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Baseline high viral load and unfavorable patterns of alanine aminotransferase change predict virological relapse in patients with chronic hepatitis C genotype 1 or 2 obtaining rapid virological response during antiviral therapy.

Lin KH, Yu HC, Hsu PI, Tsai WL, Chen WC, Lin CK, Chan HH, Tsay FW, Lai KH - Hepat Mon (2013)

Bottom Line: Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR.Among the HVL patients, the VR rate of those using peg-IFN-α-2a was relatively low (9.1%).Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005).

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan ; Physical Examination Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

ABSTRACT

Background: Rapid virological response (RVR) strongly predicts sustained virological response (SVR) in patients with chronic hepatitis C (CHC), and abbreviates antiviral therapy in some patients.

Objectives: To identify factors predicting virological relapse (VR) in CHC patients who attained RVR.

Patients and methods: Medical records of 133 CHC patients with an RVR after completing 24 weeks of antiviral therapy (a combination of pegylated interferon-α and ribavirin) were analyzed. Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR. Patients with normal alanine aminotransferase (ALT) levels at weeks 4 and 12 and at the end-of-treatment (EoT) and patients with elevated, but constantly decreasing, ALT levels were classified as having favorable patterns of ALT change. A trend of increasing ALT levels either between weeks 4 and 12 or between weeks 12 and EoT was classified as unfavorable. A high viral load (HVL) was defined as a baseline HCV RNA ≥ 600000 IU/mL.

Results: In total, 116 (87.2%) patients had a SVR and 14 (10.5%) had VR. The VR rates were comparable between patients with genotype-1 (13.1%) and genotype-2 infection (8.7%) (P = 0.572). Multivariate analysis revealed that HVL (P = 0.015; odds ratio [OR] = 14.754; 95% confidence interval (CI) = 1.671-130.240), and unfavorable ALT patterns (P = 0.039; OR = 4.397; 95% CI = 1.078-17.930) independently predicted VR. In subgroup analysis, low viral load (LVL) patients had a minimal VR rate (1.8%). Among the HVL patients, the VR rate of those using peg-IFN-α-2a was relatively low (9.1%). Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005).

Conclusions: In southern Taiwan, 24 weeks of antiviral therapy achieved a high SVR rate in patients with CHC attaining RVR, except in the subgroup of patients treated with peg-IFN-α-2b with HVL and on-treatment unfavorable ALT patterns.

No MeSH data available.


Related in: MedlinePlus

Proposed Algorithm With Modified Durations for Peg-IFN and RBV Combination Therapy in Patients With Chronic Hepatitis C Attaining RVRHVL, baseline high viral load; LVL, baseline low viral load; WB, weight-based (dose of RBV)
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fig6684: Proposed Algorithm With Modified Durations for Peg-IFN and RBV Combination Therapy in Patients With Chronic Hepatitis C Attaining RVRHVL, baseline high viral load; LVL, baseline low viral load; WB, weight-based (dose of RBV)

Mentions: Further subgroup analysis disclosed that the VR rate in patients receiving Peg-IFN-α-2a was considerably low, even in the G-1 infected patients with HVL (9.1%), which concurred with the data from Yu et al. (11.1%) (4). Among the patients treated with Peg-IFN-α-2a, the role of genotype, viral load, and patterns of ALT change in predicting VR were limited; however, combining HVL and unfavorable patterns of ALT change could identify a high-risk subgroup for VR (~50%) in patients receiving Peg-IFN-α-2b, regardless of genotype status. Those results suggest that 48 weeks of therapy should be offered to G-1, HVL patients with unfavorable patterns of ALT receiving combination therapy with Peg-IFN-α-2b, even if they achieve an RVR. Forty-eight weeks of therapy should also be considered for G-2, HVL patients who achieve an RVR, but have unfavorable patterns of ALT, even though current treatment guidelines still recommend a 24 week treatment course. Despite extended therapy, prescription with weight-based RBV since the start may overcome the “low responsiveness” resulting from factors such as HVL, advanced fibrosis, or insulin resistance (1). In a study conducted by Yu et al. patients with G-2 HCV who received weight-based RBV and attained an RVR, could achieve extremely high SVR rates (97.7–100%) (12). That superior response rate was considered to be contributed by higher RBV doses (mean dose was 15.3 mg/kg/day) in contrast to the 9.52 mg/kg/day in the ACCELERATE trial, which reported an SVR rate of 85% in G-2 patients with RVR (12, 30 ). In contrast, an abbreviated 24 week course prescribed to patients with G-1, HVL, attaining RVR, and with favorable patterns of ALT during combination therapy with Peg-IFN-α-2b may be sufficient. An explosive increase in the expenditure of antiviral therapy for CHC is expected in the near future, because current practical guideline has included direct antiviral agents in the first-line regimen (31). Therefore, it is important to identify some “super-responders” whose antiviral therapies could be simplified and/or abbreviated, if possible, without compromise to efficacy, to reduce the growth of expenditure, and to avoid unnecessary adverse effects. Based on the aforementioned subgroup analyses, an algorithm, including genotype, baseline VL, treatment drugs, and patterns of ALT change was proposed by the authors of this study for patients with CHC attaining RVR (Figure 2).


Baseline high viral load and unfavorable patterns of alanine aminotransferase change predict virological relapse in patients with chronic hepatitis C genotype 1 or 2 obtaining rapid virological response during antiviral therapy.

Lin KH, Yu HC, Hsu PI, Tsai WL, Chen WC, Lin CK, Chan HH, Tsay FW, Lai KH - Hepat Mon (2013)

Proposed Algorithm With Modified Durations for Peg-IFN and RBV Combination Therapy in Patients With Chronic Hepatitis C Attaining RVRHVL, baseline high viral load; LVL, baseline low viral load; WB, weight-based (dose of RBV)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842527&req=5

fig6684: Proposed Algorithm With Modified Durations for Peg-IFN and RBV Combination Therapy in Patients With Chronic Hepatitis C Attaining RVRHVL, baseline high viral load; LVL, baseline low viral load; WB, weight-based (dose of RBV)
Mentions: Further subgroup analysis disclosed that the VR rate in patients receiving Peg-IFN-α-2a was considerably low, even in the G-1 infected patients with HVL (9.1%), which concurred with the data from Yu et al. (11.1%) (4). Among the patients treated with Peg-IFN-α-2a, the role of genotype, viral load, and patterns of ALT change in predicting VR were limited; however, combining HVL and unfavorable patterns of ALT change could identify a high-risk subgroup for VR (~50%) in patients receiving Peg-IFN-α-2b, regardless of genotype status. Those results suggest that 48 weeks of therapy should be offered to G-1, HVL patients with unfavorable patterns of ALT receiving combination therapy with Peg-IFN-α-2b, even if they achieve an RVR. Forty-eight weeks of therapy should also be considered for G-2, HVL patients who achieve an RVR, but have unfavorable patterns of ALT, even though current treatment guidelines still recommend a 24 week treatment course. Despite extended therapy, prescription with weight-based RBV since the start may overcome the “low responsiveness” resulting from factors such as HVL, advanced fibrosis, or insulin resistance (1). In a study conducted by Yu et al. patients with G-2 HCV who received weight-based RBV and attained an RVR, could achieve extremely high SVR rates (97.7–100%) (12). That superior response rate was considered to be contributed by higher RBV doses (mean dose was 15.3 mg/kg/day) in contrast to the 9.52 mg/kg/day in the ACCELERATE trial, which reported an SVR rate of 85% in G-2 patients with RVR (12, 30 ). In contrast, an abbreviated 24 week course prescribed to patients with G-1, HVL, attaining RVR, and with favorable patterns of ALT during combination therapy with Peg-IFN-α-2b may be sufficient. An explosive increase in the expenditure of antiviral therapy for CHC is expected in the near future, because current practical guideline has included direct antiviral agents in the first-line regimen (31). Therefore, it is important to identify some “super-responders” whose antiviral therapies could be simplified and/or abbreviated, if possible, without compromise to efficacy, to reduce the growth of expenditure, and to avoid unnecessary adverse effects. Based on the aforementioned subgroup analyses, an algorithm, including genotype, baseline VL, treatment drugs, and patterns of ALT change was proposed by the authors of this study for patients with CHC attaining RVR (Figure 2).

Bottom Line: Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR.Among the HVL patients, the VR rate of those using peg-IFN-α-2a was relatively low (9.1%).Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005).

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan ; Physical Examination Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

ABSTRACT

Background: Rapid virological response (RVR) strongly predicts sustained virological response (SVR) in patients with chronic hepatitis C (CHC), and abbreviates antiviral therapy in some patients.

Objectives: To identify factors predicting virological relapse (VR) in CHC patients who attained RVR.

Patients and methods: Medical records of 133 CHC patients with an RVR after completing 24 weeks of antiviral therapy (a combination of pegylated interferon-α and ribavirin) were analyzed. Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR. Patients with normal alanine aminotransferase (ALT) levels at weeks 4 and 12 and at the end-of-treatment (EoT) and patients with elevated, but constantly decreasing, ALT levels were classified as having favorable patterns of ALT change. A trend of increasing ALT levels either between weeks 4 and 12 or between weeks 12 and EoT was classified as unfavorable. A high viral load (HVL) was defined as a baseline HCV RNA ≥ 600000 IU/mL.

Results: In total, 116 (87.2%) patients had a SVR and 14 (10.5%) had VR. The VR rates were comparable between patients with genotype-1 (13.1%) and genotype-2 infection (8.7%) (P = 0.572). Multivariate analysis revealed that HVL (P = 0.015; odds ratio [OR] = 14.754; 95% confidence interval (CI) = 1.671-130.240), and unfavorable ALT patterns (P = 0.039; OR = 4.397; 95% CI = 1.078-17.930) independently predicted VR. In subgroup analysis, low viral load (LVL) patients had a minimal VR rate (1.8%). Among the HVL patients, the VR rate of those using peg-IFN-α-2a was relatively low (9.1%). Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005).

Conclusions: In southern Taiwan, 24 weeks of antiviral therapy achieved a high SVR rate in patients with CHC attaining RVR, except in the subgroup of patients treated with peg-IFN-α-2b with HVL and on-treatment unfavorable ALT patterns.

No MeSH data available.


Related in: MedlinePlus