Direct-Acting Antiviral Drugs and Occurrence of Hepatocellular Carcinoma: Unjust or Oppressed

Figures & data

Table 1 Baseline Characteristics of Studied Patients

	No. (n= 350)	%
Age (years)
<60	198	56.6
≥60	152	43.4
Mean ± SD (Range)	58.11 ± 7.48 (32–76)
Sex
Males	194	55.4
Females	156	44.6
DM
Yes	106	30.3
No	244	69.7
HTN
Yes	77	22.0
No	273	78.0
Treatment experience
Naïve	295	84.3
Experience	55	15.7
Regimen experience
S+R	33	60.0
S+S	12	21.8
Interferon	2	3.6
S+R+ Interferon	8	14.5
Current regimen
s+d±r	350	100.0
Duration of current treatment (months)	3.45 ± 1.07 (3–6)
PCR Median (range)	511,897 (52–815,000,000)

Abbreviations: DM, diabetes mellitus; HTN, hypertension; S+R, sofosbuvir+ribavirin; S+S, sofosbuvir+Semiprevir; s+d±r, sofosbuvir+daclatasvir±ribavirin.

Table 2 Clinical and Biochemical Characteristics of SVR Patients Before and After Treatment

	Before Treatment (n= 329)		After Treatment (n= 329)		P-value
	Mean ± SD		Mean ± SD
HE	8	2.4%	2	0.6	0.056
Ascites	41	12.5%	21	6.4%	0.008*
BIL					0.000*
Mean ± SD	1.18 ± 0.64		0.94 ± 0.68
Median (range)	1.0 (0.2–3.4)		0.8 (0.1–6.0)
ALB					0.000*
Mean ± SD	3.50 ± 0.56		4.00 ± 0.63
Median (range)	3.5 (2.0–5.2)		4.0 (2.2–5.5)
INR					0.424
Mean ± SD	1.19 ± 0.22		1.18 ± 0.21
Median (range)	1.1 (1.0–2.1)		1.1 (1.0–2.6)
S. creatinine					0.001*
Mean ± SD	0.91 ± 0.22		0.97 ± 0.34
Median (Range)	0.9 (0.1–1.6)		0.9 (0.1–3.6)
Child score					0.000*
Mean ± SD	5.92 ± 1.01		5.47 ± 0.92
Median (range)	6.0 (5.0–9.0)		5.0 (5.0–11.0)
MELD score					0.335
Mean ± SD	9.28 ± 2.68		9.21 ± 2.88
Median (range)	9.0 (6.0–18.0)		9.0 (6.0–20.0)
AFP					0.000*
Mean ± SD	15.16 ± 20.68		28.75 ± 331.25
Median (range)	9.4 (0.1–167.0)		5.0 (0.1–5987.0)
WBCs					0.590
Mean ± SD	5.41 ± 2.17		5.36 ± 2.25
Median (range)	5.0 (1.1–17.0)		4.9 (1.2–19.0)
HB					0.000*
Mean ± SD	13.09 ± 1.66		12.38 ± 1.73
Median (range)	13.0 (10.0–19.5)		12.0 (8.3–23.0)
PLT					0.002*
Mean ± SD	137.86 ± 63.31		149.43 ± 72.79
Median (range)	127.0 (37.0–463.0)		139.0 (28.0–475.0)
ALT					0.000*
Mean ± SD	59.05 ± 37.34		25.74 ± 19.69
Median (range)	50.0 (7.0–233.0)		23.0 (2.0–330.0)
AST					0.000*
Mean ± SD	63.16 ± 37.99		29.71 ± 13.64
Median (range)	57.0 (6.8–292.0)		27.0 (5.0–157.0)

Note: *Significant.

Abbreviations: SVR, sustained virological response; HE, hepatic encephalopathy; BIL, bilirubin; ALB, albumin; INR, international normalized ratio; AFP, alpha-fetoprotein; WBCs, white blood cells; HB, hemoglobin; PLT, platelets; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Table 3 Clinical Data of SVR and Non-SVR Patients Before and After Treatment

	SVR (n= 329)		Non-SVR (n= 21)		P-value
	Mean ± SD		Mean ± SD
Age (years)					0.558
Mean ± SD	58.20 ± 7.36		56.67 ± 9.20
Median (range)	58.0 (32.0–76.0)		57.0 (32.0–72.0)
Sex					0.048*
Males	178	54.1%	16	76.2%
Females	151	45.9%	5	23.8%
DM	101	30.7%	5	23.8%	0.505
HTN	76	23.1%	1	4.8%	0.056
Treatment experience					0.756
Naïve	278	84.5%	17	81.0%
Experience	51	15.5%	4	19.0%
Duration of current treatment: (months)					0.940
Mean ± SD	3.45 ± 1.07		3.43 ± 1.08
Median (range)	3.0 (3.0–6.0)		3.0 (3.0–6.0)
HE before	8	2.4%	1	4.8%	0.431
HE after	2	0.6	1	4.8%	0.170
Ascites before	41	12.5%	2	9.5%	1.000
Ascites after	21	6.4%	1	4.8%	1.000

Note: *Significant.

Abbreviations: SVR, sustained virological response; DM, diabetes mellitus; HTN, hypertension; HE, hepatic encephalopathy.

Table 4 De-Novo Occurrence of HCC After Treatment in SVR and Non-SVR Patients

	SVR (n= 329)	Non-SVR (n= 21)	P-value
	Mean ± SD	Mean ± SD
PCR			0.768
Median	550,000	483,000
Range	52–815,000,000	13,000–474,000,000
HCC after treatment			0.016*
Yes	22 (6.7%)	5 (23.8%)
No	307 (93.3%)	16 (76.2%)

Note: *Significant.

Abbreviations: SVR, sustained virological response; HCC, hepatocellular carcinoma.

Table 5 Characteristics of HCC Patients with SVR and Non-SVR

Case No.	Duration of HCC After TTT	1st Year	2nd Year	SVR	Non-SVR	AFP Before TTT	AFP After TTT	Age	DM
1	24 m		+	+		148	86	65
2	10m	+			+	1.2	1.2	72
3	7m	+		+		2.3	5	51	+
4	0 m at SVR12	+		+		9.6	7.8	60
5	8m	+		+		2	3.5	48
6	24m		+	+		14.7	11	60
7	10m	+		+		5	5.6	61	+
8	6m	+			+	18	33	57
9	2m	+		+		0.3	6.8	69
10	10m	+			+	45	9.9	54	+
11	24m		+	+		12	9.8	50
12	0 m at SVR 12	+		+		8	4.3	58	+
13	5m	+		+		14	60	53	+
14	5m	+		+		15	15	65
15	2m	+		+	+	71.7	380	62
16	0 m (non-SVR 12)	+			+	12	5.4	44
17	4m	+		+		6.7	6.7	60	+
18	14m		+			10.7	5	59
19	14m		+	+		7.1	454	68
20	14m		+	+		6.1	5	63
21	1m	+		+		11	10	67
22	15m		+	+		27	0.5	72
23	2m	+		+		7.8	3.6	73
24	5m	+		+		0.1	1	67	+
25	16m		+	+		16	19.5	65
26	20m		+	+		5	5987	57	+
27	18m		+	+		9.7	12	56
No.	27	17	10	22	5				8

Abbreviations: No, number; HCC, hepatocellular carcinoma; SVR, sustained virological response; Non-SVR, non-sustained virological response; TTT, treatment; m, month; AFP, alpha-fetoprotein; DM, diabetes mellitus.

Figure 1 Kaplan–Meier curve for HCC occurrence after treatment.