Abnormal ALT Values Research Articles

Methotrexate Monitoring in Dermatology: A Follow-Up Retrospective Cohort Study

Introduction: There have been no large-scale studies looking at the efficacy and safety of methotrexate. Prior research by our team investigated whether certain monitoring practices were associated with lab abnormalities resulting in clinically relevant events (CREs) within the first 90 days of methotrexate treatment and concluded that dermatologists may consider postponing lab monitoring until 15 days after methotrexate initiation in patients without concerning baseline disease. This follow-up study was performed to determine when within the first 90 days of treatment CREs were most likely to occur and to define the specific numeric values at which abnormal labs resulted in a CRE.
 Methods: The medical records of 243 dermatology patients were retrospectively reviewed.
 Results: Week 11 had the highest percentage of CREs (11.1%, p=0.00003), with slight peaks at weeks 2 and 5. ALT (22%) and AST (27%) were the most commonly abnormal labs, and elevated ALT (p=0.00087) and AST (p=0.03) values were significantly higher in CREs.
 Discussion: This data suggests that lab frequency can be reduced within the first few months; optimal timing of lab draws may be around weeks 2-5 and 11-12. In summary, we found that 1) abnormal labs most frequently led to a CRE at week 11 of monitoring, 2) ALT and AST were the most frequently abnormal labs, and 3) abnormal ALT and AST values were significantly higher in patients with CREs. This study provides valuable insight into an understudied dermatologic topic and hopefully will inform clinicians regarding methotrexate laboratory monitoring and spur further investigation.

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients' outcomes: a single-center Greek study.

BackgroundAbnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized.MethodsA total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded.ResultsOn admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003).ConclusionsElevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.

From the Editor’s Desk...

From the Editor’s Desk...

Ficolin-2 a newmarker for severity of liver inflammation in patients with chronic hepatitis C

Background: ficolin-2 is a kind of human serum complement lectin with a structure similar to mannan-binding lectin (MBL) and it has been implicated in innate immunity. Recent studies have shown that complement pathway activation may contribute to hepatitis. However, the relationship between ficolin-2 and viral hepatitis remains largely elusive. Aim of the work: this study aimed to determine the dynamics of ficolin-2 in patients with chronic hepatitis C. Patients and Methods: Thirty patients who had not yet received therapy and twenty normal control subjects were included in this study. A sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the ficolin-2 concentrations in all serum samples of patients and 20 healthy donors. Results: we found that the concentrations of ficolin-2 were significantly higher in chronic hepatitis C patients with abnormal ALT values than in chronic hepatitis C patients with normal ALT values and healthy controls. Ficolin-2 concentrations in chronic hepatitis C patients with abnormal ALT values were positively correlated with ALT levels (*P 0.05). Conclusion: our findings suggested that early increased ficolin-2 is highly correlated with hepatic inflammation and rapid viral response.

Ficolin-2 a newmarker for severity of liver inflammation in patients with chronic hepatitis C

Background: ficolin-2 is a kind of human serum complement lectin with a structure similar to mannan-binding lectin (MBL) and it has been implicated in innate immunity. Recent studies have shown that complement pathway activation may contribute to hepatitis. However, the relationship between ficolin-2 and viral hepatitis remains largely elusive. Aim of the work: this study aimed to determine the dynamics of ficolin-2 in patients with chronic hepatitis C. Patients and Methods: Thirty patients who had not yet received therapy and twenty normal control subjects were included in this study. A sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the ficolin-2 concentrations in all serum samples of patients and 20 healthy donors. Results: we found that the concentrations of ficolin-2 were significantly higher in chronic hepatitis C patients with abnormal ALT values than in chronic hepatitis C patients with normal ALT values and healthy controls. Ficolin-2 concentrations in chronic hepatitis C patients with abnormal ALT values were positively correlated with ALT levels (*P 0.05). Conclusion: our findings suggested that early increased ficolin-2 is highly correlated with hepatic inflammation and rapid viral response.

Seroprevalence of hepatitis E in HIV infected patients in Greece.

HEV infection is an emerging public health problem worldwide Data concerning HEV infection in HIV+ patients in Greece is scare. The aim of the study was to determine HEV seroprevalence in patients with HIV infection in Greece. We studied 243 HIV(+) patients 214 men (88%) and 29 women (12%) with a median age of 45 years (range 19-83) who attended the HIV unit of Pathophysiology Department of Laikon General Hospital in Athens for the presence of anti-HEV IgG antibodies with (EIA) (EIA HEV IgG, Adaltis, Rome, Italy Eighteen/243 patients (7.3%) were positive for HEV IgG antibodies, a seroprevalence that was not different from that described for the blood donors group from Greece There was no difference of the presence of HbsAg, hepatitis C and hepatitis A between the HEV(+) and HEV(-) patients. There was no statistically significant difference between the HEV(+) and HEV(-) group in terms of HIV acquisition, sexual orientation, median duration of HIV infection, ART treatment, or duration of ART. Only the median age of HEV(+) was 52 years (35-78) while that of HEV(-) was 44 years (19-83)(P = 0.03). Only 2/18(11.1%) HEV(+) HIV(+) patients had abnormal ALT and AST values. The seroprevalence of hepatitis E in HIV(+) patients in Greece seems to be the same with that of the general population thus implying that HIV infection is not a risk factor for HEV infection and only age shows a positive correlation with seropositivity.

Cannabinoid receptor 2-63 QQ variant is associated with persistently normal aminotransferase serum levels in chronic hepatitis C.

Background and AimTo evaluate in anti-HCV-positive patients the clinical impact of the rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R).Patients and Methods253 consecutive anti-HCV-/HCV-RNA-positive patients were enrolled, of whom 53 were HCV carriers with persistently normal ALT (PNALT group) and 200 had a history of steadily abnormal serum ALT values (abnormal ALT group). All patients were naive for antiviral therapy and were screened for the CNR2 rs35761398 polymorphism by a TaqMan assay.ResultsSubjects in the PNALT group, compared with those in the abnormal ALT group were older (58.5±12 vs. 50.7±12.4 years, p = 0.001), more frequently female (66% vs. 42%, p = 0.003), with lower body massindex (BMI) (24.5±3.1 vs. 26.6±4.6, p = 0.003), and more frequently with HCV genotype 2 (43.1% vs 17.7%, p = 0.0002) and CB2-63 QQ variant (34% vs. 11%, p = 0.0001). Considering all 253 patients, no difference in the demographic, biochemical, or virological data was observed between patients in the different CB2-63 variants. The logistic regression analysis identified CB2-63 QQ, HCV genotype 2, older age and lower BMI as independent predictors of PNALT (p<0.00001).DiscussionThe CB2-63 QQ variant in HCV patients was independently associated with the PNALT status.

Epidemiological, clinical and laboratory features of chronic hepatitis B infection in a cohort of immigrant and Italian patients from Ferrara, Italy

Background. Italy has recently become a land of immigration. Two hundred and fifty thousand carriers are immigrants and chronic HBV infection is the prevalent form. Considering the elevated number of foreigners resident in our province and the potential risk of transmission to local people, we retrospectively investigated the patterns of chronic hepatitis B (CHB) in 154 patients (76 foreigners, 78 Italians) observed in our Institution, with regard to demographic and clinical/laboratory characteristics.Results. The immigrants were younger (mean age 31 years) compared to Italians (51.5) and mainly came from East Europe. Regarding exposure to HBV, the intra-familial risk factor was most frequently observed in foreigners, compared to Italians (p = 0.03). Foreigners also showed a higher prevalence of HBeAg positive forms, HDV co-infection (7.9%) and abnormal ALT and/or HBV-DNA values, compared to Italians. HBeAg positivity was more associated with increased ALT (OR = 36.6, p = 0.001) than with elevated HBV viremia (OR = 6.5, p = 0.049); age was a protective factor (OR = 0.1; p = 0.014). No significant association was found between increased ALT and foreign nationality. The simultaneous presence of increased ALT and viremia was more frequent among foreigners, (OR = 7.6, p = 0,014) and increased with age (OR = 1.06, p = 0.013). Antiviral therapy was given in 7.8% of foreign citizens.Conclusion. Immigrants constitute a vulnerable population subgroup that would benefit from a more active approach regarding doctor-patient relationship for early recognition of HBV and treatment programmes.

Impact of nucleic acid amplification technology (NAT) in Italy in the three years following implementation (2001-2003).

The use of NAT technology to screen blood donations in Italy became mandatory on 28 June 2002, but had been available experimentally since 2001. During the transition period, an EIA test to detect hepatitis C core antigen (HCVcoreAg) had also been permitted. Considering the large number of blood transfusion centres in Italy, an initial reorganisation of the biological validation of blood units was necessary, with a partial centralisation of NAT testing. The Gruppo Italiano per lo Studio delle Malattie Trasmissibili con la Trasfusione (Italian Group for the Study of Transfusion-Transmissible Diseases) conducted a national survey evaluating NAT testing, based on an annual collection of data through a questionnaire sent to all centres. In the first three years of the investigation, 219 blood transfusion centres returned the questionnaires. In the period between January 2001 and December 2003, 3 894 894 blood donations were investigated for HCV RNA and 2 186 468 for HIV RNA. Of these, 12 were found to be HCV RNA positive and four HIV RNA positive, with an observed NAT versus antibody-based assay yield of 3.1/106 donations for HCV and 1.8/106 donations for HIV, respectively. Five of the 12 HCV RNA positive and anti-HCV negative donors had abnormal ALT values and their donations would have been discarded even in absence of NAT testing. Thus the final NAT yield for HCV is 1.79/106. The residual risk for HCV or HIV transmission by blood transfusion after NAT implementation is currently estimated to be extremely low in Italy.

Prevalence of liver complications in pediatric patients on home parenteral nutrition: indications for intestinal or combined liver-intestinal transplantation

Parenteral nutrition (PN) is the only treatment for patients affected by chronic intestinal failure (CIF). Home parenteral nutrition (HPN) programs are started when patients need prolonged PN. Unfortunately, many patients on prolonged PN develop liver disease (LD). The aim of our study was to assess the prevalence of LD in our series of patients on HPN. We reviewed our records of patients discharged from the hospital on HPN for CIF. HPN was started when one parent was fully trained in the use of this treatment and if the social and familial home environment was reliable. All patients received total PN by a central venous catheter. All patients with abnormal AST, ALT, ALK, γGT, and bilirubin values for more than 3 months were considered affected by PN-related LD. Thirty-six patients (23 of whom were boys and 13 girls) were discharged on HPN. During the study period, for CIF, 16 were affected by short bowel syndrome (SBS), of whom 6 had ultra-short bowel; 16 with functional intestinal failure, and 4 with chronic intestinal pseudobstruction (CIPO). Mean duration of HPN was 2.1 years/patient. Nine of 36 patients (25%) on HPN for CIF showed LD. Seven of the 16 patients (43%) with LD were affected by SBS and 2 (12.5%) patients by functional intestinal failure. No patients with CIPO developed LD. In patients affected by SBS, the onset of LD was very earlier than in patients with ID.

Risk factors for antituberculous chemotherapy-induced hepatotoxicity in Japanese pediatric patients.

Our objective was to clarify risk factors associated with the development of severe hepatotoxicity during antituberculosis chemotherapy in Japanese children. In a retrospective analysis in a 350-bed referral children's hospital in a metropolitan area, the medical charts of all pediatric patients who received antituberculosis chemotherapy between January 1995 and November 1999 were surveyed. Univariate and multivariate analyses were performed to find any demographic parameters (ie, sex, age, height, and body weight), clinical characteristics (ie, nutritional or developmental status, co-infection with hepatitis viruses [B or C] or human immunodeficiency virus, presence of extrapulmonary tuberculosis, or medical history of liver disease), or individual antituberculosis agents used that would be associated with the likelihood of development of severe hepatotoxicity during antituberculous chemotherapy. Severe hepatotoxicity (defined as an elevation of ALT and AST levels that were greater than 5 times the respective reference values) was attributed to the chemotherapy when it developed in children with normal pretreatment values for these parameters and no other potential causes were identified. Those who had abnormal ALT or AST values before treatment were excluded from analysis. Among the 117 patients surveyed (58 males and 59 females; age range, 0 to 16 years), 18 were excluded from the analysis because of abnormal baseline ALT and AST values. Severe hepatotoxicity developed in 8 of the 99 eligible children, and all 8 of those children were younger than 5 years old. The univariate analysis revealed that the children in whom hepatotoxicity developed were significantly (P <.05) younger, were predominantly male, had extrapulmonary tuberculosis, and were given pyrazinamide more often than those who had no hepatotoxicity. However, the multivariate logistic regression analysis revealed that only age and the administration of pyrazinamide would have a significant contribution (P <.05) to the development of severe hepatotoxicity, with odds ratios of 143 (95% confidence interval, 4.2 to 4934.9) and 0.60 (95% confidence interval, 0.39 to 0.90), respectively: the estimated probability of development of hepatotoxicity in a typical pediatric patient at 1, 5, and 10 years receiving pyrazinamide with rifampin (INN, rifampicin) and isoniazid would be 0.95, 0.72, and 0.16, respectively. This study indicated that intensive monitoring of hepatotoxicity should be performed for younger children (<5 years) receiving pyrazinamide for antituberculosis chemotherapy.

Effects of interferon alpha 2a on incidence of hepatocellular carcinoma in chronic active hepatitis without cirrhosis. Hepatitis Treatment Study Group.

To determine the incidence of hepatocellular carcinoma among patients with chronic hepatitis C who received interferon (IFN) therapy, 63 patients with chronic hepatitis C who underwent IFN therapy (IFN alpha 2a 9 x 10(6) IU daily for 2 weeks and followed 9 x 10(6) IU three times weekly for 14 weeks) from January to December 1992, were studied. Selection criteria were as follows: within six months before IFN therapy patients were diagnosed with chronic active hepatitis without cirrhosis by hepatic histological examination, and were hepatitis C virus antibody positive. Furthermore, patients had records of follow-up liver function tests (once a month) for more than six months after IFN therapy completion, and of ultrasound scanning (once in three to four months) before and for at least more than six months after the therapy completion. An average period of observation was 2.7 years (0.6 to 3.8 years). Twenty five of 63 patients (39.7%) returned to normal values of serum ALT, whereas 38 of 63 (60.3%) still showed abnormal values at six months after IFN therapy completion. Nine of 63 (14.2%) and 6/63 (9.5%) developed cirrhosis and hepatocellular carcinoma, respectively. All patients who developed cirrhosis and hepatocellular carcinoma were from those (n = 38) that showed abnormal ALT values after therapy completion. The five of six patients that progressed to hepatocellular carcinoma were associated with cirrhosis. No patients who returned to normal ALT values developed hepatocellular carcinoma during the period of observation. These results suggest that IFN therapy is effective to prevent the development of hepatocellular carcinoma.

Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia

A prospective study has been made of the incidence of changes in transaminase levels, hyperkalaemia and thrombocytopenia in three groups of patients: 89 consecutive patients with venous thrombosis receiving therapeutic heparinization, 49 patients admitted because of hip fracture and receiving prophylactic low-dose conventional heparin, and 43 patients admitted because of hip fracture and randomly allocated to receive low molecular weight heparin. Laboratory measurements were made on admission and 8 days after commencing heparin. Only two patients on high-dose heparin developed thrombocytopenia. Increased transaminases were frequent with conventional heparin (18% and 32% of patients on high-dose heparin developed abnormal AsT and AlT values, respectively compared with 14% and 17% patients on low dose therapy). In contrast, only one patient on low molecular weight heparin developed abnormal AlT activity. Hyperkalaemia was uncommon in patients on any form of heparin therapy, and severe hyperkalaemia occurred in only one patient.

The high risk of chronic liver disease in multitransfused juvenile hemophiliac patients

Eighty-seven asymptomatic children with either hemophilia A or B were treated before they were 21 years of age. Seventy-two received factor concentrates and 15 cryoprecipitate or fresh-frozen plasma only. Thirty-two of the 72 in the former group have persistently elevated alanine aminotransferase values compared to one of 15 in the latter group. In a subset of children treated with factor concentrates before five years of age, four of seven are chronically HBsAg positive. Liver biopsies were performed in 13 of the 32 asymptomatic patients with abnormal ALT values in the fraction group. It is recommended that until further data become available, children with mild hemophilia and all less than 5 years of age should receive only cryo or FFP.