Liver disease epidemiology and burden in patients with alterations in plasma protein metabolism: German retrospective insurance claims analysis

Table 1 Demographics and baseline characteristics, n (%)

	Patients with APPM and liver disease: APPM cohort, n = 2680			Patients without APPM and with liver disease: Control cohort, n = 26299
	All patients, n = 2680	Patients with fibrosis, n = 96	Patients with cirrhosis, n = 26261
Total observed patient-years	6118	283	5944	70261
Median follow-up, yr (IQR)	1.5 (0.4-3.7)	2.3 (0.8-4.7)	1.5 (0.4-3.7)	2.0 (0.5-4.4)
Female sex2	840 (31.3)	41 (42.7)	815 (31.0)	8595 (32.7)
Median age, yr (IQR)3	63.0 (54.0-73.0)	64.5 (53.0-76.5)	63.0 (54.0-73.0)	65.0 (56.0-76.0)
0-14 yr	14 (0.5)	6 (6.3)	10 (0.4)	49 (0.2)
15-29 yr	10 (0.4)	0	10 (0.4)	156 (0.6)
30-44 yr	183 (6.8)	10 (10.4)	177 (6.7)	1420 (5.4)
45-59 yr	818 (30.5)	21 (21.9)	814 (31.0)	7516 (28.6)
60-74 yr	1046 (39.0)	31 (32.3)	1029 (39.2)	9564 (36.4)
75-89 yr	577 (21.5)	25 (26.0)	557 (21.2)	7090 (27.0)
≥ 90 yr	32 (1.2)	3 (3.1)	29 (1.1)	504 (1.9)
With care needs4	547 (20.4)	33 (34.3)	528 (20.1)	4934 (18.8)
Median CCI5 (IQR)	3.0 (1.0-5.0)	4.0 (1.5-6.0)	3.0 (1.0-5.0)	3.0 (1.0-5.0)
Most common liver-related comorbidities
“Other” liver disease6	679 (25.3)	26 (27.1)	669 (25.5)	6298 (23.9)
Non-alcoholic steatohepatitis	17 (0.6)	1 (1.0)	16 (0.6)	150 (0.6)
Chronic hepatitis	12 (0.5)	0	12 (0.5)	163 (0.6)
Respiratory system-related comorbidities	827 (30.9)	41 (42.7)	806 (30.7)	8333 (31.7)
Most common comorbidities
Hypertension	1751 (65.3)	64 (66.7)	1710 (65.1)	17278 (65.7)
Type 2 diabetes mellitus	1103 (41.2)	40 (41.7)	1082 (41.2)	10766 (40.9)
Dyslipidaemia	832 (31.0)	35 (36.5)	813 (31.0)	8932 (34.0)
Alcohol-related disorders7	650 (24.3)	17 (17.7)	649 (24.7)	6127 (23.3)
Heart failure	605 (22.6)	21 (21.9)	591 (22.5)	6071 (23.1)

Data are n (%) unless otherwise indicated.

¹In total, 42 patients with fibrosis progressed to cirrhosis during follow-up and are included in both fibrosis and cirrhosis subgroups.

²Patients in the alterations in plasma protein metabolism (AAPM) cohort were significantly younger than patients in the control cohort (Wilcoxon rank-sum test: P < 0.001).

³There was no statistically significant difference in the proportion of females between cohorts (Wilcoxon rank-sum test: P = 0.159).

⁴Dummy variable for patients who were classified in any of the five care levels which determine the benefits from long-term care insurance in Germany.

⁵Assessed based on diagnoses observed in the 12 mo before the index date.

⁶Captured using the K76 code in the German Modification of the International Classification of Diseases-10^th Revision, and includes central hemorrhagic necrosis of the liver, chronic congestive liver, fatty liver (not otherwise classified), hepatorenal syndrome, liver infarction, peliosis hepatis, portal hypertension, veno-occlusive liver disease and other/unspecified liver disease.

⁷Patients with alcohol-related disorders diagnosed before [1172 (43.7%)] and after [1042 (38.9%)] diagnosis of APPM were detected in the cohort with APPM and liver disease.

CCI: Charlson comorbidity index; IQR: Interquartile range.

Table 2 Diagnostic procedures within 12 mo after the index date, n (%)

Diagnostic procedure	Patients with APPM and liver disease: APPM cohort, n = 2680
Imaging procedure1	1778 (66.3)
Laboratory test2	1366 (51.0)
Liver biopsy	207 (7.7)
AAT phenotyping	55 (2.1)
Liver function test3	13 (0.5)

Data are n (%).

¹Included sonographies, computed tomography scans, magnetic resonance imaging procedures, angiographies of the abdomen and magnetic resonance elastographies.

²Included albumin and bilirubin measurements.

³Liver function test with intravenous application of a ¹³C-labeled substrate.

AAT: Alpha-1 antitrypsin; APPM: Alterations in plasma protein metabolism.

Table 3 Procedures indicating disease progression stratified by fibrosis or cirrhosis

Parameter	Patients with fibrosis				Patients with cirrhosis
	Liver resection		Liver transplantation		Liver resection		Liver transplantation
	Patients with APPM, n = 96	Patients without APPM, n = 1445	Patients with APPM, n = 96	Patients without APPM, n = 1445	Patients with APPM, n = 2626	Patients without APPM, n = 25134	Patients with APPM, n = 2626	Patients without APPM, n = 25134
Patients with event during follow-up	15 (15.6)	93 (6.4)	6 (6.3)	3 (0.2)	87 (3.3)	488 (1.9)	78 (3.0)	31 (0.1)
Patients included in the KM analysis1	85 (88.5)	1373 (95.0)	94 (97.9)	1442 (99.8)	2606 (99.2)	24849 (98.9)	2621 (99.8)	25034 (99.6)
Median follow-up in patients without an event, yr (IQR)2	2.3 (0.7-5.0)	3.0 (1.2-5.2)	2.3 (0.7-4.7)	2.8 (1.2-5.1)	1.5 (0.4-3.7)	1.9 (0.5-4.4)	1.5 (0.4-3.7)	1.9 (0.5-4.4)
Failure rate
After 1 yr	3 (4.2)	15 (1.2)	1 (1.2)	1 (0.1)	40 (2.0)	198 (1.0)	26 (1.4)	8 (< 0.1)
After 3 yr	3 (4.2)	18 (1.5)	3 (4.8)	1 (0.1)	56 (3.4)	258 (1.5)	53 (3.6)	23 (0.2)
After 5 yr	3 (4.2)	20 (1.9)	4 (7.3)	1 (0.1)	64 (4.7)	289 (1.9)	66 (5.6)	25 (0.2)
P value (log-rank test)	0.025		< 0.001		< 0.001		< 0.001

Data are n (%) unless otherwise indicated.

¹Patients with the event on the index date were excluded from the Kaplan-Meier (KM) analysis. As there were no patients with liver incision in the alterations in plasma protein metabolism cohort, and only one patient in the control cohort, this outcome is not reported.

²There were no patients with fibrosis who had an infection/inflammatory reaction due to prothesis/implant/graft. For one patient in the control cohort, the index date and end date were the same; this patient was automatically excluded from the KM analysis. Median follow-up in patients without the event was estimated via the reverse KM method.

IQR: Interquartile range; APPM: Alterations in plasma protein metabolism.