Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
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
 Download: PDF(488 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
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 Author(s): 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:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-019-0707-7
https://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.
1 GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990−2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385(9963): 117–171
https://doi.org/10.1016/S0140-6736(14)61682-210.1097/MEG.0000000000001400 pmid: 25530442
2 E Gower, C Estes, S Blach, K Razavi-Shearer, H Razavi. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61(1 Suppl): S45–S57
https://doi.org/10.1016/j.jhep.2014.07.027 pmid: 25086286
3 RL Koretz, KW Lin, JP Ioannidis, J Lenzer. Is widespread screening for hepatitis C justified? BMJ 2015; 350: g7809
https://doi.org/10.1136/bmj.g7809 pmid: 25587052
4 F Ermis, E Senocak Tasci. New treatment strategies for hepatitis C infection. World J Hepatol 2015; 7(17): 2100–2109
https://doi.org/10.4254/wjh.v7.i17.2100 pmid: 26301052
5 NL Lazarevich. Molecular mechanisms of α-fetoprotein gene expression. Biochemistry (Mosc) 2000; 65(1): 117–133
pmid: 10702646
6 D Ball, E Rose, E Alpert. α-fetoprotein levels in normal adults. Am J Med Sci 1992; 303(3): 157–159
https://doi.org/10.1097/00000441-199203000-00004 pmid: 1375809
7 H Matsui, N Rimal, K Kamakura, S Uesugi, H Yamamoto, S Ikeda, K Taketa. Serum α-fetoprotein levels in healthy Japanese adults. Acta Med Okayama 1998; 52(3): 149–154
pmid: 9661742
8 H Yoshida, Y Shiratori, M Moriyama, Y Arakawa, T Ide, M Sata, O Inoue, M Yano, M Tanaka, S Fujiyama, S Nishiguchi, T Kuroki, F Imazeki, O Yokosuka, S Kinoyama, G Yamada, M Omata. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and non-cirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999; 131(3): 174–181
https://doi.org/10.7326/0003-4819-131-3-199908030-00003 pmid: 10428733
9 M Sherman. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 2005; 25(2): 143–154
https://doi.org/10.1055/s-2005-871194 pmid: 15918143
10 AM Di Bisceglie, JH Hoofnagle. Elevations in serum α-fetoprotein levels in patients with chronic hepatitis B. Cancer 1989; 64(10): 2117–2120
https://doi.org/10.1002/1097-0142(19891115)64:10<2117::AID-CNCR2820641024>3.0.CO;2-7 pmid: 2478280
11 YF Liaw, DI Tai, TJ Chen, CM Chu, MJ Huang. α-fetoprotein changes in the course of chronic hepatitis: relation to bridging hepatic necrosis and hepatocellular carcinoma. Liver 1986; 6(3): 133–137
https://doi.org/10.1111/j.1600-0676.1986.tb00279.x pmid: 2427909
12 N Bayati, AL Silverman, SC Gordon. Serum α-fetoprotein levels and liver histology in patients with chronic hepatitis C. Am J Gastroenterol 1998; 93(12): 2452–2456
https://doi.org/10.1111/j.1572-0241.1998.00703.x pmid: 9860408
13 NS Goldstein, DE Blue, R Hankin, S Hunter, N Bayati, AL Silverman, SC Gordon. Serum α-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores. Am J Clin Pathol 1999; 111(6): 811–816
https://doi.org/10.1093/ajcp/111.6.811 pmid: 10361518
14 CW Chu, SJ Hwang, JC Luo, CR Lai, SH Tsay, CP Li, JC Wu, FY Chang, SD Lee. Clinical, virologic, and pathologic significance of elevated serum α-fetoprotein levels in patients with chronic hepatitis C. J Clin Gastroenterol 2001; 32(3): 240–244
https://doi.org/10.1097/00004836-200103000-00014 pmid: 11246354
15 KQ Hu, NL Kyulo, N Lim, B Elhazin, DJ Hillebrand, T Bock. Clinical significance of elevated α-fetoprotein (AFP) in patients with chronic hepatitis C, but not hepatocellular carcinoma. Am J Gastroenterol 2004; 99(5): 860–865
https://doi.org/10.1111/j.1572-0241.2004.04152.x pmid: 15128351
16 G Fattovich, G Giustina, F Degos, F Tremolada, G Diodati, P Almasio, F Nevens, A Solinas, D Mura, JT Brouwer, H Thomas, C Njapoum, C Casarin, P Bonetti, P Fuschi, J Basho, A Tocco, A Bhalla, R Galassini, F Noventa, SW Schalm, G Realdi. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997; 112(2): 463–472
https://doi.org/10.1053/gast.1997.v112.pm9024300 pmid: 9024300
17 Y Sato, K Nakata, Y Kato, M Shima, N Ishii, T Koji, K Taketa, Y Endo, S Nagataki. Early recognition of hepatocellular carcinoma based on altered profiles of α-fetoprotein. N Engl J Med 1993; 328(25): 1802–1806
https://doi.org/10.1056/NEJM199306243282502 pmid: 7684823
18 MJ Tong, NS el-Farra, AR Reikes, RL Co. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332(22): 1463–1466
https://doi.org/10.1056/NEJM199506013322202 pmid: 7739682
19 TM Chen, PT Huang, MH Tsai, LF Lin, CC Liu, KS Ho, CP Siauw, PL Chao, JN Tung. Predictors of α-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon α 2a-ribavirin combination therapy. J Gastroenterol Hepatol 2007; 22(5): 669–675
https://doi.org/10.1111/j.1440-1746.2007.04898.x pmid: 17444854
20 S Murashima, M Tanaka, M Haramaki, S Yutani, Y Nakashima, K Harada, T Ide, R Kumashiro, M Sata. A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP. Dig Dis Sci 2006; 51(4): 808–812
https://doi.org/10.1007/s10620-006-3211-2 pmid: 16615008
21 Y Tamura, S Yamagiwa, Y Aoki, S Kurita, T Suda, S Ohkoshi, M Nomoto, Y Aoyagi; Niigata Liver Disease Study Group. Serum α-fetoprotein levels during and after interferon therapy and the development of hepatocellular carcinoma in patients with chronic hepatitis C. Dig Dis Sci 2009; 54(11): 2530–2537
https://doi.org/10.1007/s10620-008-0642-y pmid: 19093203
22 Y Arase, K Ikeda, F Suzuki, Y Suzuki, M Kobayashi, N Akuta, T Hosaka, H Sezaki, H Yatsuji, Y Kawamura, M Kobayashi, H Kumada. Prolonged-interferon therapy reduces hepatocarcinogenesis in aged-patients with chronic hepatitis C. J Med Virol 2007; 79(8): 1095–1102
https://doi.org/10.1002/jmv.20866 pmid: 17597485
23 Y Asahina, K Tsuchiya, N Tamaki, I Hirayama, T Tanaka, M Sato, Y Yasui, T Hosokawa, K Ueda, T Kuzuya, H Nakanishi, J Itakura, Y Takahashi, M Kurosaki, N Enomoto, N Izumi. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010; 52(2): 518–527
https://doi.org/10.1002/hep.23691 pmid: 20683951
24 Y Asahina, K Tsuchiya, T Nishimura, M Muraoka, Y Suzuki, N Tamaki, Y Yasui, T Hosokawa, K Ueda, H Nakanishi, J Itakura, Y Takahashi, M Kurosaki, N Enomoto, M Nakagawa, S Kakinuma, M Watanabe, N Izumi. α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C. Hepatology 2013; 58(4): 1253–1262
https://doi.org/10.1002/hep.26442 pmid: 23564522
25 Y Tachi, T Hirai, Y Ishizu, T Honda, T Kuzuya, K Hayashi, M Ishigami, H Goto. α-fetoprotein levels after interferon therapy predict regression of liver fibrosis in patients with sustained virological response. J Gastroenterol Hepatol 2016; 31(5): 1001–1008
https://doi.org/10.1111/jgh.13245 pmid: 27123974
26 Y Osaki, Y Ueda, H Marusawa, J Nakajima, T Kimura, R Kita, H Nishikawa, S Saito, S Henmi, A Sakamoto, Y Eso, T Chiba. Decrease in α-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study. J Gastroenterol 2012; 47(4): 444–451
https://doi.org/10.1007/s00535-011-0505-8 pmid: 22105231
27 HB El-Serag, J Kramer, Z Duan, F Kanwal. Epidemiology and outcomes of hepatitis C infection in elderly US Veterans. J Viral Hepat 2016; 23(9): 687–696
https://doi.org/10.1111/jvh.12533 pmid: 27040447
28 HB El-Serag, F Kanwal, P Richardson, J Kramer. Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection. Hepatology 2016; 64(1): 130–137
https://doi.org/10.1002/hep.28535 pmid: 26946190
29 K Takayama, N Furusyo, E Ogawa, H Ikezaki, M Shimizu, M Murata, J Hayashi. Direct-acting antiviral-based triple therapy on α-fetoprotein level in chronic hepatitis C patients. World J Gastroenterol 2015; 21(15): 4696–4706
https://doi.org/10.3748/wjg.v21.i15.4696 pmid: 25914481
30 T Oze, N Hiramatsu, T Yakushijin, M Miyazaki, A Yamada, M Oshita, H Hagiwara, E Mita, T Ito, H Fukui, Y Inui, T Hijioka, M Inada, K Katayama, S Tamura, H Yoshihara, A Inoue, Y Imai, E Hayashi, M Kato, T Miyagi, Y Yoshida, T Tatsumi, A Kasahara, T Hamasaki, N Hayashi, T Takehara; Osaka Liver Forum. Post-treatment levels of a-fetoprotein predict incidence of hepatocellular carcinoma after interferon therapy. Clin Gastroenterol Hepatol 2014; 12(7): 1186–1195
https://doi.org/10.1016/j.cgh.2013.11.033 pmid: 24321207
31 K Nguyen, M Jimenez, N Moghadam, C Wu, A Farid, J Grotts, D Elashoff, G Choi, FA Durazo, MM El-Kabany, SB Han, S Saab. Decrease of α-fetoprotein in patients with cirrhosis treated with direct acting agents. J Clin Transl Hepatol 2017; 5(1): 43–49
pmid: 28507926
32 E Miyaki, M Imamura, N Hiraga, E Murakami, T Kawaoka, M Tsuge, A Hiramatsu, Y Kawakami, H Aikata, CN Hayes, K Chayama. Daclatasvir and asunaprevir treatment improves liver function parameters and reduces liver fibrosis markers in chronic hepatitis C patients. Hepatol Res 2016; 46(8): 758–764
https://doi.org/10.1111/hepr.12621 pmid: 26574180
33 R Fouad, A Elsharkawy,, SA, EL Alem, M Kassas, , M Alboraie, A Sweedy, S Afify, Z Abdellatif, M Khairy, G Esmat. Clinical impact of serum α-fetoprotein and its relation on changes in liver fibrosis in hepatitis C virus patients receiving direct-acting antivirals. Eur J Gastroenterol Hepatol 2019 Mar 20. [Epub ahead of print]
https://doi.org/10.1097/MEG.0000000000001400 pmid: 30896550
34 T Huynh, J Zhang, KQ Hu. Hepatitis C virus clearance by direct acting antiviral results in rapid resolution of hepatocytic injury as indicated by both alanine aminotransferase and aspartate aminostransferase normalization. J Clin Transl Hepatol 2018; 6(3): 258–263
https://doi.org/10.14218/JCTH.2018.00014 pmid: 30271737
35 AM Di Bisceglie, RK Sterling, RT Chung, JE Everhart, JL Dienstag, HL Bonkovsky, EC Wright, GT Everson, KL Lindsay, AS Lok, WM Lee, TR Morgan, MG Ghany, DR Gretch; HALT-C Trial Group. Serum α-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial. J Hepatol 2005; 43(3): 434–441
https://doi.org/10.1016/j.jhep.2005.03.019 pmid: 16136646
[1] Ruoxi Zhang, Jing Chen, Diangang Liu, Yu Wang. Urotensin II receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCl4-induced cirrhotic rats[J]. Front. Med., 2019, 13(3): 398-408.
[2] Xuefu Wang, Zhigang Tian. γδ T cells in liver diseases[J]. Front. Med., 2018, 12(3): 262-268.
[3] James S. Park,Calvin Pan. Current recommendations of managing HBV infection in preconception or pregnancy[J]. Front. Med., 2014, 8(2): 158-165.
[4] Jiangyi Zhu, Yongquan Shi, Xinmin Zhou, Zengshan Li, Xiaofeng Huang, Zheyi Han, Jianhong Wang, Ruian Wang, Jie Ding, Kaichun Wu, Ying Han, Daiming Fan. Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study[J]. Front Med, 2013, 7(2): 255-263.
[5] Cong Tong, Xinsen Xu, Chang Liu, Tianzheng Zhang, Kai Qu. Assessment of liver volume variation to evaluate liver function[J]. Front Med, 2012, 6(4): 421-427.
[6] Lili LIU MM , Jiyao WANG MD , Weimin SHE MM , . Correlation between viral load and liver cirrhosis in chronic hepatitis B patients[J]. Front. Med., 2009, 3(3): 271-276.
[7] Ling YANG, Rui ZHU, Qingjing ZHU, Dan DAN, Jin YE, Keshu XU, Xiaohua HOU. Influence of β-elemene on the secretion of angiotensin II and expression of AT1R in hepatic stellate cells[J]. Front Med Chin, 2009, 3(1): 36-40.
[8] CHU Deyong, LI Conglei, SHEN Jilong, WU Qiang. Paeoniflorin prevents hepatic fibrosis of by inhibiting TGF-&#946;1 production from macrophages in mice[J]. Front. Med., 2008, 2(2): 154-165.
[9] LIU Jie, WANG Jiyao, WEI Liming, LU Ye, Jin Hong. Effects of Decoction on plasma proteome in cirrhosis: preliminary experimental study with rats[J]. Front. Med., 2008, 2(1): 39-44.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed