IMPACT OF HEPATIC STEATOSIS ON DISEASE COURSE IN PATIENTS WITH COMPENSATED HEPATITIS C VIRUS-RELATED CIRRHOSIS RECEIVING INTERFERON-FREE THERAPY (PARITAPREVIR, RITONAVIR, OMBITASVIR DASABUVIR AND RIBAVIRINA)
Aim: In Romania, genotype 1 of hepatitis C virus (HCV) is the most common and the aim of this study was to assess comparatively the biochemical, hematological and virological parameters in patients with different degrees of steatosis before the initiation of interferon-free therapy (paritaprevir/ritonavir/ombitasvir/ dasabuvir plus ribavirin) (PrOD-R) and at its completion. Material and methods: This retrospective study included 113 patients with compensated liver cirrhosis with C-genotype 1b, treated with PrOD-R evaluated and clinically-biologically monitored at the Iasi Hospital of Infectious Diseases between November 2015 and May 2017. Results: We found an advanced steatosis (grades ≥2) in 54% of patients. Associated cardiovascular and kidney diseases and diabetes mellitus were more frequent in the group of patients with advanced steatosis compared to the group with incipient steatosis (19.5% vs. 8% and 10.6% vs. 0.9%, respectively) (p = 0.02 and p = 0.003, respectively). In most patients the hepatic cytolysis syndrome was identified before the initiation of therapy (93%) with a significant difference between patients with advanced versus low grade steatosis (53% vs. 40%, respectively, p = 0.014). In patients with steatosis grade ≥2, GGT levels above the normal range were detected in 52.2% cases and in the group with steatosis grade <2 in 31% (p = 0.0003). At the time of treatment initiation, only 3.5% of patients presented various grades of anemia, but at the end of therapy 38% had different grades of anemia, this anomaly being more common in patients with advanced steatosis (23% vs. 15%, respectively, p = 0.27). At the end of therapy, only 14.2% still had higher-than-normal ALT levels, most of them in the group with advanced steatosis (11.5% vs. 2.6%, respectively, p = 0.018). Conclusions: We found a significant correlation between the advanced grade of hepatic steatosis and the levels of hepatic cytolysis enzymes and GGT both before initiation of therapy and at its completion in patients with advanced steatosis.
2. Kumar D, et al. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Hepatology 2002; 36: 1466-1472.
3. Irshad M, Mankotia DS, Irshad K. An insight into the diagnosis and pathogenesis of hepatitis C virus infection. World J Gastroenterol. 2013; 19(44): 7896–7909.
4. Oem JK, Jackel-Cram C, Li YP, Zhou Y, Zhong J, Shimano H, Babiuk LA, Liu Q. Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2. J Gen Virol 2008; 89: 1225-1230.
5. Ticehurst JR, Hamzeh FM, Thomas DL. Factors Affecting Serum Concentrations of Hepatitis C Virus (HCV) RNA in HCV Genotype 1-Infected Patients with Chronic Hepatitis. J. Clin. Microbiol 2007; 45(8): 2426-2433
6. Clément S, Pascarella S, Negro F. Hepatitis C virus infection: molecular pathways to steatosis, insulin resistance and oxidative stress. Viruses 2009; 1: 126–143.
7. ***Tratament fara interferon (Casa Nationala de asigurari de sanatate) http://www.cnas.ro/casmb/ category/ tratament-fara-intereron.html.
8. *** Consensus Statement on HCV Infection in Romania Working Group. Chiriac LC, Constandiş F, Cupşa A, Curescu MG, Dorobăț CM, Itu Mureşan C, Lăzureanu VE, Lupşe M, Miftode E, Rugină S, Săndulescu O, Streinu-Cercel A. GERMS 2017; 7(1): 32-39.
9. Kralj D, Jukić LV, Stojsavljević S, Duvnjak M, Smolić M, Čurčić IB. Hepatitis C Virus, Insulin Resistance, and Steatosis. J Clin Translatio Hepatol 2016; 4(1): 66-75.
10. Modaresi Esfeh J, Ansari-Gilani K. Steatosis and hepatitis C. Gastroenterology Report 2016; 4(1): 24-29.
11. Stevenson HL, Utay NS. Hepatic steatosis in HCV-infected persons in the direct-acting antiviral era. Tro Dis, Travel Med Vacci 2016; 2: 21.
12. Cavalcante LN, Lyra AC. Predictive factors associated with hepatitis C antiviral therapy re-sponse. World J Hepatol 2015; 7(12): 1617-1631.
13. Jackel-Cram C, Babiuk LA, Liu Q. Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. J Hepatol. 2007; 46(6): 999-1008.
14. Kara B, Gunesacar R, Doran F, Kara IO, Akkiz H.Correlation of serum adiponectin levels and hepatic steatosis in hepatitis C virus genotype 1 infection. Adv Ther. 2007; 24(5): 972-982.
15. Mousa N, Gad Y, Abdel-Aziz A, Abd-Elaal I. Increased -Fetoprotein Predicts Steatosis among Patients with Chronic Hepatitis C Genotype 4. Intern J Hepatol 2012; 636392: 1-5.
16. Chen CH, Lin ST, Kuo CL, Nien CK. Clinical significance of elevated alpha-fetoprotein (AFP) in chronic hepatitis C without hepatocellular carcinoma. Hepatogastroenterology 2008; 55(85): 1423-1427.
17. Trifan, C. Stanciu, L. Gheroghe, M. Curescu, C. Cijevschi Prelipcean, G. Stefanescu, I. Girleanu, S. Chiriaca, C. Mihai, C. Brisc, A. Goldis, I. Sporea, E. Miftode, S. Bataga, I. Rogoveanu, C. Preda, F. A. Caruntu, AM Singeap. Efficacy and safety of paritaprevir/ritonavir, ombitasvir and dasabuvir with ribavirin for the treatment of HCV genotype 1b compensated cirrhosis in patients aged 70 years or older. Medicine 2017; 96: 50(e9271).
18. Otelea M, Rascu A, Postolache P. Interrelationship between pathophysiological mechanisms of vitamin D deficit and chronic obstructive pulmonary disease. Rev. Med. Chir. Soc. Med. Nat. Iasi 2016; 120(3): 497-502.
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