Impact of hepatitis delta virus infection on waiting list outcomes: A competing-risks analysis

doi:10.4254/wjh.124709

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Observational Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Hepatol. Oct 27, 2026; 18(10): 124709
Published online Oct 27, 2026. doi: 10.4254/wjh.124709

Table 1 Baseline characteristics of the delta and hepatitis B virus monoinfection groups, n (%)/median (interquartile range)

Characteristic	Delta (n = 174)	HBV monoinfection (n = 30)	SMD	P value
Age (years)	48.0 (42.0-54.0)	52.0 (47.0-57.8)	0.42	0.037
Female sex	78 (45)	6 (20)	0.55	0.019
Rural residence	107 (61)	14 (47)	0.30	0.185
BMI (kg/m²)	24.8 (22.8-27.1)	27.1 (24.7-30.4)	0.54	0.004
ALT (U/L)	58.1 (39.3-93.1)	43.3 (26.9-64.2)	0.27	0.009
AST (U/L)	76.8 (55.5-116.6)	61.1 (44.2-90.5)	0.27	0.067
Platelets (× 10⁹/L)	72.0 (49.0-103.5)	98.0 (68.5-161.3)	0.44	0.005
Albumin (g/L)	28.0 (24.9-31.9)	29.4 (24.0-35.6)	0.07	0.643
Total bilirubin (μmol/L)	40.6 (23.5-60.5)	45.0 (21.8-79.1)	0.23	0.477
INR	1.5 (1.3-1.7)	1.4 (1.2-1.7)	0.14	0.252
Creatinine (μmol/L)	66.8 (57.7-75.0)	71.2 (57.1-79.2)	0.21	0.327
Sodium (mmol/L)	138.0 (135.0-140.1)	139.0 (136.0-140.8)	0.09	0.466
Ascites	110 (63)	15 (50)	0.27	0.242
Hepatic encephalopathy	68 (39)	10 (33)	0.12	0.676
Esophageal variceal hemorrhage	35 (20)	5 (17)	0.09	0.660
Hepatocellular carcinoma	31 (18)	8 (27)	0.21	0.375
MELD	15.0 (12.0-17.0)	15.5 (11.0-17.0)	0.01	0.992
MELD-Na	15.0 (12.0-18.8)	15.5 (11.0-18.0)	0.07	0.510
MELD 3.0	16.5 (13.0-20.0)	16.5 (12.0-19.0)	0.10	0.652
Waiting-list time (days)	247.5 (102.5-631)	281 (135.2-762.2)	0.13	0.593
Waiting-list death	78 (44.8)	19 (63.3)	0.38	0.094
Transplantation	72 (41.4)	6 (20.0)	0.48	0.043
Delisted	1 (0.6)	0 (0.0)	0.11	1.000
Active in waiting list	23 (13.2)	5 (16.7)	0.10	0.826

HBV: Hepatitis B virus; SMD: Standardized mean difference; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; MELD-Na: Model for end-stage liver disease-sodium; MELD: Model for end-stage liver disease.

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Table 2 Baseline characteristics of the delta and non-delta viral infection groups, n (%)/median (interquartile range)

Characteristic	Delta group (n = 174)	Non-delta viral group (n = 92)	SMD	P value
Age (years)	48.0 (42.0-54.0)	53.0 (48.0-58.0)	0.58	< 0.001
Female sex	78 (45)	30 (33)	0.25	0.072
Rural residence	107 (61)	38 (41)	0.41	0.003
BMI (kg/m²)	24.8 (22.8-27.1)	26.4 (24.5-28.1)	0.40	< 0.001
ALT (U/L)	58.1 (39.3-93.1)	48.3 (27.0-77.6)	0.19	0.005
AST (U/L)	76.8 (55.5-116.6)	65.2 (44.0-93.0)	0.23	0.034
Platelets (×10⁹/L)	72.0 (49.0-103.5)	97.8 (71.5-124.2)	0.30	< 0.001
Albumin (g/L)	28.0 (24.9-31.9)	30.8 (25.7-36.0)	0.34	0.004
Total bilirubin (μmol/L)	40.6 (23.5-60.5)	34.2 (20.6-56.5)	0.07	0.198
INR	1.5 (1.3-1.7)	1.4 (1.2-1.6)	0.18	0.063
Creatinine (μmol/L)	66.8 (57.7-75.0)	69.3 (60.3-80.9)	0.29	0.070
Sodium (mmol/L)	138.0 (135.0-140.1)	139.1 (136.0-141.0)	0.22	0.065
Ascites	110 (63)	46 (50)	0.27	0.051
Hepatic encephalopathy	68 (39)	25 (27)	0.26	0.067
Esophageal variceal hemorrhage	35 (20)	25 (27)	0.17	0.190
Hepatocellular carcinoma	31 (18)	18 (20)	0.04	0.854
MELD	15.0 (12.0-17.0)	14.0 (10.0-17.0)	0.15	0.249
MELD-Na	15.0 (12.0-18.8)	15.0 (10.0-17.2)	0.22	0.074
MELD 3.0	16.5 (13.0-20.0)	15.0 (11.0-18.2)	0.29	0.029
Waiting-list time (days)	247.5 (102.5-631)	601.5 (173.5-1936.5)	0.60	< 0.001
Waiting-list death	78 (44.8)	42 (45.7)	0.02	1.00
Transplantation	72 (41.4)	20 (21.7)	0.43	0.002
Delisted	1 (0.6)	5 (5.4)	0.29	0.035
Active in waiting list	23 (13.2)	25 (27.2)	0.35	0.008

¹Non-delta viral: Hepatitis B virus monoinfection + hepatitis B virus/hepatitis C virus + epatitis C virus.

SMD: Standardized mean difference; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; MELD: Model for end-stage liver disease; MELD-Na: Model for end-stage liver disease-sodium.

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Table 3 Cumulative incidence of waiting-list death and transplantation at 1 and 5 years, by group, 95%CI

Group	Death 1 year	Death 5 years	Gray P	Transplantation 1 year	Transplantation 5 years	Gray P value
Delta group vs non-delta viral group
Delta group	23.7 (17.1-30.2)	45.9 (38.1-53.8)	0.696	31.7 (24.6-38.8)	43.1 (35.4-50.9)	0.001
Non-delta viral group	15.7 (8.1-23.3)	42.9 (32.1-53.7)	0.696	19.2 (10.9-27.5)	21.7 (13.0-30.4)	0.001
Delta group vs HBV monoinfection group
Delta group	23.7 (17.1-30.2)	45.9 (38.1-53.8)	0.065	31.7 (24.6-38.8)	43.1 (35.4-50.9)	0.030
HBV monoinfection group	27.7 (10.9-44.5)	66.4 (47.3-85.5)	0.065	20.7 (5.5-35.9)	20.7 (5.5-35.9)	0.030

Values are Aalen-Johansen cumulative incidence. HBV: Hepatitis B virus.

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Table 4 Multivariable cause-specific Cox models

Covariate	Death, csHR (95%CI)	Transplantation, csHR (95%CI)
HDV infection	2.01 (1.40-2.89)^a	2.41 (1.56-3.73)^a
Age (year)	1.01 (1.00-1.03)	1.01 (0.99-1.03)
Female sex	0.53 (0.37-0.77)^a	1.05 (0.71-1.56)
MELD-Na (per point)	1.07 (1.03-1.11)^a	1.06 (1.02-1.11)^a
Era II vs I	1.00 (0.69-1.45)	1.30 (0.86-1.95)

^aP < 0.01.

csHR: Cause-specific hazard ratio; HDV: Hepatitis delta virus; MELD-Na: Model for end-stage liver disease–sodium.

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Table 5 Multivariable fine-gray subdistribution hazard models

Covariate	Death, sHR (95%CI)	Transplantation, sHR (95%CI)
HDV infection	1.20 (0.89-1.62)	1.89 (1.25-2.86)^a
Age (year)	1.01 (0.99-1.02)	1.00 (0.98-1.02)
Female sex	0.59 (0.44-0.81)^a	1.24 (0.86-1.79)
MELD-Na (per point)	1.04 (1.01-1.07)^a	1.04 (1.00-1.08)
Era II vs I	0.79 (0.57-1.09)	1.15 (0.79-1.68)

^aP < 0.01.

sHR: Subdistribution hazard ratio; HDV: Hepatitis delta virus; MELD-Na: Model for end-stage liver disease–sodium.

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Table 6 Hepatitis delta virus effect on waiting-list death, by comparator and model

Comparison and model	n	csHR (95%CI)	sHR (95%CI)
Delta group vs non-delta viral group	266	2.12 (1.38-3.24)^b	1.19 (0.84-1.68)
Delta group vs HBV monoinfection group	204	0.82 (0.49-1.35)	0.60 (0.40-0.91)^a
Model with MELD 3.0	313	2.03 (1.41-2.92)^b	1.20 (0.89-1.62)

^aP < 0.05.

^bP < 0.01.

csHR: Cause-specific hazard ratio; sHR: Subdistribution hazard ratio; MELD: Model for end-stage liver disease; HBV: Hepatitis B virus.

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Table 7 Hepatitis delta virus effect on access to transplantation, by comparator and model

Comparison and model	n	csHR (95%CI)	sHR (95%CI)
Delta group vs all non-delta (primary)	313	2.41 (1.56-3.73)^b	1.89 (1.25-2.86)^b
Delta group vs non-delta viral group	266	2.71 (1.58-4.64)^b	2.09 (1.20-3.64)^b
Delta group vs HBV monoinfection group	204	2.18 (0.95-5.02)	2.38 (1.02-5.56)^a

^aP < 0.05.

^bP < 0.01.

Models adjusted for hepatitis delta virus, age, sex, model for end-stage liver disease-sodium and era. csHR: Cause-specific hazard ratio; sHR: Subdistribution hazard ratio; HBV: Hepatitis B virus.

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Table 8 Incremental adjustment of the hepatitis delta virus effect on waiting-list death

Model	Covariates added	sHR (95%CI)	csHR (95%CI)
M0	HDV	1.17 (0.87-1.57)	1.88 (1.32-2.66)^b
M1	+ age	1.17 (0.87-1.58)	1.93 (1.35-2.74)^b
M2	+ sex	1.20 (0.89-1.61)	2.11 (1.48-3.03)^b
M3	+ MELD-Na	1.17 (0.87-1.57)	2.01 (1.40-2.88)^b
M4	+ era	1.20 (0.89-1.62)	2.01 (1.40-2.89)^b
M5	+ albumin + ascites	1.16 (0.86-1.57)	1.99 (1.37-2.87)^b

^bP < 0.01.

csHR: Cause-specific hazard ratio; sHR: Subdistribution hazard ratio; MELD-Na: Model for end-stage liver disease-sodium; HDV: Hepatitis delta virus.

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Table 9 Extended multivariable models for waiting-list death

Covariate	csHR (95%CI)	sHR (95%CI)
HDV infection	1.90 (1.30-2.77)^b	1.14 (0.84-1.55)
Age (year)	1.01 (0.99-1.03)	1.00 (0.99-1.02)
Female sex	0.60 (0.41-0.88)^b	0.63 (0.46-0.86)^b
MELD-Na per point	1.07 (1.03-1.11)^b	1.03 (1.00-1.07)
Era II vs I	0.86 (0.57-1.31)	0.75 (0.53-1.08)
Albumin (per g/L)	1.01 (0.97-1.04)	0.99 (0.97-1.02)
Ascites	1.50 (1.02-2.21)^a	1.31 (0.95-1.80)
Hepatocellular carcinoma	2.38 (1.48-3.84)^b	1.33 (0.91-1.93)
Antiviral therapy	0.92 (0.48-1.76)	0.88 (0.49-1.57)

^aP < 0.05.

^bP < 0.01.

csHR: Cause-specific hazard ratio; sHR: Subdistribution hazard ratio; MELD-Na: Model for end-stage liver disease-sodium; HDV: Hepatitis delta virus.

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Table 10 Proportional-hazards diagnostics-scaled schoenfeld residuals (cause-specific Cox models)

Covariate	Waiting-list death (P value)	Transplantation (P value)
HDV	0.479	0.061
Age (year)	0.537	0.334
Female sex	0.894	0.377
MELD-Na (per point)	0.938	0.556
Era 2018-2025	0.230	0.971
Global	0.819	0.408

Schoenfeld proportionality test for each cause-specific model; the global row is the omnibus test. All P > 0.05: Proportionality holds. MELD-Na: Model for end-stage liver disease-sodium; HDV: Hepatitis delta virus.

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Table 11 Subdistribution proportionality for hepatitis delta virus (fine-gray hepatitis delta virus × time interaction)

Model	Hepatitis delta virus × time coefficient	P value
Waiting-list death	-0.22	0.036
Transplantation	-0.07	0.550

For transplantation the assumption holds (P = 0.550). For death the interaction is significant (P = 0.036). This reflects the competing risk of transplantation increasing over time rather than a decline in the risk of death.

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Table 12 Cause-specific hepatitis delta virus hazard ratio by follow-up interval (split at 1 year)

Follow-up interval	Waiting-list death, csHR (95%CI)	Transplantation, csHR (95%CI)
< 1 year	1.81 (1.05-3.14)	1.81 (1.11-2.97)
≥ 1 year	2.16 (1.35-3.44)	4.95 (2.13-11.50)

All four estimates are significant (P < 0.05). The cause-specific hazard of death for hepatitis delta virus does not attenuate (1.81 to 2.16), whereas that for transplantation rises sharply after one year (1.81 to 4.95). This explains the hepatitis delta virus × time interaction. csHR: Cause-specific hazard ratio.

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Table 13 Hepatitis delta virus subdistribution hazard ratios after excluding early transplantation

Model	Excluded, n	HDV-death, sHR (95%CI)	HDV-transplantation, sHR (95%CI)
Full model (reference)	0	1.20 (0.85-1.70)	1.89 (1.22-2.92)^a
Excluding transplant < 30 days	13	1.18 (0.83-1.69)	2.14 (1.35-3.39)^a
Excluding transplant < 90 days	33	1.32 (0.92-1.90)	1.95 (1.18-3.24)^a

^aP < 0.01.

Fine-gray subdistribution hazard ratios for hepatitis delta virus, adjusted for age, sex, MELD-Na and era. Early transplantation was defined by time from listing to transplantation below the stated threshold, used as an objective proxy for urgent prioritization. sHR: Subdistribution hazard ratio; HDV: Hepatitis delta virus.

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Citation: Peltec A, Buga D, Hotineanu A, Wedemeyer H. Impact of hepatitis delta virus infection on waiting list outcomes: A competing-risks analysis. World J Hepatol 2026; 18(10): 124709
URL: https://www.wjgnet.com/1948-5182/full/v18/i10/124709.htm
DOI: https://dx.doi.org/10.4254/wjh.124709

Peltec A, Buga D, Hotineanu A, Wedemeyer H. Impact of hepatitis delta virus infection on waiting list outcomes: A competing-risks analysis. World J Hepatol 2026; 18(10): 124709 [DOI: 10.4254/wjh.124709]

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