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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (6) : 658-666    https://doi.org/10.1007/s11684-019-0707-7
RESEARCH ARTICLE
Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma
Tung Huynh1, Ke-Qin Hu2()
1. Department of Pharmacy, University of California, Irvine, School of Medicine, Orange, CA 92868, USA
2. Division of Gastroenterology and Hepatology, University of California, Irvine, School of Medicine, Orange, CA 92868, USA
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Abstract

Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12–213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (>5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP>5.5 was associated with the presence of cirrhosis (P=0.001), co-existing non-alcoholic steatohepatitis (NASH) (P = 0.035), and GT 1 (P = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis (P = 0.003), Child--Pugh score<6 (P = 0.015), and baseline AFP<10 (P = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child--Pugh score<6, and baseline AFP<10.

Keywords chronic hepatitis C      α fetoprotein      direct acting antiviral treatment      cirrhosis     
Corresponding Authors: Ke-Qin Hu   
Just Accepted Date: 04 September 2019   Online First Date: 30 October 2019    Issue Date: 16 December 2019
 Cite this article:   
Tung Huynh,Ke-Qin Hu. Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma[J]. Front. Med., 2019, 13(6): 658-666.
 URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-019-0707-7
http://academic.hep.com.cn/fmd/EN/Y2019/V13/I6/658
Characteristics n (% or range)
Mean age 57.8 (20–85)
Male:female 73:68 (51.7:48.3)
Ethnicity
?Caucasian 75 (53.1)
?Asian 27 (19.1)
?Hispanic 22 (15.6)
?African American 7 (4.9)
?Other 10 (7)
Mean BMI 27.3 (18–48)
Mean post-Rx follow-up (week) 99 (12–213)
Cirrhosis 67 (47.5)
Mean MELD 9.6 (6–32)
Mean Child–Pugh score 5.6 (5–9)
Child–Pugh class A 57 (85.1)
Child–Pugh class B 10 (14.9)
Decompensation 9 (13.4)
Steatosis 79 (56)
Co-existing NASH 12 (8.5)
Co-existing AIH 4 (2.8)
Genotype 1 112 (79.4)
Genotype 2 12 (8.5)
Genotype 3 11 (7.8)
Genotype 4 2 (1.4)
Genotype 5 1 (0.7)
Genotype 6 3 (2.1)
Treatment naïve 60 (42.5)
Mean AFP (ng/mL) 13.3 (1.1–197)
Mean log 10 HCV RNA (IU/mL) 5.88 (2.6–7.26)
Mean baseline ALT (IU/L) 71.7 (8–496)
Mean baseline AST (IU/L) 63.5 (10–244)
Mean total bilirubin (mg/dL) 0.8 (0.2–3.9)
Mean INR 1.08 (0.88–2.23)
Mean albumin (g/dL) 3.9 (2.3–5.2)
Mean platelets (103/µL) 171 (32–467)
Mean creatinine (mg/dL) 1.16 (0.3–8)
Tab.1  Baseline clinical demographics and laboratory values in 141 study subjects
Baseline Overall, n (%) With cirrhosis, n (%) Without cirrhosis, n (%) P-value
Total patients 141 67 (47.5) 74 (52.5)
AFP mean and range (ng/mL) 13.3 (1.1–197) 20.4 (2–197) 5.2 (1.1–17.1) 0.0029
AFP?>?5.5 68 (48.2) 47 (70) 21 (28.4) 0.0001
AFP?>?10 35 (24.8) 28 (41.7) 7 (9.5) 0.0001
AFP?>?25 9 (6.3) 9 (13.4) 0 (0) 0.003
AFP?>?50 5 (3.5) 5 (7.4) 0 (0) 0.042
ALT mean and range (IU/L) 71.7 (8–496) 82 (12–496) 56.1 (8–365) 0.056
AST mean and range (IU/L) 63.5 (10–244) 77 (19–239) 46.5 (10–244) 0.001
Tab.2  Mean and frequency (%) of baseline AFP elevation and ALT/AST in patients with cirrhosis vs. without cirrhosis
Baseline analysis Post-Rx wk 24 analysis
Variables Baseline AFP elevation ?>?5.5 ng/mL Univariate ?P-value Multivariate ?P-value Post-Rx wk 24
?AFP?≤?5.5 ng/mL
Univariate
?P-value
Multivariate
?P-value
Gender 141 63
?Male 39/73 (53.4) 0.236 23/33 (69) 0.599
?Female 27/68 (39.7) 21/30 (70)
Age 121 63
?≥?50 years 58/102 (56.8) 0.175 37/55 (67.3) 0.234
?<?50 years 8/19 (42.1) 7/8 (87.5)
BMI 121 63
?≥?30 kg/m2 21/35 (60) 0.286 11/16 (68.8) 0.573
?<?30 kg/m2 45/86 (53.2) 33/47 (70.2)
Genotype 141 63
?1 66/112 (58.8) 0.05 0.029 32/48 (66.7) 0.26
?2–6 11/29 (37.5) 12/15 (80)
Histologic grade 73 41
?1–2 14/33 (45.2) 0.016 18/20 (90) 0.13
?3–4 28/40 (70) 14/21 (66.6)
Hepatic fibrosis 75 41
?0–2 15/36 (41.7) 0.008 20/23 (87) 0.216
?3–4 28/39 (71.8) 13/18 (72.2)
NASH 121 63
?Yes 9/10 (90) 0.018 0.035 5/8 (62.5) 0.455
?No 57/111 (51.4) 39/55 (70.9)
Cirrhosis 121 63
?Yes 45/63 (71.4) 0.001 0.001 18/33 (54.5) 0.005 0.003
?No 21/58 (36.2) 26/30 (86.7)
Baseline ALT 121 63
?≥?40 49/81 (60.5) 0.047 29/45 (64.4) 0.119
?<?40 17/40 (42.5) 15/18 (83.3)
Baseline AST 121 63
?≥?40 47/76 (61.8) 0.028 25/41 (61) 0.032
?<?40 19/45 (42.2) 19/22 (86.4)
Baseline ALT-AST 121 63
?≥?40 53/90 (58.9) 0.077 31/49 (63.3) 0.029
?<?40 13/31 (41.9) 13/14 (92.3)
Child–Pugh score 63 34
?≥?6 16/23 (69.5) 0.512 4/13 (30.8) 0.024 0.015
?<?6 29/40 (72.5) 15/21 (71.4)
Baseline AFP 141 56
?≥?10 35 (24.8) 7/20 (35) 0.001 0.015
?<?10 106 (75.2) 30/36 (83)
Tab.3  Clinical variables associated with baseline AFP elevation and post-treatment week 24 AFP normalization
Fig.1  Dynamic changes in mean serum α fetoprotein (AFP) during direct acting antiviral (DAA) and following DAA Treatment. The mean serum AFP levels (ng/mL) are shown on the y-axis. The baseline and timeline of the DAA treatment and post treatment follow-up are shown on the x-axis with treatment week (RxW), end of treatment (EOT), post treatment week (PRxW), and end of follow-up (EOF). An AFP level of 5.5 ng/mL is the upper normal limit. A steady decline of serum AFP was observed during DAA treatment, and continued AFP reduction was obvious up to the end of follow-up.
Fig.2  Dynamic changes in mean hepatitis C virus (HCV) RNA and serum α fetoprotein (AFP) during and following direct acting antiviral (DAA) treatment. The dynamic changes of serum AFP (ng/mL) and mean log 10 HCV RNA (IU/mL) with standard deviations are shown on the y-axis. Baseline and timeline of the DAA treatment and post treatment follow-up are shown on the x-axis with treatment week (RxW), end of treatment (EOT), post treatment week (PRxW), and end of follow-up (EOF). A rapid decline in HCV RNA concentration was observed as early as treatment week 2 and continued to decline to undetectable at EOF. The AFP decline was gradual and continued even after the DAA treatment.
Fig.3  Dynamic changes in mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and serum α fetoprotein (AFP) during and following direct acting antiviral (DAA) treatment. The dynamic changes of mean ALT and AST (IU/L) and serum AFP (ng/mL) with standard deviations are shown on the y-axis. Baseline and timeline of the DAA treatment and post treatment follow-up are shown on the x-axis with treatment week (RxW), end of treatment (EOT), post treatment week (PRxW), and end of follow-up (EOF). A rapid decline in both ALT and AST was observed as early as treatment week 2 of DAA treatment, with stabilization at treatment week 4, and minimal decline after treatment week 4. AFP decline was gradual and continued even after the DAA treatment.
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