Risteys · CHRONHEP

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 — K73.89, K73.9 Cause of death: ICD-10 — K73.89, K73.9 2 out of 7 registries used, show all original rules.	473
4. Check minimum number of events None	473
5. Include endpoints None	473
6. Filter based on genotype QC (FinnGen only)	473

Summary Statistics

↥

-FinRegistry-

Key figures

	All	Female	Male
Number of individuals
Whole population	3280	1919	1341
Only index persons	2815	1703	1112
Unadjusted period prevalence (%)
Whole population	0.05	0.05	0.04
Only index persons	0.05	0.06	0.04
Median age at first event (years)
Whole population	55.85	57.41	53.52
Only index persons	54.73	56.41	52.15

-FinnGen-

Key figures

	All	Female	Male
Number of individuals	473	311	162
Unadjusted period prevalence (%)	0.09	0.11	0.07
Median age at first event (years)	53.72	53.41	54.32

-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)

↥

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
423: Matched controls
4230

Code

Vocabulary

Description

Odds Ratio

-log₁₀(p)

N matched cases

N matched controls

K73.9

ICD-10 Finland

Chronic hepatitis, unspecified

+∞

323.0

395

K73.2

ICD-10 Finland

Chronic active hepatitis, not elsewhere classified

1627.0

128.0

118

JJ2AT

NOMESCO Finland

Biopsy of liver with ultrasound guidance

51.3

114.4

137

L04AX01

ATC

azathioprine; systemic

24.5

89.2

130

A05AA02

ATC

ursodeoxycholic acid; oral

46.8

80.5

JN1AE

NOMESCO Finland

Ultrasound examination of upper part of abdomen

11.1

70.5

148

196

K75.9

ICD-10 Finland

Inflammatory liver disease, unspecified

61.4

65.8

K76.9

ICD-10 Finland

Liver disease, unspecified

60.4

64.7

K75.4

ICD-10 Finland

Autoimmune hepatitis

653.6

59.2

202

Kela drug reimbursment

Connective tissue diseases, rheumatoid arthritis and comparable disease

7.9

57.6

150

274

K74.3

ICD-10 Finland

Primary biliary cirrhosis

71.4

49.6

A07EA06

ATC

budesonide; oral, local oral

15.4

45.5

UJD10

NOMESCO Finland

Esophagoscopy, gastroscopy and duodenoscopy

4.4

42.5

207

749

K73.89

ICD-10 Finland

Other long-term hepatitis, not classified differently

+∞

41.3

K73.0

ICD-10 Finland

Chronic persistent hepatitis, not elsewhere classified

+∞

34.9

K83.0

ICD-10 Finland

Cholangitis

30.2

34.5

R74.0

ICD-10 Finland

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

18.5

31.0

K74.6

ICD-10 Finland

Other and unspecified cirrhosis of liver

33.8

31.0

K76.0

ICD-10 Finland

Fatty (change of) liver, not elsewhere classified

13.6

29.7

H02AB06

ATC

prednisolone; systemic

3.2

29.2

259

1383

JN3AE

NOMESCO Finland

Abdominal ultrasound examination

4.7

29.1

113

306

R17

ICD-10 Finland

Hyperbilirubinaemia, with or without jaundice, not elsewhere classified

33.6

28.6

A12AX

ATC

Calcium, combinations with vitamin D and/or other drugs

3.2

26.8

201

933

JJ1LE

NOMESCO Finland

Ultrasound elastography of liver

55.2

22.3

A02BC02

ATC

pantoprazole; systemic

2.8

21.0

312

2102

TJJ00

NOMESCO Finland

Percutaneous needle biopsy of liver

115.7

20.8

UJF32

NOMESCO Finland

Coloscopy

2.8

18.7

151

696

ZX120

NOMESCO Finland

Intravenous

4.1

18.4

223

I85.9

ICD-10 Finland

Oesophageal varices without bleeding

21.2

18.0

UJF30

NOMESCO Finland

Ileoscopy through colon

4.1

17.8

213

N02AX02

ATC

tramadol; systemic, rectal

2.5

17.8

211

1205

L01BB02

ATC

mercaptopurine; oral

26.9

17.1

C03DA01

ATC

spironolactone; oral

3.9

17.0

216

K70.3

ICD-10 Finland

Alcoholic cirrhosis of liver

15.3

16.0

JKE98

NOMESCO Finland

Other transduodenal endoscopic operation on bile duct or ampulla of Vater

11.9

16.0

H02AB07

ATC

prednisone; oral

3.3

15.8

322

K51.5

ICD-10 Finland

Left sided colitis

7.2

15.7

A06AD11

ATC

lactulose; oral

3.4

15.3

287

L04AA06

ATC

mycophenolic acid; systemic

11.9

15.0

Z94.4

ICD-10 Finland

Liver transplant status

26.1

14.8

208

Kela drug reimbursment

Ulcerative colitis and Crohn's disease

5.2

14.7

5714B

ICD-9 Finland

Chronic liver disease and cirrhosis, Chronic hepatitis[HEPATITIS CHRONICA ACTIVA (HBSAG-)]

+∞

14.7

GD1AA

NOMESCO Finland

Thorax X-ray examination

2.3

14.6

202

1206

A07EC02

ATC

mesalazine; oral, rectal

4.7

14.5

116

K51.9

ICD-10 Finland

Ulcerative colitis, unspecified

6.2

14.1

L04AD01

ATC

ciclosporin; systemic

9.1

14.0

JN1CG

NOMESCO Finland

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

7.6

13.8

K73.8

ICD-10 Finland

Other chronic hepatitis, not elsewhere classified

+∞

13.6

K73.80

ICD-10 Finland

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

41.5

13.2

C03CA01

ATC

furosemide; systemic

2.5

13.1

129

640

NK6QA

NOMESCO Finland

Measurement of bone density from tow or more locations with X-ray

4.2

13.0

130

JJC00

NOMESCO Finland

Allogenic transplantation of liver

33.1

12.7

R10.4

ICD-10 Finland

Other and unspecified abdominal pain

2.2

12.1

181

1088

TPH04

NOMESCO Finland

Cathetrisation of vein

2.5

12.0

108

507

JJA20

NOMESCO Finland

Open biopsy of liver

48.1

11.9

R94.5

ICD-10 Finland

Abnormal results of liver function studies

17.0

11.8

UJK02

NOMESCO Finland

ERCP

8.5

11.7

UJK12

NOMESCO Finland

Peroral cholangioscopy

66.8

11.7

D97

ICPC

Liver disease NOS

23.7

11.6

JN1DG

NOMESCO Finland

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

9.7

11.6

R18

ICD-10 Finland

Ascites

9.7

11.6

JL5SB

NOMESCO Finland

Endoscopic retrograd cholangiopancreaticography

13.2

11.2

JL5BG

NOMESCO Finland

MRI examinaiton of bile and pancreas ducts with high intesity magnet

7.4

11.2

L04AD02

ATC

tacrolimus; systemic (calcineurin inhibitors)

20.7

11.2

M35.0

ICD-10 Finland

Sicca syndrome [Sjögren]

10.4

10.6

JN3DE

NOMESCO Finland

Abdominal extensive ultrasoudn examination with blood flow measurements after transplantation

33.4

10.4

JJ9AE

NOMESCO Finland

Ultrasound examination of liver transplant

33.4

10.4

K72.9

ICD-10 Finland

Hepatic failure, unspecified

24.0

10.3

JL5AG

NOMESCO Finland

Simple MRI examinaiton of bile and pancreas ducts with high intesity magnet

12.6

9.9

Z04.8

ICD-10 Finland

Examination and observation for other specified reasons

2.8

9.9

266

127

Kela drug reimbursment

Transplant complication

8.7

9.7

JA3AT

NOMESCO Finland

Cathetrisation of abdominal cavity with ultrasound guidance

10.4

9.6

F10.1

ICD-10 Finland

Mental and behavioural disorders due to use of alcohol, Harmful use

3.6

9.5

130

K72.0

ICD-10 Finland

Acute and subacute hepatic failure

30.8

9.4

K74.5

ICD-10 Finland

Biliary cirrhosis, unspecified

+∞

9.4

K50.8

ICD-10 Finland

Other Crohn disease

11.0

9.4

K80.2

ICD-10 Finland

Calculus of gallbladder without cholecystitis

2.8

9.3

257

UJD02

NOMESCO Finland

Gastroscopy

4.1

9.3

H02AB04

ATC

methylprednisolone; systemic

2.5

9.1

327

R10.1

ICD-10 Finland

Pain localized to upper abdomen

2.4

9.0

399

Z01.8

ICD-10 Finland

Other specified special examinations

2.2

9.0

108

578

K51.1

ICD-10 Finland

Ulcerative (chronic) ileocolitis

9.8

8.8

J01MA02

ATC

ciprofloxacin; systemic

1.9

8.8

175

1140

D64.9

ICD-10 Finland

Anaemia, unspecified

3.0

8.7

195

JN3BD

NOMESCO Finland

Extensive abdominal CT

2.7

8.6

243

JKE02

NOMESCO Finland

Transduodenal endoscopic incision of common bile duct orifice

10.3

8.6

R50.9

ICD-10 Finland

Fever, unspecified

2.5

8.5

306

5719X

ICD-9 Finland

Chronic liver disease and cirrhosis, Unspecified chronic liver disease without mention of alcohol

+∞

8.4

B18.2

ICD-10 Finland

Chronic viral hepatitis C

14.8

8.2

C10AC01

ATC

colestyramine; oral

5.3

8.0

B99

ICD-10 Finland

Other and unspecified infectious diseases

7.6

7.7

A10AE04

ATC

insulin glargine; parenteral

2.8

7.7

188

K74.0

ICD-10 Finland

Hepatic fibrosis

45.8

7.7

M05BA04

ATC

alendronic acid; oral

3.0

7.6

159

S97

ICPC

Chronic ulcer skin

3.6

7.6

I85.0

ICD-10 Finland

Oesophageal varices with bleeding

25.5

7.6

K70.1

ICD-10 Finland

Alcoholic hepatitis

25.5

7.6

A10AB05

ATC

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

3.1

7.5

147

GD1UA

NOMESCO Finland

Thorax X-ray examination outside radiological department

2.3

7.5

334

K75.2

ICD-10 Finland

Nonspecific reactive hepatitis

81.4

7.4

JN3CD

NOMESCO Finland

Abdominal CT examination both without and with contrast

4.8

7.3

JCA22

NOMESCO Finland

Endoscopic ligature of oesophageal varices

16.1

7.3

D50.0

ICD-10 Finland

Iron deficiency anaemia secondary to blood loss (chronic)

5.2

7.2

K51.8

ICD-10 Finland

Other ulcerative colitis

6.2

7.1

A09

ICD-10 Finland

Other gastroenteritis and colitis of infectious and unspecified origin

2.2

7.1

413

XF400

NOMESCO Finland

ECG with 12 standard connections

2.3

7.1

342

A10AC01

ATC

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

2.9

7.1

149

R74.8

ICD-10 Finland

Abnormal levels of other serum enzymes

3.8

7.0

A49.9

ICD-10 Finland

Bacterial infection, unspecified

2.5

6.9

227

A02BC03

ATC

lansoprazole; oral

1.9

6.9

128

800

K72.1

ICD-10 Finland

Chronic hepatic failure

40.7

6.8

SPAT1250

SPAT

Comprehensive monitoring of chronic illness

1.9

6.7

116

709

J18.9

ICD-10 Finland

Pneumonia, unspecified

2.0

6.6

540

K92.1

ICD-10 Finland

Melaena

3.6

6.6

D50.9

ICD-10 Finland

Iron deficiency anaemia, unspecified

3.0

6.6

130

JN3AD

NOMESCO Finland

Abdominal CT examination

2.8

6.5

155

J01MA12

ATC

levofloxacin; systemic

2.0

6.5

452

A02BC01

ATC

omeprazole; systemic

1.8

6.5

119

741

B19.9

ICD-10 Finland

Unspecified viral hepatitis without hepatic coma

70.8

6.4

0709X

ICD-9 Finland

Viral hepatitis, Unspecified viral hepatitis without mention of hepatic coma

70.8

6.4

WX700

NOMESCO Finland

Respiratory and circulatory monitoring

2.1

6.4

377

N02AA05

ATC

oxycodone; systemic

2.2

6.4

335

V03AE01

ATC

polystyrene sulfonate; oral

11.2

6.3

5714X

ICD-9 Finland

Chronic liver disease and cirrhosis, Chronic hepatitis[HEPATITIS CHRONICA ALIA SEU NUD]

+∞

6.3

C07AB07

ATC

bisoprolol; oral

1.7

6.2

182

1302

K80.5

ICD-10 Finland

Calculus of bile duct without cholangitis or cholecystitis

5.0

6.1

GD1PA

NOMESCO Finland

X-ray examination of the lungs in one projection

2.7

6.0

152

E0000UV

ATC

1.7

6.0

164

1147

Mortality – FinRegistry

↥

Association

Association between endpoint CHRONHEP_NAS and mortality.

Females

Parameter	HR [95% CI]	p-value
CHRONHEP_NAS	2.925 [2.5, 3.42]	< 0.001
Birth year	0.991 [0.98, 1.0]	0.054

During the follow-up period (1.1.1998 — 31.12.2019), 507 out of 1704 females with CHRONHEP_NAS died.

Males

Parameter	HR [95% CI]	p-value
CHRONHEP_NAS	3.58 [2.98, 4.31]	< 0.001
Birth year	0.987 [0.98, 1.0]	0.008

During the follow-up period (1.1.1998 — 31.12.2019), 430 out of 1151 males with CHRONHEP_NAS died.

Mortality risk

Mortality risk for people of age

years, who have CHRONHEP_NAS.

N-year risk	Females	Males
1	0.192%	0.504%
5	1.625%	3.958%
10	3.561%	9.484%
15	6.913%	18.168%
20	12.624%	29.866%

Relationships between endpoints

↥

Index endpoint: CHRONHEP_NAS – Chronic hepatitis NAS

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	CHRONHEP_NAS
CONTROL_EXCLUDE
CONTROL_PRECONDITIONS
CONTROL_CONDITIONS
SEX
INCLUDE
PRE_CONDITIONS
CONDITIONS
OUTPAT_ICD
OUTPAT_OPER
HD_MAINONLY
HD_ICD_10_ATC
HD_ICD_10	K7389\|K739
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	K7389\|K739
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

Chronic hepatitis NAS

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