Supplemental Table 1. ICD-9 and CPT codes used to identify cirrhosis etiology, bleeding outcomes, and portal hypertension complications
CIRRHOSIS ETIOLOGY*
VIRAL HEPATITIS
070.0 viral hepatitis A with hepatic coma 070.1 viral hepatitis A without hepatic coma
070.20 viral hepatitis B with hepatic coma acute or unspecified without hepatitis delta 070.21 viral hepatitis B with hepatic coma acute or unspecified with hepatitis delta 070.22 chronic viral hepatitis B with hepatic coma without hepatitis delta
070.23 chronic viral hepatitis B with hepatic coma with hepatitis delta
070.30 viral hepatitis B without hepatic coma acute or unspecified without hepatitis delta 070.31 viral hepatitis B with hepatic coma acute or unspecified with hepatitis delta 070.32 chronic viral hepatitis B without hepatic coma without hepatitis delta 070.33 chronic viral hepatitis B without hepatic coma with hepatitis delta 070.41 acute hepatitis C with hepatic coma
070.42 hepatitis delta without active hepatitis B with hepatic coma 070.43 hepatitis E with hepatic coma
070.44 chronic hepatitis C with hepatic coma
070.49 other specified viral hepatitis with hepatic coma 070.51 acute hepatitis C without mention of hepatic coma
070.52 hepatitis delta without active hepatitis B disease or hepatic coma 070.53 hepatitis E without hepatic coma
070.54 chronic hepatitis C without hepatic coma
070.59 other specified viral hepatitis without hepatic coma 070.6 unspecified viral hepatitis with hepatic coma 070.70 unspecified viral hepatitis C without hepatic coma 070.71 unspecified viral hepatitis C with hepatic coma 070.9 unspecified viral hepatitis without hepatic coma
V02.60 carrier or suspected carrier of viral hepatitis unspecified V02.61 carrier or suspected carrier of hepatitis B
V02.62 carrier or suspected carrier of hepatitis C V02.69 carrier or suspected carrier of other viral hepatitis 571.40 chronic hepatitis unspecified
571.41 chronic persistent hepatitis 571.42 autoimmune hepatitis 571.49 chronic hepatitis
573.1 hepatitis in viral diseases classified elsewhere
573.2 hepatitis in other infectious diseases classified elsewhere
ALCOHOL
571.0 alcoholic fatty liver disease 571.1 acute alcoholic hepatitis 571.2 alcoholic cirrhosis of liver 571.3 alcoholic liver damage
AUTOIMMUNE / BILIARY
571.6 biliary cirrhosis 571.42 autoimmune hepatitis 576.1 primary sclerosing cholangitisNAFLD / OTHER
571.5 cirrhosis without alcohol + none of the above categories
OUTCOMES
BLEEDING OUTCOMES
Gastrointestinal Bleeding 578.0 hematemesis 578.1 blood in stool578.9 hemorrhage of gastrointestinal tract, unspecified 530.82 esophageal hemorrhage
531.00 Acute gastric ulcer with hemorrhage, without mention of obstruction 531.01 Acute gastric ulcer with hemorrhage, with obstruction
531.20 Acute gastric ulcer with hemorrhage and perforation, without mention of obstruction 531.21 Acute gastric ulcer with hemorrhage and perforation, with obstruction
531.40 Chronic or unspecified gastric ulcer with hemorrhage, without mention of obstruction 531.41 Chronic or unspecified gastric ulcer with hemorrhage, with obstruction
531.60 Chronic or unspecified gastric ulcer with hemorrhage and perforation, without mention of obstruction 531.61 Chronic or unspecified gastric ulcer with hemorrhage and perforation, with obstruction
532.00 Acute duodenal ulcer with hemorrhage, without mention of obstruction 532.01 Acute duodenal ulcer with hemorrhage, with obstruction
532.20 Acute duodenal ulcer with hemorrhage and perforation, without mention of obstruction 532.21 Acute duodenal ulcer with hemorrhage and perforation, with obstruction
532.40 Chronic or unspecified duodenal ulcer with hemorrhage, without mention of obstruction 532.41 Chronic or unspecified duodenal ulcer with hemorrhage, with obstruction
532.60 Chronic or unspecified duodenal ulcer with hemorrhage and perforation, without mention of obstruction 532.61 Chronic or unspecified duodenal ulcer with hemorrhage and perforation, with obstruction
533.00 Acute peptic ulcer of unspecified site with hemorrhage, without mention of obstruction 533.01 Acute peptic ulcer of unspecified site with hemorrhage, with obstruction
533.20 Acute peptic ulcer of unspecified site with hemorrhage and perforation, without mention of obstruction 533.21 Acute peptic ulcer of unspecified site with hemorrhage and perforation, with obstruction
533.40 Chronic or unspecified peptic ulcer of unspecified site with hemorrhage, without mention of obstruction 533.41 Chronic or unspecified peptic ulcer of unspecified site with hemorrhage, with obstruction
533.60 Chronic or unspecified peptic ulcer of unspecified site with hemorrhage and perforation, without mention of obstruction 533.61 Chronic or unspecified peptic ulcer of unspecified site with hemorrhage and perforation, with obstruction
534.00 Acute gastrojejunal ulcer with hemorrhage, without mention of obstruction
534.20 Acute gastrojejunal ulcer with hemorrhage and perforation, without mention of obstruction 534.21 Acute gastrojejunal ulcer with hemorrhage and perforation, with obstruction
534.40 Chronic or unspecified gastrojejunal ulcer with hemorrhage, without mention of obstruction 534.41 Chronic or unspecified gastrojejunal ulcer, with hemorrhage, with obstruction
535.01 Acute gastritis, with hemorrhage 535.11 Atrophic gastritis, with hemorrhage
535.21 Gastric mucosal hypertrophy, with hemorrhage 535.31 Alcoholic gastritis, with hemorrhage
535.41 Other specified gastritis, with hemorrhage
535.51 Unspecified gastritis and gastroduodenitis, with hemorrhage 535.61 Duodenitis, with hemorrhage
537.83 Angiodysplasia of stomach and duodenum with hemorrhage Non-Gastrointestinal Bleeding
362.81, 379.23 Retinal hemorrhage and vitreous hemorrhage
430, 431, 432 Intracranial hemorrhage (subarachnoid, intracerebral, other and unspecified intracranial hemorrhage) 441.0, 441.1, 441.3 Dissection of aorta, thoracic aneurysm (ruptured), and abdominal aneurysm (ruptured)
459.0 Unspecified hemorrhage
568.81 Hemoperitoneum (nontraumatic) 599.7 Hematuria
626.2 Excessive or frequent menstruation 719.1 Hemarthrosis
784.7 Epistaxis 786.3 Hemoptysis
PORTAL HYPERTENSION COMPLICATION
Ascites: 789.5 ascites; 789.59 other ascites; 54.91 percutaneous abdominal drainage Prescription claim for furosemide or spironolactone
CPT code 49080, 49081, 49082, or 49083: abdominal paracentesis Hepatic Encephalopathy: 572.2
Prescription claim for lactulose or rifaximin HRS / Acute Kidney Failure
399.5 Hemodialysis
572.4 Hepatorenal syndrome
584.5 Acute kidney failure with lesion of tubular necrosis 584.6 Acute kidney failure with lesion of renal cortical necrosis
584.7 Acute kidney failure with lesion of renal medullary [papillary] necrosis 584.8 Acute kidney failure with other specified pathological lesion in kidney 584.9 Acute kidney failure, unspecified
585.6 End stage renal disease 586 Renal failure, unspecified Variceal Bleed
456.0 Esophageal varices with bleeding
456.2 Esophageal varices in diseases classified elsewhere
CPT 43243 Esophagogastroduodenoscopy, flexible, transoral; injection sclerosis of esophageal/gastric varices CPT 43244 Esophagogastroduodenoscopy, flexible, transoral; band ligation of esophageal/gastric varices Varices (without bleeding)
456.1 Esophageal varices without mention of bleeding Other
155.0 Hepatocellular Carcinoma 782.4 Jaundice
576.23 Spontaneous Bacterial Peritonitis
CPT 37182 Transjugular intrahepatic portosystemic shunt (TIPS)
^For etiology: “alcohol only” defined as any alcohol code but not viral hepatitis. “Viral hepatitis only” defined as any viral hepatitis code but not alcohol. “Both alcohol/viral” defined as codes from both populations. Autoimmune/biliary etiologies included codes for PBC, PSC, AIH excluding cases with ETOH or viral hepatitis codes. NAFLD/other defined as 571.5 code excluding codes for alcohol, viral hepatitis, PBC, PSC, or AIH.
Abbreviations: Current Procedural Terminology (CPT); Gastrointestinal (GI), International Classification of Diseases-9 Codes (ICD-9), Non-alcoholic fatty liver disease (NAFLD)
Supplemental Table 2. Definition of Anticoagulants, Anti-Platelets, and Prescription Non-Steroidal Anti-Inflammatory Medications (NSAIDS)
CATEGORY GENERIC MEDICATIONS (BRAND NAME)*
ANTICOAGULANTS (AC)
Apixaban (Eliquis)*
Dabigatran (Pradaxa)*
Dalteparin (Fragmin) Desirudin (Iprivask) Eptifibatide (Integrelin) Edoxaban (Savaysa)*
Enoxaparin (Lovenox) Fondaparinux (Arixtra) Rivaroxaban (Xarelto)*
Warfarin (Coumadin)
ANTI-PLATELETS (AP)
Abciximab (Reopro) Clopidogrel (Plavix) Dipyridamole (Persantine) Prasugrel (Effient)
Ticagrelor (Brillinta) Ticlopidine (Ticlid) Tirofiban (Aggrastat) Vorapaxar (Zontivity)
NON-STEROIDAL ANTI-INFLAMMATORY (NSAIDS)
Diclofenac (Zorvolex/Voltaren) Diclofenac-misosprostol (Arthotec) Celecoxib (Celebrex)
Ketorolac (Toradol) Piroxicam (Feldene) Indomethacin (Indocin) Meloxicam (Mobic/Vilodex)
Ketoprofen (Orudis/ Oruvail / Actron) Sulindac (Clinoril)
Diflunisal (Dolobid) Nabumetone (Relafen) Etofolac (Lodine)
* Asterisk denotes a direct oral anticoagulant (DOAC)
Supplemental Table 3. Bleeding and Decompensation Outcomes 6-18 Months After Cirrhosis Diagnosis
*OUTCOMES FREQUENCY+ n (%)
TOTAL AC AP NSAIDS NONE p-value
Bleeding Outcomes by ICD-9 / CPT codes N=18,070 N=377 N=385 N=1,231 N=16,077
Variceal GI bleed 525 (2.9%) 2 (0.5%) 5 (1.3%) 27 (2.2%) 491 (3.1%) 0.002 Non-variceal GI bleed 1210 (6.7%) 19 (5.0%) 32 (8.3%) 87 (7.1%) 1072 (6.7%) 0.314 Total bleeds requiring claim$ 2285 (12.6%) 50 (13.3%) 63 (16.4%) 168 (13.6%) 2004 (12.5%) 0.088 Development of Portal HTN Complications by ICD-9 / CPT^ N=11,563& N=164 N=218 N=884 N=10,297
Total Portal HTN Complications 1925 (16.6%) 30 (18.3%) 49 (22.5%) 139 (15.7%) 1707 (16.6%) 0.101 Ascites 987 (8.5%) 20 (12.2%) 26 (11.9%) 66 (7.5%) 875 (8.5%) 0.062 Hepatic Encephalopathy 512 (4.4%) 6 (3.7%) 11 (5.0%) 37 (4.2%) 458 (4.4%) 0.906
HCC 131 (1.1%) 1 (0.6%) 4 (1.8%) 13 (1.5%) 113 (1.1%) 0.498
HRS / Acute Renal Failure / CKD 230 (2.0%) 3 (1.8%) 9 (4.1%) 23 (2.6%) 195 (1.9%) 0.062 Jaundice 152 (1.3%) 3 (1.8%) 1 (0.5%) 10 (1.1%) 138 (1.3%) 0.605
SBP 34 (0.3%) 0 (0.0%) 1 (0.5%) 1 (0.1%) 32 (0.3%) 0.621
TIPS 20 (0.2%) 0 (0.0%) 1 (0.5%) 0 (0.0%) 19 (0.2%) 0.403
Varices 737 (6.4%) 5 (3.0%) 11 (5.0%) 47 (5.3%) 674 (6.5%) 0.119
* Development of outcomes was evaluated in the outcome assessment period defined as the year following the end of the landmark time (i.e., from 6 months to 18 months after cirrhosis index date).
+Anticoagulant, antiplatelet, prescription NSAIDs evaluated from cirrhosis index to six months after index.
$ Includes variceal bleeds, non-variceal GI bleeds, and other bleeds requiring claim as delineated in Supplemental Table 1
& Note different sample size due to different population exclusions in landmark period. This sample size is comprised of everyone who did NOT experience a decompensation event from cirrhosis index
through six months after index (i.e., during drug exposure). This population still could have had portal hypertensive complications prior to cirrhosis index.
^ Complications were defined as having at least one ICD-9 or CPT code for portal hypertensive complications as delineated in Supplemental Table 1.
Abbreviations: Anticoagulant (AC); Anti-platelet (AP); Charlson Comorbidity Index (CCI); Current Procedural Terminology (CPT); Gastrointestinal (GI); International Classification of Diseases (ICD); Non- steroidal anti-inflammatory drugs (NSAIDS)
