Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review

Table 1 Characteristics of the studies included in the systematic analysis

Ref.	Study design	No. of patients	Age (yr)	Weight	HCV genotype	Baseline treatment history	Child-Pugh class	Treatment
Syed et al[12]	Retrospective cohort study	104	52 ± 7.6	82 ± 15 kg (mean weight)	1, 2, 3	Naive and previously treated	A	Pegylated interferon alpha 2a (180 μg/wk) or alpha 2b (1-1.5 μg/kg per week)
								Ribavirin (800-1200 mg/d)
Butt et al[13]	Prospective cohort study	66	46.2 ± 10.1	22.3 ± 3.1 kg/m² (mean BMI)	3	Naive and previously treated	A, B	Pegylated interferon alpha 2a (180 μg/wk) or alpha 2b (1 μg/kg per week)
								Ribavirin (10-12 mg/kg per day)
Giannini et al[14]	Retrospective cohort study	85	56 ± 9	Not specified	1, 2, 3, 4	Naive and previously treated	A, B	Pegylated interferon alpha 2a (180 μg/wk) or alpha 2b (1.5 μg/kg per week)
								Ribavirin (800-1200 mg/ d)
Helbling et al[15]	Randomized controlled trial (standard doses vs low doses)	64	47 (median age)	74 kg (median weight)	1, 2, 3, 4	Naive	A	Pegylated interferon alpha 2a (180 μg/wk)
								Ribavirin (1000-1200 mg/ d)
Iacobellis et al[16]	Prospective cohort study	94	Not specified	Not specified	1, 2, 3, 4	Naive	B	Pegylated interferon alpha 2b (1.5 μg/kg per week)
								Ribavirin (800-1200 mg/d)
Roffi et al[17]	Randomized controlled trial (pegylated interferon vs IFN standard)	57	56 (median age)	75 kg (median weight)	1, 2, 3	Naive	A	Pegylated interferon alpha 2b (1 μg/kg per week)
								Ribavirin (800-1200 mg/d)
Sood et al[18]	Retrospective cohort study	28	48.3 ± 7	73.9 ± 11.2 kg (mean weight)	3 (25/28 patients) and not specified for the other patients	Naive	A, B	Pegylated interferon alpha 2b (1 μg/kg per week)
								Ribavirin (10-12 mg/kg per day)
Tekin et al[19]	Cohort study	20	54.2 ± 5.9	Not specified	1	Not specified	A, B	Pegylated interferon alpha 2a (135 μg/wk)
								Ribavirin (1000-1200 mg/d)
Moreno Planas et al[20]	Cohort study	12	52 ± 8	Not specified	1, 3	Naive and previously treated	A, B	Pegylated interferon alpha 2b (1.5 μg/kg per week)
								Ribavirin (10.6 mg/kg per day)
Di Marco et al[21]	Randomized controlled trial (pegylated interferon alpha 2B + ribavirin vs pegylated interferon alpha 2b)	52	57 ± 6.6	71 ± 10.1 kg (mean weight)	1, 2, 3, 4	Naive and previously treated	A, B	Pegylated interferon alpha 2b (1 μg/kg per week)
								Ribavirin (800 mg/d)
Höroldt et al[22]	Retrospective cohort study	61	Not specified	Not specified	1, 2, 3	Naive	A, B	Pegylated interferon alpha 2a or alpha 2b + ribavirin
Bruno et al[23]	Randomized study	106	Not specified	Not specified	1, 2, 3, 4	Naive	A	Pegylated interferon alpha 2a (180 μg/wk)
								Ribavirin (1000-1200 mg/d)
Floreani et al[24]	Prospective cohort study	87	55.7 ± 9.1	25.3 ± 3.1 kg/m² (mean BMI)	1, 2, 3	Naive	A	Pegylated interferon alpha 2b (80-100 μg/wk)
								Ribavirin (1000-1200 mg/d)
Annicchiarico et al[25]	Prospective cohort study	15	51.5	Not specified	1, 2, 3	Naive and previously treated	B, C	Pegylated interferon alpha 2b (1.5 μg/kg per week)
								Ribavirin (800-1200 mg/d)
Aghemo et al[26]	Prospective cohort study	106	57 ± 9.3	72.5 ± 11.8 kg (mean weight)	1, 2, 3, 4	Naive	A	Pegylated interferon alpha 2b (1.5 μg/kg per week)
								Ribavirin (≥ 10.6 mg/kg per day)
Kim et al[27]	Cohort study	86	56.4 ± 9.6	Not specified	1 and non-1	Not specified	A	Pegylated interferon alpha 2b (1.5 μg/kg per week)
								or Pegylated interferon alpha 2a (180 μg/wk)
								Ribavirin (1000-1200 mg/d)
Reiberger et al[28]	Prospective cohort study	90	51 ± 8	26.6 ± 5 kg/m² (mean BMI)	1, 2, 3, 4	Not specified	A	Pegylated interferon alpha 2b (1.5 μg/kg per week)
								or pegylated interferon alpha 2a (180 μg/wk)
								Ribavirin (1000-1200 mg/d)

HCV: Hepatitis C virus; BMI: Body mass index; IFN: Interferon.

Table 2 Description of severe adverse event leading to premature discontinuation of antiviral treatment in hepatitis C virus cirrhotic patients (%)

Name of severe adverse event	No. of patient discontinuities
Severe thrombocytopenia and/or neutropenia	27 (23.2)
Psychiatric disorders (depression, psychosis, confusion, lethargy)	18 (15.5)
Decompensation of liver cirrhosis (ascites with or without spontaneous bacterial peritonitis; jaundice; hepatic encephalopathy)	14 (12.1)
Severe anemia	13 (11.2)
Occurrence of malignancies	6 (5.1) - 4 cases of hepatocellular carcinoma, 1 case of tongue carcinoma and 1 case of Non-Hodgkin’s lymphoma recurrence
Allergic reactions to medication	5 (4.3)
Severe infections	5 (4.3)
Severe fatigue	5 (4.3) - in 2 cases accompanied also by “flu-like” syndrome
Neurological disorders (stroke, polyneuropathy, hemiparesthesia)	5 (4.3)
Heart disease (heart failure or acute coronary syndrome)	3 (2.5)
Endocrinology disorders	3 (2.5)
Diabetes decompensation	2 (1.7)
Persistent fever	2 (1.7)
Severe denutrition	2 (1.7)
Aminotransferases flare	1 (0.8)
Severe decrease of vision	1 (0.8)
Upper gastrointestinal bleeding	1 (0.8) - the cause of bleeding was not specified
Acute pancreatitis	1 (0.8)
Severe flare of psoriasis	1 (0.8)