Disease Progression in Chronic Hepatitis B Patients under Long-Term Antiviral Therapy
1
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Background/Aims: We investigated factors associated with the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients during long-term oral nucleos(t)ide analog (NA) therapy. Methods: This retrospective study included 524 naive CHB patients who received oral NA therapy for more than 48 weeks between January 2003 and December 2007. The primary outcome was 5-year cumulative probability of disease progression and HCC development. Disease progression was defined as cirrhosis development, cirrhotic complications, HCC or liver-related mortality. Results: For the 524 patients, the cumulative probabilities of disease progression and HCC development at 1, 2, 3, 4 and 5 years were 1.1%, 6.3%, 9.0%, 11.6%, and 16.2% and 0.2%, 1.8%, 3.6%, 5.8%, and 9.3%, respectively. In multivariate analysis, age >50 years (hazard ratio [HR], 1.05) and cirrhosis (HR, 2.95) were significant factors for disease progression. Similarly, age >50 years (HR, 1.05), family history of HCC (HR, 5.48), and cirrhosis (HR, 17.16) were significant factors for HCC development. Importantly, longer duration (>12 months) of maintained virological response (<20 IU/mL) reduced the risks of disease progression (HR, 0.19) and HCC development (HR, 0.09). Conclusions: Longer duration of maintained virological response significantly reduces the risk of disease progression or HCC development in CHB patients undergoing long-term oral NA therapy.
Abstract
Background/Aims: We investigated factors associated with the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients during long-term oral nucleos(t)ide analog (NA) therapy. Methods: This retrospective study included 524 naive CHB patients who received oral NA therapy for more than 48 weeks between January 2003 and December 2007. The primary outcome was 5-year cumulative probability of disease progression and HCC development. Disease progression was defined as cirrhosis development, cirrhotic complications, HCC or liver-related mortality. Results: For the 524 patients, the cumulative probabilities of disease progression and HCC development at 1, 2, 3, 4 and 5 years were 1.1%, 6.3%, 9.0%, 11.6%, and 16.2% and 0.2%, 1.8%, 3.6%, 5.8%, and 9.3%, respectively. In multivariate analysis, age >50 years (hazard ratio [HR], 1.05) and cirrhosis (HR, 2.95) were significant factors for disease progression. Similarly, age >50 years (HR, 1.05), family history of HCC (HR, 5.48), and cirrhosis (HR, 17.16) were significant factors for HCC development. Importantly, longer duration (>12 months) of maintained virological response (<20 IU/mL) reduced the risks of disease progression (HR, 0.19) and HCC development (HR, 0.09). Conclusions: Longer duration of maintained virological response significantly reduces the risk of disease progression or HCC development in CHB patients undergoing long-term oral NA therapy.
참고문헌 (30)
- Lavanchy D, "Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures", J Viral Hepat, 11, pp.97~107 (2004)
- Chen CJ, "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level", JAMA, 295, pp.65~73 (2006)
- Iloeje UH, "Predicting cirrhosis risk based on the level of circulating hepatitis B viral load", Gastroenterology, 130, pp.678~686 (2006)
- Iloeje UH, "Risk and predictors of mortality associated with chronic hepatitis B infection", Clin Gastroenterol Hepatol, 5, pp.921~931 (2007)
- Yuen MF, "Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease", Antivir Ther, 12, pp.1295~1303 (2007)
- Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
- Di Marco V, "Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine", Hepatology, 40, pp.883~891 (2004)
- Liaw YF, "2-Year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B", Gastroenterology, 136, pp.486~495 (2009)
- Yoon EL, "Comparison of clevudine and entecavir for treatment-naive patients with chronic hepatitis B virus infection: two-year follow-up data", J Clin Gastroenterol, 45, pp.893~899 (2011)
- Marcellin P, "Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B", N Engl J Med, 348, pp.808~816 (2003)
- Hadziyannis SJ, "Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B", N Engl J Med, 348, pp.800~807 (2003)
- Schiff ER, "Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients", Hepatology, 38, pp.1419~1427 (2003)
- Rapti I, "Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B", Hepatology, 45, pp.307~313 (2007)
- Lampertico P, "Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients", Gastroenterology, 133, pp.1445~1451 (2007)
- Sherman M, "Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical, and serology outcomes through 96 weeks", Hepatology, 48, pp.99~108 (2008)
- Chang TT, "A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B", N Engl J Med, 354, pp.1001~1010 (2006)
- Lai CL, "Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B", N Engl J Med, 354, pp.1011~1020 (2006)
- Marcellin P, "Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B", N Engl J Med, 359, pp.2442~2455 (2008)
- Pawlotsky JM, "Virologic monitoring of hepatitis B virus therapy in clinical trials and practice: recommendations for a standardized approach", Gastroenterology, 134, pp.405~415 (2008)
- Han KH, "Comparison of multiplex restriction fragment mass polymorphism and sequencing analyses for detecting entecavir resistance in chronic hepatitis B", Antivir Ther, 16, pp.77~87 (2011)
- Suk KT, "Revision and update on clinical practice guideline for liver cirrhosis", Korean J Hepatol, 18, pp.1~21 (2012)
- European Association for the Study of the Liver, "EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma", J Hepatol, 56, pp.908~943 (2012)
- Korean Association for the Study of the Liver, "KASL clinical practice guidelines: management of chronic hepatitis B", Clin Mol Hepatol, 18, pp.109~162 (2012)
- Dienstag JL, "Histological outcome during long-term lamivudine therapy", Gastroenterology, 124, pp.105~117 (2003)
- Hadziyannis SJ, "Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years", Gastroenterology, 131, pp.1743~1751 (2006)
- Toyama T, "Long-term outcomes of add-on adefovir dipivoxil therapy to ongoing lamivudine in patients with lamivudine-resistant chronic hepatitis B", Hepatol Res, 42, pp.1168~1174 (2012)
- Wong GL, "Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis", Hepatology, 58, pp.1537~1547 (2013)
- Hosaka T, "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection", Hepatology, 58, pp.98~107 (2013)
- Kim CH, "Prognosis of hepatitis B-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents", J Gastroenterol Hepatol, 27, pp.1589~1595 (2012)
- Papatheodoridis GV, "Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review", J Hepatol, 53, pp.348~356 (2010)