Supplemental material



Supplemental materialSupplemental Table S1. Patient clinical profile in the Marketscan databaseAll patientsN = 8,722All patients with an HE diagnosis1, with no HE treatment prior to diagnosis, and ≥ 12 months of continuous health plan enrollment prior to diagnosisN = 3,244Etiology of new HE patients2, N (%)Alcoholic cirrhosis1,789(55.1%)NASH1,298(40.0%)Viral594(18.3%)Other744(22.9%)Etiology of new HE patients - mutually exclusive categories2, N (%)Alcoholic only816(25.2%)NASH only445(13.7%)Viral only181(5.6%)Alcoholic + NASH only645(19.9%)Alcoholic + viral only205(6.3%)NASH + viral only85(2.6%)Alcoholic + NASH + viral123(3.8%)Other744(22.9%)Location of first HE diagnosis, N (%)??IP1,796(55.4%)Emergency room258(8.0%)Outpatient1,186(36.6%)Other4(0.1%)Specialty of provider of first HE diagnosis, N (%)Gastroenterology608(18.7%)Internal medicine622(19.2%)Emergency medicine425(13.1%)General or family medicine250(7.7%)Pathology79(2.4%)Other1,260(38.8%)Gastroenterology visit after diagnosis2,463(75.9%)Time from diagnosis to first gastroenterology visit (days), mean ± SD [median]72.8 ± 126.5 [29.0]0 - 7 days, N (%)341(13.8%)8 - 30 days, N (%)924(37.5%)31 - 60 days, N (%)509(20.7%)61 - 90 days, N (%)211(8.6%)> 90 days, N (%)478(19.4%)All patients with an HE diagnosis1, with no HE treatment prior to diagnosis and 12 months of continuous health plan enrollment prior to and following diagnosisN = 1,608Patients who received treatment, N (%)1,138(70.8%)Time from diagnosis to first treatment (days), mean ± SD [median]85.3 ± 182.9 [10.0]0 - 7 days, N (%)521(45.8%)8 - 30 days, N (%)240(21.1%)31 - 60 days, N (%)112(9.8%)61 - 90 days, N (%)42(3.7%)> 90 days, N (%)223(19.6%)Patients who received lactulose as first treatment, N (%)697(61.2%)Time to first treatment with lactulose (days), mean ± SD [median]84.4 ± 182.6 [8.0]0 - 7 days, N (%)333(47.8%)8 - 30 days, N (%)136(19.5%)31 - 60 days, N (%)65(9.3%)61 - 90 days, N (%)27(3.9%)> 90 days, N (%)136(19.5%)Received rifaximin after lactulose332(47.6%)Patients who received rifaximin (with or without lactulose) as first treatment, N (%)441(38.8%)Time to first treatment with rifaximin (days), mean ± SD [median]86.6 ± 183.7 [11.0]0 - 7 days, N (%)188(42.6%)8 - 30 days, N (%)104(23.6%)31 - 60 days, N (%)47(10.7%)61 - 90 days, N (%)15(3.4%)> 90 days, N (%)87(19.7%)CCI: Charlson comorbidity index; HE: hepatic encephalopathy; IBS-D: irritable bowel syndrome with diarrhea; IP: inpatient; NASH: Nonalcoholic steatohepatitis; SD: standard deviation.Notes:1. Hepatic encephalopathy was defined as International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9-CM codes: 572.2; ICD-10-CM codes: K72.90, K72.91, K70.41, K71.11, K72.01, K72.11).2. Etiology is based on diagnoses for cirrhosis and related diseases observed any time prior to the study index date.Supplemental Figure S1. Patient selection in the Marketscan databaseDRG: diagnosis-related group; HE: hepatic encephalopathy; IBS-D: irritable bowel syndrome with diarrhea; ICD-9/10-CM: International Classification of Diseases, 9th/10th Revision, Clinical Modification; IP: inpatient; SIBO: small intestinal bacterial overgrowthNotes:1. Hepatic encephalopathy was defined as International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9-CM codes: 572.2; ICD-10-CM codes: K72.90, K72.91, K70.41, K71.11, K72.01, K72.11).2. Unspecified encephalopathy was defined using the following codes: ICD-9-CM codes: 348.30, 348.31, 348.39; ICD-10-CM: G93.40, G93.41, G93.49.3. Identified through prescription fills for either lactulose or rifaximin (550mg) between 1 day before admission and up to 45 days post discharge of IP with selected DRG or next admission, whichever occurred earlier.4. Defined as another lactulose prescription filled in the following 90 days.5. Index date was defined as the fill date of first prescription for HE-related treatment (i.e., lactulose or rifaximin [550mg]).6. The transplant date was defined as admission date if the transplant was performed in an IP setting.7. The follow-up period was the period spanned from index date to 1) last date of data availability, 2) continuous enrollment, or 3) liver transplant, whichever occurred earlier.Supplemental Figure S2. Patient selection in the Optum databaseDRG: diagnosis-related group; HE: hepatic encephalopathy; IBS-D: irritable bowel syndrome with diarrhea; ICD-9/10-CM: International Classification of Diseases, 9th/10th Revision, Clinical Modification; SIBO: small intestinal bacterial overgrowthNotes:1. Hepatic encephalopathy was defined as International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9-CM codes: 572.2; ICD-10-CM codes: K72.90, K72.91, K70.41, K71.11, K72.01, K72.11).2. Unspecified encephalopathy was defined using the following codes: ICD-9-CM codes: 348.30, 348.31, 348.39; ICD-10-CM: G93.40, G93.41, G93.49.3. Identified through prescription fills for either lactulose or rifaximin (550mg) between 1 day before admission and up to 45 days post discharge of IP with selected DRG or next admission, whichever occurred earlier.4. Defined as another lactulose prescription filled in the following 90 days.5. Index date was defined as the fill date of first prescription for HE-related treatment (i.e., lactulose or rifaximin [550mg]).6. The transplant date was defined as admission date if the transplant was performed in an inpatient setting.7. The follow-up period was the period spanned from index date to 1) last date of data availability, 2) continuous enrollment, or 3) liver transplant, whichever occurred earlier. ................
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