The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patients
2.2. Data Collection and Definitions
2.3. Sample Collection and Bead-Based Cytometry
2.4. Statistical Analysis
3. Results
3.1. Baseline Patients’ Characteristics
3.2. Baseline Cytokine and Chemokine Concentrations According to Steatosis and Fibrosis Stage
3.3. Cytokine and Growth Factor Kinetics in CHC Patients before, during and after DAA Treatment
3.4. Association between Cytokine and Growth Factor Concentrations with Steatosis and Fibrosis Regression after DAA Treatment
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- World Health Organization. Global Hepatitis Report 2024: Action forAccess in Low- and Middle-Income Countries; WHO: Geneva, Switzerland, 2024. [Google Scholar]
- Elgretli, W.; Chen, T.; Kronfli, N.; Sebastiani, G. Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact. Biomedicines 2023, 11, 271. [Google Scholar] [CrossRef] [PubMed]
- Sung, P.S.; Racanelli, V.; Shin, E.C. CD8(+) T-Cell Responses in Acute Hepatitis C Virus Infection. Front. Immunol. 2014, 5, 266. [Google Scholar] [CrossRef] [PubMed]
- Kisseleva, T.; Brenner, D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 151–166. [Google Scholar] [CrossRef] [PubMed]
- Rios, D.A.; Casciato, P.C.; Caldirola, M.S.; Gaillard, M.I.; Giadans, C.; Ameigeiras, B.; De Matteo, E.N.; Preciado, M.V.; Valva, P. Chronic Hepatitis C Pathogenesis: Immune Response in the Liver Microenvironment and Peripheral Compartment. Front. Cell. Infect. Microbiol. 2021, 11, 712105. [Google Scholar] [CrossRef] [PubMed]
- Ferreira, J.; Oliveira, M.; Bicho, M.; Serejo, F. Role of Inflammatory/Immune Response and Cytokine Polymorphisms in the Severity of Chronic Hepatitis C (CHC) before and after Direct Acting Antiviral (DAAs) Treatment. Int. J. Mol. Sci. 2023, 24, 1380. [Google Scholar] [CrossRef] [PubMed]
- Bader El Din, N.G.; Farouk, S. Exploring the Impact of Different Inflammatory Cytokines on Hepatitis C Virus Infection. J. Interferon Cytokine Res. 2024, 44, 233–243. [Google Scholar] [CrossRef] [PubMed]
- Asselah, T.; Rubbia-Brandt, L.; Marcellin, P.; Negro, F. Steatosis in chronic hepatitis C: Why does it really matter? Gut 2006, 55, 123–130. [Google Scholar] [CrossRef] [PubMed]
- Rinella, M.E.; Lazarus, J.V.; Ratziu, V.; Francque, S.M.; Sanyal, A.J.; Kanwal, F.; Romero, D.; Abdelmalek, M.F.; Anstee, Q.M.; Arab, J.P.; et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J. Hepatol. 2023, 79, 1542–1556. [Google Scholar] [CrossRef] [PubMed]
- Adinolfi, L.E.; Rinaldi, L.; Guerrera, B.; Restivo, L.; Marrone, A.; Giordano, M.; Zampino, R. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations. Int. J. Mol. Sci. 2016, 17, 803. [Google Scholar] [CrossRef] [PubMed]
- Rau, M.; Buggisch, P.; Mauss, S.; Boeker, K.H.W.; Klinker, H.; Muller, T.; Stoehr, A.; Schattenberg, J.M.; Geier, A. Prognostic impact of steatosis in the clinical course of chronic HCV infection-Results from the German Hepatitis C-Registry. PLoS ONE 2022, 17, e0264741. [Google Scholar] [CrossRef] [PubMed]
- Tsai, P.S.; Cheng, Y.M.; Wang, C.C.; Kao, J.H. The impact of concomitant hepatitis C virus infection on liver and cardiovascular risks in patients with metabolic-associated fatty liver disease. Eur. J. Gastroenterol. Hepatol. 2023, 35, 1278–1283. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.L.; Huang, C.H.; Wu, V.C.; Wu, C.L.; Huang, Y.T.; Chang, S.H. Prognostic Effects of Liver Fibrosis and Steatosis Determined Using Transient Elastography in Patients with Chronic Hepatitis B or C. Dig. Dis. Sci. 2023, 68, 2747–2756. [Google Scholar] [CrossRef] [PubMed]
- Chuaypen, N.; Siripongsakun, S.; Hiranrat, P.; Tanpowpong, N.; Avihingsanon, A.; Tangkijvanich, P. Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants. PLoS ONE 2022, 17, e0269641. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.H.; Chang, Y.P.; Fang, Y.J.; Cheng, P.N.; Chen, C.Y.; Kao, W.Y.; Lin, C.L.; Yang, S.S.; Shih, Y.L.; Peng, C.Y.; et al. Dynamic change of metabolic dysfunction-associated steatotic liver disease in patients with hepatitis C virus infection after achieving sustained virologic response with direct-acting antivirals. J. Gastroenterol. 2024, 59, 609–620. [Google Scholar] [CrossRef] [PubMed]
- Rout, G.; Nayak, B.; Patel, A.H.; Gunjan, D.; Singh, V.; Kedia, S.; Shalimar. Therapy with Oral Directly Acting Agents in Hepatitis C Infection Is Associated with Reduction in Fibrosis and Increase in Hepatic Steatosis on Transient Elastography. J. Clin. Exp. Hepatol. 2019, 9, 207–214. [Google Scholar] [CrossRef] [PubMed]
- Gehrke, N.; Schattenberg, J.M. Metabolic Inflammation-A Role for Hepatic Inflammatory Pathways as Drivers of Comorbidities in Nonalcoholic Fatty Liver Disease? Gastroenterology 2020, 158, 1929–1947.e1926. [Google Scholar] [CrossRef]
- Rinaldi, L.; Giorgione, C.; Mormone, A.; Esposito, F.; Rinaldi, M.; Berretta, M.; Marfella, R.; Romano, C. Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review. Viruses 2023, 15, 1730. [Google Scholar] [CrossRef] [PubMed]
- Lin, Z.H.; Xin, Y.N.; Dong, Q.J.; Wang, Q.; Jiang, X.J.; Zhan, S.H.; Sun, Y.; Xuan, S.Y. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: An updated meta-analysis. Hepatology 2011, 53, 726–736. [Google Scholar] [CrossRef] [PubMed]
- Sterling, R.K.; Lissen, E.; Clumeck, N.; Sola, R.; Correa, M.C.; Montaner, J.; Sulkowski, M.S.; Torriani, F.J.; Dieterich, D.T.; Thomas, D.L.; et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006, 43, 1317–1325. [Google Scholar] [CrossRef] [PubMed]
- Angulo, P.; Hui, J.M.; Marchesini, G.; Bugianesi, E.; George, J.; Farrell, G.C.; Enders, F.; Saksena, S.; Burt, A.D.; Bida, J.P.; et al. The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007, 45, 846–854. [Google Scholar] [CrossRef] [PubMed]
- Newsome, P.N.; Sasso, M.; Deeks, J.J.; Paredes, A.; Boursier, J.; Chan, W.K.; Yilmaz, Y.; Czernichow, S.; Zheng, M.H.; Wong, V.W.; et al. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: A prospective derivation and global validation study. Lancet Gastroenterol. Hepatol. 2020, 5, 362–373. [Google Scholar] [CrossRef] [PubMed]
- Jonsson, J.R.; Barrie, H.D.; O’Rourke, P.; Clouston, A.D.; Powell, E.E. Obesity and steatosis influence serum and hepatic inflammatory markers in chronic hepatitis C. Hepatology 2008, 48, 80–87. [Google Scholar] [CrossRef] [PubMed]
- Baranova, A.; Jarrar, M.H.; Stepanova, M.; Johnson, A.; Rafiq, N.; Gramlich, T.; Chandhoke, V.; Younossi, Z.M. Association of serum adipocytokines with hepatic steatosis and fibrosis in patients with chronic hepatitis C. Digestion 2011, 83, 32–40. [Google Scholar] [CrossRef] [PubMed]
- Palmer, C.; Corpuz, T.; Guirguis, M.; O’Toole, S.; Yan, K.; Bu, Y.; Jorgenson, J.; Talbot, M.; Loi, K.; Lloyd, A.; et al. The effect of obesity on intrahepatic cytokine and chemokine expression in chronic hepatitis C infection. Gut 2010, 59, 397–404. [Google Scholar] [CrossRef] [PubMed]
- Lopez-Prieto, J.; Gonzalez-Reimers, E.; Aleman-Valls, M.R.; de la Vega-Prieto, M.J.; Abreu-Gonzalez, P.; Pelazas-Gonzalez, R.; Hernandez-Luis, R.; Jorge-Ripper, C.; Santolaria-Fernandez, F. Iron and proinflammatory cytokines in chronic hepatitis C virus infection. Biol. Trace Elem. Res. 2013, 155, 5–10. [Google Scholar] [CrossRef] [PubMed]
- Llorens-Revull, M.; Costafreda, M.I.; Rico, A.; Guerrero-Murillo, M.; Soria, M.E.; Piriz-Ruzo, S.; Vargas-Accarino, E.; Gabriel-Medina, P.; Rodriguez-Frias, F.; Riveiro-Barciela, M.; et al. Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy. PLoS ONE 2021, 16, e0254243. [Google Scholar] [CrossRef]
- Auma, A.W.N.; Shive, C.L.; Kostadinova, L.; Anthony, D.D. Variable Normalization of Naive CD4+ Lymphopenia and Markers of Monocyte and T Cell Activation over the Course of Direct-Acting Anti-Viral Treatment of Chronic Hepatitis C Virus Infection. Viruses 2021, 14, 50. [Google Scholar] [CrossRef] [PubMed]
- Aregay, A.; Owusu Sekyere, S.; Deterding, K.; Port, K.; Dietz, J.; Berkowski, C.; Sarrazin, C.; Manns, M.P.; Cornberg, M.; Wedemeyer, H. Elimination of hepatitis C virus has limited impact on the functional and mitochondrial impairment of HCV-specific CD8+ T cell responses. J. Hepatol. 2019, 71, 889–899. [Google Scholar] [CrossRef] [PubMed]
- Hengst, J.; Falk, C.S.; Schlaphoff, V.; Deterding, K.; Manns, M.P.; Cornberg, M.; Wedemeyer, H. Direct-Acting Antiviral-Induced Hepatitis C Virus Clearance Does Not Completely Restore the Altered Cytokine and Chemokine Milieu in Patients With Chronic Hepatitis C. J. Infect. Dis. 2016, 214, 1965–1974. [Google Scholar] [CrossRef] [PubMed]
- Du, Y.; Khera, T.; Liu, Z.; Tudrujek-Zdunek, M.; Dworzanska, A.; Cornberg, M.; Xu, C.J.; Tomasiewicz, K.; Wedemeyer, H. Controlled Attenuation Parameter Is Associated with a Distinct Systemic Inflammatory Milieu after Clearance of HCV Infection. Biomedicines 2023, 11, 1529. [Google Scholar] [CrossRef] [PubMed]
- Ouyang, W.; O’Garra, A. IL-10 Family Cytokines IL-10 and IL-22: From Basic Science to Clinical Translation. Immunity 2019, 50, 871–891. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.J.; Wang, X.Z. Interleukin-10 and chronic liver disease. World J. Gastroenterol. 2006, 12, 1681–1685. [Google Scholar] [CrossRef] [PubMed]
- Solleiro-Villavicencio, H.; Mendez-Garcia, L.A.; Ocampo-Aguilera, N.A.; Baltazar-Perez, I.; Arreola-Miranda, J.A.; Aguayo-Guerrero, J.A.; Alfaro-Cruz, A.; Gonzalez-Chavez, A.; Fonseca-Sanchez, M.A.; Fragoso, J.M.; et al. Decreased Hepatic and Serum Levels of IL-10 Concur with Increased Lobular Inflammation in Morbidly Obese Patients. Medicina 2024, 60, 862. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Cao, R.; Zhou, F.; Wang, B.; Xu, Q.; Li, R.; Zhang, C.; Xu, H. The role of Interleukin-22 in severe acute pancreatitis. Mol. Med. 2024, 30, 60. [Google Scholar] [CrossRef] [PubMed]
- Pan, C.X.; Tang, J.; Wang, X.Y.; Wu, F.R.; Ge, J.F.; Chen, F.H. Role of interleukin-22 in liver diseases. Inflamm. Res. 2014, 63, 519–525. [Google Scholar] [CrossRef]
- Leonard, W.J.; Lin, J.X.; O’Shea, J.J. The gamma(c) Family of Cytokines: Basic Biology to Therapeutic Ramifications. Immunity 2019, 50, 832–850. [Google Scholar] [CrossRef] [PubMed]
- Ali, M.E.; El-Badawy, O.; Afifi, N.A.; Eldin, A.S.; Hassan, E.A.; Halby, H.M.; El-Mokhtar, M.A. Role of T-Helper 9 Cells in Chronic Hepatitis C-Infected Patients. Viruses 2018, 10, 341. [Google Scholar] [CrossRef]
- Wong, S.W.; Ting, Y.W.; Yong, Y.K.; Tan, H.Y.; Barathan, M.; Riazalhosseini, B.; Bee, C.J.; Tee, K.K.; Larsson, M.; Velu, V.; et al. Chronic inflammation involves CCL11 and IL-13 to facilitate the development of liver cirrhosis and fibrosis in chronic hepatitis B virus infection. Scand. J. Clin. Lab. Investig. 2021, 81, 147–159. [Google Scholar] [CrossRef] [PubMed]
- Roeb, E. Interleukin-13 (IL-13)-A Pleiotropic Cytokine Involved in Wound Healing and Fibrosis. Int. J. Mol. Sci. 2023, 24, 12884. [Google Scholar] [CrossRef] [PubMed]
- Radmanic, L.; Zidovec-Lepej, S. The Role of Stem Cell Factor, Epidermal Growth Factor and Angiopoietin-2 in HBV, HCV, HCC and NAFLD. Life 2022, 12, 2072. [Google Scholar] [CrossRef] [PubMed]
- Derbak, M.A.; Lizanets, N.V.; Hanych, O.T.; Horlenko, O.M.; Mashura, H.Y.; Boiko, S.O.; Rozumykova, N. Dynamics of Fibrotic Changes in the Liver after the Successful Eradication of Hepatitis C Virus in Patients with Nafld. Wiad. Lek. 2022, 75, 2392–2396. [Google Scholar] [CrossRef] [PubMed]
- Hernandez-Bartolome, A.; Lopez-Rodriguez, R.; Borque, M.J.; Gonzalez-Moreno, L.; Real-Martinez, Y.; Garcia-Buey, L.; Moreno-Otero, R.; Sanz-Cameno, P. Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C. World J. Gastroenterol. 2016, 22, 9744–9751. [Google Scholar] [CrossRef] [PubMed]
- Liu, N.; Liu, M.; Fu, S.; Wang, J.; Tang, H.; Isah, A.D.; Chen, D.; Wang, X. Ang2-Targeted Combination Therapy for Cancer Treatment. Front. Immunol. 2022, 13, 949553. [Google Scholar] [CrossRef] [PubMed]
- Virzi, A.; Roca Suarez, A.A.; Baumert, T.F.; Lupberger, J. Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis. Cold Spring Harb. Perspect. Med. 2020, 10, a037366. [Google Scholar] [CrossRef] [PubMed]
- Shehata, F.; Abdel Monem, N.; Sakr, M.; Kasem, S.; Balbaa, M. Epidermal growth factor, its receptor and transforming growth factor-beta1 in the diagnosis of HCV-induced hepatocellular carcinoma. Med. Oncol. 2013, 30, 673. [Google Scholar] [CrossRef] [PubMed]
- Chang, W.J.; Song, L.J.; Yi, T.; Shen, K.T.; Wang, H.S.; Gao, X.D.; Li, M.; Xu, J.M.; Niu, W.X.; Qin, X.Y. Early activated hepatic stellate cell-derived molecules reverse acute hepatic injury. World J. Gastroenterol. 2015, 21, 4184–4194. [Google Scholar] [CrossRef] [PubMed]
- Marin-Serrano, E.; Rodriguez-Ramos, C.; Diaz-Garcia, F.; Martin-Herrera, L.; Fernandez-Gutierrez-Del-Alamo, C.; Giron-Gonzalez, J.A. Hepatocyte growth factor and chronic hepatitis C. Rev. Esp. Enferm. Dig. 2010, 102, 365–371. [Google Scholar] [CrossRef] [PubMed]
- Cienfuegos, J.A.; Rotellar, F.; Baixauli, J.; Martinez-Regueira, F.; Pardo, F.; Hernandez-Lizoain, J.L. Liver regeneration—The best kept secret. A model of tissue injury response. Rev. Esp. Enfermedades Dig. 2014, 106, 171–194. [Google Scholar]
- Elpek, G.O. Angiogenesis and liver fibrosis. World J. Hepatol. 2015, 7, 377–391. [Google Scholar] [CrossRef] [PubMed]
Liver Steatosis | No Liver Steatosis | p-Value * | |
---|---|---|---|
Age, years | 58 (45–63) | 55 (45–63) | 0.5995 |
Male sex | 14 (50%) | 18 (64.29%) | 0.4182 |
Obesity (BMI > 30 kg/m2) | 7 (25.0%) | 1 (3.57%) | 0.0511 |
BMI, kg/m2 | 26 (23–30) | 25 (22–26) | 0.0294 |
Duration of HCV infection, years | 22 (14–30) | 20 (10–32) | 0.6505 |
HCV genotype | |||
1a | 6 (21.4%) | 6 (21.4%) | 0.8009 |
1b | 13 (46.4%) | 16 (57.1%) | |
3 | 7 (25.0%) | 5 (17.9%) | |
2 | 1 (3.6%) | 1 (3.6%) | |
4 | 1 (3.6%) | 0 | |
HCV viremia, log10 | 5.7 (5.3–6.3) | 6.0 (5.7–6.3) | 0.1389 |
Liver stiffness, kPa | 14 (9.5–20) | 12 (6.9–19) | 0.2319 |
CAP, dB/m | 277 (244–324) | 219 (192–224) | <0.0001 |
Advanced fibrosis (F3–4) | 17 (60.71%) | 16 (57.14%) | 0.9999 |
DAA treatment regiment | |||
Sofosbuvir + velpatasvir | 13 (46.4%) | 10 (35.7%) | 0.7157 |
Glecaprevir + pibrentasvir | 11 (39.3%) | 13 (46.4%) | |
Elbasvir + grazoprevir | 4 (14.3%) | 5 (17.9%) | |
Comorbidities | |||
T2DM | 6 (21.43%) | 2 (7.14%) | 0.2516 |
Arterial hypertension | 13 (46.43%) | 8 (28.57%) | 0.2695 |
Dyslipidemia | 6 (21.43%) | 3 (10.71%) | 0.4688 |
Cardiovascular comorbidities | 2 (7.14%) | 1 (3.57%) | 0.9999 |
PWID | 7 (25.0%) | 4 (14.29%) | 0.5027 |
Laboratory | |||
Hemoglobin | 144 (132–157) | 139 (129–149) | 0.3423 |
Leukocytes, ×109 | 6.2 (5.1–6.8) | 6.3 (4.7–7.1) | 0.7112 |
Neutrophil-to-lymphocyte ratio | 1.5 (1.0–2.0) | 1.7 (1.3–2.5) | 0.1221 |
Platelets | 152 (117–188) | 190 (134–217) | 0.1231 |
Platelets-to-lymphocyte ratio | 78 (53–102) | 96 (70–123) | 0.0497 |
Total bilirubin | 14 (11–20) | 11 (10–17) | 0.1353 |
AST | 55 (40–92) | 58 (34–91) | 0.8997 |
ALT | 56 (37–93) | 64 (40–32) | 0.7791 |
GGT | 56 (38–120) | 40 (32–75) | 0.1230 |
ALP | 86 (65–105) | 81 (69–107) | 0.7604 |
AFP | 4.7 (2.5–9.2) | 3.7 (2.4–9.4) | 0.7235 |
Albumins, g/L | 42 (40–44) | 43 (41–46) | 0.2381 |
Fasting glucose | 6.1 (5.3–7.8) | 5.5 (4.7–6.1) | 0.0312 |
Cholesterol | 4.8 (4.2–5.3) | 4.3 (3.2–5.4) | 0.2065 |
LDL | 2.5 (2.0–2.8) | 2.6 (1.8–3.0) | 0.9500 |
HDL | 1.3 (1.1–1.7) | 1.4 (1.0–1.7) | 0.7904 |
Triglycerides | 1.7 (1.1–2.2) | 1.3 (0.83–1.9) | 0.1861 |
pg/mL | Liver Steatosis | No Liver Steatosis | p-Value * |
---|---|---|---|
IL-2 | 0.73 (0.61–0.77) | 0.73 (0.63–0.73) | 0.7824 |
IL-4 | 1.7 (0.88–1.7) | 1.7 (1.2–1.7) | 0.3473 |
IL-5 | 4.5 (2.3–7.0) | 5.0 (3.7–14) | 0.1154 |
IL-6 | 6.2 (6.0–9.5) | 7.4 (6.2–14) | 0.2426 |
IL-9 | 3.6 (1.7–3.6) | 3.6 (3.6–6.0) | 0.0227 |
IL-10 | 1.1 (0.82–1.6) | 1.9 (1.1–3.0) | 0.0188 |
IL-13 | 8.2 (3.2–8.2) | 8.2 (5.9–15) | 0.0445 |
IL-17A | 0.45 (0.37–0.49) | 0.46 (0.30–0.59) | 0.7850 |
IL-17F | 2.6 (1.4–2.7) | 2.3 (2.0–2.7) | 0.7059 |
IL-22 | 1.8 (1.1–2.3) | 2.2 (1.8–4.0) | 0.0201 |
TNF-α | 4.5 (1.5–6.2) | 5.6 (4.5–6.0) | 0.1958 |
IFN-γ | 9.8 (5.7–10) | 9.8 (5.0–17) | 0.3423 |
Growth factors | |||
EGF | 40 (13–130) | 7.2 (2.0–36) | 0.0017 |
EPO | 398 (293–634) | 418 (274–598) | 0.8997 |
HGF | 526 (348–901) | 597 (439–939) | 0.4663 |
SCF | 102 (67–117) | 82 (52–155) | 0.9385 |
VEGF | 146 (114–230) | 90 (57–175) | 0.0102 |
ANG | 2884 (2063–4074) | 1822 (1368–2781) | 0.0110 |
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Radmanic Matotek, L.; Zidovec-Lepej, S.; Salek, N.; Vince, A.; Papic, N. The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment. J. Clin. Med. 2024, 13, 4849. https://doi.org/10.3390/jcm13164849
Radmanic Matotek L, Zidovec-Lepej S, Salek N, Vince A, Papic N. The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment. Journal of Clinical Medicine. 2024; 13(16):4849. https://doi.org/10.3390/jcm13164849
Chicago/Turabian StyleRadmanic Matotek, Leona, Snjezana Zidovec-Lepej, Nikolina Salek, Adriana Vince, and Neven Papic. 2024. "The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment" Journal of Clinical Medicine 13, no. 16: 4849. https://doi.org/10.3390/jcm13164849