Observational Study
Copyright ©The Author(s) 2022.
World J Hepatol. Jul 27, 2022; 14(7): 1438-1458
Published online Jul 27, 2022. doi: 10.4254/wjh.v14.i7.1438
Table 1 Baseline characteristics of patients included in each cohort
BCLC1 cohort
BCLC2 cohort
Northern Italy cohort
Naples cohort
Patients, n827922169
Gender (Male)73 (89.02)67 (84.81)184 (83.26)60 (86.96)
Age (Years)63 (56-71)63 (56-72)69 (60-74)70 (60-74)
AGT1 (rs699)
AA26 (31.71)25 (31.65)72 (32.58)22 (31.88)
AG34 (41.46)35 (44.3)101 (45.7)38 (55.07)
GG22 (26.83)19 (24.05)47 (21.27)9 (13.04)
NA0 (0)0 (0)1 (0.45)0 (0)
AGT2 (rs4762)
AA5 (6.1)3 (3.8)5 (2.26)0 (0)
AG16 (19.51)10 (12.66)44 (19.91)15 (21.74)
GG61 (74.39)66 (83.54)172 (77.83)54 (78.26)
AHT (Yes)37 (45.12)36 (45.57)65 (29.41)45 (65.22)
Diabetes (Yes)22 (26.83)28 (35.44)61 (27.6)23 (33.33)
HBV (Yes)10 (12.2)6 (7.59)46 (20.81)12 (17.39)
HCV (Yes)54 (65.85)38 (48.1)111 (50.23)44 (63.77)
HIV (Yes)2 (2.44)1 (1.27)3 (1.36)0 (0)
Child-Pugh
A: 5-670 (85.37)63 (79.75)207 (93.67)58 (84.06)
B: 7-910 (12.2)11 (13.93)14 (6.33)10 (14.49)
Not applicable2 (2.44)5 (6.33)0 (0)1 (1.45)
ECOG-PS (0)77 (93.9)74 (93.67)155 (70.14)69 (100)
Ascites (Yes)11 (13.41)9 (11.39)25 (11.31)14 (20.29)
Encephalopathy (Yes)0 (0)0 (0)11 (4.98)0 (0)
Extrahepatic spread (Yes)24 (29.27)27 (34.18)79 (35.75)23 (33.33)
Vascular Invasion (Yes)22 (26.83)26 (32.91)61 (27.6)31 (44.93)
BCLC (A1 or B / C)42 (51.22) / 40 (48.78)36 (45.57) / 43 (54.43)76 (34.39) / 145 (65.61)20 (28.99) / 49 (71.01)
Alpha-fetoprotein (ng/mL)20.5 (7-212.5)25 (8-228)100.5 (10-869)98 (5-1903)
Hemoglobin basal (g/dL)13.8 (12.95-14.95)13.1 (11.9-14.5)12.5 (11.2-14)13 (11.9-13.9)
Prothrombin time (%)88.3 (76.5-95.6)76 (65-88)NA84.5 (76-100)
International normalized ratioNANA1.1 (1-1.22)1.13 (1.03-1.24)
Total bilirubin (mg/dL)1 (0.8-1.6)1.1 (0.6-1.7)0.9 (0.72-1.3)0.95 (0.7-1.4)
AST (UI/L)78 (46-119)54 (34-84)NA52 (35-80)
ALT (UI/L)72 (35-106.5)44 (25-65)43 (23-56)42 (32-55)
GGT (UI/L)134.5 (93.5-285.5)143 (83-264)NA96 (48-204)
Albumin (mg/L)38.5 (35-43)40 (35-43)38 (35-40)3.6 (3.3-4)
Initial dosage of sorafenib (mg)
4005 (6.1)2 (2.6)19 (8.6)0 (0)
6000 (0)0 (0)5 (2.26)0 (0)
80077 (93.9)77 (97.4)197 (89.14)69 (100)
Descriptive statistics are frequencies (%) or median (IQR: Interquartile range), as appropriate. AHT: Arterial Hypertension; HCV: Hepatitis C Virus; HBV: Hepatitis B Virus; HIV: Human immunodeficiency virus; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma glutamyl transpeptidase; IQR: Interquartile range; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; BCLC: Barcelona Clinic Liver Cancer; INR: International normalized ratio; NA: Not available.
15 BCLC A patients.
Table 2 Overall survival of each cohort by single-nucleotide polymorphisms
SNP alleles (A/G)
Patients at risk
Events
Median OS (95%CI), months
P value (log-rank)
BCLC1cohort827518.81 (14.76-23.58)
BCLC2 cohort794718.32 (13.05-26.44)
Northern Italy cohort22118014.3 (11.84-17.99)
Naples cohort69579.9 (7.69-12.82)
BCLC1 cohortAGT1 (rs699)82750.16
AA262318.73 (11.84-41.4)
AG343318.43 (10.75-22.76)
GG221918.81 (9.67-30.42)
AGT2 (rs4762)82750.4
AA5541.34 (0.39-74.12)
AG161513.95 (7.3-23.87)
GG615519.11 (14.86-24.47)
BCLC2 cohortAGT1 (rs699)79470.15
AA251523.74 (7.46-26.5)
AG351921.74 (11.15-33.77)
GG19136.64 (3.42-30.29)
AGT2 (rs4762)79470.3
AA31NE (13.61-NE)
AG10530.29 (3.88-32.69)
GG664116.41 (8.78-23.74)
Northern Italy cohortAGT1 (rs699)2201790.5
AA725813.58 (10.92-19.2)
AG1018317.59 (10.85-20.68)
GG473812.43 (8.81-20.68)
AGT2 (rs4762)2211800.7
AA52NE (1.94-NE)
AG443614.3 (7.46-20.68)
GG17214214.9 (11.25-18.09)
Naples cohortAGT1 (rs699)69570.7
AA221912.66 (6.15-18.25)
AG38318.32 (4.9-11.71)
GG9710.95 (2.6-21.83)
AGT2 (rs4762)69570.6
AG15119.8 (2.89-24.93)
GG544610.1 (7.14-12.82)
NE: Not estimable; OS: Overall survival; 95%CI: 95% confidence interval; SNP: Single-nucleotide polymorphisms; BCLC: Barcelona clinic liver cancer.
Table 3 Follow-up and evolutionary events in the included patients of each cohort
BCLC1cohort
BCLC2cohort
Northern Italy cohort
Naples cohort
Patients, n827922169
Follow-up (mo)18.58 (10.33-34.17)13.05 (6.64-22.36)12.73 (6.05-25.88)9.87 (4.51-18.25)
Treatment duration (mo)9.06 (4.11-17.46)5.95 (2.14-13.52)8.52 (2.56-20.78)8.06 (3.72-16.97)
Adverse Events
Gastrointestinal (Yes)35 (42.68)27 (34.18)23 (10.41)38 (55.07)
Dermatologic (Yes)42 (51.22)28 (35.44)32 (14.48)27 (39.13)
Early Dermatologic (Yes)33 (40.24)22 (27.85)28 (12.67)25 (36.23)
Performance status deterioration (Yes)44 (53.66)46 (58.23)53 (23.98)0 (0)
Cardiovascular (Yes)18 (21.95)14 (17.72)16 (7.24)16 (23.19)
Dermatologic and Cardiovascular simultaneously (Yes) 7 (8.54)5 (6.33)0 (0)10 (14.49)
Other (Yes)48 (58.54)34 (43.04)45 (20.36)65 (94.2)
Death (Yes)75 (91.46)47 (59.49)180 (81.44)57 (82.61)
Cause of death
HCC74 (98.67)46 (97.87)118 (65.56)48 (84.21)
Not HCC related0 (0)1 (2.13)58 (32.22)9 (15.79)
Others11 (1.33)0 (0)4 (2.22)0 (0)
Descriptive statistics are frequencies (%) or median (IQR: Interquartile range), as appropriate. AE: Adverse events; DAE: Dermatological adverse events; eDAE: early Dermatological adverse events.
1Other causes of Exitus are: 1 Sudden death, 4 unknown.
Table 4 Cox regression models for eDAE and DAE by AGT1 (rs699)
Event
Centre
AGT1(rs699)
HR (95%CI)
P value
HR (95%CI) adjusted by BCLC + ECOG-PS
P value
HR (95%CI) adjusted by BCLC + ECOG-PS + AHT + DM
P value
HR (95%CI) adjusted for AHT + DM
P value
HR (95%CI) adjusted for DM
P value
HR (95%CI) adjusted for AHT
P value
eDAEBCLC1 cohortAA vs AG2.31 (1.03-5.14)0.042.3 (1.02-5.16)0.042.34 (1.02-5.37)0.042.33 (1.03-5.24)0.042.45 (1.1-5.5)0.032.24 (1-5.03)0.049
AA vs GG1.68 (0.71-3.97)0.21.69 (0.71-4)0.21.64 (0.69-3.93)0.31.65 (0.69-3.92)0.31.75 (0.74-4.13)0.21.62 (0.68-3.87)0.3
AG vs GG0.73 (0.29-1.85)0.50.73 (0.29-1.89)0.50.7 (0.27-1.82)0.50.71 (0.28-1.79)0.50.71 (0.28-1.8)0.50.72 (0.29-1.84)0.5
BCLC2 cohortAA vs AG0.66 (0.25-1.76)0.40.63 (0.24-1.7)0.40.71 (0.26-1.93)0.50.72 (0.27-1.93)0.50.72 (0.27-1.91)0.50.68 (0.25-1.83)0.5
AA vs GG1.13 (0.32-4.01)0.91.08 (0.3-3.84)0.91.35 (0.37-4.95)0.71.36 (0.38-4.9)0.71.32 (0.37-4.72)0.71.13 (0.32-4)0.9
AG vs GG1.71 (0.55-5.3)0.41.7 (0.55-5.28)0.41.89 (0.6-5.91)0.31.89 (0.6-5.9)0.31.85 (0.6-5.74)0.31.66 (0.53-5.17)0.4
Northern Italy cohortAA vs AG0.8 (0.33-1.95)0.60.75 (0.3-1.86)0.51.02 (0.4-2.61)0.90.96 (0.39-2.36)0.90.83 (0.34-2.02)0.70.91 (0.37-2.23)0.8
AA vs GG0.9 (0.31-2.6)0.80.71 (0.24-2.1)0.50.96 (0.31-2.98)0.91.22 (0.4-3.73)0.70.96 (0.33-2.8)0.91.12 (0.37-3.36)0.8
AG vs GG1.12 (0.42-3.01)0.80.95 (0.35-2.58)0.90.94 (0.33-2.69)0.91.27 (0.46-3.49)0.71.15 (0.43-3.12)0.81.23 (0.45-3.34)0.7
Naples cohortAA vs AG1.26 (0.54-2.95)0.61.21 (0.51-2.86)0.71.35 (0.56-3.27)0.51.36 (0.57-3.25)0.51.23 (0.52-2.93)0.61.44 (0.61-3.39)0.4
AA vs GG1.26 (0.34-4.66)0.71.18 (0.31-4.43)0.81.33 (0.35-5)0.71.34 (0.36-4.96)0.71.27 (0.34-4.68)0.71.35 (0.37-5)0.7
AG vs GG1 (0.28-3.51)0.90.97 (0.28-3.43)0.90.98 (0.28-3.49)0.90.99 (0.28-3.49)0.91.03 (0.29-3.65)0.90.94 (0.27-3.3)0.9
BCLC2 cohort + Naples cohort + Northern Italy cohortAA vs AG0.87 (0.52-1.47)0.60.85 (0.51-1.43)0.50.84 (0.5-1.41)0.50.85 (0.51-1.43)0.60.87 (0.52-1.47)0.60.85 (0.51-1.43)0.6
AA vs GG1.05 (0.54-2.04)0.90.95 (0.49-1.86)0.90.92 (0.47-1.81)0.81.01 (0.52-1.97)0.91.05 (0.54-2.04)0.91.01 (0.52-1.97)0.9
AG vs GG1.2 (0.65-2.22)0.61.12 (0.61-2.08)0.71.1 (0.59-2.05)0.81.18 (0.64-2.18)0.61.2 (0.65-2.22)0.61.18 (0.64-2.18)0.6
BCLC1 cohort + Naples cohort + Northern Italy cohortAA vs AG1.35 (0.84-2.17)0.21.35 (0.84-2.18)0.21.33 (0.82-2.15)0.21.31 (0.81-2.11)0.31.35 (0.84-2.18)0.21.3 (0.81-2.1)0.3
AA vs GG1.19 (0.67-2.12)0.61.13 (0.6-2.01)0.71.08 (0.6-1.93)0.81.1 (0.61-1.97)0.81.19 (0.67-2.12)0.61.09 (0.61-1.96)0.8
AG vs GG0.88 (0.5-1.55)0.70.83 (0.47-1.48)0.50.81 (0.46-1.43)0.50.84 (0.48-1.48)0.60.88 (0.5-1.55)0.70.84 (0.48-1.48)0.6
BCLC1cohort + BCLC2 cohort + Naples cohortAA vs AG1.32 (0.81-2.15)0.31.29 (0.79-2.11)0.31.3 (0.79-2.12)0.31.31 (0.81-2.14)0.31.33 (0.82-2.17)0.31.31 (0.8-2.13)0.3
AA vs GG1.4 (0.75-2.6)0.31.38 (0.7-2.57)0.31.44 (0.77-2.69)0.31.45 (0.78-2.7)0.21.46 (0.79-2.72)0.21.38 (0.74-2.57)0.3
AG vs GG1.06 (0.58-1.94)0.91.06 (0.58-1.95)0.91.11 (0.6-2.03)0.81.1 (0.6-2.02)0.81.1 (0.6-2.01)0.81.06 (0.58-1.94)0.9
DAEBCLC1 cohortAA vs AG2.7 (1.27-5.75)0.012.68 (1.25-5.77)0.012.52 (1.16-5.47)0.022.6 (1.21-5.57)0.012.82 (1.32-6.06)0.0082.5 (1.17-5.35)0.02
AA vs GG1.26 (0.62-2.58)0.51.24 (0.61-2.55)0.61.11 (0.53-2.31)0.81.13 (0.55-2.35)0.81.3 (0.63-2.66)0.51.12 (0.54-2.32)0.8
AG vs GG0.47 (0.21-1.05)0.060.46 (0.2-1.06)0.070.44 (0.19-1.01)0.0530.44 (0.19-0.98)0.0450.46 (0.2-1.03)0.060.45 (0.2-1.01)0.052
BCLC2 cohortAA vs AG0.98 (0.43-2.2)0.90.94 (0.42-2.13)0.90.99 (0.43-2.26)0.91.01 (0.45-2.3)0.91.03 (0.45-2.32)0.90.95 (0.42-2.16)0.9
AA vs GG1.89 (0.59-6.04)0.31.78 (0.55-5.76)0.32.08 (0.63-6.85)0.22.18 (0.67-7.03)0.192.08 (0.65-6.66)0.21.88 (0.59-6.01)0.3
AG vs GG1.94 (0.64-5.9)0.21.89 (0.62-5.77)0.32.12 (0.69-6.49)0.192.15 (0.7-6.57)0.182.02 (0.66-6.15)0.21.98 (0.65-6.05)0.2
Northern Italy cohortAA vs AG0.89 (0.39-2.06)0.80.85 (0.37-1.98)0.71.01 (0.42-2.41)0.91 (0.42-2.33)0.90.91 (0.39-2.11)0.80.95 (0.41-2.22)0.9
AA vs GG0.62 (0.25-1.57)0.30.54 (0.21-1.37)0.20.6 (0.23-1.6)0.30.74 (0.28-1.92)0.50.64 (0.25-1.62)0.40.7 (0.27-1.79)0.5
AG vs GG0.7 (0.3-1.62)0.30.63 (0.27-1.48)0.20.6 (0.25-1.43)0.20.74 (0.32-1.72)0.50.71 (0.3-1.63)0.40.73 (0.31-1.69)0.5
Naples cohortAA vs AG1.29 (0.57-2.92)0.51.23 (0.54-2.81)0.61.35 (0.58-3.15)0.51.38 (0.6-3.17)0.51.23 (0.54-2.81)0.61.49 (0.66-3.4)0.3
AA vs GG1.38 (0.38-5.03)0.61.28 (0.35-4.73)0.71.45 (0.39-5.36)0.61.49 (0.41-5.41)0.61.39 (0.38-5.05)0.61.51 (0.41-5.51)0.5
AG vs GG1.07 (0.31-3.72)0.91.04 (0.3-3.62)0.91.08 (0.31-3.77)0.91.08 (0.31-3.79)0.91.13 (0.32-3.96)0.91.01 (0.29-3.52)0.9
BCLC2 cohort + Naples cohort + Northern Italy cohortAA vs AG1 (0.62-1.61)0.90.98 (0.61-1.57)0.90.95 (0.59-1.54)0.90.97 (0.6-1.56)0.91.01 (0.63-1.62)0.90.96 (0.6-1.55)0.9
AA vs GG1.13 (0.61-2.08)0.71.04 (0.56-1.92)0.90.98 (0.53-1.81)0.91.05 (0.57-1.95)0.91.12 (0.61-2.07)0.71.05 (0.57-1.95)0.9
AG vs GG1.13 (0.63-2)0.71.06 (0.59-1.89)0.81.02 (0.57-1.83)0.91.09 (0.61-1.94)0.81.12 (0.63-1.99)0.71.09 (0.61-1.95)0.8
BCLC1 cohort + Naples cohort +Northern Italy cohortAA vs AG1.43 (0.91-2.24)0.121.43 (0.91-2.24)0.121.39 (0.88-2.19)0.151.36 (0.87-2.14)0.181.44 (0.92-2.26)0.111.35 (0.86-2.12)0.19
AA vs GG0.94 (0.57-1.56)0.80.9 (0.54-1.51)0.70.82 (0.49-1.38)0.50.83 (0.49-1.39)0.50.94 (0.57-1.57)0.80.82 (0.49-1.38)0.5
AG vs GG0.66 (0.4-1.09)0.10.63 (0.38-1.050.080.59 (0.36-0.99)0.040.61 (0.37-1.01)0.0520.66 (0.4-1.08)0.10.61 (0.37-1.01)0.053
BCLC1 cohort + BCLC2 cohort + Naples cohortAA vs AG1.54 (0.98-2.41)0.061.49 (0.95-2.34)0.081.48 (0.94-2.32)0.091.52 (0.97-2.37)0.071.55 (0.99-2.43)0.0551.5 (0.96-2.35)0.07
AA vs GG1.35 (0.78-2.32)0.31.3 (0.75-2.25)0.31.32 (0.76-2.28)0.31.35 (0.78-2.33)0.31.39 (0.81-2.4)0.21.3 (0.76-2.24)0.3
AG vs GG0.88 (0.51-1.51)0.60.87 (0.51-1.5)0.60.89 (0.52-1.54)0.70.89 (0.52-1.54)0.70.9 (0.52-1.54)0.70.87 (0.5-1.49)0.6
eDAE: early Dermatological adverse events; DAE: Dermatological adverse events; HR: Hazard ratio; 95%CI: 95% confidence interval; BCLC: Barcelona Clinic Liver Cancer; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; AHT: Arterial hypertension; DM: Diabetes mellitus.
Table 5 Cox regression models for eDAE and DAE by AGT2 (rs4762)
Event
Center
AGT2(rs4762)
HR (95%CI)
P value
HR (95%CI) adjusted for BCLC + ECOG-PS
P value
HR (95%CI) adjusted for BCLC + ECOG-PS + AHT + DM
P value
HR (95%CI) adjusted for AHT + DM
P value
HR (95%CI) adjusted for DM
P value
HR (95%CI) adjusted for AHT
P value
eDAEBCLC1 cohortAA vs AG1.14 (0.22-5.89)0.90.98 (0.19-5.12)0.90.97 (0.18-5.04)0.91.09 (0.21-5.64)0.91.15 (0.22-5.95)0.91.11 (0.21-5.72)0.9
AA vs GG0.84 (0.2-3.53)0.80.73 (0.17-3.15)0.70.71 (0.16-3.1)0.70.81 (0.19-3.4)0.80.8 (0.19-3.39)0.80.84 (0.2-3.54)0.8
AG vs GG0.73 (0.28-1.91)0.50.74 (0.28-1.94)0.50.74 (0.28-1.97)0.60.74 (0.28-1.94)0.60.7 (0.27-1.82)0.50.76 (0.29-1.98)0.6
BCLC2 cohortAA vs AG3.71 (0.62-22.39)0.23.52 (0.58-21.5)0.24.8 (0.74-31.28)0.14.81 (0.74-31.24)0.14.78 (0.76-29.88)0.094.46 (0.7-28.35)0.11
AA vs GG4.43 (1.01-19.39)0.0484.24 (0.95-19.06)0.066.14 (1.28-29.55)0.026.28 (1.32-29.95)0.026.25 (1.35-28.89)0.025.34 (1.15-24.86)0.03
AG vs GG1.19 (0.35-4.08)0.81.21 (0.35-4.15)0.81.28 (0.37-4.45)0.71.31 (0.38-4.47)0.71.31 (0.38-4.47)0.71.2 (0.35-4.08)0.8
Northern Italy cohortAA vs AG2.72 (0.57-13.1)0.23.21 (0.64-15.99)0.155.61 (1.01-31.12)0.0483.43 (0.69-16.96)0.132.69 (0.56-12.97)0.23.2 (0.66-15.6)0.15
AA vs GG4.54 (1.05-19.64)0.045.15 (1.17-22.63)0.038.51 (1.78-40.54)0.0075.51 (1.25-24.33)0.024.72 (1.09-20.48)0.044.93 (1.13-21.41)0.03
AG vs GG1.67 (0.69-4.02)0.31.6 (0.66-3.9)0.31.52 (0.6-3.82)0.41.61 (0.66-3.9)0.31.75 (0.73-4.24)0.21.54 (0.63-3.73)0.3
Naples cohortAG vs GG1.2 (0.48-3.01)0.71.2 (0.48-3.02)0.71.25 (0.5-3.15)0.61.26 (0.5-3.16)0.61.2 (0.48-3)0.71.29 (0.51-3.23)0.6
BCLC2 cohort + Naples cohort + Northern Italy cohortAA vs AG2.76 (0.92-8.27)0.072.95 (0.97-9.84)0.062.78 (0.9-8.56)0.072.61 (0.87-7.86)0.092.75 (0.92-8.25)0.072.61 (0.87-7.86)0.09
AA vs GG3.5 (1.27-9.67)0.023.8 (1.36-10.58)0.013.67 (1.31-10.3)0.013.39 (1.22-9.37)0.023.5 (1.27-9.66)0.023.38 (1.22-9.37)0.02
AG vs GG1.27 (0.73-9.67)0.41.29 (0.74-2.25)0.41.32 (0.75-2.32)0.31.3 (0.74-2.27)0.41.27 (0.73-2.22)0.41.3 (0.74-2.27)0.4
BCLC1 cohort + Naples cohort +Northern Italy cohortAA vs AG1.66 (0.65-4.9)0.41.63 (0.55-4.85)0.41.53 (0.51-4.57)0.51.54 (0.52-4.57)0.41.66 (0.56-4.9)0.41.54 (0.52-4.57)0.4
AA vs GG1.83 (0.67-5.03)0.21.73 (0.63-4.77)0.31.7 (0.62-4.69)0.31.8 (0.65-4.94)0.31.85 (0.67-5.08)0.21.79 (0.65-4.93)0.3
AG vs GG1.1 (0.65-1.86)0.71.06 (0.63-1.81)0.81.11 (0.65-1.9)0.71.17 (0.69-1.97)0.61.11 (0.66-1.88)0.71.16 (0.69-1.97)0.6
BCLC1 cohort + BCLC2 cohort + Naples cohortAA vs AG1.67 (0.55-5.09)0.41.6 (0.53-4.87)0.41.61 (0.53-4.92)0.41.66 (0.55-5.06)0.41.71 (0.56-5.19)0.41.63 (0.54-4.95)0.4
AA vs GG1.7 (0.62-4.67)0.31.67 (0.61-4.59)0.31.68 (0.61-4.63)0.31.7 (0.62-4.67)0.31.7 (0.62-4.67)0.31.68 (0.61-4.62)0.3
AG vs GG1.01 (0.57-1.81)0.91.04 (0.58-1.86)0.91.04 (0.58-1.86)0.91.02 (0.57-1.82)0.90.99 (0.56-1.78)0.91.03 (0.58-1.84)0.9
DAEBCLC1 cohortAA vs AG2.8 (0.78-10.01)0.12.45 (0.68-8.81)0.22.73 (0.74-9.99)0.133.09 (0.85-11.2)0.092.85 (0.79-10.22)0.112.86 (0.8-10.28)0.11
AA vs GG1.82 (0.64-5.16)0.31.61 (0.56-4.64)0.41.89 (0.64-5.57)0.22.12 (0.74-6.1)0.161.79 (0.63-5.08)0.32.03 (0.71-5.78)0.19
AG vs GG0.65 (0.27-1.56)0.30.66 (0.27-1.59)0.40.69 (0.28-1.72)0.40.69 (0.28-1.68)0.40.63 (0.26-1.52)0.30.71 (0.29-1.71)0.4
BCLC2 cohortAA vs AG3.83 (0.64-23.05)0.13.71 (0.61-22.68)0.23.91 (0.62-24.73)0.154.05 (0.65-25.33)0.144.49 (0.73-27.55)0.13.79 (0.61-23.44)0.15
AA vs GG3.22 (0.75-13.76)0.13.27 (0.74-14.38)0.13.74 (0.82-17.15)0.093.7 (0.82-16.76)0.094.04 (0.91-18)0.073.18 (0.72-14.13)0.13
AG vs GG0.84 (0.25-2.8)0.80.88 (0.26-2.96)0.80.96 (0.28-3.24)0.90.92 (0.27-3.06)0.90.9 (0.27-3.01)0.90.84 (0.25-2.8)0.8
Northern Italy cohortAA vs AG2.85 (0.59-13.73)0.23.28 (0.66-16.21)0.14.71 (0.89-24.91)0.073.4 (0.69-16.77)0.132.83 (0.59-13.64)0.23.13 (0.65-15.21)0.16
AA vs GG3.68 (0.86-15.63)0.084.15 (0.96-17.87)0.065.97 (1.32-27.01)0.024.41 (1.02-19.03)0.0463.97 (0.93-16.94)0.063.8 (0.89-16.16)0.07
AG vs GG1.29 (0.55-3.01)0.61.26 (0.54-2.96)0.61.27 (0.53-3.05)0.61.3 (0.55-3.05)0.61.4 (0.6-3.29)0.41.21 (0.52-2.84)0.7
Naples cohortAG vs GG1.12 (0.45-2.77)0.81.11 (0.45-2.76)0.81.12 (0.45-2.79)0.81.13 (0.46-2.82)0.81.12 (0.45-2.77)0.91.16 (0.47-2.88)0.8
BCCL2 cohort + Naples cohort + Northern Italy cohortAA vs AG2.79 (0.93-8.35)0.073.04 (1-9.21)0.0492.72 (0.88-8.34)0.082.54 (0.84-7.63)0.12.74 (0.92-8.21)0.072.56 (0.85-7.7)0.09
AA vs GG2.96 (1.08-8.13)0.033.27 (1.18-9.05)0.023.07 (1.1-8.56)0.032.81 (1.02-7.73)0.0452.94 (1.07-8.07)0.042.83 (1.03-7.78)0.04
AG vs GG1.06 (0.62-1.83)0.81.07 (0.62-1.86)0.81.13 (0.65-1.96)0.71.11 (0.64-1.92)0.71.07 (0.62-1.85)0.81.11 (0.64-1.91)0.7
BCLC1 cohort + Naples cohort + Northern Italy cohortAA vs AG2.82 (1.13-7.07)0.032.9 (1.15-7.32)0.022.7 (1.06-6.84)0.042.66 (1.06-6.69)0.042.81 (1.12-7.05)0.032.68 (1.07-6.74)0.04
AA vs GG2.86 (1.24-6.58)0.012.84 (1.23-6.54)0.012.85 (1.24-6.57)0.012.94 (1.28-6.77)0.012.91 (1.27-6.7)0.012.94 (1.28-6.77)0.01
AG vs GG1.01 (0.61-1.68)0.90.98 (0.59-1.63)0.91.06 (0.63-1.77)0.81.1 (0.67-1.83)0.71.04 (0.63-1.71)0.91.1 (0.66-1.82)0.7
BCLC1 cohort + BCLC2 cohort + Naples cohortAA vs AG2.94 (1.14-7.6)0.032.85 (1.1-7.39)0.033.12 (1.2-8.14)0.023.21 (1.23-8.34)0.023.05 (1.18-7.9)0.022.9 (1.12-7.5)0.03
AA vs GG2.49 (1.08-5.73)0.032.48 (1.08-5.72)0.032.73 (1.18-6.32)0.022.75 (1.19-6.34)0.022.54 (1.1-5.85)0.032.51 (1.09-5.77)0.03
AG vs GG0.85 (0.49-1.48)0.60.87 (0.5-1.52)0.60.87 (0.5-1.53)0.70.86 (0.49-1.5)0.60.83 (0.48-1.45)0.50.87 (0.5-1.51)0.6
eDAE: early Dermatological adverse events; DAE: Dermatological adverse events; HR: Hazard ratio; 95%CI: 95% confidence interval; BCLC: Barcelona Clinic Liver Cancer; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; AHT: Arterial hypertension; DM: Diabetes mellitus.
  • Citation: Sapena V, Iavarone M, Boix L, Facchetti F, Guarino M, Sanduzzi Zamparelli M, Granito A, Samper E, Scartozzi M, Corominas J, Marisi G, Díaz A, Casadei-Gardini A, Gramantieri L, Lampertico P, Morisco F, Torres F, Bruix J, Reig M. Polymorphism AGT2 (rs4762) is involved in the development of dermatologic events: Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib. World J Hepatol 2022; 14(7): 1438-1458
  • URL: https://www.wjgnet.com/1948-5182/full/v14/i7/1438.htm
  • DOI: https://dx.doi.org/10.4254/wjh.v14.i7.1438