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World Journal of Gastroenterology
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1007-9327
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Observational Study
Copyright ©The Author(s) 2025.
World J Gastroenterol. Dec 21, 2025; 31(47): 111637
Published online Dec 21, 2025. doi: 10.3748/wjg.v31.i47.111637
Table 1 Characteristics of hepatitis B surface antigen +/anti-hepatitis delta virus positive patients by sex, n (%)
Anti-HDV positive
P value
Males
Females
3161 (61.6)1971 (38.4)0.738
Age, median (Q1-Q3)56 (48-63)56 (45-62)0.409
≤ 4035 (11.1)37 (18.8)0.143
41-5059 (18.7)38 (19.3)
51-60114 (36.1)58 (29.4)
61-7085 (26.9)50 (25.4)
> 7023 (7.3)14 (7.2)
Non-Italian natives81 (25.6)92 (46.7)< 0.001
Injection drug use (any time)45 (17.3)3 (1.7)< 0.001
ALT > 35 IU/L199 (64.8)108 (56.5)0.065
GGT > 50 IU/L116 (46.6)44 (27.3)< 0.001
HBeAg positive16 (5.3)12 (6.3)0.612
HDV RNA positive (n = 430 tested)176 (68.0)124 (72.5)0.314
Cirrhosis232 (73.4)130 (66.0)0.073
Child-Pugh class
A197 (86.8)103 (82.4)0.231
B25 (11.0)21 (16.8)
C5 (2.2)1 (0.8)
MELD ≥ 206 (3.0)0 (0.0)0.097
HCC40 (12.6)11 (5.6)0.010
PLT ≤ 150000177 (57.8)108 (56.5)0.776
Previous IFN104 (35.4)49 (27.7)0.084
Cofactors of liver disease
BMI 25-3084 (37.8)45 (33.1)0.124
BMI ≥ 3019 (8.6)21 (15.4)
Ongoing alcohol use61 (23.0)10 (6.1)< 0.001
Past use58 (21.9)15 (9.2)
Diabetes28 (8.9)4 (2.0)0.002
Steatotic liver disease84 (26.6)36 (18.3)0.031
Anti-HCV positive (all HCV RNA negative)42 (14.7)1 (0.6)< 0.001
Anti-HIV positive22 (8.1)1 (0.6)0.001
NUC treatment
Ongoing NUC therapy234 (74.3)138 (70.4)0.338
Years of NUC therapy, median (Q1-Q3)4.2 (1.7-7.9)4.2 (2.0-7.6)0.733
1Proportions are based on available data. Inconsistencies are due to missing values.
HDV: Hepatitis delta virus; ALT: Alanine transaminase; BMI: Body mass index; GGT: Gamma-glutamyl transpeptidase; HBeAg: Hepatitis Be antigen; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; IFN: Interferon; PLT: Platelet; Q1: Quarter 1; Q3: Quarter 3; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; NUC: Nucleos(t)ide analogue.
Full Size Table
Table 2 Characteristics of hepatitis B surface antigen +/anti-hepatitis delta virus positive patients with F4/cirrhosis by sex, n (%)
CharacteristicsF4/cirrhosis
P value
Males (n = 2321)
Females (n = 1301)
Age, median (Q1-Q3)57 (50-64)57 (46-62)0.163
≤ 4015 (6.5)21 (16.1)0.052
41-5043 (18.5)23 (17.7)
51-6081 (34.9)44 (33.8)
61-7073 (31.5)34 (26.1)
> 7020 (8.6)8 (6.1)
Non-Italian natives55 (23.7)53 (40.8)0.001
Injection drug use (any time)31 (16.4)3 (2.6)< 0.001
Liver biopsy (any time)58 (30.2)30 (28.0)0.693
ALT > 35 IU/L152 (67.9)83 (65.3)0.632
GGT > 50 IU/L101 (55.8)40 (38.1)0.004
HBeAg positive10 (4.5)9 (7.2)0.289
HDV-RNA tested193 (83.2)114 (87.7)0.252
HDV-RNA positive137 (71.0)92 (80.7)0.059
HDV RNA, median (Q1-Q3)95614 (3096-1000000)34563 (3971-377359)0.932
Child-Pugh class
A197 (86.8)103 (82.4)0.231
B25 (11.0)21 (16.8)
C5 (2.2)1 (0.8)
MELD ≥ 206 (3.0)0 (0.0)0.097
HCC38 (16.5)11 (8.6)0.036
PLT ≤ 150000166 (74.1)100 (78.7)0.330
Previous IFN75 (34.6)35 (29.7)0.362
Cofactors of liver disease
Ongoing alcohol use39 (19.8)3 (2.6)< 0.001
Past use50 (25.4)11 (9.6)
BMI 25-3061 (38.4)27 (31.0)0.385
BMI ≥ 3015 (9.4)12 (13.8)
Diabetes22 (9.5)2 (1.5)0.004
Steatotic liver disease63 (27.2)23 (17.7)0.042
Anti-HCV positive (all HCV RNA negative)33 (15.9)1 (0.9)< 0.001
anti-HIV positive14 (7.1)1 (1.0)0.024
NUC treatment
Ongoing NUC therapy186 (80.5)102 (79.1)0.742
Years of NUC therapy, median (Q1-Q3)4.8 (1.5-8.2)4.3 (2.1-7.7)0.683
1Proportions are based on available data. Inconsistencies are due to missing values.
HDV: Hepatitis delta virus; ALT: Alanine transaminase; BMI: Body mass index; GGT: Gamma-glutamyl transpeptidase; HBeAg: Hepatitis Be antigen; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; IFN: Interferon; PLT: Platelet; Q1: Quarter 1; Q3: Quarter 3; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; NUC: Nucleos(t)ide analogue.
Full Size Table
Table 3 Characteristics of hepatitis delta virus-RNA positive patients by sex, n (%)
CharacteristicsHDV-RNA positive
P value
Males (n = 1761)
Females (n = 1241)
Age, median (Q1-Q3)55 (46.5-63)56 (43.5-62.5)0.599
≤ 4023 (13.1)29 (23.4)0.226
41-5037 (21.0)23 (18.5)
51-6054 (30.7)31 (25.0)
61-7048 (27.3)31 (25.0)
> 7014 (7.9)10 (8.1)
Non-Italian natives55 (31.2)65 (52.4)< 0.001
HDV RNA, median (Q1-Q3)66457 (1720-669213)50739 (4060.9-372159)0.932
ALT > 35 IU/L138 (81.2)87 (73.1)0.104
GGT >50 IU/L79 (57.7)33 (34.0)< 0.001
HBeAg positive8 (4.7)9 (7.6)0.316
Cirrhosis137 (77.8)92 (74.2)0.464
Child-Pugh class
A119 (87.5)77 (88.5)> 0.999
B16 (11.8)10 (11.5)
C1 (0.7)0 (0.0)
MELD ≥ 203 (2.6)0 (0.0)0.284
HCC31 (17.9)7 (5.8)0.002
PLT ≤ 150000103 (61.3)76 (63.9)0.660
Previous IFN64 (39.5)33 (30.0)0.108
NUC treatment
Ongoing NUC therapy137 (78.3)90 (73.2)0.308
Years of NUC therapy, median (Q1-Q3)4.1 (1.6-7.4)4.2 (2.1-7.2)0.653
1Proportions are based on available data. Inconsistencies are due to missing values.
HDV: Hepatitis delta virus; ALT: Alanine transaminase; GGT: Gamma-glutamyl transpeptidase; HBeAg: Hepatitis Be antigen; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; IFN: Interferon; PLT: Platelet; Q1: Quarter 1; Q3: Quarter 3; NUC: Nucleos(t)ide analogue.
Full Size Table
Table 4 Propensity score analysis and weighted logistic regression model
Balanced variables
Unweighted (std-diff)
Weighted (std-diff)
P value
Age (Ref. ≤ 55 years)0.1229701-0.0728242
HDV-RNA (Ref. neg)0.1365088-0.013608
HBV DNA (Ref. neg)0.0022074-0.0190112
Previous IFN (Ref. no IFN)0.0422737-0.0327822
Years of NUC therapy (continuous variable)-0.0770610.0570684
Alcohol use (Ref. no alcohol)-0.64361890.0261042
Diabetes (Ref. no diabetes)-0.1993716-0.0714145
BMI 25-30 (Ref. < 25)-0.0935022-0.0181635
BMI ≥ 30 (Ref. < 25)0.0949776-0.0145787
Multivariable analysisOR95%CI
Sex (Ref. female)1.851.004-3.400.048
Outcome: Cirrhosis/hepatocellular carcinoma. Study population: Hepatitis B surface antigen +/anti-hepatitis delta virus positive patients, excluding patients coinfected by human immunodeficiency virus and hepatitis C virus. BMI: Body mass index; CI: Confidence interval; HDV: Hepatitis delta virus; HBV: Hepatitis B virus; IFN: Interferon; neg: Negative; NUC: Nucleos(t)ide analogue; OR: Odds ratio; Std-diff: Standardized difference.
Full Size Table
  • Citation: Coco B, Quaranta MG, Tosti ME, Ferrigno L, Brancaccio G, Ciancio A, Coppola C, Messina V, Gentile I, Claar E, Morisco F, Santantonio T, Viganò M, Cacciola I, Pompili M, Russo FP, Izzi A, Niro GA, Coppola N, Soria A, Federico A, Morsica G, Puoti M, Villa E, Lampertico P, Gaeta GB, Kondili LA, Brunetto MR, PITER Collaborating Investigators. Sex-based differences in hepatitis delta virus infection: Insights from the Italian PITER hepatitis delta virus cohort. World J Gastroenterol 2025; 31(47): 111637
  • URL: https://www.wjgnet.com/1007-9327/full/v31/i47/111637.htm
  • DOI: https://dx.doi.org/10.3748/wjg.v31.i47.111637
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