Risk Of Elevated Alanine Aminotransferase Research Articles

Circulating metabolites are associated with persistent elevations of ALT in patients with chronic hepatitis B with complete viral suppression.

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

Omicron in Infants-Respiratory or Digestive Disease?

The Omicron variant of SARS-CoV-2 has caused a large number of cases and hospitalizations in the pediatric population. Infants due to their age are susceptible to viral infections that may have a worse prognosis. Therefore, the aim of the current study has been to characterize the clinical features and the outcome of infants hospitalized with confirmed SARS-CoV-2 infection during the Omicron wave. We conducted a retrospective study of all consecutive infants hospitalized with symptomatic COVID-19 and no other co-infections, from January to September 2022 in one of the largest infectious diseases hospitals from Bucharest, Romania. A total of 613 infants were included in the analysis. The median age was 5 months (IQR: 3, 8 months). The clinical features were dominated by fever (96.4%), cough (64.8%) and loss of appetite (63.3%), and overall, respiratory symptoms were the most numerous (76.0%). Infants between 1-3 months old had a 1.5-fold increased risk of elevated alanine aminotransferase (ALT) values, and a longer length of hospitalization as compared to older infants. Infants between 7-9 months of age had 1.5-fold higher odds of loss of appetite, 1.7-fold more frequent cough and 1.6-fold more frequent digestive symptoms compared to infants in other age groups. The presence of digestive symptoms increased the probability of hepatic cytolysis (increased ALT) by 1.9-fold. Continued monitoring of COVID-19 among infants is very necessary, given the progressive character of SARS-CoV-2, in order to take correct and rapid therapeutic measures and to adapt to clinical changes driven by viral variant change.

The association of the paraoxonase 1 Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD.

The present study aimed to investigate the association of the paraoxonase 1 (PON1) Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD. This cross-sectional study was conducted on 428 patients undergoing angiography. The data related to demographic information and physical activity were collected by valid and reliable questionnaires. The PON-1 genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique. The Gensini and SYNTAX score, anthropometric measurements, and biochemical and clinical parameters were measured by standard protocols. Findings indicated that the odds of obesity was significantly higher in people with the RR genotype compared to the QQ genotype carriers (OR: 2.95 CI: 1.25-6.93, P = 0.014) and also odds of low high-density lipoprotein cholesterol (HDL-C) was marginally higher (OR: 2.31 CI: 0.97-5.49, P = 0.056). There was no significant association between other CAD risk factors with PON1 Q192R polymorphism (P > 0.05). Further analysis showed a significant interaction between sex and 192QR (P = 0.019) and 192 RR (P = 0.007) genotypes on body mass index (BMI). More specifically, the risk of obesity in men carrying the RR genotype was 3.38 times (OR: 3.38 CI: 1.08-10.58, P = 0.036). Also, a significant joint effect of the RR genotype and sex on HDL-C was seen (P = 0.003). The stratification based on sex showed that the risk of low HDL-C is significantly higher in women carrying the RR genotype (OR: 6.18 CI: 1.21-31.46, P = 0.028). A marginal sex-genotype interaction was also found in the risk of elevated alanine aminotransferase (ALT) (P = 0.057). In summary, the findings showed that the risk of obesity and low HDL-C was higher in people carrying the RR genotype. On the other hand, a Q192R polymorphism-sex interaction was observed on the risk of obesity, elevated ALT, and low HDL-C.

External beam radiotherapy for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma is the most common liver neoplasm, the sixth most common cancer worldwide, and the third most common cause of cancer mortality. Moreover, its incidence has increased dramatically in the past decade. While surgical resection and liver transplantation are the main curative treatments, only around 20% of people with early hepatocellular carcinoma may benefit from these therapies. Current treatment options for unresectable hepatocellular carcinoma include various ablative and transarterial therapies in addition to the drug sorafenib. To assess the benefits and harms of external beam radiotherapy in the management of localised unresectable hepatocellular carcinoma. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), Science Citation Index Expanded (Web of Science), and clinicaltrials.gov registry. We also checked reference lists of primary original studies and review articles manually for further related articles (cross-references) up to October 6, 2016. Eligible studies included all randomised clinical trials comparing external beam radiotherapy either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other systemic or locoregional therapies for people with unresectable hepatocellular carcinoma. We used standard methodological procedures expected by Cochrane. We used a random-effects model as well as a fixed-effect model meta-analysis but in case of discrepancy between the two models (e.g. one giving a significant intervention effect, the other no significant intervention effect), we reported both results; otherwise, we reported only the results from the fixed-effect model meta-analysis. We assessed risk of bias of the included trials using predefined risk of bias domains; assessed risks of random errors with Trial Sequential Analysis; and presented the review results incorporating the methodological quality of the trials using GRADE. Nine randomised clinical trials with 879 participants fulfilled our inclusion criteria. All trials were at high risk of bias, and we rated the evidence as low to very low quality. All of the included trials compared combined external beam radiotherapy plus chemoembolisation versus chemoembolisation alone in people with unresectable hepatocellular carcinoma; moreover, three of the trials compared external beam radiotherapy alone versus chemoembolisation alone. All trials were conducted in China. The median age in most of the included trials was around 52 years, and most trial participants were male. The median follow-up duration ranged from one to three years. None of the trials reported data on cancer-related mortality, quality of life, serious adverse events, or time to progression of the tumour. For the comparison of radiotherapy plus chemoembolisation versus chemoembolisation alone, the risk ratio for one-year all-cause mortality was 0.51 (95% confidence interval (CI) 0.41 to 0.62; P < 0.001; 9 trials; low-quality evidence); for complete response rate was 2.14 (95% CI 1.47 to 3.13; P < 0.001; 7 trials; low-quality evidence); and for overall response rate defined as complete response plus partial response was 1.58 (95% CI 1.40 to 1.78; P < 0.001; 7 trials; low-quality evidence), all in favour of combined treatment with external beam radiotherapy plus transarterial chemoembolisation and seemingly supported by our Trial Sequential Analysis. Additionally, the combined treatment was associated with a higher risk of elevated total bilirubin and elevated alanine aminotransferase. The risk ratio for the risk of elevated alanine aminotransferase was 1.41 (95% CI 1.08 to 1.84; P = 0.01; very low-quality evidence), while for elevated total bilirubin it was 2.69 (95% CI 1.34 to 5.40; P = 0.005; very low-quality evidence). For the comparison of radiotherapy versus chemoembolisation, the risk ratio for one-year all-cause mortality was 1.21 (95% CI 0.97 to 1.50; 3 trials; I2 = 0%; very low-quality evidence) which was not supported by our Trial Sequential Analysis.In addition, we found seven ongoing randomised clinical trials evaluating different external beam radiotherapy techniques for people with unresectable hepatocellular carcinoma. We found very low- and low-quality evidence suggesting that combined external beam radiotherapy and chemoembolisation may be associated with lower mortality and increased complete and overall response rates, despite an increased toxicity as expressed by a higher rise of bilirubin and alanine aminotransferase. A high risk of systematic errors (bias) as well as imprecision and inconsistency suggest that these findings should be considered cautiously and that high-quality trials are needed to assess further the role of external beam radiotherapy for unresectable hepatocellular carcinoma.

Prevalence of abnormal serum liver enzymes in patients with type 2 diabetes mellitus: a cross-sectional study from China

ABSTRACTObjectives: This cross-sectional study aimed to determine the prevalence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in Chinese type 2 diabetic patients and identify contributing risk factors.Methods: This cross-sectional study was conducted in rural areas of China, and 1,198 type 2 diabetic patients with complete data were recruited. Elevated ALT and AST levels were defined as >40 U/L. Prevalence of abnormal liver enzymes was analyzed and multivariable analysis was used to identify independent risk factors.Results: 10.3% and 6.1% diabetic patients had elevated ALT and elevated AST, respectively. The prevalence of elevated liver enzymes was gender-related; it was 13.8% in men and 7.5% in women for elevated ALT, and 7.4% in men and 3.1% in women for elevated AST. High triglyceride was positively associated with both elevated ALT (OR 1.80, 95% CI 1.08–3.01, p = 0.024) and elevated AST (OR 2.24, 95%CI 1.08–4.65, p = 0.031), while taking anti-diabetes medicine was inversely related to both elevated ALT (OR 0.48, 95% CI 0.29–0.80, p = 0.005) and elevated AST (OR 0.37, 95% CI 0.17–0.82, p = 0.014). The risk of elevated ALT in diabetic patients increased with the presence of obesity (OR 2.54, 95% CI 1.07–6.01, p = 0.034), and was lower in women (OR 0.37, 95% CI 0.19–0.72, p = 0.003). Hypertension (OR 4.33, 95% CI 1.41–13.30, p = 0.011), current drinking status (OR 2.90, 95% CI 1.21–6.96, p = 0.017) and national minority (OR 3.26, 95%CI 1.31–8.12, p = 0.011) were risk factors for elevated AST.Conclusion: A relatively high prevalence of abnormal serum liver enzymes in diabetic patients was demonstrated in China, especially in males. More attention should be paid to preventing liver injuries in diabetic patients.

Longitudinal association of obesity, metabolic syndrome and diabetes with risk of elevated aminotransferase levels in a cohort of Mexican health workers.

In Mexico, chronic liver disease have been increasingly found along with the rapidly growing prevalence of obesity, diabetes and metabolic syndrome (MS). We aimed to investigate the longitudinal association between these three factors and risk of elevated alanine aminotransferase (ALT) levels (>40U/L), a marker for liver damage, in a cohort of Mexican adults. Data were obtained from two separate waves of the Mexican Health Worker Cohort Study: Wave 1 (2004-2006) and Wave 2 (2011-2013). Unconditional logistic regression models were employed to determine the cross-sectional and longitudinal association between these risk factors and elevated ALT levels. The prevalence of elevated ALT was significantly higher among men, individuals aged under 60years, those who were overweight or obese, diabetic, with MS or heavy/binge drinkers. The longitudinal results indicated that weight gain between waves that resulted in a change in body mass index, along with remaining overweight or obese, were significantly associated with an increased risk of elevated ALT levels. A significantly increased risk of developing elevated ALT was also observed among those who acquired diabetes or MS from Wave 1 to Wave 2. Weight gain and acquiring diabetes or MS are associated with a significant risk of having elevated ALT. These results, within the context of the rapid increase in global obesity rates, call urgently for programs to help to prevent chronic liver disease.

Coffee consumption is associated with lower serum aminotransferases in the general Korean population and in those at high risk for hepatic disease.

The favourable effects of coffee on liver enzymes have been reported worldwide. This study investigated the association between coffee consumption and serum aminotransferase concentration in Korean adults. Data were obtained from the fourth and fifth Korea National Health and Nutrition Examination Surveys. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentration were defined as >30 IU/L for men and >19 IU/L for women. The risk of elevated ALT and AST according to general characteristics and frequency of coffee consumption were tested by chi-square tests and multiple logistic regression analyses. The prevalence of elevated ALT was 27.4%, 27.8%, and 26.9% in subjects who drank <1, 1, and >=2 times/day, respectively. The proportions of individuals with elevated AST were 32.5%, 33.1%, and 26.7% in subjects who drank <1, 1, and >=2 times/day, respectively. The aORs for elevated ALT and AST were significantly lower in subjects who drank >=2 times of coffee/day than in those who drank <1 time/day (ALT: aOR=0.86, 95% CI=0.79-0.94; AST: aOR=0.83, 95% CI=0.76-0.91). In subgroup analysis, consumption of >=2 times/day was associated with lower ORs for elevated ALT in the high-risk group overall and in the viral hepatitis and obesity subgroups, respectively. In sensitivity analysis, reduced frequency of coffee consumption was associated with an increased risk for elevated liver enzymes, although an association between coffee consumption and elevated ALT was not observed in women or current smokers. Higher coffee consumption was associated with lower risk of elevated aminotransferase concentration in Korean adults.

Modifiable clinical and lifestyle factors are associated with elevated alanine aminotransferase levels in newly diagnosed type 2 diabetes patients: results from the nationwide DD2 study

Current literature lacks data on markers of non-alcoholic fatty liver disease (NAFLD) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. We therefore, conducted a cross-sectional study to examine modifiable clinical and lifestyle factors associated with elevated alanine aminotransferase (ALT) levels as a marker of NAFLD in new T2DM patients. Alanine aminotransferase levels were measured in 1026 incident T2DM patients enrolled in the nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. We examined prevalence of elevated ALT (>38 IU/L for women and >50 IU/L for men) and calculated prevalence ratios associated with clinical and lifestyle factors using Poisson regression. We examined the association with other biomarkers by linear regression. The median value of ALT was 24 IU/L (interquartile range: 18-32 IU/L) in women and 30 IU/L (interquartile range: 22-41 IU/L) in men. Elevated ALT was found in 16% of incident T2DM patients. The risk of elevated ALT was increased in patients who were <40 years old at diabetes debut [adjusted prevalence ratio (aPR): 1.96, 95% confidence interval (CI): 1.15-3.33], in those with alcohol overuse (>14/>21 drinks per week for women/men) (aPR: 1.60, 95% CI: 1.03-2.50), and in those with no regular physical activity (aPR: 1.42, 95% CI: 1.04-1.93). Obesity and metabolic syndrome per se showed no association with elevated ALT when adjusted for other markers, whereas we found positive associations of ALT with increased C-peptide (β = 0.14, 95% CI: 0.06-0.21) and fasting blood glucose (β = 0.07, 95% CI: 0.03-0.11). Among newly diagnosed T2DM patients, several modifiable clinical and lifestyle factors are independent markers of elevated ALT levels.

한국인에서 커피 및 녹차의 섭취빈도가 간염증 수치 및 대사증후군에 미치는 영향

본 연구의 목적은 한국에서 커피 및 녹차 등을 섭취하는 생활습관이 혈청 AST, ALT 및 대사증후군에 미치는 영향에 대하여 알아보고자 하였다. 국민건강영양조사를 받은 모든 연령의 약 4만 8천명 중 19세부터 79세의 성인남녀를 대상으로 하였다. 지난 1년간 흡연, 음주력의 여부, 1개월 간 흡연양, 알코올 섭취량, 체중, 체질량지수, 중성지방, 고밀도 지단백, 혈청 AST, ALT를 측정을 하였고 이를 바탕으로 대사성 증후군을 평가하였다. 커피를 많이 마실수록 통계적으로 유의하게 체중(<TEX>$p{\leq}0.001$</TEX>)과 체질량 지수(<TEX>$p{\leq}0.001$</TEX>)는 높았다. 커피를 많이 마시는 사람에서 혈청 AST는 낮았다(p=0.017). 하루에 커피를 한잔 이상 섭취하는 경우 고혈압의 유병률, 공복혈당 이상 및 고지혈증의 빈도가 낮았으며, 대사증후군의 발생빈도가 의미 있게 낮았다. 녹차 섭취 빈도 증가는 혈청 AST, ALT에 영향을 미치지 않았다. 녹차를 많이 마시는 것과 체질량지수, 대사성 증후군의 유병률과는 연관이 없었다. 결론적으로 커피 섭취를 많이 마시는 사람에서 혈청 AST수치가 낮았다. 커피를 하루에 두잔 이상 섭취하는 군에서 총에너지 섭취와 체질량 지수가 높았으나 고혈압, 고지혈증, 공복혈당이 의미 있게 낮았으며 대사증후군의 발생률도 낮았다. We investigated whether coffee and green tea consumption reduced the risk of elevated alanine aminotransferase(ALT)/aspartate aminotransferase(AST) activity and the prevalence of metabolic syndrome. Participants were 5,283 adults, aged 19-79 years, in the Third Korean National Health and Nutrition Examination Survey, with excessive alcohol consumption, overweight, viral hepatitis, metabolic syndrome. Increased coffee and green tea consumption was not associated with decreased serum ALT. However, amount of coffee consumption had negative correlation with serum AST activity. Moreover, coffee consumption reduced the prevalence of metabolic syndrome (p for trend <0.001). Hypertension, impaired glucose metabolism and dyslipidemia was involved as subgroup of metabolic syndrome. Comparing persons who drank more than 2 cups per day with less than 1 cup per day, the prevalence of all subgroups was declined significantly. In this large, national, population-based study, consumption of coffee was associated with lower the risk of metabolic syndrome.

Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States

Based on experimental and epidemiologic studies, we investigated whether coffee and caffeine consumption reduced the risk of elevated alanine aminotransferase (ALT) activity in persons at high risk for liver injury in a national, population-based study. Participants were 5944 adults in the Third US National Health and Nutrition Examination Survey, 1988-1994, with excessive alcohol consumption, viral hepatitis, iron overload, overweight, or impaired glucose metabolism. Liver injury was indicated by abnormal serum ALT activity (>43 U/L). Elevated ALT activity was found in 8.7% of this high-risk population. In unadjusted analysis, lower ALT activity was associated with increasing consumption of coffee ( P = .001) and caffeine ( P = .001). Multivariate logistic regression analyses showed that the risk of elevated ALT activity declined with increasing intake of coffee ( P for trend = .034) and caffeine ( P < .001). Comparing persons who drank more than 2 cups per day with noncoffee drinkers, the odds ratio was .56 (95% confidence interval, .31-1.0). Comparing persons in the highest caffeine quintile with the lowest, the odds ratio was .31 (95% confidence interval, .16-.61). These relationships were consistent across subgroups at risk for liver injury and were relatively unchanged when analyses included the entire population or when limited to persons without impaired liver function or right upper quadrant pain. Fasting insulin concentrations did not mediate the effects. In this large, national, population-based study, among persons at high risk for liver injury, consumption of coffee and especially caffeine was associated with lower risk of elevated ALT activity.