A Concise Review on Hepatitis C Virus Infection-Associated Type 2 Diabetes Mellitus and Its Impact on Anti-HCV Therapy
Hepatitis C virus (HCV), an RNA-containing virus, has infected more than 170 million people worldwide and is one of the leading causes of deaths in developing countries due to its propensity to progress to chronic states, followed by multiple fibrosis and scar formation (cirrhosis) and even hepatocellular carcinoma. Type 2 diabetes mellitus (T2DM), a metabolic disorder, is one of the diseases of civilization, and its prevalence has shown an increasing tendency globally. At present, more than 350 million people worldwide are suffering from T2DM. T2DM is considered the most common extrahepatic linkage of HCV infection, which is associated with prevalent morbidity and mortality patterns. Several studies have reported that HCV patients are more prone to developing T2DM as compared to healthy non-infected individuals. Extensive studies have revealed that HCV patients tend to develop insulin resistance (IR), which plays a crucial role in the development of T2DM. IR develops through several pathophysiological mechanisms, including the inhibition of insulin signaling pathway that induces central IR by HCV proteins and increased lipolysis as well as the overproduction of inflammatory cytokines, which promote peripheral IR. IR has a direct effect on the association of HCV with T2DM, and it has been found associated with impaired sustained virological response (SVR) and a higher incidence of hepatocellular carcinoma in HCV patients. Therefore, it has been suggested that chronic HCV patients must be treated with anti-HCV therapy along with antidiabetic medications to better achieve SVR. In this review, we briefly describe HCV infection, its diagnosis, global epidemiology, treatment options, and its association with DM, along with its impact on anti-HCV therapy.
Lonardo, A.; Adinolfi, L.E.; Petta, S.; Craxì, A.; Loria, P. Hepatitis C and diabetes: The inevitable coincidence. Expert Rev. Anti. Infect. Ther., 2009, 7, 293–308.
Al Ashgar, H.; Khanm, M.Q.; Helmy, A.; Al Swat, K.; Al Shehri, A.; Al Kalbani, A.; Peedikayel, M.; Al Kahtani, K.; Al Quaiz, M.; Rezeig, M.; Kagevi, I.; Al Fadda, M. Sustained virologic response to peginterferon Α-2a and ribavirin in 335 patients with chronic hepatitis C: A tertiary care center experience. Saudi J. Gastroenterol., 2008, 14, 58–65.
Albertoni, G.; Girão, M.J.B.; Schor, N. Mini review: Current molecular methods for the detection and quantification of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus Type 1. Int. J. Infect. Dis, 2014, 2, 145–9.
Alborino, F.; Burighel, A.; Tiller, F.W.; Van Helden, J.; Gabriel, C.; Raineri, A.; Catapano, R.; Stekel, H. Multicentre evaluation of a fully automated third-generation anti-HCV antibody screening test with excellent sensitivity and specificity. Med. Microbiol. Immunol., 2011, 200, 77–83.
Hung, C.H.; Lee, C.M.; Lu, S.N. Hepatitis C virus-associated insulin resistance: Pathogenic mechanisms and clinical implications. Expert Rev. Anti Infect. Ther., 2011, 9, 525–33.
Manns, M.; Pockros, P.; Norkrans, G.; Smith, C.; Morgan, T.; Häussinger, D.; Shiffman, M.; Hadziyannis, S.; Schmidt, W.; Jacobson, I.; Bárcena, R.; Schiff, E.R.; Shaikh, O.S.; Bacon, B.; Marcellin, P.; Deng, W.; Esteban-Mur, R.; Poynard, T.; Pedicone, L.D.; Brass, C.A.; Albrecht, J.K.; Gordon, S.C. Long-term clearance of hepatitis C virus following interferon a‐2b or peginterferon a-2b, alone or in combination with ribavirin. J. Viral Hepat., 2013, 20, 524–9.
Angulo, P. Global epidemiology: Non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther., 2007, 25, 883–9.
Anwar, M.I.; Rahman, M.; Hassan, M.U.; Iqbal, M. Prevalence of active hepatitis C virus infections among general public of Lahore, Pakistan. Virol. J., 2013, 10, 351.
Attaullah, S.; Khan, S.; Ali I. Hepatitis C virus genotypes in Pakistan: A systemic review. Virol. J., 2011, 8, 433.
Aytug, S.; Reich, D.; Sapiro, L.E.; Bernstein, D.; Begum, N. Impaired Irs-1/Pi3-kinase signalling in patients with HCV: A mechanism for increased prevalence of Type 2 diabetes. Hepatology, 2003, 38, 1384–92.
Barker, L.F.; Shulman, N.R.; Murray, R.; Hirschman, R.J.; Ratner, F.; Dieffenbachia, W.C.; Geller, H.M. Transmission of serum hepatitis. JAMA, 1966, 276, 841–4.
Boesecke, C.; Grint, D.; Soriano, V.; Lundgren, J.D.; Monforte, A.D.; Mitsura, V.M.; Chentsova, N.; Hadziosmanovic, V.; Kirk, O.; Mocroft, A., Peters, L.; Rockstroh, J.K.; EuroSIDA in EuroCoord. Hepatitis C seroconversions in HIV infection across Europe: Which regions and patient groups are affected? Liver Int., 2015, 35, 2384–91.
Kaddai, V.; Negro, F. Current understanding of insulin resistance in hepatitis C. Expert Rev. Gastroenterol. Hepatol., 2011, 5, 503–16.
White, D.L.; Ratziu, V.; El-Serag, H.B. Hepatitis C infection and risk of diabetes: A systematic review and meta-analysis. J. Hepatol., 2008, 49, 831–44.
Chatterjee, S.; Majumder, B.; Basu, D. A review to explore the association between diabetes mellitus and hepatitis. IOSR J. Dent. Med. Sci., 2021, 20, 13–22.
Campos-Outcalt, D. Hepatitis C new CDC screening recommendations: Screen everyone born between 1945 and 1965-regardless of risk level. J. Fam. Pract., 2012, 61, 744–7.
Chevaliez, S.; Pawlotsky, J.M. Virology of hepatitis C virus infection. Best Pract. Res. Clin. Gastroenterol., 2012, 26, 381–9.
Chevaliez, S.; Pawlotsky, J.M. How to use virological tools for optimal management of chronic hepatitis C. Liver Int., 2009, 29, 9–14.
Chitturi, S.; Farrell, G.C.; Hashimoto, E.; Saibara, T.; Lau, G.K.; Sollano, J.D.; Asia-Pacific Working Party on NAFLD. Non‐alcoholic fatty liver disease in the Asia-Pacific region: Definitions and overview of proposed guidelines. J. Gastroenterol. Hepatol., 2007, 22, 778–87.
Chou, C.J.; Haluzik, M.; Gregory, C.; Dietz, K.R.; Vinson, C.; Gavrilova, O.; Reitman, M.L. A peroxisome proliferator-activated receptor alpha (PPARα) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipo atrophic A-Zip/F-1 mice. J. Biol. Chem., 2002, 277, 24484–9.
Lima, L.R.; De Almeida, A.J.; Tourinho, R.D.S.; Hasselmann, B.; Ximenez, L.L.; De Paula, V.S. Evidence of hepatitis a virus person-to-person transmission in household outbreaks. PLoS One, 2014, 9, E102925.
Costantini, S.; Capone, F.; Guerriero, E.; Marfella, R.; Sorice, A.; Maio, P.; Di Stasio, M.; Paolisso, G.; Castello, G.; Colonna, G. Cytokinome profile of patients with Type 2 diabetes and chronic hepatitis C infection. PLoS One, 2012, 7, e39486.
Naing, C.; Mak, J.W.; Ahmed, S.I.; Maung, M. Relationship between hepatitis C virus infection and Type 2 diabetes mellitus: Meta-analysis. World J Gastroenterol, 18, 1642-1651El-Zayadi R (2009). Hepatitis C comorbidities affecting the course and response to therapy. World J. Gastroenterol., 2012, 15, 4993–9.
Fattovich, G.; Giustina, G.; Christensen, E.; Pantalena, M.; Zagni, I.; Realdi, G.; Schalm, S. Influence of hepatitis Delta virus infection and morbidity and mortality in compensated cirrhosis Type B. Gut, 2000, 46, 420–6.
Li, H.C.; Lo, S.Y. Hepatitis C virus: Virology, diagnosis and treatment. World J. Hepatol., 2015, 7, 1377.
Franceschini, L.; Realdon, S.; Marcolongo, M.; Mirandola, S.; Bortoletto, G.; Alberti, A. Reciprocal interference between insulin and interferon-alpha signaling in hepatic cells: A vicious circle of clinical significance. Hepatology, 2011, 54, 484–94.
Ghouri, N.; Preiss, D.; Sattar, N. Liver enzymes non-alcoholic fatty liver disease, and incident of cardiovascular disease: A narrative review and clinical perspective of prospective data. Hepatology, 2010, 52, 1156–61.
Leroy, V.; Asselah, T. Universal hepatitis B vaccination: The only way to eliminate hepatocellular carcinoma. J. Hepatol., 2015, 63, 1303.
Hsu, Y.C.; Lin, J.T.; Ho, H.J.; Kao, Y.H.; Huang, Y.T.; Hsiao, N.W.; Wu, M.S.; Liu, Y.;Y.; Wu, C.Y. Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology, 2014, 59, 1293–302.
Hui, J.M.; Sud, A.; Farrell, G.C.; Bandara, P.; Byth, K.; Kench, J.G.; Mccaughan, G.W.; George, J. Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression. Gastroenterology, 2003, 125, 1695–704.
Allison, M.E.; Wreghitt, T.; Palmer, C.R.; Alexander, G. Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. J. Hepatol., 1994, 21, 1135–9.
Imazeki, F.; Yokosuka, O.; Fukai, K.; Kanda, T.; Kojima, H.; Saisho, H. Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: Comparison with hepatitis B virus‐infected and hepatitis C virus‐cleared patients. Liver Int., 2008, 28, 355–62.
Mehta, S.H.; Brancati, F.L.; Sulkowski, M.S.; Strathdee, S.A.; Szklo, M.; Thomas, D.L. Prevalence of Type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Hepatology, 2001, 33, 1554.
Jun, T.; Ohira, H.; Kazumichi, A.; Yokokawa, J.; Takiguchi, J.; Tsuyoshi, R.; Shishido, S.; Kasukawa, R. Autoimmune hepatitis accompanied by systemic lupus erythematosus. Internal Med., 2004, 43, 258–62.
Chou, C.J.; Haluzik, M.; Gregory, C.; Dietz, K.R.; Vinson, C.; Gavrilova, O.; Reitman, M.L. WY14, 643, a peroxisome proliferator-activated receptor α (PPARα) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipoatrophic A-ZIP/F-1 mice. J. Biol. Chem., 2002, 277, 24484–9.
Negro, F. Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases. J. Hepatol., 2004, 61, S69–78.
Memon, M.S.; Arain, Z.I.; Naz, F.; Zaki, M.; Kumar, S.; Burney, A.A. Prevalence of Type 2 diabetes mellitus in hepatitis C virus infected population: A Southeast Asian study. J. Diabetes Res., 2013, 2013, 539361.
Larson, A.M.; Polson, J.; Fontana, R.J.; Davern, T.J.; Lalani, E.; Hynan, L.S.; Reisch, J.S.; Schiødt, F.V.; Ostapowicz, G.; Shakil, A.O. Acetaminophen‐induced acute liver failure: Results of a United States multi-centre, prospective study. Hepatology, 2005, 42, 1364–72.
Parvaiz, F.; Manzoor, S.; Tariq, H.; Javed, F.; Fatima, K.; Qadri, I. Hepatitis C virus infection: Molecular pathways to insulin resistance. Virol J., 2011, 8, 474.