Appendix 2. Rates (%) of the most common (>10%) adverse effects after antiviral drugs in adults with chronic hepatitis B (Pooled with random effect models from randomized controlled clinical trials)
Monotherapy
Placebo / Adefovir / Entecavir / LAM / Telbivudine / Interferon alpha 2b / PegIFN alfa 2A / PegIFN alfa 2B1 adverse event: 77 / Any adverse event: 95 / Any adverse event: 85 / At least one adverse effect: 68 / Total adverse effect: 76 / Malaise and fatigue: 100 / >1 reported AE: 89 / Adverse effects: 75
Incidence of elevation ofserum ALT to more than 5 times the ULN: 55 / Total adverse effect: 64 / Any adverse effect: 77 / Any adverse effect: 66 / At least one adverse event: 70 / Adverse effects: 75 / Pyrexia: 57 / Flu-like syndrome: 54
Malaise/fatigue: 32 / ALT Grade 3 (>5–10 times the ULN): 37 / ALT >2× reference value and >5× ULN: 10 / >1 Reported adverse: 47 / Influenza: 17 / Headache: 67 / Headache: 39 / Fatigue: 38
Ear, nose, and throat: 30 / Pharyngitis: 30 / Upper respiratory tract symptoms: 38 / Fever/chills: 61 / Dose modification due to Laboratory abnormality: 37 / Headache: 35
Respiratory infection: 29 / Asthenia: 30 / Any adverse event: 36 / Muscle pain: 57 / Myalgia: 36 / Myalgia: 26
Viral respiratory infection: 28 / Incidence of elevation ofserum ALT to more than 5 times the ULN: 28 / Respiratory infection: 35 / Viral respiratory infections: 53 / Fatigue: 29 / Local reaction: 23
Malaise and fatigue: 22 / Insomnia: 21 / Asthenia: 32 / Nausea and vomiting: 49 / Alopecia: 26 / Reduction in dose of Interferon due to adverse events: 21
Abdominal discomfort: 20 / Rash: 21 / Pharyngitis: 32 / Fatigue: 48 / Decreased appetite: 15 / Depression: 19
Nausea/vomiting: 20 / Proteinuria mg/dL(<100): 18 / Viral respiratory infection: 28 / Anorexia: 47 / Dizziness: 14 / Neutropenia (<1·5*109/L): 19
Headache: 17 / Headache: 17 / Abdominal pain: 26 / Abdominal discomfort and pain: 33 / Anorexia: 14 / Loss of >10% bodyweight: 18
Throat and tonsil disorder: 17 / Flu-like syndrome: 17 / ALT »2 times above base-line levels: 26 / Arthralgia: 33 / Upper respiratory tract infection: 13 / Abdominal pain: 17
Abnormal ALT/AST: 16 / Sinusitis: 16 / Rhinitis: 26 / Hair loss and alopecia: 30 / Nausea: 12 / Alopecia: 17
Grade III or IV laboratory abnormalities in ALT: 13 / Fever: 16 / Sinusitis: 26 / Dizziness: 27 / Insomnia: 12 / Nausea: 16
Hematuria>100 RBCs: 13 / Hematuria10–100 RBCs: 14 / Increased ALT level: 24 / Diarrhea: 23 / Diarrhea: 12 / Anorexia: 14
>1 treatment-related event: 12 / Hematuria>100 RBCs: 12 / Throat and tonsil discomfort/pain: 23 / Reduction in dose due to adverse effects: 21 / Rash: 10 / Arthralgia: 14
Cough: 11 / Serum Glucose Grade 3 abnormalities: 11 / Ear, nose, and throat infection: 21 / Mouth dryness: 19 / Pruritus: 10 / Thrombocytopenia (<75*109/L): 11
Hematuria10–100 RBCs: 10 / Urine Glucose Grade3: 11 / Urine Glucose Grade3 (3+): 21 / Nausea: 12 / Diarrhea: 10
Proteinuria mg/dL(<100): 10 / Dyspepsia: 10 / Influenza: 21 / Dose reduction due to depression, fatigue, hair loss, and headache: 11
Pain: 10 / Pain : 10 / Malaise or fatigue: 18
Upper respiratory tract infection: 10 / Abnormal ALT/AST: 18
Malaise and fatigue: 18
Influenza-like sympt: 17
ALT >2× baseline and >5× ULN: 17
Abnormal enzymes (amylase/CPK): 16
ALT Grade 4 >10 times the ULN): 16
Amylase Grade3 (>2–5 times the ULN): 16
Gastroenteritis: 16
Increased cough: 16
Pharyngolaryngeal pain: 16
Serum glucose Grade3 (30–39 mg/dL; 251–500 mg/dL): 16
Abdominal discomfort or pain: 15
ALT »3 times above base-line levels: 15
Cough: 15
Throat discomfort or pain : 14
Grade III abnormality in ALT: 14
Malaise: 14
Headache: 12
Grade4 (>10 times the ULN): 11
Grade III or IV laboratory abnormalities ALT: 10
Hair loss and alopecia: 10
Gastrointestinal events: 10
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Combined therapy
Interferon Alfa 2b + Corticosteroid / Interferon Alfa 2b + LamivudineLamivudine / Peginterferon alfa-2a+Lamivudin / Peginterferon alfa-2b + Lamivudine / Telbivudine + LamivudineLeucopenia: 20 / Malaise/fatigue: 95 / ≥1 Reported adverse event: 89 / Upper respiratory tract symptoms: 74 / At least one adverse: 71
Reduction in dose due to adverse effects: 12 / Fever: 95 / Pyrexia: 55 / Fever: 72 / Influenza: 24
Malaise and fatigue: 87 / Dose modification due to Laboratory abnormality: 38 / Flu-like syndrome: 63 / Headache: 14
Influenza-like symptoms: 64 / Fatigue: 37 / Abdominal discomfort: 44 / Back pain: 10
Fever/chills: 61 / Headache: 30 / Malaise: 44 / Upper respiratory tract infection: 10
Nausea/vomiting: 59 / Alopecia: 29 / Headache: 40
Muscle pain: 47 / Myalgia: 28 / Fatigue: 36
Headache: 45 / Decreased appetite: 13 / Alopecia: 33
Nausea and vomiting: 43 / Dizziness: 12 / Myalgia: 28
Anorexia: 39 / Diarrhea: 10 / Local reaction: 25
Hair loss and alopecia: 39 / Local erythematous reaction: 24
Viral respiratory in: 38 / Reduced appetite: 24
Feeding problems: 30 / Reduction in dose due to adverse events: 24
Decreased WBCs: 25 / Neutropenia (<1·5*109/L): 22
Rheumatism: 25 / Allergic rashes: 18
Abnormal ALT/AST: 16 / Depression: 18
Pain: 16 / Arthralgia: 18
Musculoskeletal pain: 16 / Abdominal pain: 16
Diarrhea: 14 / Dizziness: 16
Abdominal discomfort: 14 / Increased ALT level: 16
Abnormal enzymes : 13 / Loss of >10% bodyweight: 16
Arthralgia: 12 / Anorexia: 14
Dizziness: 12 / Vomiting or diarrhea: 14
Depression: 11 / Weight loss (>10%): 14
Insomnia: 13
Pruritus: 12
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