Risteys · FIBROLIV

Endpoint definition steps	FinnGen
Phenotype data	520210
1. Apply sex-specific rule None	520210
2. Check conditions None	520210
3. Check pre-conditions, main-only, mode, registry filters Registry filters: Hospital discharge: ICD-10 — K74.0 Cause of death: ICD-10 — K74.0 2 out of 7 registries used, show all original rules.	222
4. Check minimum number of events None	222
5. Include endpoints None	222
6. Filter based on genotype QC (FinnGen only)	222

Summary Statistics

↥

-FinRegistry-

Key figures

	All	Female	Male
Number of individuals
Whole population	1501	735	747
Only index persons	1232	625	607
Unadjusted period prevalence (%)
Whole population	0.02	0.02	0.02
Only index persons	0.02	0.02	0.02
Median age at first event (years)
Whole population	59.22	59.75	58.57
Only index persons	58.22	58.24	58.20

-FinnGen-

Key figures

	All	Female	Male
Number of individuals	222	115	107
Unadjusted period prevalence (%)	0.04	0.04	0.05
Median age at first event (years)	57.16	55.12	59.34

-FinRegistry-

Age distribution of first events

-FinnGen-

Age distribution of first events

-FinRegistry-

Year distribution of first events

-FinnGen-

Year distribution of first events

-FinRegistry-

Cumulative Incidence Function

-FinnGen-

Cumulative Incidence Function

No data

CodeWAS (R11)

↥

CodeWAS is a tool for exploring the associations between an endpoint and all of the medical codes and drug codes.

This is a new tool, please reach out using the contact form for feedback and improvement ideas.

First, a cohort is built by matching controls to the endpoint cases using year of birth and sex. Then, a Fisher test is done for all the medical codes and drug codes between the cases and controls of this cohort. Codes are reported in the table below if they have −log₁₀(p-value) ≥ 6.

Matched cohort

Matched cases
195: Matched controls
1949

Code

Vocabulary

Description

Odds Ratio

-log₁₀(p)

N matched cases

N matched controls

K74.0

ICD-10 Finland

Hepatic fibrosis

+∞

282.3

195

K74.6

ICD-10 Finland

Other and unspecified cirrhosis of liver

+∞

57.1

JJ2AT

NOMESCO Finland

Biopsy of liver with ultrasound guidance

56.9

43.9

JN1AE

NOMESCO Finland

Ultrasound examination of upper part of abdomen

13.2

37.5

UJD10

NOMESCO Finland

Esophagoscopy, gastroscopy and duodenoscopy

6.8

33.6

118

358

I85.9

ICD-10 Finland

Oesophageal varices without bleeding

+∞

27.8

K76.0

ICD-10 Finland

Fatty (change of) liver, not elsewhere classified

23.7

26.0

A05AA02

ATC

ursodeoxycholic acid; oral

50.3

25.4

K70.3

ICD-10 Finland

Alcoholic cirrhosis of liver

246.5

22.1

JJ1LE

NOMESCO Finland

Ultrasound elastography of liver

38.8

21.8

R74.0

ICD-10 Finland

Elevation of levels of transaminase and lactic acid dehydrogenase [LDH]

29.5

21.1

E11.9

ICD-10 Finland

Type 2 diabetes mellitus, without complications

4.5

18.7

264

C03DA01

ATC

spironolactone; oral

7.3

18.5

103

Kela drug reimbursment

Diabetes, insulin-treated

4.1

17.6

325

R18

ICD-10 Finland

Ascites

28.7

17.4

K74.3

ICD-10 Finland

Primary biliary cirrhosis

69.7

17.1

Z94.4

ICD-10 Finland

Liver transplant status

+∞

16.9

JN3DE

NOMESCO Finland

Abdominal extensive ultrasoudn examination with blood flow measurements after transplantation

98.7

16.9

JCA22

NOMESCO Finland

Endoscopic ligature of oesophageal varices

+∞

15.8

JJC00

NOMESCO Finland

Allogenic transplantation of liver

+∞

15.8

JN3AE

NOMESCO Finland

Abdominal ultrasound examination

5.0

15.7

146

JA3AT

NOMESCO Finland

Cathetrisation of abdominal cavity with ultrasound guidance

27.6

15.0

A10BA02

ATC

metformin; oral

3.6

14.8

348

A10AE04

ATC

insulin glargine; parenteral

6.2

14.8

K76.9

ICD-10 Finland

Liver disease, unspecified

22.1

14.1

C03CA01

ATC

furosemide; systemic

3.5

13.3

298

215

Kela drug reimbursment

Diabetes, non-insulin-treated

3.4

12.7

306

T90

ICPC

Diabetes non-insulin dependent

3.5

12.3

276

K75.9

ICD-10 Finland

Inflammatory liver disease, unspecified

19.7

12.3

K73.2

ICD-10 Finland

Chronic active hepatitis, not elsewhere classified

49.9

12.0

K83.0

ICD-10 Finland

Cholangitis

32.3

11.8

L04AX01

ATC

azathioprine; systemic

7.7

11.6

JJ9AE

NOMESCO Finland

Ultrasound examination of liver transplant

+∞

11.6

127

Kela drug reimbursment

Transplant complication

16.8

11.0

E11.8

ICD-10 Finland

Type 2 diabetes mellitus, with unspecified complications

5.1

10.8

C07AA05

ATC

propranolol; systemic

3.4

10.1

196

A10AB05

ATC

insulin aspart; parenteral (insulins and analog. for injection, fast-acting)

5.7

10.1

JN1CG

NOMESCO Finland

Extensive MRI examination of upper part of abdomen with high intensity magnet

9.9

9.8

K72.9

ICD-10 Finland

Hepatic failure, unspecified

104.9

9.5

K73.80

ICD-10 Finland

Non-alcoholic fatty liver (NASH, Non Alcoholic Steatohepatitis)

104.9

9.5

C22.0

ICD-10 Finland

Malignant neoplasm: Liver cell carcinoma

104.9

9.5

K70.0

ICD-10 Finland

Alcoholic fatty liver

104.9

9.5

K70.4

ICD-10 Finland

Alcoholic hepatic failure

+∞

9.4

A12AX

ATC

Calcium, combinations with vitamin D and/or other drugs

2.7

9.3

388

285

Kela drug reimbursment

Dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide (adults)

7.2

9.3

A41.9

ICD-10 Finland

Sepsis, unspecified

9.8

9.3

JN3AD

NOMESCO Finland

Abdominal CT examination

5.0

9.2

JN1DG

NOMESCO Finland

Very extensive MRI examination of upper part of abdomen with high intensity magnet

16.6

9.2

L04AD01

ATC

ciclosporin; systemic

16.6

9.2

B18.2

ICD-10 Finland

Chronic viral hepatitis C

38.6

9.1

D50.9

ICD-10 Finland

Iron deficiency anaemia, unspecified

5.2

9.1

SPAT1262

SPAT

Handing over of treatment supplies

3.1

8.9

217

A10BH01

ATC

sitagliptin; oral

4.1

8.5

K70.9

ICD-10 Finland

Alcoholic liver disease, unspecified

+∞

8.4

K74.2

ICD-10 Finland

Hepatic fibrosis with hepatic sclerosis

+∞

8.4

E11.7

ICD-10 Finland

Type 2 diabetes mellitus, with multiple complications

7.5

8.0

L04AA06

ATC

mycophenolic acid; systemic

11.5

7.9

D97

ICPC

Liver disease NOS

46.9

7.8

202

Kela drug reimbursment

Connective tissue diseases, rheumatoid arthritis and comparable disease

3.5

7.5

119

A10BB12

ATC

glimepiride; oral

5.1

7.5

ZXE40

NOMESCO Finland

More than seven and less than nine hours

10.0

7.4

SPAT1156

SPAT

Guidance concerning treatment of rash and skin

3.5

7.4

115

A10AC01

ATC

insulin (human); parenteral (insulins and analog. for injection, intermediate-acting)

4.7

7.3

JJ5AT

NOMESCO Finland

+∞

7.3

K72.1

ICD-10 Finland

Chronic hepatic failure

+∞

7.3

R17

ICD-10 Finland

Hyperbilirubinaemia, with or without jaundice, not elsewhere classified

16.5

7.3

D64.9

ICD-10 Finland

Anaemia, unspecified

3.4

7.2

117

N17.9

ICD-10 Finland

Acute renal failure, unspecified

7.5

7.2

160

Kela drug reimbursment

exenatide

10.6

7.1

UJF30

NOMESCO Finland

Ileoscopy through colon

3.8

7.0

L04AD02

ATC

tacrolimus; systemic (calcineurin inhibitors)

14.5

7.0

SPAT1250

SPAT

Comprehensive monitoring of chronic illness

2.5

7.0

349

A07EA06

ATC

budesonide; oral, local oral

6.9

6.8

E11.6

ICD-10 Finland

Type 2 diabetes mellitus, with other specified complications

23.5

6.7

TPH15

NOMESCO Finland

Insertion of central venous catheter through external or internal jugular vein

4.3

6.7

D69.6

ICD-10 Finland

Thrombocytopenia, unspecified

10.6

6.6

TPH07

NOMESCO Finland

Cathetrisation of artery

3.4

6.6

107

J01EE01

ATC

sulfamethoxazole and trimethoprim; systemic

4.8

6.6

R50.9

ICD-10 Finland

Fever, unspecified

3.0

6.5

139

8170/3-C22.0

ICD-O-3

Hepatocellular carcinoma, NOS, of liver

72.1

6.5

GD1AA

NOMESCO Finland

Thorax X-ray examination

2.2

6.5

606

Z04.8

ICD-10 Finland

Examination and observation for other specified reasons

3.1

6.4

133

TK800

NOMESCO Finland

Hemodialysis

9.7

6.4

A10AD05

ATC

insulin aspart; parenteral (insulins and analog. for injection, intermediate- or long-acting comb. with fast-acting)

11.6

6.4

JL5BG

NOMESCO Finland

MRI examinaiton of bile and pancreas ducts with high intesity magnet

7.5

6.3

JA2AT

NOMESCO Finland

Abdominal puncture with ultrasound guidance

18.8

6.3

I85.0

ICD-10 Finland

Oesophageal varices with bleeding

+∞

6.3

A07AA11

ATC

rifaximin; oral

+∞

6.3

K74.5

ICD-10 Finland

Biliary cirrhosis, unspecified

+∞

6.3

TJJ00

NOMESCO Finland

Percutaneous needle biopsy of liver

27.7

6.3

K29.6

ICD-10 Finland

Other gastritis

27.7

6.3

GD1UA

NOMESCO Finland

Thorax X-ray examination outside radiological department

2.9

6.1

157

A10AE05

ATC

insulin detemir; parenteral

4.8

6.1

E66.00

ICD-10 Finland

Metabolic syndrome

4.1

6.0

PH2AE

NOMESCO Finland

Ultrasound examination of lower leg veins

3.3

6.0

Mortality – FinRegistry

↥

Association

Association between endpoint FIBROLIV and mortality.

Females

Parameter	HR [95% CI]	p-value
FIBROLIV	3.993 [3.15, 5.06]	< 0.001
Birth year	1.0 [0.99, 1.01]	0.94

During the follow-up period (1.1.1998 — 31.12.2019), 199 out of 599 females with FIBROLIV died.

Males

Parameter	HR [95% CI]	p-value
FIBROLIV	5.7 [4.11, 7.91]	< 0.001
Birth year	0.983 [0.97, 0.99]	< 0.001

During the follow-up period (1.1.1998 — 31.12.2019), 263 out of 545 males with FIBROLIV died.

Mortality risk

Mortality risk for people of age

years, who have FIBROLIV.

N-year risk	Females	Males
1	0.386%	1.014%
5	2.546%	5.439%
10	6.983%	14.34%
15	12.573%	25.688%
20	21.768%	40.077%

Relationships between endpoints

↥

Index endpoint: FIBROLIV – Fibrosis of liver

GWS hits: -

Endpoint

Case Overlap

Survival Analysis

Genetic Correlations

Genetic Signals

N (Jaccard index)

HR [CI]

Extremity

rg [CI]

Extremity

Hits

Coloc Hits

FinRegistry

FinnGen

FinRegistry

FinnGen

Loading data

NAME	FIBROLIV
CONTROL_EXCLUDE	CIRRHOSIS_BROAD
CONTROL_PRECONDITIONS
CONTROL_CONDITIONS
SEX
INCLUDE
PRE_CONDITIONS
CONDITIONS
OUTPAT_ICD
OUTPAT_OPER
HD_MAINONLY
HD_ICD_10_ATC
HD_ICD_10	K740
HD_ICD_9	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
HD_ICD_8	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
HD_ICD_10_EXCL
HD_ICD_9_EXCL
HD_ICD_8_EXCL
COD_MAINONLY
COD_ICD_10	K740
COD_ICD_9	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
COD_ICD_8	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
COD_ICD_10_EXCL
COD_ICD_9_EXCL
COD_ICD_8_EXCL
OPER_NOM
OPER_HL
OPER_HP1
OPER_HP2
KELA_REIMB
KELA_REIMB_ICD
KELA_ATC_NEEDOTHER
KELA_ATC
KELA_VNRO_NEEDOTHER
KELA_VNRO
CANC_TOPO
CANC_TOPO_EXCL
CANC_MORPH
CANC_MORPH_EXCL
CANC_BEHAV

Fibrosis of liver

Endpoint definition

Endpoint definition steps

FinnGen

Phenotype data

1. Apply sex-specific rule

2. Check conditions

3. Check pre-conditions, main-only, mode, registry filters

4. Check minimum number of events

5. Include endpoints

6. Filter based on genotype QC (FinnGen only)

Similar endpoints

Case counts by codes

Summary Statistics

-FinRegistry-

Key figures

-FinnGen-

Key figures

-FinRegistry-

Age distribution of first events

-FinnGen-

Age distribution of first events

-FinRegistry-

Year distribution of first events

-FinnGen-

Year distribution of first events

-FinRegistry-

Cumulative Incidence Function

-FinnGen-

Cumulative Incidence Function

CodeWAS (R11)

Matched cohort

Mortality – FinRegistry

Association

Females

Males

Mortality risk

Relationships between endpoints