly positively correlated with HBV DNA but negatively correlated with liver fibrosis.

Obesity Predicts Liver Function Testing and Abnormal Liver Results.

Abnormal liver function tests in children and young people (CYP) predict a greater burden of liver disease in adulthood, especially in the context of obesity. This study aimed to determine whether obesity and metabolic risk factors predict liver function testing and abnormal liver test results in CYP. This was a retrospective cross-sectional population study using electronic health care records from 257,746 CYP aged 10 to 25 years who were registered with 170 contiguous general practices in London, UK. Demographic and clinical data were extracted, including serum alanine aminotransferase (ALT) tests between 2015 and 2017. BMI category thresholds were adjusted according to age group and ethnicity. Fourteen percent of CYP had ALT measured, of whom 5.4% had abnormal results; 36.3% had BMI indicating overweight or obesity. Nonalcoholic fatty liver disease was the most common liver diagnosis. Multivariate analyses demonstrated that overweight or obesity was an independent predictor of ALT testing in young people (ages 18-25) but not in children (ages 10-17) and of abnormal test results in all CYP, irrespective of ALT threshold. Overweight and obesity are predictors of liver testing (not in children) and abnormal test results, irrespective of ALT threshold. Given the rising prevalence of metabolic dysfunction, a coordinated strategy is needed for liver testing and interpreting results in this young population.

Alanine Aminotransferase Results Differ by Analyzer Manufacturer in a National Integrated Health Setting, 2012-2017.

Disease guidelines specify universal alanine aminotransferase (ALT) thresholds for clinical decision-making, yet the effect of variability among ALT analyzers remains unclear. To compare ALT results from different analyzers from 2012-2017. Veterans Health Administration (VHA) laboratories perform external ALT proficiency testing using standardized College of American Pathologists (CAP) samples in analyzers by 5 manufacturers. In this operational analysis, we evaluated 22 950 ALT values from 80 independent CAP samples tested at 223 laboratories. Using mixed effects modeling, we estimated the association between analyzer manufacturer and CAP outcome, adjusting for manufacturer, facility, and calendar year. We performed subgroup analyses on CAP samples with overall means near clinical guideline-specified thresholds, including less than 50 U/L (n = 10) and less than 35 U/L (n = 5). The VHA used Abbott Laboratories (n = 3175; 14%), Beckman Coulter Diagnostics (n = 8723; 38%), Roche Diagnostics (n = 2595; 11%), Siemens Healthineers USA (n = 5713; 25%), and Vitros/Ortho Clinical Diagnostics (n = 2744; 12%) analyzers. The CAP samples (n = 80 samples, n = 22 950 tests) covered a wide range of mean ALT values (21-268 U/L). The average difference in mean ALT value per sample between the highest-reading and lowest-reading manufacturers was 15.4 U/L (SD = 1.8) for the 10 samples with mean ALT less than 50 U/L, and it was 10.4 U/L (SD = 3.6) overall (n = 80). In linear mixed effects modeling, we found statistically significant differences in ALT values between the different manufacturers in each year. We found statistically and clinically meaningful differences between analyzers across the ALT spectrum in each year, including at ALT levels lower than 50 U/L and lower than 35 U/L. Universal ALT thresholds should be avoided as a trigger for clinical action until differences between analyzers can be resolved.

Comparison of diagnostic accuracy of screening tests ALT and ultrasound for pediatric non-alcoholic fatty liver disease

Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). No direct comparison of these two modalities in children exists. We aimed to compare head-to-head the diagnostic accuracy of ALT and US and their combination for detecting NAFLD in children with obesity. Ninety-nine children with severe obesity underwent simultaneous serum-ALT and abdominal ultrasound (US steatosis score 0–3). Proton magnetic resonance spectroscopy was used as reference standard for detecting steatosis/NAFLD. ROC curve analyses were performed to determine diagnostic performance and to determine optimum screening cut-points aiming for a specificity ≥ 80%. The area under the ROC (AUROC) of ALT and US were not significantly different (0.74 and 0.70, respectively). At the optimal ALT threshold (≥40 IU/L), sensitivity was 44% and specificity was 89%. At the optimal US steatosis score (≥ 2), sensitivity was 51% and specificity was 80%. Combining ALT and US did not result in better accuracy than ALT or US alone.Conclusion: ALT and US have comparable and only moderate diagnostic accuracy for detecting hepatic steatosis in children with obesity. A stepwise screening strategy combining both methods does not improve diagnostic accuracy.What is Known:• Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD).• ALT and ultrasound have mediocre accuracy in detecting steatosis in children with obesity.What is New:• In a head-to-head comparison, the difference in diagnostic accuracy of ALT and ultrasound in detecting steatosis is not significant.• A stepwise screening strategy combining both methods does not improve diagnostic accuracy.

Diagnostic accuracy of serum alanine aminotransferase as biomarker for nonalcoholic fatty liver disease and insulin resistance in healthy subjects, using 3T MR spectroscopy.

Recognition of the close relationship of nonalcoholic fatty liver disease (NAFLD) with diabetes mellitus 2, obesity, metabolic syndrome, and cardiovascular disease has stimulated growing interest in NAFLD as a public health problem. Serum alanine aminotransferase (ALT) has been proposed as a marker of NAFLD, but levels are within the range currently considered “normal” in a large proportion of NAFLD subjects.The aim of the study was to determine the diagnostic accuracy of serum ALT for identifying individuals with NAFLD, using 3-Tesla (T) magnetic resonance spectroscopy (1H-MRS).A cross-sectional study was conducted in 129 healthy subjects. Liver triglyceride content was quantified by 1H-MRS. NAFLD was defined as liver triglyceride content greater than 5.56%.Liver triglyceride content was >5.56% in 79 participants (NAFLD) and lower in the remaining 50 (normal). Serum ALT levels correlated positively with liver triglyceride content (r = 0.58, P < .001), Homeostatic Model Assessment for Insulin Resistance (r = 0.32, P < .01), and fasting insulin (r = 0.31, P < .01), and inversely correlated with adiponectin (r = 0.35, P < .01) and high-density lipoprotein cholesterol (r = 0.32, P < .01). Regression analysis showed that serum ALT was the best predictor of NAFLD (P < .01). Optimal serum ALT cut-off to predict NAFLD was 23 IU/L (area under receiver-operating characteristic curve: 0.93; sensitivity: 0.94; specificity: 0.72).This study shows that serum ALT is a sensitive and accurate biomarker of NAFLD if the “normal” ALT value is revised and established at a lower level. An ALT threshold of 23 IU/L identified 94% of individuals with NAFLD in the present series, using 3-T 1H-MRS for liver triglyceride quantification.

Shenfu decoction as adjuvant therapy for improving quality of life and hepatic dysfunction in patients with symptomatic chronic heart failure

Ethnopharmacological relevanceShenfu decoction (SFD) is a water extract of the dried root or root stalk of Panax ginseng C. A. Mey (Asian ginseng) and the lateral root of Aconitum carmichaeli Debx (prepared by Fuzi, Heishunpian in Chinese). It has been used to treat heart failure for over a thousand years. The main active components of SFD, ginsenosides and higenamine, enhance heart contractility, increase the coronary blood supply, improve ischemic myocardial metabolism, scavenge free radicals and protect myocardial ultrastructure. Aim of the studyTo investigate the effect of SFD on quality of life (QOL) and hepatic function in symptomatic chronic heart failure (CHF) patients. Materials and methodsForty patients enrolled in the study were randomized into two groups: an SFD group (18 cases) and a control group (22 cases). All the patients received standard heart failure therapy, and the SFD group patients were also treated with Shenfu granules for 14 days as an adjunctive therapy. The effects of SFD on QOL, plasma alanine aminotransferase (ALT) level, cardiac function, left ventricular ejection fraction (LVEF) and tumor necrosis factor-α (TNF-α) level were studied. ALT threshold in hepatic injury are 21U/L for men and 17U/L for women. ResultsMinnesota Living with Heart Failure Questionnaire (MLHFQ) scores were improved by 35.27±10.72 vs. 23.87±11.96 in the SFD and control groups respectively (p<0.01). Subgroup analysis of the MLHFQ results demonstrated that both physical and emotional scores were significantly higher in the SFD group (21.00±5.66 vs. 16.75±6.25, p<0.05; 4.64±4.84 vs. 1.13±2.85, p<0.05). Circulating ALT was significantly decreased by SFD (13.3IU/L vs. 0.6IU/L, p<0.01). The grading of cardiac function and LVEF were increased by 1.6±0.5 vs. 1.1±0.3 and 18%±13% vs. 8%±8% in the SFD and control groups respectively (p<0.05 and p<0.05). The level of TNF-α declined more in SFD than control group (64.8±5.0 to 57.6±4.1, p<0.05; vs. 61.6±5.9 vs. 57.7±3.2. p>0.05). ConclusionCompared with standard heart failure treatment, oral SFD as an adjuvant therapy significantly improved QOL and hepatic injury in CHF patients.

A proposed modification to Hy's law and Edish criteria in oncology clinical trials using aggregated historical data

Identifying drug-induced liver injury is a critical task in drug development and postapproval real-world care. Severe liver injury is identified by the liver chemistry threshold of alanine aminotransferase (ALT) >3× upper limit of normal (ULN) and bilirubin >2× ULN, termed Hy's law by the Food and Drug Administration. These thresholds require discontinuation of the causative drug and are seldom exceeded in most patient populations. However, because maintenance of therapy is critical in the treatment of advanced cancer, customized thresholds may be useful in oncology patient populations, particularly for those with baseline liver chemistries elevations. Liver chemistry data from 31 aggregated oncology clinical trials were modeled through a truncated robust multivariate outlier detection (TRMOD) method to develop the decision boundary or threshold for examining liver injury in oncology clinical trials. The boundary of TRMOD identified outliers with an ALT limit 5.0× ULN and total bilirubin limit 2.7× ULN. In addition, TRMOD was applied to the aggregated oncology data to examine fold-baseline ALT and total bilirubin, revealing limits of ALT 6.9× baseline and bilirubin 6.5× baseline. Similar ALT and bilirubin threshold limits were observed for oncology patients both with and without liver metastases. These higher liver chemistry thresholds examining fold-ULN and fold-baseline data may be valuable in identifying potential severe liver injury and detecting liver safety signals of clinical concern in oncology clinical trials and postapproval settings while helping to avoid premature discontinuation of curative therapy.

Upper normal threshold of serum alanine aminotransferase in identifying individuals at risk for chronic liver disease

Serum alanine aminotransferase (ALT) is an easily available, low-cost screening tool for detecting silent chronic liver disease. Recent studies have suggested that the currently accepted healthy ALT thresholds be lowered. In this retrospective cross-sectional study, we determined upper thresholds for ALT values in a nationally representative healthy cohort (n = 3337) from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV). Sensitivity and specificity of the currently used ALT threshold (40 IU/L, regardless of gender) was compared against study-derived, gender-specific ALT thresholds for detecting individuals at risk for chronic liver disease in 27 913 health check-up participants. The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free KNHANES participants were 34 IU/L for men and 25 IU/L for women. The prevalence of ALT elevation among health check-up participants was 11.0% in currently used thresholds, and increased to 22.6% with study-derived, gender-specific thresholds. Of the population who were additionally defined to have elevated ALT levels under new ALT threshold, 65.7% were at risk for chronic liver disease. Sensitivity for detecting individuals at risk for chronic liver disease improved from 18 to 33% with new thresholds whereas a trade-off in specificity (from 96 to 88%) was observed. It is recommendable to lower the current ALT thresholds to better identify individuals at risk for chronic liver disease.

Large‐scale population analysis reveals an extremely low threshold for “non‐healthy” alanine aminotransferase that predicts diabetes mellitus

Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM. We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years. Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ∼55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels. Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either 'normal' or 'healthy', with the later reflecting much lower values, above which an individual is at increased risk for DM.

Estimation of the healthy upper limits for serum alanine aminotransferase in Asian populations with normal liver histology

A recent study in young Italian subjects suggested that the healthy thresholds for serum alanine aminotransferase (ALT) levels should be adjusted to 30 IU/L for men and 19 IU/L for women when assessing risk factors for nonalcoholic fatty liver disease. Our aim was to assess serum ALT concentrations in healthy Korean individuals and to determine the factors affecting ALT levels in these populations. We included 1,105 potential liver donors (643 men and 462 women) with biopsy-proven normal livers. Median ages were 25 years in men and 30 years in women, with a median body mass index (BMI) of 22.3 kg/m(2) in men and 21.4 kg/m(2) in women. The calculated thresholds for ALT values in these subjects were 35 IU/L for men and 26 IU/L for women. Age and BMI were independently correlated with ALT levels in both sexes, whereas serum total cholesterol concentration was significant only in men and blood glucose level only in women (P < 0.05). When we chose a subgroup of 665 individuals (346 men and 319 women) using Prati criteria, modified by the BMI cutoff points for Asians (<23 kg/m(2)), we found that the healthy ALT values were 33 IU/L for men and 25 IU/L for women. The mean ALT concentrations for subjects within the Prati criteria were significantly lower than for those outside the criteria (16.7 versus 19.5 IU/L for men, 12.8 versus 14.9 IU/L for women; P < 0.001). The healthy ALT thresholds in biopsy-proven normal Asians were clearly lower than the previously accepted thresholds, as has also been noted in Europeans. Age, BMI, and/or other metabolic parameters significantly affect ALT levels, even in subjects with normal livers.

Blunt abdominal trauma in children: how predictive is ALT for liver injury?

Background:The liver is the second most commonly injured intra-abdominal organ in children. CT scanning is currently regarded as the “gold standard” in screening for intra-abdominal injury following blunt trauma. However,...

Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States

In the United States, elevated serum alanine aminotransferase (ALT) activity in the absence of viral hepatitis or excessive alcohol consumption is most commonly attributed to nonalcoholic fatty liver disease (NAFLD). NAFLD is related to predictors of coronary heart disease (CHD) such as insulin resistance and central obesity. We examined the association between elevated serum ALT activity and the 10-year risk of CHD as estimated using the Framingham risk score (FRS). We performed a cross-sectional analysis comparing participants in the Third National Health and Nutrition Examination Survey with normal and elevated ALT activity (>43 IU/L), examining the mean levels of FRS. Among participants without viral hepatitis or excessive alcohol consumption, those with elevated ALT activity (n=267) had a higher FRS than those with normal ALT activity (n=7259), both among men (mean difference in FRS 0.25, 95% CI 0.07-0.4; hazard ratio for CHD 1.28, 95% CI 1.07-1.5) and women (mean difference in FRS 0.76, 95% CI 0.4-1.1; hazard ratio for CHD 2.14, 95% CI 1.5-3.0). The ALT threshold for increased risk of CHD was higher in men (>43 IU/L) than in women (>30 IU/L). Elevated ALT activity was not associated with higher FRS among nonobese participants with viral hepatitis or excessive alcohol consumption. In condusion, individuals with elevated serum ALT activity in the absence of viral hepatitis or excessive alcohol consumption, most of whom have NAFLD, have an increased calculated risk of CHD. This association is more prominent in women.

Predictive value of ALT levels for histologic findings in chronic hepatitis C: A European collaborative study

The aim of this retrospective study was to determine the predictive value of alanine aminotransferase (ALT) levels for histologic findings in patients with chronic hepatitis C virus (HCV) infection. Data on 864 HCV RNA–positive patients were collected. ALT values were obtained at the time of biopsy (before treatment), and normal ALT values were defined as normal values obtained at serial evaluations during a 6-month period. Histologic results were scored using the METAVIR system. Among all patients, 99% of those with elevated ALT levels had a score of at least F1 (positive predictive value [PPV], 99%) and 88% had a score greater than A1F1. Among patients with persistently normal ALT values, 65% had a score of at least F1 (negative predictive value [NPV], 35%) and 26% had a score greater than A1F1. The receiver operating characteristics analysis indicates that the ALT threshold for the best compromise sensitivity-specificity was about 2.25 times the upper limit of normal (ULN). In conclusion, almost all HCV RNA–positive patients with elevated ALT levels have some degree of fibrosis. However, an important proportion of patients with persistently normal ALT levels also show some histologic signs of fibrosis; the degree of fibrosis is usually mild but is sometimes more marked, and in rare cases cirrhosis may be present. In this subset of patients, the indication of liver biopsy and the potential benefit of therapy need to be further evaluated. These results suggest the need to revisit the algorithm for liver biopsy practice. (H EPATOLOGY 2002;36:973-977.)

Should Donor Blood Be Screened for Elevated Alanine Aminotransferase Levels?

We examined the cost-effectiveness of alanine aminotransferase (ALT) screening of donor blood to prevent non-A, non-B posttransfusion hepatitis. Based on estimated costs of ALT screening, blood replacement, and medical evaluation of donors with high ALT levels, we concluded that screening at an ALT level of 45 IU would cost $3.82 per unit. In a population requiring an average of 3.7 units per transfusion, one case of hepatitis would be prevented for every 115 units screened, resulting in a cost of $439 per case prevented. With an estimated direct medical cost of $1,181 per case of non-A, non-B hepatitis, expected net savings for each case prevented would be $742. Screening at other ALT thresholds would be less cost-saving. Sensitivity analyses indicate that screening would be cost-saving for a wide range of cost estimates and number of units per transfusion. Alanine aminotransferase screening is warranted until more sensitive and specific screening tests for transmissibility of non-A, non-B hepatitis become available.