Hepatitis C virus enhances incidence of idiopathic pulmonary fibrosis

Table 1 Diagnostic criteria of IPF

Number	Criteria
Major criteria 1	Exclusion of other known caused of interstitial lung disease, such as certain drug toxicities, environmental exposures, and connective tissue diseases
Major criteria 2	Abnormal pulmonary function studies that include evidence of restriction (reduced breathing vital capacity) and impaired gas exchange (increased AaPO2 with rest or after exercising or decreased diffusion lung capacity)
Major criteria 3	Bibasilar reticular abnormalities with minimal ground glass opacities on conventional chest radiographs or high-resolution computed tomography scans
Major criteria 4	Histological lung examination or bronchoalveolar lavage showing no features to support an alternative diagnosis
Minor criteria 1	Age > 50 yr
Minor criteria 2	Insidious onset of otherwise unexplained dyspnea on exertion
Minor criteria 3	Duration of illness ≥ 3 mo
Minor criteria 4	Bibasilar, inspiratory crackles (dry or “Velcro” type in quality)

Table 2 Clinical characteristics¹

	Total	HBV-group	HCV-group	P
Number (n)	8200	2050	6150
Age (yr)	51.8 ± 9.0	51.7 ± 8.7	51.8 ± 9.1	1
Sex (male, %)	77.8% (6380)	77.8% (1595)	77.8% (4785)	1
Liver cirrhosis2	20.2% (1659)	18.5% (379)	20.8% (1280)	< 0.001
Total alcohol intake of > 200 kg3	23.0% (1490/6465)	17.4% (253/1450)	24.7% (1237/5015)	< 0.001
Smoking index of > 203	27.9% (1680/6032)	23.5% (293/1246)	29.0% (1387/4786)	< 0.001
AST (IU/L)	75.9 ± 124.5	82.9 ± 138.2	73.8 ± 120.3	< 0.001
ALT (IU/L)	104.2 ± 107.5	124.4 ± 119.9	98.5 ± 103.6	< 0.001
Total bilirubin (mg/dL)	0.83 ± 0.94	0.98 ± 0.85	0.81 ± 0.77	< 0.001
γGTP (IU/L)	74.0 ± 106.2	77.1 ± 128.7	73.2 ± 99.8	0.951
Platelet count (x 104/mm3)	19.3 ± 18.7	19.1 ± 14.4	19.4 ± 19.7	0.725

¹Data are percent (number of patients) or mean ± SD;

²The 1594 (77.8%) out of 2050 in HBV-group and 5232 (85.1%) of 6150 in HCV-group were diagnosed by laparoscopy and/or liver biopsy. The breakdown of histological staging in HCV-group was as follows: stage 1, 2707; stage 2, 1188; stage 3, 300; stage 4 (liver cirrhosis), 1037. The outbreak of histological staging in HBV-group was as follows: stage 1, 705; stage 2, 439; stage 3, 157; stage 4 (liver cirrhosis), 293;

³Smoking index = (package/d) × yr; Total alcohol intake and smoking index indicate the sum of before and after first consultation.

Table 3 Predictive factors for IPF development¹

Factor	Univariate analysis				Multivariate analysis1
	Category	Hazard ratio	95% CI	P	Category	Hazard ratio	95% CI	P
Age (yr)	< 55/≥ 55	1/11.78	3.52-39.37	< 0.001	< 55/≥ 55	1/12.52	3.52-44.59	< 0.001
Smoking index1	< 20/≥ 20	1/4.56	1.52-13.61	0.007	< 20/≥ 20	1/5.90	1.95-17.82	0.002
Liver staging (fibrosis)	Non-LC/LC	1/3.67	1.29-10.48	0.015	Non-LC/LC	1/3.00	1.04-8.64	0.042
Sex	Male/Female	1/0.45	0.13-1.62	0.223
Platelet (x 104/mm3)	< 15/≥ 15	1/0.47	0.10-2.23	0.341
γGTP (IU/L)	< 110/≥ 110	1/1.95	0.41-9.31	0.405
Total alcohol intake1	< 200/≥ 200	1/1.50	0.50-4.48	0.467
AST (IU/L)	< 76/≥ 76	1/1.16	0.30-4.53	0.834
ALT (IU/L)	< 100/≥ 100	1/1.05	0.29-3.74	0.946

Data are number of patients or mean ± SD.

¹Smoking index = (package/d) × year. Total alcohol intake and smoking index indicate the sum of before and after first consultation

Table 4 Characteristics of patients with IPF in the HCV-group

Case	Age (yr)1	Sex	Liver disease1	Smoking index2	Age at the time of IPF onset	Period after IPF development2	Alive or death2	Cause of death
1	49	M	LC	25	57	5.7	Death	HCC
2	50	M	CH	38	62	12.3	Death	IPF
3	52	M	CH	0	73	3.8	Death	IPF
4	57	M	LC	28	68	8.7	Death	d-LC
5	58	M	LC	22	68	1.1	Death	IPF
6	61	M	LC	0	71	6	Death	IPF
7	61	F	LC	30	66	3.2	Death	IPF
8	62	M	LC	0	72	10.2	Death	HCC
9	62	F	LC	5	66	3.5	Death	d-LC
10	63	M	CH	26	75	10.6	Alive
11	63	M	CH	34	64	12.1	Death	HCC
12	64	M	CH	40	69	10.1	Alive
13	66	F	CH	24	79	1.8	Alive
14	69	M	LC	0	70	2.3	Death	HCC
15	70	M	LC	42	76	4.1	Death	HCC

CH: Chronic hepatitis; d-LC: Decompensated liver cirrhosis; HCC: Hepatocellular carcinoma; IPF: Idiopathic pulmonary fibrosis; LC: Liver cirrhosis.

¹Characteristics of patients at the first consultation;

²Smoking index = (package/d) × year, Smoking index indicates the sum of before and after first consultation; Period after IPF development, period (yr) between onset of IPF and final consultation; Alive or death, alive or death at the final consultation