Rising incidence, progression and changing patterns of liver disease in Wales 1999-2019

Table 1 International Classification of Diseases-10 code case definition for liver disease aetiology, stratified into hierarchical tiers based of clinical importance

Tier 1			Tier 2			Tier 3
Descriptor		ICD-10 code	Descriptor		ICD-10 code	Descriptor		ICD-10 code
Autoimmune liver disease	Autoimmune hepatitis	K75.4	Hepatitis not specified	Inflammatory liver disease unspecified	K76.9	Miscellaneous	Peliosis hepatis	K76.4
	Primary biliary cholangitis	K74.3		Other specified inflammatory liver disease	K75.8		Other specified diseases of the liver	K76.8
	Granulomatous hepatitis not elsewhere specified	K75.3		Chronic hepatitis not elsewhere classified	K73.0-K73.9		Liver disorders in diseases classified elsewhere	K77
Metabolic liver disease	Haemochromatosis	E83.11	Congestive hepatopathy	Chronic passive congestion of the liver	K76.1
	Alpha 1 anti-trypsin deficiency	E88.01		Central haemorrhagic necrosis of the liver	K76.2
	Wilson’s disease	E83.01		Hepatic veno-occlusive disease	K76.5
HBV	Hepatitis B without D	B18.1	Toxic liver disease	Toxic liver disease	K71
	Hepatitis B with D	B18.0
HCV	Hepatitis C	B18.2
Alcohol-related liver disease	Alcoholic liver disease	K70-K70.9
Non-alcoholic fatty liver disease	Non-alcoholic fatty liver disease	K76.0

ICD-10: International Classification of Diseases-10; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 2 International Classification of Diseases-10 codes to define the advanced stages of liver disease

Aetiological diagnoses (stage 1)	Cirrhosis (stage 2)	Portal hypertension (stage 3)	Hepatic decompensation (stage 4)	Hepatocellular carcinoma (stage 5)
As defined in Table 1	Alcoholic cirrhosis, K70.3	Portal hypertension, K76.6	Chronic hepatic failure, K72.1	Primary liver cancer C22.0
	Hepatic fibrosis or sclerosis, K74.0-K74.2	Portal vein thrombosis, I81	Hepatorenal syndrome, K76.7	Hepatocellular carcinoma C22.1
	Secondary biliary cirrhosis, K74.4	Oesophageal varices without bleeding I85.9	Oesophageal varices with bleeding, I85.0
	Biliary cirrhosis unspecified, K74.5	Oesophageal varices without bleeding in diseases specified elsewhere, I98.2	Hepatic failure unspecified K72
	Cirrhosis, other, K74.6

Table 3 The number, age and sex of individuals with aetiological liver disease diagnoses in Wales 1999-2019 following application of aetiology hierarchy

Aetiology	n	% of total cohort	Mean/median age (yr)	% male
Tier 1
ArLD	16143	26.1%	54.9/55	67.8%
NAFLD	13390	21.6%	57/58	47%
Metabolic	7131	11.5%	63/67	52.5%
HCV	2889	4.7%	43/41	66.8%
ArLD overlap	2979	4.8%	51.2/51	65.3%
Autoimmune liver diseases	2312	3.7%	61.8/64	20.5%
HBV	904	1.5%	43.5/39	53.3%
Non ArLD overlap	955	1.5%	51.2/51	55.8%
Tier 2
Hepatitis not specified	6069	9.8%	63/66	50.9%
Congestive hepatopathy	894	1.4%	64.7/70	49.6%
Toxic liver disease	820	1.3%	46.3/44	38.4%
Tier 3
Miscellaneous	7430	12%	66.7/70	42%

ArLD: Alcohol-related liver disease; NAFLD: Non-alcoholic fatty liver disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 4 Progression of liver disease over 10 years by aetiology

	0	6 mo	1 yr	2 yr	3 yr	5 yr	10 yr
ArLD
Stage 1	48.75	40.27	36.14	31.54	28.36	24.21	19.18
Stage 2	16.52	14.12	12.93	11.75	10.82	9.65	7.87
Stage 3	13.47	13.93	13.92	12.8	11.86	10.18	8.1
Stage 4	4.49	4.8	5.09	5.3	5.33	4.97	4.25
Stage 5	0.63	0.5	0.49	0.44	0.38	0.34	0.34
Stage 6	16.14	26.38	31.43	38.17	43.25	50.64	60.25
NAFLD
Stage 1	86.3	82.52	80.42	77.98	76.25	73.93	70.7
Stage 2	2.54	2.28	2.31	2.21	2.22	2.18	1.98
Stage 3	2.87	2.99	2.87	2.7	2.52	2.29	2.07
Stage 4	0.82	0.93	0.98	1.01	1.01	0.95	0.91
Stage 5	0.4	0.38	0.36	0.28	0.3	0.22	0.24
Stage 6	7.07	10.89	13.07	15.82	17.71	20.43	24.1
Autoimmune liver disease
Stage 1	72.94	66.33	63.31	59.57	56.44	51.89	44.83
Stage 2	10.79	10.53	10.12	9.67	9.07	8.51	7.73
Stage 3	8.7	9.29	9.41	9.07	8.77	7.69	6.83
Stage 4	2.43	2.8	2.84	2.95	3.02	3.21	2.99
Stage 5	0.86	0.9	0.82	0.67	0.63	0.56	0.6
Stage 6	4.29	10.15	13.51	18.07	22.06	28.14	37.03
HBV
Stage 1	88.96	86.25	84.58	82.6	81.46	79.69	78.02
Stage 2	2.5	1.77	1.98	1.98	1.88	1.88	1.88
Stage 3	2.71	2.71	2.5	2.5	2.4	1.98	2.08
Stage 4	0.94	1.04	1.04	0.94	0.94	1.04	1.25
Stage 5	2.19	1.46	1.25	1.25	1.25	0.94	0.83
Stage 6	2.71	6.77	8.65	10.73	12.08	14.48	15.94
HCV
Stage 1	88.02	85.5	83.54	80.68	78.51	75.38	71.59
Stage 2	4.15	3.88	3.94	4.06	4.12	4.06	3.61
Stage 3	2.8	2.59	2.53	2.53	2.59	2.35	2.29
Stage 4	0.87	1.05	1.14	1.17	1.2	1.17	1.2
Stage 5	1.38	1.2	1.17	1.11	1.08	1.17	1.17
Stage 6	2.77	5.78	7.67	10.44	12.49	15.86	20.13
Metabolic
Stage 1	82.03	67.35	63.3	59.25	56.3	52.51	47.7
Stage 2	1.73	1.37	1.29	1.21	1.16	1.11	1.05
Stage 3	1.36	1.24	1.16	1.2	1.07	0.99	0.96
Stage 4	0.63	0.52	0.53	0.57	0.56	0.56	0.49
Stage 5	0.56	0.4	0.24	0.23	0.23	0.28	0.23
Stage 6	13.69	29.12	33.48	37.54	40.69	44.55	49.57
Congestive hepatopathy
Stage 1	70.36	55.3	50.05	43.44	38.58	34.79	31.1
Stage 2	2.24	1.65	1.65	1.07	0.78	0.58	0.58
Stage 3	3.21	3.01	2.62	2.33	2.04	1.94	1.46
Stage 4	2.04	1.75	1.75	1.75	1.94	1.85	2.04
Stage 5	0.68	0.29	0.29	0.29	0.29	0.19	0.19
Stage 6	21.48	38	43.63	51.12	56.37	60.64	64.63
Toxic
Stage 1	80.87	76.09	73.96	71.31	69.48	67.45	62.87
Stage 2	1.22	0.92	1.02	0.81	0.71	0.61	0.61
Stage 3	1.63	1.93	1.73	1.42	1.73	1.53	1.42
Stage 4	3.46	3.15	3.36	3.26	3.36	3.15	2.95
Stage 5	0.31	0.2	0.2	0.2	0.2	0.2	0.1
Stage 6	12.51	17.7	19.74	22.99	24.52	27.06	32.04
Miscellaneous
Stage 1	91.24	80.46	75.76	70.45	67.05	63.04	57.4
Stage 2	0.62	0.57	0.49	0.42	0.35	0.31	0.29
Stage 3	0.94	0.97	0.99	0.94	0.94	0.9	0.75
Stage 4	0.37	0.34	0.37	0.39	0.39	0.35	0.37
Stage 5	0.62	0.64	0.57	0.45	0.38	0.35	0.28
Stage 6	6.21	17.02	21.82	27.35	30.89	35.04	40.91

The percentage of the individuals with a liver disease diagnosis who have progressed from aetiology only (stage 1), aetiology and cirrhosis (stage 2), aetiology, cirrhosis and portal hypertension (stage 3), aetiology, cirrhosis and portal hypertension and decompensation (stage 4), aetiology and liver cancer stage 5, and aetiology and mortality by any cause (stage 6). At baseline entry of registry between 1999 and 2019 and up to 10 yr of follow up. ArLD: Alcohol-related liver disease; NAFLD: Non-alcoholic fatty liver disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus.