Gut Liver. 2021;15(2):295-306.

Comorbidities and Prescribed Medications in Korean Patients with Chronic Hepatitis C: A Nationwide, Population-Based Study.

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제1저자 정정화, 최화영 · 교신저자 정숙향

PMID 32616682 PMC7960981 DOI 10.5009/gnl19387 IF 4.1 소화기내과

소속 (2)

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.

Abstract

BACKGROUND/AIMS Extrahepatic comorbidities and comedication are important to consider in the treatment of chronic hepatitis C (CHC) patients with direct-acting antivirals (DAAs) due to the risk of drug-drug interaction (DDI) and the effect of comorbidities on clinical outcomes. This study aimed to investigate the detailed profiles of comorbidities and comedication among Korean CHC patients.

METHODS All adult patients (≥18 years old) with a primary diagnostic code of CHC in 2013 were selected from the National Health Insurance claims database. For each patient, all ICD-10 codes listed as primary or secondary diagnoses and all prescribed medications were collected.

RESULTS Among 47,104 CHC patients (median age, 57 years; male, 49.3%), 84.8% had at least one comorbidity for a mean number of 2.4, which increased with age. The most prevalent comorbidities were hypertension, esophagitis, dyslipidemia, diabetes mellitus, and peptic ulcer. Overall, 96.8% of the patients took at least one prescribed medication, with a mean of 8.1 medications/ year, and the three most common drug types were analgesics, gastrointestinal agents, and antibacterials. Use of at least one drug with a DDI risk category of "contraindicated medication" or "required dose-reduction/additional monitoring" was observed in 97% of the overall patients. The proportion of prescribed medications that were contraindicated with DAAs varied from 2.0% to 38.9% depending on the hepatitis C virus regimen.

CONCLUSIONS The majority of CHC patients had comorbidities; almost all patients took multiple prescribed medications, the number of which increased with age, and significant DDI risk was present in 97% of this Korean patient cohort. Comorbidities and comedication profiles should be considered during DAA therapy.

Keywords

ComorbidityDrug interactionsDrug therapyHepatitis CLiver cirrhosischronic

Figures

**Fig. 1** Comorbidities, defined by International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes, according to age group in Korean chronic hepatitis C patients (n=47,104); (A) the proportion of patients having at least one comorbidity and (B) the mean number of comorbidities per patient. Hepatocellular carcinoma (ICD-10 codes: C22, C22.0 and C22.9) was excluded from the comorbidity category of “Neoplasm.” Acute hepatitis (ICD-10 codes: B15-17) and sequelae of viral hepatitis (ICD-10 code: N94.2) were excluded from the comorbidity category of “Certain infectious and parasitic diseases” in order to prevent overestimation of viral hepatitis.

**Fig. 2** The mean number of prescription drugs per patient according to age group in Korean chronic hepatitis C patients (n=47,104). Prescribed medications were classified into therapeutic drug classes based on information derived from https://www.hep-druginteractions.org/ by Liverpool University (Supplementary Table 2). The “hepatotonics” category was specifically listed by the investigators because hepatotonics are one of the most commonly prescribed classes of medication in Korea.

**Fig. 3** The proportions of the types of predicted drug-drug interaction between the prescribed medications and each direct-acting antiviral regimen available in Korean chronic hepatitis C patients (n=47,104). The predicted proportions of contraindicated medications for each regimen are presented with statistical analysis. Among the genotype 1 regimens, compared to EBR/GZR, OBV/PTV/r+DSV (odds ratio [OR], 19.01; 95% confidence interval [CI], 17.82 to 20.30), DCV+ASV (OR, 18.9; 95% CI, 17.72 to 20.19), SOF+DCV (OR, 13.4; 95% CI, 12.55 to 14.32), and LDV/SOF (OR, 2.05; 95% CI, 1.89 to 2.21) showed significantly increased proportions of contraindicated medications. Among the genotype 2 regimen, compared to SOF/RBV, LDV/SOF (OR, 1.79; 95% CI, 1.66 to 1.93), and SOF/DCV (OR, 11.72; 95% CI, 11.02 to 12.47) showed a significantly increased proportions of contraindicated medications as well (all *p<0.0001). The predicted interactions are based on the information derived from https://www.hep-druginteractions.org/ by Liverpool University and from the Korean pharmaceutical inserts. OBV, ombitasvir; PTV, paritaprevir; r, ritonavir; DSV, dasabuvir; DCV, daclatasvir; ASV, asunaprevir; SOF, sofosbuvir; LDV, ledipasvir; RBV, ribavirin; EBR, elbasvir; GZR, grazoprevir; DDI, drug-drug interaction.

**Fig. 4** The proportions of Korean chronic hepatitis C patients (n=47,104) who were prescribed at least one drug with a drug-drug interaction (DDI) risk according to age group. Use of at least one drug in the DDI risk category of “contraindicated medication” increased with age. The predicted interactions are based on the information derived from https://www.hep-druginteractions.org/ by Liverpool University and from the Korean pharmaceutical inserts.

그림 출처: PubMed Central 공개 논문 (PMC7960981)

Conflict of interest statement

CONFLICTS OF INTEREST. No potential conflict of interest relevant to this article was reported.

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