Sunday, October 1, 2023

Association between weight loss agents and elevated liver enzymes: a population-based cross-sectional study – Scientific Reports

Data source and study subjects

We conducted a cross-sectional study using data from the sixth wave (2013–15), seventh wave (2016–18), and eighth wave (2019) of the KNHANES conducted by the Korea Disease Control and Prevention Agency of the Ministry of Health and Welfare. All participants were selected using multi-stage clustered probability sampling and comprised a representative sample of non-institutionalized civilians in South Korea. All participants gave written informed consent before study participation23,25.

A total of 55,327 participants completed the KNHANES questionnaire between 2013 and 2019. Of these, we included 44,029 adults aged 19 and older. We excluded 5,618 respondents who lacked liver enzyme test information and had completed a weight control questionnaire. Additionally, we excluded 306 respondents diagnosed with hepatitis B, hepatitis C, or liver cirrhosis. We also excluded 1,736 respondents with a history of various cancers, including stomach, liver, colorectal, breast, cervical, lung, thyroid, and others. Finally, we excluded 110 respondents diagnosed with renal failure (Fig. 3).

Figure 3

Study flow. AST aspartate transaminase; ALT alanine transferase.


This study complies with the Declaration of Helsinki, and the requirement for ethical review and approval was waived for this study by the Asan Medical Center Institutional Review Board (2021–1666), because the KNHANES database contains anonymized data that cannot allow patients’ identification. All participants gave written informed consent before study participation. However, the need for written or verbal consent was waived due to the observational nature of the study and the fact that the patient identifiers were fully encrypted prior to data analysis.

Weight control methods

We extracted data on participants’ experiences with weight management and the strategies they employed over a 1-year period. The data were collected by administering a questionnaire that asked: “Have you made any conscious efforts to manage your weight in the past year?” and “Please list all the methods you used to either lose or maintain your weight over the past year.” We recorded attempts at weight control, including no control, efforts to gain weight, and efforts to lose or maintain weight. Only participants who indicated they had tried to lose or maintain weight answered the subsequent question. We documented the weight control methods, which included exercise, fasting, reducing food intake, skipping meals, using prescription weight-loss drugs, using over-the-counter weight-loss drugs, using herbal medicine, consuming functional foods, and adhering to a single-food diet. We classified weight control methods into two categories: the use of weight loss agents (prescription and non-prescription weight loss medication, traditional herbal medicine, and dietary supplements), and other methods (exercise, fasting, reducing food intake, skipping meals, single-food diet, and so on)3.

Liver enzymes

Liver aminotransferases (ALT and AST) are markers commonly used in routine serum liver enzyme tests. Levels of these enzymes increase when hepatocytes are damaged under disease conditions such as hepatitis, cholestasis, severe steatosis, and others. ALT and AST levels were obtained from venous blood samples and measured using the Hitachi Automatic Analyzer 7600–210 (Hitachi, Tokyo, Japan). The measurement was conducted using the International Federation of Clinical Chemistry method, which employs ultraviolet light without pyridoxal-5′-phosphate, and utilized the Pureauto S series reagent (Sekisui, Tokyo, Japan)25,26. Although a lower cut-off has been suggested to define an elevated status of AST or ALT, we primarily classified elevated liver enzymes using the traditional cut-off levels of > 40 IU/L27. Sensitivity analyses of several cut-offs were conducted to investigate the robustness of the results as follows: 1) American College of Gastroenterology Clinical Guideline (ACG CG): AST > 43 IU/L and ALT > 33 IU/L for males, AST > 32 IU/L and ALT > 25 IU/L for females, 2) higher than borderline elevation defined using 2 times the upper limit of normal (ULN) of the traditional cut-off level: AST or ALT > 80 IU/L, and 3) higher than borderline elevation using 2 times the ULN of the ACG CG: AST > 80 IU/L and ALT > 86 IU/L for males, AST > 64 IU/L and ALT > 50 IU/L for females28.


To comprehensively evaluate potential confounding factors and account for their effects, we incorporated demographics, behavioral factors, comorbidities, and family history into our analysis. The demographic variables we considered included age, sex, survey year, household income (categorized as low, medium–low, medium–high, or high), occupational type (classified as unemployed or economically inactive, non-manual workers, manual workers, service or sales workers, or unknown/no response), marital status (either married or not), and educational status (grouped as middle school or less, high school, or college and above). Behavioral factors encompassed stress recognition levels (rated as high, moderate, low, or unknown/no response), BMI, obesity, smoking status (categorized as non-smoker, ex-smoker, current smoker, or unknown/no response), alcohol consumption (classified as heavy, light-to-moderate, non-drinker, or unknown/no response), and participation in medium-intensity physical activity (either yes, no, or unknown/no response). We defined obesity as a BMI of 25 kg/m2 or higher, in accordance with the Asia–Pacific criteria set by the World Health Organization guidelines29. We also took into account the participants’ history of comorbidities, which included hypertension, hyperlipidemia, diabetes, depressive disorders, and thyroid disease. Furthermore, we collected information on family history of hepatitis B virus infection, as it was deemed a relevant confounding factor in the analysis.

Statistical analysis

Data for continuous variables are presented as means ± standard deviation (SD), and data for categorical variables are presented as the number of cases with a percentage. Analysis of variance and the chi-square test were used to examine differences between weight control methods. We analyzed associations between elevated liver enzymes and weight control methods using logistic regression models. To adjust for confounders, we selected variables that demonstrated statistical differences between exposure groups. We then conducted logistic regression to identify statistically significant risk factors for elevated liver enzymes, using a p-value of < 0.1 as the threshold for significance. We also stratified our data by sex, age group (either under 40 years or 40 years and above), and BMI (non-obese < 25 kg/m2, obese ≥ 25.0 kg/m2), because the susceptibility to elevated liver enzymes and attempts at weight control vary according to sex, age, and BMI30,31,32. We also performed a sensitivity analysis where AST and ALT were treated as continuous variables using a linear regression model. All statistical analyses were performed with SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). A p-value < 0.05 was considered to indicate statistical significance.

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