title: Rapid normalization of alanine aminotransferase predicts viral response during combined peginterferon and ribavirin treatment in chronic hepatitis C patients.
abstract: OBJECTIVE
  The treatment for chronic hepatitis C (CHC) is removal of the virus in order to prevent progression to liver cirrhosis and hepatocellular carcinoma (HCC). Few data have been presented regarding the clinical significance of changes in the alanine aminotransferase (ALT) level in this context. We analyzed the patterns of changes in ALT level and investigated the relationship between the rapid normalization of ALT and sustained virologic response (SVR) after combined treatment with peginterferon and ribavirin.
  
  
  METHODS
  CHC patients (n=370) were classified into four groups according to the initial ALT level and subsequent changes: (1) initially abnormal ALT level and sustained abnormal ALT level during treatment, (2) initially abnormal ALT level but achievement of ALT normalization, (3) initially normal ALT level and variable ALT abnormality during treatment, and (4) initially normal ALT level and sustained normalization of ALT level during treatment. We subdivided groups 1 and 2 into those with patterns of decreased and normalization of ALT, with or without rapid normalization. We checked the end-treatment response (ETR) and SVR rates in each group and the factors associated with SVR, including patterns of changes in ALT level.
  
  
  RESULTS
  A total of 168 patients completed the therapy (age=54.34±10.64 years [mean±SD], 95 males [56.5%], genotype 1:82 [48.8%]). SVR was achieved in 115 (68.45%) of the completely treated patients. The SVR rate was significantly lower in group 1 than in group 2 (37.8 vs. 81.6%, P<0.001), and significantly higher in the rapid normalization group than in the group without rapid normalization (78.5% vs. 41.2%, P<0.001). Multiple logistic regression analysis revealed that age (odds ratio [OR]=0.94, 95% confidence interval [CI]=0.91-0.98, P=0.005), viral genotype (OR=2.76, 95% CI=1.20-6.38, P=0.017), and initial hepatitis C virus RNA titer (OR=0.28, 95% CI=0.10-0.75, P=0.012) were identified as independent significant predictive factors for SVR.
  
  
  CONCLUSIONS
  The SVR rate is significantly associated with normalization, and especially rapid normalization of ALT. Rapid normalization of ALT by 4 weeks after treatment might be a useful response factor that is readily available in clinical practice, and especially for genotype 1 patients.
authors.affiliation: Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Byoung Kuk
authors.initials: BK
authors.lastname: Jang
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Kim
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Park
authors.forename: Kwang Bum
authors.initials: KB
authors.lastname: Cho
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Chung
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a