Table 3.
Resource use (excluding inpatient visits) across included studies
| Study | Country | Population | N | Outcome | Resource use |
|---|---|---|---|---|---|
| LT-related | |||||
| Agopian et al. [22] | US | Patients who underwent primary LT, 1993–2011 | Mechanical ventilator use before LT, % |
NASH vs non-NASH: 16 vs 17 HCV: 15; HBV: 12; ALD: 24; CC: 22; PBC/PSC: 12 |
|
|
NASH aetiology Non-NASH aetiology HBV HCV ALD CC PBC/PSC |
144 1150 691 127 185 58 89 |
Vasopressor use before LT, % |
NASH vs non-NASH: 17 vs 10* HCV: 8*; HBV: 8*; ALD: 19; CC: 16; PBC/PSC: 7 |
||
| Dialysis before LT, % |
NASH vs non-NASH: 45 vs 31* HCV: 26*; HBV: 16*; ALD: 47; CC: 37; PBC/PSC: 28* |
||||
| Operative time, mins |
NASH vs non-NASH: 402 vs 322* HCV: 323*; HBV: 308*; ALD: 330*; CC: 315*; PBC/PSC: 322* |
||||
| Intraoperative transfusion, uPRBC, % |
NASH vs non-NASH: 18 vs 14* HCV: 14*; HBV: 13*; ALD: 16; CC: 14*; PBC/PSC: 12* |
||||
| Retransplantation, % |
NASH vs non-NASH: 7 vs 7 HCV: 8; HBV: 2; ALD: 6; CC: 3; PBC/PSC: 6 |
||||
| Cirrhosis-related | |||||
| Axley et al. [27] | US | Hospital admissions for cirrhosis with ACLF (2006–2014) | NASH vs non-NASH: | ||
|
Total NASH aetiology Non-NASH |
112,174 8903 103,271b |
Endoscopic evaluation, % Dialysis use, % Ventilator use, % Long-term care, % |
5 vs 2–10; p NR 45 vs 36; p < 0.0001 78 vs 76–82; p NR 32 vs 26; p = 0.0001 |
||
| NASH-related with or without comorbidities | |||||
| Balp et al. [26] | EU5a | Respondents to the National Health and Wellness Survey | Healthcare resource use in past 6 months, adjusted mean (SE): | NASH vs matched general population: | |
|
NASH Unmatched general pop. Matched general pop. Unmatched T2D Matched T2D |
184 79,267 736 4783 368 |
General/family practitioner visits | 3.80 (0.33) vs 2.23 (0.10); p < 0.001 | ||
| Specialists (any type) visits | 6.94 (0.69) vs 3.77 (0.19); p < 0.001 | ||||
| Cardiologist visits | 0.32 (0.05) vs 0.19 (0.02); p = 0.013 | ||||
| Gastroenterologist visits | 0.28 (0.06) vs 0.07 (0.01); p < 0.001 | ||||
| Endocrinologist visits | 0.27 (0.05) vs 0.04 (0.01); p < 0.001 | ||||
| Internist visits | 0.28 (0.06) vs 0.12 (0.02); p = 0.002 | ||||
| Diabetologist visits | 0.22 (0.06) vs 0.09 (0.02); p = 0.007 | ||||
| Psychiatrist visits | 0.37 (0.12) vs 0.16 (0.04); p = 0.034 | ||||
| Hepatologist visits | 0.07 (0.02) vs 0.01 (0.00); p = 0.000 | ||||
| HCP visits | 10.73 (NR) vs 6.01 (NR); p < 0.001 | ||||
| ER visits | 0.57 (NR) vs 0.22 (NR); p < 0.001 | ||||
| Healthcare resource use in past 6 months, adjusted mean (SE): | NASH vs matched T2D: | ||||
| General/family practitioner visits | 3.68 (0.36) vs 2.81 (0.19); p = 0.033 | ||||
| Specialists (any type) visits | 7.13 (0.73) vs 5.01 (0.35); p = 0.008 | ||||
| Cardiologist visits | 0.31 (0.07) vs 0.23 (0.04); p = 0.333 | ||||
| Gastroenterologist visits | 0.28 (0.07) vs 0.08 (0.02); p = 0.001 | ||||
| Endocrinologist visits | 0.27 (0.07) vs 0.09 (0.02); p = 0.004 | ||||
| Internist visits | 0.26 (0.09) vs 0.23 (0.05); p = 0.740 | ||||
| Diabetologist visits | 0.26 (0.05) vs 0.27 (0.04); p = 0.964 | ||||
| Psychiatrist visits | 0.38 (0.11) vs 0.16 (0.04); p = 0.041 | ||||
| Hepatologist visits | 0.09 (0.03) vs 0.00 (0.00); p < 0.001 | ||||
| HCP visits | 10.85 (NR) vs 7.86 (NR); p = 0.006 | ||||
| ER visits | 0.65 (NR) vs 0.23 (NR); p = 0.009 | ||||
| Prescription treatment for T2D, % | NASH vs general population vs T2D: | ||||
| Use of a prescription | 20.1 vs 5.0 vs 82.6 | ||||
| Use of insulin prescription | 5.4 vs 1.4 vs 23.0 | ||||
| Use of non-insulin prescription | 19.6 vs 4.5 vs 75.1 | ||||
| Geier et al. [29] | US, France, Germany | NASH patients (NASH-Atlas program July–November 2017) | Annual non-routine HCRU, mean (SD) | Total population: 4.2 (3.1) | |
|
Total BC NASH Phenotypic NASH French NASH population German NASH population US NASH population F1 fibrosis F2 fibrosis F3 fibrosis F4 fibrosis |
1216 786 430 227 287 702 175 278 211 47 |
Physician visits |
BC vs phenotypic NASH: 4.5 vs 3.7 FR vs DE vs US: 4.6 vs 4.6 vs 3.9 |
||
| Outpatient visits |
Total population: 1.6 (2.0) BC vs phenotypic NASH: 1.8 vs 1.4 FR vs DE vs US: 2.3 vs 1.3 vs 1.5 |
||||
| ER visits |
Total population: 0.3 (1.0) BC vs phenotypic NASH: 0.4 vs 0.4 FR vs DE vs US: 0.4 vs 0.5 vs 0.2 |
||||
| Tests/procedures used for NASH diagnosis, % | |||||
| Liver biopsy |
Total NASH vs BC NASH: 66.0 vs 100 FR vs DE vs US: 47.1 vs 65.9** vs 72.1** |
||||
| Ultrasound |
Total NASH vs BC NASH: 62.5 vs 59.0 FR vs DE vs US: 67.4** vs 57.1 vs 63.1 |
||||
| FibroScan (transient elastography) |
Total NASH vs BC NASH: 23.2 vs 21.1 FR vs DE vs US: 54.6*** vs 23.7** vs 12.8 |
||||
| Serum transaminase (ALT, AST) |
Total NASH vs BC NASH: 65.3 vs 64.5 FR vs DE vs US: 72.7*** vs 62.0 vs 64.2 |
||||
| GGT |
Total NASH vs BC NASH: 43.8 vs 38.3 FR vs DE vs US: 70.0*** vs 58.2** vs 29.3 |
||||
| Lipid profile |
Total NASH vs BC NASH: 49.3 vs 37.3 FR vs DE vs US: 58.1** vs 57.8** vs 43.0 |
||||
| Platelet count |
Total NASH vs BC NASH: 44.4 vs 40.4 FR vs DE vs US: 59.9*** vs 43.9 vs 39.6 |
||||
| Clotting studiesd |
Total NASH vs BC NASH: 33.1 vs 27.1 FR vs DE vs US: 32.6 vs 45.6*** vs 28.2 |
||||
| ARFI imaging |
Total NASH vs BC NASH: 2.2 vs 2.4 FR vs DE vs US: 1.9 vs 1.3 vs 3.8 |
||||
| CT scan |
Total NASH vs BC NASH: 16.2 vs 17.2 FR vs DE vs US: 19.2 vs 9.3 vs 14.3 |
||||
| MRI |
Total NASH vs BC NASH: 9.5 vs 9.0 FR vs DE vs US: 7.1 vs 9.7 vs 15.0 |
||||
| MRE |
Total NASH vs BC NASH: 4.5 vs 5.0 FR vs DE vs US: 4.3 vs 3.5 vs 5.9 |
||||
| FibroTest/FibroSure |
Total NASH vs BC NASH: 19.6 vs 17.4 FR vs DE vs US: 15.7 vs 40.1 vs 12.9 |
||||
| Fibrosis-4 index |
Total NASH vs BC NASH: 6.2 vs 6.6 FR vs DE vs US: 5.7 vs 5.7 vs 7.7 |
||||
| APRI |
Total NASH vs BC NASH: 20.6 vs 21.6 FR vs DE vs US: 22.6 vs 18.5 vs 17.1 |
||||
| Steatosis, activity and fibrosis score |
Total NASH vs BC NASH: 8.1 vs 8.9 FR vs DE vs US: 8.3 vs 6.2 vs 9.1 |
||||
| NashTest |
Total NASH vs BC NASH: 9.5 vs 10.2 FR vs DE vs US: 5.3 vs 13.2 vs 17.1 |
||||
| NAFLD fibrosis score |
Total NASH vs BC NASH: 14.8 vs 15.5 FR vs DE vs US: 14.4 vs 13.2 vs 17.1 |
||||
| NAFLD activity score |
Total NASH vs BC NASH: 15.9 vs 18.7 FR vs DE vs US: 15.7 vs 9.7 vs 21.3 |
||||
| Enhanced liver fibrosis panel score |
Total NASH vs BC NASH: 3.9 vs 3.4 FR vs DE vs US: 3.3 vs 0.4 vs 8.4 |
||||
| Circulating levels of CK-18 |
Total NASH vs BC NASH: 4.4 vs 5.2 FR vs DE vs US: 2.4 vs 2.6 vs 10.5 |
||||
| Tests/procedures used for NASH monitoring, % | |||||
| Liver biopsy |
Total NASH vs BC NASH: 11.6 vs 16.7 FR vs DE vs US: 13.1 vs 2.6 vs 15.0 |
||||
| Ultrasound |
Total NASH vs BC NASH: 54.4 vs 57.3 FR vs DE vs US: 53.7 vs 48.9 vs 60.6 |
||||
| FibroScan (transient elastography) |
Total NASH vs BC NASH: 17.6 vs 18.2 FR vs DE vs US: 11.7 vs 49.3 vs 21.6 |
||||
| Serum transaminase (ALT, AST) |
Total NASH vs BC NASH: 61.8 vs 61.6 FR vs DE vs US: 64.1 vs 69.2 vs 61.7 |
||||
| GGT |
Total NASH vs BC NASH: 41.1 vs 38.8 FR vs DE vs US: 22.8 vs 62.1 vs 57.5 |
||||
| Lipid profile |
Total NASH vs BC NASH: 49.3 vs 37.3 FR vs DE vs US: 30.5 vs 31.7 vs 58.5 |
||||
| Platelet count |
Total NASH vs BC NASH: 44.4 vs 40.4 FR vs DE vs US: 37.7 vs 45.4 vs 42.9 |
||||
| Clotting studiesd |
Total NASH vs BC NASH: 33.1 vs 27.1 FR vs DE vs US: 22.9 vs 19.4 vs 43.2 |
||||
| ARFI imaging |
Total NASH vs BC NASH: 2.5 vs 3.4 FR vs DE vs US: 2.1 vs 1.3 vs 4.2 |
||||
| CT scan |
Total NASH vs BC NASH: 8.2 vs 9.5 FR vs DE vs US: 9.8 vs 1.8 vs 9.4 |
||||
| MRI |
Total NASH vs BC NASH: 5.9 vs 6.0 FR vs DE vs US: 4.8 vs 4.0 vs 10.1 |
||||
| MRE |
Total NASH vs BC NASH: 5.0 vs 3.8 FR vs DE vs US: 1.6 vs 3.1 vs 7.3 |
||||
| FibroTest/FibroSure |
Total NASH vs BC NASH: 17.4 vs 16.3 FR vs DE vs US: 12.7 vs 29.1 vs 12.9 |
||||
| Fibrosis-4 index |
Total NASH vs BC NASH: 6.6 vs 7.8 FR vs DE vs US: 6.0 vs 4.0 vs 8.7 |
||||
| APRI |
Total NASH vs BC NASH: 21.6 vs 18.6 FR vs DE vs US: 18.7 vs 10.1 vs 20.2 |
||||
| Steatosis, activity and fibrosis score |
Total NASH vs BC NASH: 8.9 vs 6.2 FR vs DE vs US: 5.7 vs 4.0 vs 8.0 |
||||
| NashTest |
Total NASH vs BC NASH: 10.2 vs 9.3 FR vs DE vs US: 5.3 vs 5.3 vs 16.4 |
||||
| NAFLD fibrosis score |
Total NASH vs BC NASH: 15.5 vs 12.9 FR vs DE vs US: 9.3 vs 9.3 vs 18.1 |
||||
| NAFLD activity score |
Total NASH vs BC NASH: 18.7 vs 15.9 FR vs DE vs US: 11.5 vs 8.4 vs 23.3 |
||||
| Enhanced liver fibrosis panel score |
Total NASH vs BC NASH: 3.4 vs 4.3 FR vs DE vs US: 3.6 vs 0.4 vs 7.7 |
||||
| Circulating levels of CK-18 |
Total NASH vs BC NASH: 5.2 vs 5.3 FR vs DE vs US: 2.8 vs 2.2 vs 8.4 |
||||
| NASH diagnosis and monitoring tests, mean number (SD) | |||||
| Liver biopsy |
Total NASH vs BC NASH: 1.2 (0.7) vs 1.2 (0.7) FR vs DE vs US: 1.2 (0.8) vs 1.1 (0.5) vs 1.2 (0.5) |
||||
| Ultrasound |
Total NASH vs BC NASH: 2.7 (2.3) vs 2.9 (2.5) FR vs DE vs US: 2.4 (2.4) vs 2.5 (1.4) vs 3.7 (2.5) |
||||
| ARFI imaging |
Total NASH vs BC NASH: 1.5 (1.2) vs 1.6 (1.2) FR vs DE vs US: 1.5 (1.0) vs 1.0 (1.2) vs 1.8 (1.3) |
||||
| CT scan |
Total NASH vs BC NASH: 1.4 (0.8) vs 1.5 (0.8) FR vs DE vs US: 1.4 (0.8) vs 1.6 (0.9) vs 1.4 (0.8) |
||||
| MRI |
Total NASH vs BC NASH: 1.5 (1.2) vs 1.7 (1.4) FR vs DE vs US: 1.6 (1.4) vs 1.5 (0.7) vs 1.6 (1.0) |
||||
| MRE |
Total NASH vs BC NASH: 1.7 (1.1) vs 1.8 (1.3) FR vs DE vs US: 1.6 (1.2) vs 1.6 (1.0) vs 1.9 (1.1) |
||||
| Fibroscan (transient elastography) |
Total NASH vs BC NASH: 2.0 (1.4) vs 2.1 (1.5) FR vs DE vs US: 2.0 (1.6) vs 2.1 (1.3) vs 2.0 (1.1) |
||||
| Serum transaminases (AST, ALT) |
Total NASH vs BC NASH: 5.0 (4.0) vs 5.0 (4.2) FR vs DE vs US: 4.7 (4.2) vs 5.3 (3.2) vs 5.4 (4.2) |
||||
| GGT |
Total NASH vs BC NASH: 4.7 (3.6) vs 5.0 (3.9) FR vs DE vs US: 3.8 (3.6) vs 5.1 (3.1) vs 5.5 (3.9) |
||||
| FibroTest/FibroSure |
Total NASH vs BC NASH: 2.0 (1.4) vs 2.2 (1.3) FR vs DE vs US: 2.0 (1.4) vs 2.3 (1.5) vs 1.7 (1.1) |
||||
| Fibrosis-4 Index |
Total NASH vs BC NASH: 2.3 (1.6) vs 2.3 (1.7) FR vs DE vs US: 2.4 (1.8) vs 2.8 (1.7) vs 1.9 (1.2) |
||||
| APRI |
Total NASH vs BC NASH: 3.5 (2.6) vs 3.4 (2.7) FR vs DE vs US: 3.6 (2.8) vs 3.1 (2.0) vs 3.3 (2.1) |
||||
| Steatosis, activity and fibrosis score |
Total NASH vs BC NASH: 2.0 (1.4) vs 1.9 (1.3) FR vs DE vs US: 1.7 (1.2) vs 3.0 (1.1) vs 2.2 (1.6) |
||||
| NashTest |
Total NASH vs BC NASH: 1.7 (1.3) vs 1.8 (1.4) FR vs DE vs US: 2.0 (1.8) vs 1.5 (0.7) vs 1.6 (0.9) |
||||
| NAFLD fibrosis score |
Total NASH vs BC NASH: 2.5 (2.1) vs 2.4 (2.2) FR vs DE vs US: 2.7 (2.4) vs 2.7 (1.6) vs 1.8 (1.2) |
||||
| NAFLD activity score |
Total NASH vs BC NASH: 2.6 (2.8) vs 2.6 (2.8) FR vs DE vs US: 2.8 (3.1) vs 2.8 (3.6) vs 2.3 (1.5) |
||||
| Enhanced liver fibrosis panel score |
Total NASH vs BC NASH: 2.0 (1.3) vs 1.9 (1.3) FR vs DE vs US: 2.1 (1.3) vs 2.0 (1.4) vs 1.8 (1.3) |
||||
| Circulating levels of CK-18 |
Total NASH vs BC NASH: 2.4 (1.5) vs 2.6 (1.6) FR vs DE vs US: 2.3 (2.0) vs 2.5 (1.2) vs 2.5 (1.3) |
||||
| Lipid profilec |
Total NASH vs BC NASH: 4.1 (3.6) vs 4.1 (3.6) FR vs DE vs US: 3.4 (3.4) vs 4.3 (3.0) vs 5.1 (4.0) |
||||
| Platelet count |
Total NASH vs BC NASH: 5.0 (4.2) vs 5.0 (4.0) FR vs DE vs US: 4.8 (4.8) vs 5.1 (3.3) vs 5.2 (3.6) |
||||
| Clotting studiesd |
Total NASH vs BC NASH: 4.4 (4.0) vs 4.4 (3.6) FR vs DE vs US: 4.0 (4.6) vs 4.4 (2.9) vs 4.8 (3.6) |
||||
| Non-invasive laboratory tests by fibrosis stage, mean number while under physician management | F1 vs F2 vs F3 vs F4: | ||||
| Platelet count | 3.9 vs 5.1 vs 5.1 vs 7.1 | ||||
| Serum transaminases | 4.1 vs 5.1 vs 5.4 vs 6.9 | ||||
| GGT | 4.4 vs 4.9 vs 4.9 vs 7.5 | ||||
| Clotting studies | 4.0 vs 4.4 vs 4.2 vs 6.9 | ||||
| Lipid profile | 3.3 vs 4.2 vs 4.3 vs 5.8 | ||||
| APRI | 3.5 vs 3.1 vs 3.4 vs 5.5 | ||||
| CK-18 | 2.3 vs 2.8 vs 2.6 vs NR | ||||
| Non-invasive procedures by fibrosis stage, mean number while under physician management | F1 vs F2 vs F3 vs F4: | ||||
| Ultrasound | 2.4 vs 3.1 vs 2.7 vs 4.0 | ||||
| Fibroscan (transient elastography) | 1.6 vs 2.2 vs 2.3 vs 2.6 | ||||
| MRE | 2.3 vs 1.8 vs 1.8 vs 0.7 | ||||
| MRI | 1.3 vs 1.9 vs 1.9 vs 1.3 | ||||
| ARFI | 1.3 vs 1.6 vs 1.4 vs 3.0 | ||||
| CT scan | 1.3 vs 1.6 vs 1.4 vs 1.7 | ||||
| Current pharmacological interventions, % of total population | |||||
| Statins | 2.5 | ||||
| Vitamin E | 23.8 | ||||
| Metformin | 20.2 | ||||
| Vitamin D | 10.4 | ||||
| Ursodeoxycholic acid | 9.3 | ||||
| Omega-3 fatty acids | 7.5 | ||||
| Thiazolidinediones | 5.5 | ||||
| Fibrates (fenofibrate) | 4.5 | ||||
| Orlistat | 3.9 | ||||
| GLP-1 analogues | 4.0 | ||||
| Pentoxifylline | 3.7 | ||||
| Betaine | 1.2 | ||||
| Current non-pharmacological interventions, % of total population | |||||
| Lifestyle modification | 64.6 | ||||
| Watchful waiting | 14.6 | ||||
| Bariatric surgery | 6.3 | ||||
| Endoscopic intervention | 5.7 | ||||
| Put on a waiting list for a liver transplant | 3.6 | ||||
| O’Hara et al. [30] | US and EU5a | NASH | Diagnostic/imaging tests, % | ||
|
Total US EU5 Spain |
3754 1221 2533 522 |
Liver biopsy | Total: NR; US vs ES: 57 vs 25 | ||
| Ultrasound imaging | Total: 68; EU5 vs US: 76 vs 51 | ||||
| Fibroscan (transient elastography) | Total: 33; EU5 vs US: 42 vs 13 | ||||
| AST/ALT ratio | Total: 23 | ||||
| NAFLD fibrosis score | Total: 9 | ||||
| BARD scoree | Total: 3 | ||||
| FIB-4 score | Total: 3 | ||||
| CK-18 | Total: 3 | ||||
aEU5 includes France, Germany, Italy, Spain and the UK
bNon-NASH total is sum of alcohol-related cirrhosis (n = 27,890), viral hepatitis cirrhosis (n = 9491) and ‘other’ cirrhosis (n = 65,890)
cCholesterol, LDL, HDL and triglycerides
dProthrombin time, international normalised ratio
eBARD score is a simple clinical score based on BMI ≥28 kg/m2, AST/ALT Ratio ≥0.8 and Diabetes mellitus
ACLF acute-on-chronic liver failure, ALD alcoholic liver disease, ALT alanine aminotransferase, APRI AST to Platelet Ratio Index, ARFI acoustic radiation force impulse, AST aspartate aminotransferase, BC biopsy-confirmed, CC compensated cirrhosis, CK-18 cytokeratin-18, CT computed tomography, DE German cohort, ER emergency room, ES Spanish cohort, F fibrosis stage, FIB-4 Fibrosis-4, FR French cohort, GGT gamma-glutamyl transferase, GLP glucagon-like peptide, HBV hepatitis B virus, HCP healthcare professional, HCRU healthcare resource utilisation, HCV hepatitis C virus, HDL high-density lipoprotein, LDL low-density lipoprotein, LT liver transplantation, MRE magnetic resonance enterography, MRI magnetic resonance imaging, NAFLD non-alcoholic fatty liver disease, NASH non-alcoholic steatohepatitis, NASH-Atlas Growth from Knowledge (currently Ipsos) Disease Atlas Real-World Evidence program, NR not reported, PBC primary biliary cirrhosis, PSC primary sclerosing cholangitis, SD standard deviation, SE standard error, T2D type 2 diabetes, uPRBC units packed red blood cells, US US cohort
*p < 0.05 versus NASH or NAFLD/NASH; **p < 0.05 versus lowest reporting country; ***p < 0.05 versus all other countries