Median Alanine Aminotransferase Research Articles

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma - An Observational Study from Taiwan.

Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear. In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns. One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses. Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.

Sandfly Virus Infection in Adana, Türkiye.

We described the clinical and laboratory characteristics of the patients infected by sandfly viruses between August and September 2008 in Adana, Türkiye. The immunofluorescence antibody test (EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany) was used for diagnosis. Antibodies of immunoglobulin M (IgM) type against Cyprus and Sicily species of phleboviruses were detected in 15 patients. In one patient, IgM antibodies against Naples and Tuscany species were found to be positive. The mean age of the patients was 28, and 47% was female. The most common symptoms were myalgia, fatigue, fever, and arthralgia. The mean duration of fever was four days, and the mean duration of the symptoms was 7-10 days. The median platelet count was 137,000/mL, the median white blood cell count was 3040/mL, the median aspartate transaminase (AST) was 57 (22-1251) IU/L, the median alanine transaminase (ALT) was 71 (17-1137) IU/L, the median creatinine kinase was 314 (33-4638) IU/L, and the median lactate dehydrogenase (LDH) was 193 (111-490) IU/L. The sandfly virus infections should be differentiated from similar viral infectious diseases such as Crimean-Congo hemorrhagic fever.

Changing Epidemiology of Chronic Hepatitis C: A University Hospital Experience

Background: Hepatitis C virus (HCV) infection remains a significant public health problem worldwide, with varying epidemiological trends over time necessitating continual surveillance and intervention strategies. Objectives: This retrospective study aimed to examine trends in demographics, transmission routes, and disease characteristics among 635 patients diagnosed with HCV infection between 2003 and 2023. Methods: Data on demographics, HCV RNA levels, liver enzymes, genotype distribution, and transmission routes were retrospectively analyzed. The study period was divided into four segments for detailed analysis. Results: There was a gradual increase in the diagnosed cases over the study period, particularly noticeable after 2012. The mean age at diagnosis remained stable from 2003 - 2007 to 2008 - 2012 but decreased significantly in the following years (P = 0.001). Male predominance was observed throughout the study, with a notable increase in the male/female ratio over time (P &lt; 0.001). Intravenous drug use (IVDU) emerged as the predominant transmission route, reaching 68.3% in 2018 - 2022 (P &lt; 0.001). The prevalence of incarceration history among patients increased significantly, reaching 24.6% in 2018 - 2022 (P &lt; 0.001). Disease characteristics varied between periods; median HCV RNA levels were highest in 2018 - 2022, and median alanine aminotransferase (ALT) levels differed significantly between periods (P = 0.001). The genotype distribution showed a shift over time, with genotype 1 predominating initially and genotypes 3, 4, and 5 becoming more prevalent in later years (P &lt; 0.001). Conclusions: This study highlights the dynamic changes in hepatitis C epidemiology over two decades in southern Turkey, highlighting the increasing burden in younger populations, the increasing prevalence of IVDU as a transmission route, and the changing genotype distribution.

Investigating hemolysis, elevated liver enzymes and low platelet count in preeclampsia: A case-control study in Ghana.

Preeclampsia poses a heightened risk for women, particularly in the development of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, leading to adverse outcomes for both mothers and newborns. The incidence of HELLP syndrome tends to be notably higher among women with preeclampsia compared with those with normotensive pregnancies. However, there is a dearth of research on the frequency of HELLP syndrome within the context of preeclampsia specifically in Ghana. Furthermore, the potential predictive value of serum erythrocyte adenylate kinase (EAK), a marker of hemolysis, in anticipating the onset of preeclampsia remains largely unexplored. Conducted between May 2020 and April 2022, this research employed a case-control methodology at the War Memorial and Upper East Regional Hospitals. A total of 291 pregnant women participated, comprising 111 diagnosed with preeclampsia and 180 control subjects, aged between 18 and 43 years. Venous blood samples were collected and subjected to analysis for platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and EAK, utilizing automated analyzers, alongside the ELISA technique. Diagnosis of HELLP syndrome was established using the Mississippi triple-class definition. The median serum ALT level (with interquartile range) was significantly elevated in the preeclampsia group compared with controls [20.0 (13.7-27.0) vs. 13.0 (9.4-18.6); p < 0.001]. Moreover, the frequency of Mississippi class 3 HELLP syndrome was notably higher among preeclampsia cases (2/111; 1.8%) compared with controls (1/180; 0.6%). Serum ALT emerged as the superior predictor of preeclampsia, outperforming LDH (with an area under the curve of 0.73 compared with 0.58). The sensitivity and specificity of ALT were measured at 47.8% and 87.2%, respectively. Although the occurrence of HELLP syndrome in preeclampsia cases appears relatively low, it may escalate as the prevalence of preeclampsia is anticipated to rise in low and middle-income nations.

Low serum alanine aminotransferase (ALT) levels are associated with poor outcomes in acute ischemic stroke patients regardless of age

Studies have indicated that reduced serum ALT levels are commonly linked to aging and are known to predict poor outcomes in many clinical conditions as potential frailty indicators. There are close connections between the brain and peripheral organs, particularly the liver. In patients with acute ischemic stroke (AIS), the interactive effects may change ALT levels, which in turn influence stroke outcomes. Whether ALT has potential neuroprotective effects or is an indicator of frailty in AIS patients remains unknown.This retrospective analysis examined 572 AIS patients in Beijing Luhe Hospital between August 2020 and June 2021. Patient demographics and laboratory results were assembled. The National Institutes of Health Stroke Scale (NIHSS) was used to analyze stroke severity. Modified Rankin Score (mRS) determined stroke outcome 3 months after AIS, with mRS≤2 indicating a favorable outcome. Based on serum ALT measurements, patients were classified into three tertiles (T1-T3). Binary logistic regression analysis evaluated the correlation between ALT tertiles and AIS outcomes.Of the patients, 66 exhibited unfavorable outcomes. The median ALT level in this group was 13 (IQR: 11–18.25), which was lower than in the favorable outcomes cohort (16; IQR: 11–22). A decline in ALT corresponded with a higher incidence of poor outcomes at 3 months (T1, 15.5 %; T2, 11.4 %; T3, 7.0 %; p = 0.03). The lowest ALT tertile (T1) was independently linked to an adverse 3-month outcome (OR 2.50 95 %CI 1.24–5.07, p = 0.038) compared to the highest tertile. ALT levels demonstrated no correlation with age (T1, 62.59 ± 12.64; T2, 64.01 ± 11.47; T3, 65.12 ± 11.27; p > 0.05).Regardless of age, lower serum ALT levels are independently associated with poorer outcomes in AIS patients. This finding suggests the potential pivotal part of the liver in AIS outcomes, highlighting the need to consider both neurological and liver functions post-stroke.

Patterns of acetaminophen toxicity among patients with low-risk serum concentrations.

In 2012, the Commission on Human Medicines mandated lowering the acetaminophen toxicity nomogram treatment threshold in the UK to 100 µg/ml at 4 h post-ingestion. The present study aim was to evaluate biochemical and liver toxicity patterns in patients who presented with acetaminophen overdose and had low serum acetaminophen concentrations (<150 µg/ml). Patients admitted to the emergency department with a clear history of acute acetaminophen overdose with or without other medication or ethanol were consecutively enrolled into this retrospective cohort study. Patients with serum acetaminophen concentration >150 µg/ml or an unknown ingestion time were excluded. Data were extracted from electronic medical records and are presented as mean ± SD or median (interquartile range). A total of 103 patients were included (median age, 17 [4-21] years) and 80 (78%) were female. The median ingested acetaminophen dose was 5000 (2850-7650) mg. At baseline, the median serum acetaminophen concentration was 42 (4.5-64.8) µg/ml, and median alanine aminotransferase and aspartate aminotransferase levels were 22 (17-28) and 27 (16-45) IU/L, respectively. Twenty patients were treated with acetylcysteine, with none developing adverse reactions. No patient developed hepatotoxicity, including patients with initial multiple product ingestion or other risk factors. Patients presenting with an acute acetaminophen overdose with acetaminophen level <150 µg/ml, including patients with other risk factors, are at low risk of hepatotoxicity.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study

BackgroundTo assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.MethodsData of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.ResultsAfter a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15–1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15–1.20), 1.20 (1.18–1.22), 1.69 (1.47–1.93), 1.06 (1.06–1.07), 1.08 (1.07–1.09), 1.81 (1.37–2.39), or 0.29 (0.18–0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43–5.48), 4.03 (2.69–6.03), 1.97 (1.40–2.77), 4.69 (2.98–7.37), 2.51 (1.75–3.59), 2.09 (1.51–2.89), or 2.22 (1.55–3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19–1.41).ConclusionsUnhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

#1799 Liver affliction among women with pregnancy-related acute kidney injury and its impact on fetal and maternal outcome

Abstract Background and Aims Pregnancy-related acute kidney injury (PR-AKI) is a worldwide health challenge that is accompanied by an increased risk of morbidity and mortality in both the mother and the fetus. PR-AKI occurs due to several causes including prerenal (hemorrhage, sepsis, hypovolemia, etc), postrenal and intrinsic renal causes (renal cortical necrosis, acute tubular necrosis, thrombotic microangiopathy [TMA], hemolysis elevated liver enzymes, low platelet count (HELLP) syndrome, preeclampsia/eclampsia, acute fatty liver of pregnancy (AFLP), glomerulonephritis [GN], etc). Hepatic affection in the context of PR-AKI may further compromise the detrimental maternal and fetal outcomes, however this seldom has been studied. Thus, this study aimed to explore the incidence of liver affliction in women with PR-AKI and to investigate its effect on the maternal and fetal outcome. Method This three-year retrospective study included women who presented to Mansoura Nephrology and Dialysis Unit with severe PR-AKI. Patients with stage I, II AKI admitted to obstetric departments were not included in the study. Patients with incomplete data were excluded from the study. The routine laboratory data and fetal and maternal outcomes were obtained from the medical records. Results The study included 77 women with PR-AKI, the mean maternal age was 28 with a minimum of 19 and maximum of 43 years. Twelve patients had hypertension while none of them had diabetes. The causes of PR-AKI are displayed in Fig. 1. Thirty-one patients (40.3%) had liver affliction. Six of them were due to HELLP, three due to underlying liver cirrhosis, one due to AFLP, the remaining cases showed abnormally elevated liver enzymes. White blood cells and INR were significantly higher among women with liver affliction than those without (P = 0.023, 0.003, respectively), while platelets were significantly lower in women with liver affliction (P = 0.002). Patients with liver affliction showed significantly higher median alanine transaminase (99 vs 27) and aspartate transaminase (103 vs 23) than those without (P &amp;lt; 0.001 for both). On the other hand, there were no statistically significant differences between patients with and without liver affliction as regard blood hemoglobin, serum creatinine, quantitative proteinuria, bicarbonate, and gestational age at termination of pregnancy. The studied women with liver affliction experienced lower percentage of renal recovery compared to those without but with no statistical significance (54.8%vs72.5%, P = 0.122). Maternal mortality was significantly more among patients with liver affliction compared to those without (32.3% vs 9.8%, P = 0.017). On the other hand, there was no significant difference between patients with and without liver affection regarding fetal outcome (live birth 55.2% vs 55.6%, P = 0.975) (Table 1). Conclusion Liver affliction is not uncommon problem among women with PR-AKI and it is associated with higher maternal mortality and lower rates of renal recovery.

Limited Sustained Remission After Nucleos(t)ide Analog Withdrawal: Results From a Large, Global, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

Complete viral suppression with nucleos(t)ide analogs (NAs) has led to a profound reduction in hepatocellular carcinoma and mortality among patients with chronic hepatitis B. Finite therapy yields higher rates of functional cure; however, initial hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) elevations are almost certain after treatment interruption. We aimed to analyze off-treatment outcomes beyond 12 months after NA cessation. Patients with well-suppressed chronic hepatitis B who were hepatitis B e antigen-negative at NA cessation and remained off treatment without hepatitis B surface antigen (HBsAg) loss at 12 months were included (n = 945). HBV DNA and ALT fluctuations were allowed within the first 12 months. We used Kaplan-Meier methods to analyze outcomes beyond 12 months. Sustained remission was defined as HBV DNA <2,000 IU/mL and ALT <2× upper limit of normal (ULN) and an ALT flare as ALT ≥5× ULN. Cumulative probability of sustained remission was 29.7%, virological relapse was 65.2% with a mean peak HBV DNA of 5.0 ± 1.5 log 10 IU/mL, an ALT flare was 15.6% with a median peak ALT × ULN of 8.3 (5.7-11.3), HBsAg loss was 9.9% and retreatment was 34.9% at 48 months after NA cessation. A single occurrence of virological relapse or an ALT flare within the first 12 months off-treatment were associated with significantly lower rates of sustained remission beyond 12 months. Despite allowing for HBV DNA and ALT fluctuations within the first 12 months off-treatment, most patients without HBsAg loss did not maintain a sustained response thereafter. The best candidates for NA withdrawal are patients with low HBsAg levels at NA cessation, and those without profound or recurrent virological and biochemical relapses in the first off-treatment year.

Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 μmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

ERAP-1 and ERAP-2 Variants in Liver Injury After COVID-19 mRNA Vaccination: A US Multicenter Study.

The aim of this study is to describe the presenting features, genetic factors, and outcomes of 23 adults who developed liver injury after coronavirus disease 2019 (COVID-19) mRNA vaccination. Patients with suspected COVID-19 vaccine hepatitis were enrolled into the Drug-Induced Liver Injury Network. Causality was assessed using the Drug-Induced Liver Injury Network expert opinion score. High-resolution HLA sequencing was undertaken using Illumina platform. Amongst the 16 high causality cases, median time to onset was 16 days, median age was 63 years, and 75% were female. The injury was hepatocellular in 75% with a median alanine aminotransferase of 497 U/L, and 37% had jaundice. An antinuclear antibody and smooth muscle antibody were detectable in 27% and 36%, but only 12% had an elevated immunoglobulin G level. During follow-up, 37% received a short course of corticosteroids, and 88% fully recovered by 6 months with no deaths observed. HLA alleles associated with autoimmune hepatitis were not overrepresented compared with controls, but an ERAP-2 variant (rs1263907) and the ERAP-1 Hap6 haplotype were significantly overrepresented in the high causality cases vs controls ( P = 0.026 and 5 × 10 -5 , respectively). Acute liver injury may arise within 8 weeks of COVID-19 mRNA vaccination that is generally mild and self-limited in most patients. The absence of an association with the AIH HLA alleles combined with the significant ERAP-2 and ERAP-1 Hap6 haplotype associations implicates a unique but very rare host immune response to vaccine-derived antigens in the pathogenesis of COVID-19 vaccine hepatotoxicity.

Clinical, Gender, Socioeconomic Characteristics and Outcomes of Individuals Receiving Hepatitis B Treatment in Ethiopia: 18-Month Follow-Up.

There is a lack of real-world data on hepatitis B (HBV) treatment in Africa. We conducted a single-center 18-month prospective cohort study in Ethiopia to understand clinical, laboratory, and demographic variables associated with HBV treatment. One hundred fifty HBV-positive patients were included: 51 on treatment, 99 with no treatment. Median age was similar between groups. Those on treatment were more likely to be male (86%), report higher coffee intake (90% versus 70%, P < 0.05), lower khat intake (0% versus 9%, P = 0.08), lower alcohol consumption (0% versus 5%, P = 0.1), and had attained higher levels of education (56% versus 42%, P = 0.19). Individuals on treatment had higher median aspartate aminotransferase (AST), alanine aminotransferase (ALT), HBV DNA, and median Aminotransferase-to-Platelet Ratio Index and Fibrosis-4 scores. At 6 and 12 months, those on treatment showed a decrease in median AST, ALT, and fibrosis scores and had less hepatocellular carcinoma development at 6 months (2% versus 4%). Our study highlights potential demographic disparities in HBV treatment as well as benefits in a real-life setting in Africa.

The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study.

Elevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia. This multi-center, prospective study enrolled patients aged 3-216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed. Overall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001). Questioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Clinicaltrials.gov NCT04120168.

Evaluation of alanine aminotransferase responses in chronic hepatitis B patients using entecavir or tenofovir disoproxil fumarate

Background/Aim: An estimated 300 million individuals worldwide live with hepatitis B virus (HBV) infection. Alanine aminotransferase (ALT) levels, which indicate liver damage when elevated, are among the crucial laboratory parameters frequently monitored in the follow-up of chronic hepatitis B patients. The primary objectives of antiviral treatment are to reduce liver inflammation and prevent the development of hepatocellular carcinoma or cirrhosis by inhibiting HBV replication. This study evaluated ALT responses and identified factors influencing patient responses following initiating entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment. Methods: This retrospective cohort study collected data from treatment-naive and treatment-experienced patients with elevated ALT levels who received either ETV (0.5 or 1 mg per day) or TDF (245 mg per day) treatment between 2008 and 2018. Pregnant women and patients under 18 were excluded from the study. Elevated ALT levels were defined as greater than 35 IU/L for men and 25 IU/L for women. All patients underwent examinations for ALT, HBV DNA levels, HBeAg, and antiHBe at baseline and every 3–6 months. ALT levels of the patients were monitored for 60 months, and the presence of fatty liver was also documented. Results: Our study comprised 192 patients with a mean age of 53.7 (13.42) years. The majority of patients, 130 (67.7%), were male. Of these, 97 (50.5%) started ETV treatment, while 95 (49.5%) began TDF treatment. The median baseline ALT levels of the patients were 68 (44–133.5) IU/L, and the median ALT levels at the 60th month were 24 (18–32) IU/L. The median initial HBV DNA level was 114,282 (267.5–5,029,875) IU/mL, and the median HBV DNA levels from the 6th month onwards were 0 (0–0). ALT normalization was observed in 44.8% of men and 28.1% of women at 3 months, which was statistically significant (P=0.034). Normalization rates by gender remained consistent in all other months. No significant differences were noted in this regard. ALT normalization rates were 58.5% at the 6th month and 74.7% at the 24th month in the ETV group, significantly higher than in the TDF group (P=0.01, P=0.02, respectively). In patients with fatty liver, ALT normalization rates were significantly lower at 6, 12, 24, and 48 months than those without fatty liver (P=0.01, P=0.01, P=0.009, P=0.002, respectively). Conclusion: Although ALT responses to ETV treatment were more pronounced in specific months, both drugs demonstrated overall efficacy. ALT levels in patients with fatty liver remained elevated despite antiviral treatment. Therefore, patients with chronic hepatitis B and fatty liver may require additional support beyond antiviral therapy, including metabolic, nutritional, and lifestyle recommendations.

Discontinuation of Nucleos(t)ide Analog treatment in HBeAg-Negative Non-Cirrhotic Chronic Hepatitis B Patients: Real-Life Data of 20 Years.

Discontinuation of nucleos(t)ide analog is controversial in HBeAg-negative chronic hepatitis B patients not achieved HBsAg loss. We aimed to evaluate re-treatment rates and risk factors in non-cirrhotic HbeAg-negative chronic hepatitis B patients for whom nucleosi(t)ides analogs were discontinued. Demographic, clinical, and laboratory data before and at the end after discontinuation of nucleos(t)ide analogs were collected retrospectively. Seventy-two patients followed up between January 2000 and December 2019 were included; 43 were male, with a mean age of 46.3 (±10.8). Baseline median alanine aminotransferase (ALT) and hepatitis B virus DNA levels were 55.5 IU/L and 465 925 IU/mL, respectively. The median histologic activity index was 5.5 and the fibrosis score was 2. The median duration of treatment and consolidation therapy were 59 and 56 months, respectively. The median follow-up time after discontinuation of treatment was 55 months. Among 56 patients eligible for evaluation according to proposed re-treatment criteria, 29 (51.7%) patients were re-treated. The median time for relapse was 11 months. Re-treatment was significantly common in males (P = .034) and patients treated with tenofovir/entecavir (P = .04). Baseline hepatitis B virus DNA and levels of ALT, aspartate aminotransferase (AST) at the third and sixth months of treatment and at the end of treatment were statistically significantly higher in re-treated patients. A cutoff value of ≥405 000 IU/L for hepatitis B virus DNA discriminated patients for re-treatment. HBsAg was lost permanently in 2 non-re-treated patients. In resource-limited areas where follow-up of HBsAg or other markers is not possible, nucleos(t)ide analog discontinuation can be considered in patients in the early stage, with low baseline hepatitis B virus DNA and ALT levels, after a long consolidation therapy.

Low Alanine Aminotransferase, as a Marker of Sarcopenia and Frailty, Is Associated with Shorter Survival Among Prostate Cancer Patients and Survivors. A Retrospective Cohort Analysis of 4064 Patients

BackgroundSarcopenia is characterized by loss of muscle mass and function and is associated with frailty, a syndrome with higher likelihood of falls, fractures, physical disability, and mortality. Both frailty and sarcopenia are known markers of shorter survival in various cancer patient populations. Low alanine aminotransferase (ALT), reflecting loss of muscle mass (sarcopenia), may be associated with greater frailty and shorter survival in multiple cancers. ObjectiveTo assess the potential association between low ALT and shorter survival among prostate cancer (PCa) patients and survivors. Design, setting, and participantsThis was a retrospective analysis of a historical cohort of PCa patients and survivors. Patients were defined as those still actively receiving PCa treatment, while those no longer receiving such treatment were classified as PCa survivors. Outcome measurements and statistical analysisALT data were obtained from results for basic biochemical blood testing carried out for patients on their first hospital admission. Patients were divided into two groups: those with ALT ≥17 IU/l and those with ALT <17 IU/l. Univariate and multivariable analyses were conducted for between-group survival comparisons. Results and limitationsWe identified 9489 PCa records. The final study cohort with ALT data available included 4064 patients with ALT <40 IU/l. Of this cohort, 536 patients were actively receiving medical anticancer therapy for PCa. The mean age for the entire cohort was 74.6 yr (standard deviation 9.6) and the median ALT level was 19.28 IU/l; 1676 patients (41%) had low ALT (<17 IU/l). On univariate analysis, low ALT was associated with a 78% increase in mortality risk (95% confidence interval [CI] 1.62–1.97; p < 0.001). A sensitivity analysis of the 536 patients actively receiving medical anticancer treatment revealed that low ALT was associated with a 48% increase in mortality risk (95% CI 1.19–1.85; p = 0.001). In a multivariable model controlled for age, kidney disease, history of cerebrovascular event/transient ischemic attack, and baseline prostate-specific antigen, low ALT was still associated with a 35% increase in mortality risk (95% CI 1.12–1.63; p = 0.001). Limitations include the single-center, retrospective design. ConclusionsLow ALT, which is indicative of sarcopenia and frailty, is associated with shorter survival among PCa patients and survivors and could potentially be used for treatment personalization. Patient summaryWe compared survival for prostate cancer patients and survivors according to their blood level of the protein alanine aminotransferase (ALT). Low ALT levels in the general population are associated with loss of muscle mass. We found that in our group of prostate cancer patients and survivors, the risk of death from any cause was higher for those with low ALT levels.

Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase.

HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase. We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52)U/L, the mean HBV DNA was 4.5±2.1log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000IU/mL, and alanine transaminase<upper limit of normal. In multivariable Cox proportional hazards analysis adjusted for age, sex, HBeAg, HBV DNA, alanine transaminase, diabetes, and platelets, antiviral therapy remained an independent predictor of reduced HCC risk (adjusted HR = 0.3, 95% CI: 0.1-0.6, p = 0.001). Antiviral therapy reduces HCC risk by 70% among patients with indeterminate-phase CHB. These data have important implications for the potential expansion of CHB treatment criteria.

Low ALT, a marker of sarcopenia and frailty, is associated with shortened survival amongst myelodysplastic syndrome patients: A retrospective study.

Myelodysplastic Syndrome (MDS) is a common blood dyscrasia that mainly affects the elderly population. Several prognostic scores are available utilizing blood count variables and cytogenetic abnormalities, targeting the disease rather than the patient. Sarcopenia and frailty are associated with shortened survival rates in various disease states. Low Alanine Aminotransferase (ALT) levels are a marker of lowered muscle mass and frailty status. This study aimed to examine the correlation between low ALT levels and prognosis in MDS patients. This is a retrospective cohort study. We obtained the demographic, clinical, and laboratory data of patients in a tertiary hospital. Univariate and multivariate models were used to investigate the potential relationship between low ALT level and survival. The final study included 831 patients (median age 74.3 years, Interquartile range 65.6-81.8), and 62% were males. The median ALT level was 15 international units (IU)/L and 233 patients (28%) had low ALT levels (<12 IU/L). Univariate analysis showed that low ALT levels were associated with a 25% increase in mortality (95% confidence interval [CI]: 1.05-1.50, P = .014). A multivariate model controlling for age, sex, body mass index, hemoglobin and albumin concentrations, and low ALT levels was still significantly associated with increased mortality (hazard ratio [HR] = 1.25, 95% CI: 1.01-1.56, P = .041). Low ALT levels were associated with increased mortality among patients with MDS. Impact: Using ALT as a frailty metric may allow patient-centered, personalized care in this patient population. A low ALT level reflects the pre-morbid robustness of patients and is not intended to replace disease-centered characteristics.

A Single-Center Case Series of Successful Abdominal Organ Transplantation From SARS-CoV-2-infected Donors to Uninfected Recipients-Do We Need Rigorous Monitoring?

We analyzed 16 recipients (7 liver, 9 kidney) transplanted from SARS-CoV-2 nucleic acid test+ deceased donors from December 25, 2021, to February 28, 2022, who were followed-up for at least 90 d. Primary outcomes included coronavirus disease 2019-positivity, allograft loss, and all-cause mortality. Secondary outcomes included biopsy-proven rejection (BPAR), donor-specific antibodies, delayed graft function, and opportunistic infections. Unlike previous studies, we followed the recipients clinically with the intent to treat if they developed SARS-CoV-2 symptoms. All donors were SARS-CoV-2 polymerase chain reaction-positive 72 h before donation. No recipients developed SARS-CoV-2 infection. The nadir serum creatinine and estimated glomerular filtration rate were 1.33 mg/dL and 64 mL/min/1.732 m2 for kidney transplantation (KTx) respectively. The median alanine transaminase was 14.5 IU/L, aspartate aminotransferase 13 IU/L, and alkaline phosphatase 74 IU/L. Two KTx patients lost allograft, and 1 liver transplantation patient died with a failed allograft. However, this was unrelated to their SARS-CoV-2-positive donor status. One BPAR in the liver transplantation was treated with steroids. No donor-specific antibodies or BPAR were reported in the KTx. Six KTx patients experienced delayed graft function, and 4 are off dialysis. Two KTx patients developed cytomegalovirus infection because of an error in reporting the cytomegalovirus serostatus by the donor center. We did not do serial testing for SARS-CoV-2 by polymerase chain reaction, imaging, or cycle threshold score pre- or posttransplant for donor/recipient and had comparable outcomes with previous studies. Because of the low risk of transmission, serial testing might not be necessary and, thus, could be reciprocated at small-volume transplant centers.

The role of liver transaminase levels in methotrexate intolerance in juvenile idiopathic arthritis—a cross-sectional study

Methotrexate (MTX) plays a key role when treating juvenile idiopathic arthritis (JIA), but MTX-intolerance is challenging. MTX-treatment might affect the liver, causing elevated levels of alanine aminotransferase (ALT), yet the role of ALT-levels in MTX-intolerance in JIA remains unclear. Our study aimed to investigate the association between ALT-levels during MTX-treatment and MTX-intolerance in JIA. Children (> 9years old) diagnosed with JIA and treated with MTX (> 6weeks) were eligible for enrollment. MTX-intolerance was assessed using the Methotrexate Intolerance Severity Score (MISS), completed by the parents, and defined as MISS ≥ 6 with at least 1 point for a behavioral/anticipatory/associative symptom. ALT-levels were determined at enrollment. A total of 118 children were enrolled (80 girls; 38 boys). MTX-intolerance was registered in 61%. ALT-levels did not differ between the MTX-intolerant group (median = 17.0 U/L [IQR: 14.0-26.0]) and the MTX-tolerant group (median = 20.5 U/L [IQR: 16.0-27.5]; p = 0.17). MTX-intolerance was prevalent in around 60% of both boys and girls. Nine out of 50 MTX-intolerant girls had elevated ALT-levels compared to 0/22 MTX-intolerant boys, however, there was no difference in median ALT levels between the two groups. Furthermore, the MTX-intolerant girls had a higher MISS (median = 14.0 [IQR: 9.3-17]) than the MTX-intolerant boys (median = 10.0 [IQR: 7.3-12]; p = 0.009). Our study did not find a difference in ALT-levels between MTX-intolerant and MTX-tolerant children. However, only MTX-intolerant girls and no MTX-intolerant boys showed elevated ALT-levels.