Nucleos(t)ide Analogues for Reducing Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis
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Background/Aims: Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients. Methods: We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software. Results: Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001). Conclusions: ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.
Abstract
Background/Aims: Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients. Methods: We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software. Results: Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001). Conclusions: ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.
참고문헌 (60)
- Chen W, "Cancer statistics in China, 2015", CA Cancer J Clin, 66, pp.115~132 (2016)
- Torre LA, "Global cancer statistics, 2012", CA Cancer J Clin, 65, pp.87~108 (2015)
- Ozakyol A, "Global epidemiology of hepatocellular carcinoma(HCC epidemiology)", J Gastrointest Cancer, 48, pp.238~240 (2017)
- Kew MC, "Epidemiology of hepatocellular carcinoma in sub-Saharan Africa", Ann Hepatol, 12, pp.173~182 (2013)
- Venook AP, "The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective", Oncologist, 15(Suppl 4), pp.5~13 (2010)
- Centers for Disease Control and Prevention, "CDC Health Information for International Travel 2014: The Yellow Book" (2013), Oxford University Press
- Cui Y, "Update on epidemiology of hepatitis B and C in China", J Gastroenterol Hepatol, 28(Suppl 1), pp.7~10 (2013)
- Levrero M, "Mechanisms of HBV-induced hepatocellular carcinoma", J Hepatol, 64(1 Suppl), pp.S84~S101 (2016)
- 손원, "Risk score model for the development of hepatocellular carcinoma in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B", Clinical and Molecular Hepatology, 23(2), pp.170~178 (2017), 대한간학회[DOI]
- Tang LSY, "Chronic hepatitis B infection : a review", JAMA, 319, pp.1802~1813 (2018)
- Schoggins JW, "Interferon-stimulated genes and their antiviral effector functions", Curr Opin Virol, 1, pp.519~525 (2011)
- Clark DN, "Hepatitis B virus reverse transcriptase : target of current antiviral therapy and future drug development", Antiviral Res, 123, pp.132~137 (2015)
- Sacks SL, "Antiviral treatment of chronic hepatitis B virus infection : pharmacokinetics and side effects of interferon and adenine arabinoside alone and in combination", Antimicrob Agents Chemother, 21, pp.93~100 (1982)
- Terrault NA, "AASLD guidelines for treatment of chronic hepatitis B", Hepatology, 63, pp.261~283 (2016)
- Liaw YF, "Asian-Pacific consensus statement on the management of chronic hepatitis B : a 2012 update", Hepatol Int, 6, pp.531~561 (2012)
- Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
- Lai CL, "Prevention of hepatitis B virus-related hepatocellular carcinoma with antiviral therapy", Hepatology, 57, pp.399~408 (2013)
- Niro GA, "Long-term outcome of hepatitis B virus-related chronic hepatitis under protracted nucleos(t)ide analogues", J Viral Hepat, 20, pp.502~509 (2013)
- Wong GL, "Longterm use of oral nucleos(t)ide analogues for chronic hepatitis B does not increase cancer risk : a cohort study of 44 494 subjects", Aliment Pharmacol Ther, 45, pp.1213~1224 (2017)
- Lo AO, "Current developments in nucleoside", nucleotide analogues for hepatitis B, 2014, pp.8, 607~622
- European Association for the Study of the Liver, "EASL clinical practice guidelines : management of chronic hepatitis B virus infection", J Hepatol, 57, pp.167~185 (2012)
- Yin J, "Effect of antiviral treatment with nucleotide", nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma : a two-stage longitudinal clinical study, 2013, pp.31, 3647~3655
- Wu CY, "Association of nucleos(t)ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B : a nationwide cohort study", Gastroenterology, 147, pp.143~151 (2014)
- Hosaka T, "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection", Hepatology, 58, pp.98~107 (2013)
- Sung JJ, "Meta-analysis : treatment of hepatitis B infection reduces risk of hepatocellular carcinoma", Aliment Pharmacol Ther, 28, pp.1067~1077 (2008)
- Wang JP, "Nucleos(t)ide analogues associated with a reduced risk of hepatocellular carcinoma in hepatitis B patients : a population-based cohort study", Cancer, 121, pp.1446~1455 (2015)
- Lim YS, "Mortality, liver transplantation, and hepatocellular carcinoma among patients with chronic hepatitis B treated with entecavir vs lamivudine", Gastroenterology, 147, pp.152~161 (2014)
- An J, "Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA : a randomized trial", BMC Gastroenterol, 17, pp.15~ (2017)
- Idilman R, "Long-term entecavir or tenofovir disoproxil fumarate therapy in treatment-naïve chronic hepatitis B patients in the real-world setting", J Viral Hepat, 22, pp.504~510 (2015)
- Kobashi H, "Long-term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine", Hepatol Res, 41, pp.405~416 (2011)
- Riveiro-Barciela M, "Effectiveness and safety of entecavir or tenofovir in a Spanish cohort of chronic hepatitis B patients : validation of the Page-B score to predict hepatocellular carcinoma", Dig Dis Sci, 62, pp.784~793 (2017)
- Tsai MC, "A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B : a match-control study", Clin Microbiol Infect, 20, pp.O90~O100 (2014)
- Papatheodoridis GV, "Hepatocellular carcinoma risk in HBeAg-negative chronic hepatitis B patients with or without cirrhosis treated with entecavir : HepNet. Greece cohort", J Viral Hepat, 22, pp.120~127 (2015)
- Thiele M, "Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B : systematic review and meta-analysis", BMJ Open, 3, pp.e003265~ (2013)
- Coffin CS, "The incidence of hepatocellular carcinoma is reduced in patients with chronic hepatitis B on long-term nucleos(t)ide analogue therapy", Aliment Pharmacol Ther, 40, pp.1262~1269 (2014)
- Hsu YC, "Determinants of hepatocellular carcinoma in cirrhotic patients treated with nucleos(t)ide analogues for chronic hepatitis B", J Antimicrob Chemother, 69, pp.1920~1927 (2014)
- Köklü S, "Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis", Clin Gastroenterol Hepatol, 11, pp.88~94 (2013)
- Stang A, "Critical evaluation of the Newcastle-Ottawa Scale for the assessment of the quality of nonrandomized studies in metaanalyses", Eur J Epidemiol, 25, pp.603~605 (2010)
- Jadad AR, "Assessing the quality of reports of randomized clinical trials : is blinding necessary", Control Clin Trials, 17, pp.1~12 (1996)
- Zeng X, "The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline : a systematic review", J Evid Based Med, 8, pp.2~10 (2015)
- Choi J, "Risk of hepatocellular carcinoma in patients treated with entecavir vs tenofovir for chronic hepatitis B : a Korean nationwide cohort study", JAMA Oncol, 5, pp.30~36 (2019)
- Kim BG, "Mortality, liver transplantation and hepatic complications in patients with treatment-naïve chronic hepatitis B treated with entecavir vs tenofovir", J Viral Hepat, 25, pp.1565~1575 (2018)
- Nassal M, "HBV cccDNA : viral persistence reservoir and key obstacle for a cure of chronic hepatitis B", Gut, 64, pp.1972~1984 (2015)
- Wong DK, "Reduction of hepatitis B surface antigen and covalently closed circular DNA by nucleos(t)ide analogues of different potency", Clin Gastroenterol Hepatol, 11, pp.1004~1010 (2013)
- Terrault NA, "Update on prevention, diagnosis, and treatment of chronic hepatitis B : AASLD 2018hepatitis B guidance", Hepatology, 67, pp.1560~1599 (2018)
- Lingala S, "Long-term lamivudine therapy in chronic hepatitis B", Aliment Pharmacol Ther, 44, pp.380~389 (2016)
- Li W, "Efficacy of entecavir-based rescue therapy in lamivudine-resistant chronic hepatitis B patients in China : a retrospective study", Pharmazie, 73, pp.223~247 (2018)
- Lee JH, "Prior exposure to lamivudine increases entecavir resistance risk in chronic hepatitis B Patients without detectable lamivudine resistance", Antimicrob Agents Chemother, 58, pp.1730~1737 (2014)
- Tsai MC, "Long-term outcomes of hepatitis B virus-related cirrhosis treated with nucleos(t)ide analogs", J Formos Med Assoc, 116, pp.512~521 (2017)
- Flemming JA, "Tenofovir vs entecavir for hepatocellular carcinoma prevention in patients with chronic hepatitis B : one of these things is not like the other", JAMA Oncol, 5, pp.17~18 (2019)
- Yao GB, "A 7-year study of lamivudine therapy for hepatitis B virus e antigen-positive chronic hepatitis B patients in China", J Dig Dis, 10, pp.131~137 (2009)
- Xu B, "Long-term lamivudine treatment achieves regression of advanced liver fibrosis", cirrhosis in patients with chronic hepatitis B, 2015, pp.30, 372~378
- Jayakumar R, "Laboratory evaluation of three regimens of treatment of chronic hepatitis B : tenofovir, entecavir and combination of lamivudine and adefovir", J Lab Physicians, 4, pp.10~16 (2012)
- Buti M, "Modeling the cost-effectiveness of different oral antiviral therapies in patients with chronic hepatitis B", J Hepatol, 51, pp.640~646 (2009)
- Woo G, "Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B : a systematic review and Bayesian meta-analyses", Gastroenterology, 139, pp.1218~1229 (2010)
- Papatheodoridis GV, "Risk of hepatocellular carcinoma in chronic hepatitis B : assessment and modification with current antiviral therapy", J Hepatol, 62, pp.956~967 (2015)
- Wong GL, "Oral nucleos(t)ide analogues reduce recurrence and death in chronic hepatitis B-related hepatocellular carcinoma", Aliment Pharmacol Ther, 43, pp.802~813 (2016)
- Honda M, "Hepatitis B virus(HBV)core-related antigen during nucleos(t)ide analog therapy is related to intra-hepatic HBV replication and development of hepatocellular carcinoma", J Infect Dis, 213, pp.1096~1106 (2016)
- Ogawa E, "Tenofovir alafenamide in the treatment of chronic hepatitis B : design, development, and place in therapy", Drug Des Devel Ther, 11, pp.3197~3204 (2017)
- Scott LJ, "Tenofovir alafenamide : a review in chronic hepatitis B", Drugs, 77, pp.1017~1028 (2017)