Table 1Randomized controlled trials of the efficacy of pegylated interferons for chronic hepatitis C infection

Study Trial Type HIV Eligibility Exclusion N Age/Gender/Race-Ethnicity Genotype Treatment History Intervention Ribavirin daily dose Virologic Response (SR=sustained response, ETR= end of treatment response) Additional Results Biochemical Response Histologic Response
Silva 2006
Argentina, Mexico, Germany
COMPARE

Efficacy quality: Fair
H2H (early response)Treatment-naive patients between the ages of 18 and 65 years who were infected with HCV genotype 1a or 1b [with a minimum of 6.0 x 10[5] HCV-RNA IU/mL, determined by quantitative polymerase chain reaction (PCR)]. Additional inclusion criteria were ALT/AST levels =10 times the ULN, normal hemoglobin, white-blood-cell count =4000 cells/lL, neutrophil count =1500 cells/lL, and platelet count =100,000/lL.Evidence of liver disease due to causes other than chronic HCV infection, HIV positivity, hemoglobinopathy, hemophilia, severe pre-existing psychiatric disease, poorly controlled diabetes mellitus, significant ischemic heart disease, chronic obstructive lung disease, or active autoimmune disease.36Mean age: 47.0
52.78% male
47.22% female
83.3% white
16.7% Hispanic
100% genotype 1Treatment naïvePeginterferon alfa-2b
1.5 μg/kg
1x /week for 8 weeks
13 mg/kgETR: 13/18 (72.22%)
Week 8
Measured early viral response only (after 8 weeks of treatment).
Peginterferon alfa-2a
180 μg
1x /week for 8 weeks
13 mg/kgETR: 8/18 (44.44%)
Sporea 2006
Romania
Efficacy quality: Poor
H2H (early response)Presence of chronic hepatitis C virus (proven by liver biopsy performed a maximum of 6 months before treatment) and quantification of the viral load (by PCR) before treatment.Not reported116Mean age: 50.2
30.17% male
69.83% female
Not reported69.8% naïve,
21.6% relapsers,
8.6% nonresponders
Peginterferon alfa-2a
180 μg/kg
1x /week for 12 weeks
800–1200 mgETR: 48/58 (82.76%)Measured early viral response only (after 12 weeks of treatment).
Early viral response:
naïve patients: 43/48 (89.6%);
p=0.61 vs PEG-IFN alfa-2B
relapsers: 4/7 (57.1%); p=0.67
non-responders: 1/3 (33.3%);
Peginterferon alfa-2b
1.5 μg/kg
1x /week for 12 weeks
800–1200 mgETR: 39/58 (67.24%)Early viral response:
naïve patients: 25/33 (75.2%)
relapsers: 12/18 (66.6%)
non-responders: 2/7 (28.6%)
Alfaleh 2004
Saudi Arabia
Efficacy quality: Fair
PEG-IFN vs interferonPersistently raised aminotransferases for at least 6 months; serum antibodies to HCV; HCV RNA found by PCR; and a diagnosis of chronic hepatitis on liver biopsy sample taken in the preceding 12 months.Age less than 18 or more than 70 years, previous treatment with interferon or ribavirin, neutropenia (fewer than 1500 neutrophils/mm3), thrombocytopenia (fewer than 90,000 platelets/mm3), anemia, serum creatinine more than 1.5 times >ULN, serum alpha-fetoproteins concentration above 25 ng/ml, history of alcohol or hemolytic disease, decompensated cirrhosis, autoimmune hepatitis, hepatitis B infection, HIV infection, current intravenous drug use, severe depressive illness, severe comorbid disease, organ transplant, pregnancy, unwilling to practice contraception, and hepatocellular disease.96Mean age: 46.8
56.25% male
18.8% genotype 1
81.3% genotypes other than 1, 1a, or 1b
Treatment naïvepeginterferon alfa-2b
100 μg
1x /week for 48 weeks
800 mgSVR: 21/48 (43.75%)
ETR: 34/48 (70.83%)
Patients with genotype 4 (N=28):
Virologic response
ETR: 19/28 (67.9%)
p=0.42 vs IFN
SR: 12/28 (42.9%)
p=0.43 vs IFN
Biochemical response
ETR: 18/28 (64.3%)
p=0.79 vs IFN
SR: 12/28 (42.9%)
p=1.0 vs IFN
ALT: ETR: 34/48 (70.8%)
SR: 25/48 (52.1)
interferon alfa-2b
3 million units
3x /week for 48 weeks
800 mgSVR: 14/48 (29.17%)
ETR: 25/48 (52.08%)
Patients with genotype 4 (N=31):
Virologic response
ETR: 17/31 (54.8%)
SR: 10/31 (32.3%)
Biochemical response
ETR: 18/31 (58.1%)
SR: 14/31 (45.2%)
ALT: ETR: 25/48 (70.8%); SR: 21/48 (52.1)
Bruno 2004
Italy
Efficacy quality: Fair
PEG-IFN vs interferonPreviously untreated HCV RNA positive patients aged between 18 to 65 years with ALT values above 1.5 ULN, liver biopsy performed within 6 monhts prior to enrollment and a diagnosis of chronic hepatitis with any degree of fibrosis, hemoglobin >=13g/dl for males, >=12 g/dl for females, WBC cound >3,000/mm3, granulocyte count >1.500/mm3, platelet cound >80,000/,,3, bilirubin, albumin and serum creatinine levels withn normal limits.Advanced cirrhosis, i.e., large esophageal varices (F2 or more), history of gastrointestinal bleeding, ascites or encephalopathy, hepatocellular carcinoma, anti-HIV or HBsAg positivity. Alcohol abuse (>=80 g/day), parenteral drug addiction if not abtaining for at least 2 years, and any other contraindications to interferon or ribavirin.311Mean age: 49.7
62.38% male
Not reportedTreatment naïvepeginterferon alfa-2b 1x/week for 48 weeks Weight-based dosing: 100 μg for weight 65 kg or more and 80 μg for weight below 65 kg for the first 8 weeks, followed by a fixed dose of 50 μg once weekly for the next 40 weeks.1000–1200 mgSVR: 67/163 (41.1%)
ETR: 88/163 (53.99%)
Virologic response
ETR by body weight (not reported by group):
=70 kg: 85/166 (51.2%)
>70 kg: 77/145 (53.1%)
p=0.74
SR by body weight:
=70 kg: 63/166 (37.9%)
>70 kg: 48/145 (33.1%)
p=0.37
Biochemical response
ETR by body weight (not reported by group):
=70 kg: 90/166 (54.2%)
>70 kg: 70/145 (48.3%)
p=0.29
SR by body weight:
=70 kg: 66/166 (39.8%)
>70 kg: 49/145 (33.8%)
p=0.27
ALT: ETR: 90/163 (55.2%)
SR: 68/163 (41.7%)
interferon alfa-2b
6 million units every other day for 48 weeks
1000–1200 mgSVR: 44/148 (29.73%)
ETR: 61/148 (41.22%)
ALT: ETR: 70/148 (47.3%)
SR: 47/148 (31.8%)
Derbala 2005
Egypt
Efficacy quality: Poor
PEG-IFN vs interferonAdult patients with chronic active hepatitis C, detectable serum HCV-RNA by RT-PCR, elevated serum ALT activity more than double normal value and histopathological criteria of chronic active hepatitis. Alpha-fetoprotein value within normal range and ultrasound scanning was negative for hepatocellular carcinoma. Female patients had negative serum pregnancy test and were not breastfeeding. Normal serum direct and indirect bilirubin, albumin, and creatinine. Normal thyroid function prior to the study and either non-diabetic or with controlled blood glucose level with HbA1C<8.5%.Co-infected with HBV, HIV, hemochromatosis, Wilson disease, or other cause for liver disease, neutrophil count <1.5 x 103/ul, platelet count <90 x103/ul or hemoglobin <12 g/dL for female and <13 g/dl for male, positive auto-antibodies including anti-nuclear antibody, anti-mitochondrial antibody, antismooth muscle antibody, patients with history of severe psychiatric disease, seizure disorder, organ transplantation, or severe cardiac or pulmonary disease. Clinically significant retinal abnormalities, clinical gout, substance abuse (alcohol or iv drugs), or showing any medical condition requiring the administration of systemic steroids.61Mean age: 40.7
86.89% male
100% genotypes other than 1, 1a, or 1bNot reportedPeginterferon alfa-2b
1.5 units per kg/body weight
1x /week for 48 weeks
800–1200 mgSVR: 10/30 (33.33%)
ETR: 13/30 (43.33%)
ALT: 56.68 +/− 57.1
Interferon alfa-2b
3 million units
3x /week for 48 weeks
800–1200 mgSVR: 8/31 (25.81%)
ETR: 11/31 (35.48%)
ALT: 55.29 +/− 35.4
Lee 2004
Taiwan
Efficacy quality: Fair
PEG-IFN vs interferonPreviously untreated Chinese chronic hepatitis patients with positive serum antibody ot HCV, aged from 18 to 65 years, who had (1) HCV RNA detectable in serum by PCR assay, 2) undergone a liver biopsy within 1 year before entry that was consistent with chronic hepatitis, 3) elevated serum ALT defined as >=2 x ULN for at least two measurements within 6 months preceding the trial entry.Positive hepatitis B surface antigen, previous liver transplantation, neutropennia (<1500/mm3), thrombocytopenia (<100,000/mm3), anemia (<13 g/dL for males and <12 g/dL for females), HIV infection, decomensated liver disease, other causes of liver disease, abnormal serum creatinine or alfa fetoprotein level, abnormal thyroid function test, preexisting psychiatric disorders, demoglobinopathies, autoimmune type disease, poorly controlled coexisting medical conditions, or unable to use contraception.153Mean age: 44.4
68.63% male
100% Asian
0.7% genotype 1a
49.7% genotype 1b
49.6% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alpha-2b
1.5 μg/kg
1x /week for 24 weeks
1000–1200 mgSVR: 51/76 (67.11%)
ETR: 67/76 (88.16%)
Virologic response by genotype ETR, genotype 1:
PEG-IFN: 35/38 (92.1%)
IFN: 34/39 (87.5%)
p=0.254
ETR, genotype non-1:
PEG-IFN: 32/38 (84.2%)
IFN: 37/38 (97.4%)
p=0.079
SR, genotype 1:
PEG-IFN: 25/38 (65.8%)
IFN: 16/39 (41.0%)
p=0.019
ALT: 44/76 (57.9%)Histologic response at week 48
PEG-IFN (N=41) vs IFN (N=46)
Change in total Knodell score:
−3.69 (SD 0.46) vs −4.19 (SD 0.43) p=0.431
Change in Knodell necroinflammatory score:
−3.04 (SD 0.32) vs −3.40 (SD 0.30) p=0.418
Change in Knodell fibrosis score:
Interferon alpha-2b
3 million unit for 24 weeks
1000–1200 mgSVR: 49/77 (63.64%)
ETR: 71/77 (92.21%)
ALT: SR: 47/77 (61.0%)
Mangia (A) 2004
Italy

Efficacy quality: Fair
PEG-IFN vs interferonPreviously untreated patients aged 18–70 years, with histologically proven chronic hepatitis C; positive for anti-HCV and HCV RNA by PCR and had at least a 1.5-fold increase in ALT levels for at least 6 months before the start of the study. Hemoglobin levles at least 13 g/dL in males and 12 g/dL in females, leukocyte counts at least 3000/mm3 and platelet counts higher than 70,000/mm3.Contraindications to interferon, ribavirin, and amantadine; immune suppression; concomitant liver disease attributable to a cause other than HCV infection; severe systemic diseases; intravenous drug use; and/or alcohol abuse.362Mean age: 47.6
59.4% male
58.9% genotype 1
41.1% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alfa-2a (with amantadine)
180 μg
1x /week for 48 weeks
1000–1200 mgSVR: 79/121 (65.29%)
ETR: 90/121 (74.38%)
SVR by genotype
genotype 1 or 4: 37/67 (55.2%)
genotype 2 or 3: 42/54 (77.8%) (p vs other treatment groups not reported)
ALT: ETR: 81/121(66.9% )
SR: 80 /121 (66.1%)
Interferon alpha-2a (with amantadine)
3 million unit
3x /week for 48 weeks
1000–1200 mgSVR: 40/120 (33.33%)
ETR: 51/120 (42.5%)
SVR by genotype
genotype 1 or 4: 18/79 (22.8%)
genotype 2 or 3: 22/41 (53.7%)
ALT: ETR: 51/120 (42.5% )
SR: 40 /120 (33.3%)
Interferon alpha-2a
3 million unit
3x /week for 48 weeks
1000–1200 mgSVR: 54/121 (44.63%)
ETR: 59/121 (48.76%)
SVR by genotype
genotype 1 or 4: 22/78 (28.2%)
genotype 2 or 3: 32/43 (74.4%)
ALT: ETR: 62/121(51.2% )
SR: 55 /121 (45.5%)
Manns 2001
Europe, Canada, Argentina, US
Efficacy quality: Fair
PEG-IFN vs interferonAdults, previously untreated, positive HCV RNA by PCR, recent liver biopsy consistent with chronic hepatitis, elevated ALT.Decompensated cirrhosis, other causes of liver disease, HIV, organ transplantation, significant other medical or psychiatric conditions, unable to take contraception.1530Mean age: 43.3 (range: 21–68)
65.56% male
68% genotype 1 32.2% genotypes other than 1, 1a, or 1bTreatment naïvepeginterferon alfa-2b (0.5 μg/kg)
0.5 μg/kg
1x /week for 48 weeks
1000–1200 mgSVR: 244/514 (47.47%)
ETR: 289/514 (56.23%)
SVR by genotype, p vs IFN + RBV:
genotype 1: 118/349 (33.8%), p=0.94
genotype 2 or 3: 122/153 (79.7%), p=0.89
genotype 4, 5, or 6: 4/12 (33%) p>0.99
ETR not reported by genotype
Histologic response (Knodell scores):
PEG-IFN 1.5 μg/kg (N=339) vs PEG-IFN 0.5 μg/kg (N=361) vs IFN (N=334)
Inflammation (mean change):
−3.4 vs −3.4 vs −3.4 Inflammation (% with improvement): 68% vs 70% vs 69%
Fibrosis (mean change):
peginterferon alfa-2b (1.5 μg/kg)
1.5 ug/kg
1x /week for 48 weeks
800 mgSVR: 274/511 (53.62%)
ETR: 333/511 (65.17%)
SVR by genotype, p vs IFN + RBV:
genotype 1: 145/348 (41.7%), p=0.02
genotype 2 or 3: 121/147 (82.3%), p=0.46
interferon 2b
1.5 ug/kg
3x /week for 48 weeks
1000–1200 mgSVR: 235/505 (46.53%)
ETR: 271/505 (53.66%)
SVR by genotype
genotype 1: 114/343 (33.2%)
genotype 2 or 3: 115/146 (78.8%)
genotype 4, 5, or 6: 6/16 (37.5%)
Scotto 2005
Efficacy quality: Fair
PEG-IFN vs interferonHCV-positive chronic hepatitis without previous treatment with IFN-alfa; serum ALT levels at least twice the ULN for at least 6 months before treatment; presence of anti-HCV antibodies determined by means fo a third-generation ELISA and confirmed by additional third generation RIBA; presence of measurable serum HCV RNA; HCV genotype 1b; leukocyte counts >3000/mm3; platelet counts >7500/mm3; hemoglobin concentration >13 g/dl for males and >12 g/dl for females.Previous episodes of decompensated liver disease (i.e., ascites, bleeding from esophageal varicose veins, encephalopathy), HIV co-infection, active intravenous drug use or a potential cause of liver disease other than HCV.78Mean age: 37.2
46.15% male
100% genotype 1bTreatment naïvePeginterferon alfa-2b
1.5 μg/kg
1x /week for 52 weeks
800–1200 mgSVR: 14/26 (53.85%)
ETR: 17/26 (65.38%)
ALT: End of treatment: 65.4%
Sustained: 50.0%
Interferon alfa-2b (3x/week)
6 million units
3x /week for 52 weeks
800–1200 mgSVR: 7/26 (26.92%)
ETR: 13/26 (50%)
ALT: End of treatment: 50.0%
Sustained: 26.9%
Interferon alfa-2b (daily)
3 million units daily for 52 weeks
800–1200 mgSVR: 14/26 (53.85%)
ETR: 17/26 (65.38%)
ALT: End of treatment: 57.7%
Sustained: 46.1%
Tsubota 2005
Japan
Efficacy quality: Fair
PEG-IFN vs interferonHCV genotype 1b confirmed by polymerase chain reaction (PCR); serum HCV RNA levels>100,000 international units (IU)/ml on quantitative PCR assay (defined as ``high'' viral load, Amplicor HCV Monitor Version 2.0, Roche Diagnostics, Tokyo, Japan); serum alanine transaminase (ALT) concentrations above the upper limit of normal (>45 IU/L); a diagnosis of chronic hepatitis on a liver biopsy specimen obtained within the preceding 1 year, using the ranking system for grading of necroinflammation activity and staging of fibrosis; hemoglobin concentration >=12.0 g/dl; neutrophil count >=1,500/ml; platelet count >=100x103/mcl; creatinine clearance >=51 ml/min; body weight between 40 and 100 kg; and age >=20 years.Liver cancer or severe liver failure, as defined previously; other forms of liver disease; coexisting serious psychiatric or medical illness, including seizure disorders, diabetes mellitus, cardiovascular or lung disease, and autoimmune-type disease; previous organ transplantation; treatment with any other antiviral or immunomodulatory agent administered within the previous 180 days; history of IFN monotherapy or combination therapy with ribavirin; a positive test for hepatitis B surface antigen; hypersensitivity to IFN/PEG-IFN or ribavirin; pregnancy or lactation, including patients' partners; and if patients were unable to use contraception.48Median age: 53, 55 (range: 20–65)
64.58% male
100% genotype 1bTreatment naïvePeginterferon alfa-2b
1.5 μg/kg
1x /week for 48 weeks
600–1000 mgSVR: 12/28 (42.86%)
ETR: 17/28 (60.71%)
ALT: ETR: 25/28 (89.3%)
SR: 16/28 (57.1%)
Interferon alfa-2b
6 million units
3x /week for 48 weeks
600–1000 mgSVR: 8/20 (40%)
ETR: 12/20 (60%)
ALT: ETR: 14/20 (70.0%)
SR: 11/20 (55.0%)
Arizcorreta 2004
Spain
Efficacy quality: Poor
PEG-IFN vs interferonHIV subgroupHIV infection, detected by the presence of anti-HIV antibodies or by indentification of HIV RNA; HCV co-infection, defined as a postivie serological result with a second- or third-generation enzyme-linked immunosorbent assay and the detection of HCV RNA. A maintained increase of serum aminotransferase levels for >=6 months was required. Minimum fibrosis score of >=1.Clinical or biochemical crieria of decompensated cirrhosis, positive hepatitis B surface antigen, other infectious, autoimmune, tumoral, biliary or vascular-associated liver disease, active alcohol or drug ddependence, a Karnofsky index of <80, absolute neutrophil counts of <1500 cells/ul, a platelet count of <90,000 cells/ul, or a hemoglobin concentration of <11.0g/dL, poorly controlled psychiatric disease, substantial coexisting medical conditions, inability to use contraceptive measures, for any reason, and previous interferon or ribavirin therapy.21Mean age: 34 (range: 33–39)
71.43% male
52.8% genotype 1
0% genotypes other than 1, 1a, or 1b
Not reportedpeginterferon alfa-2a
180 μg
1x /week for 48 weeks
800 mgSVR: 7/11 (63.64%)
ETR not reported
interferon
3 million units
3x /week for 48 weeks
800 mgSVR: 2/10 (20%)
ETR not reported
Carra 2004
France
Efficacy quality: Fair
PEG-IFN vs interferonHIVAdults who had never received interferon and with the following characteristics: second-generation enzyme-linked immunosorbent ssay positivity for anti-HCV antibodies and polymerase chain reaction-based assay positivity for HCV-RNA in serum; interpretable results of liver biopsy performed within the previous 18 months, showing at least mild activity or fibrosis, anti HIV antibody positivity and a stable plasma HIV-1 RNA level, stable antiretroviral treatment during the preceding 3 months (or no antiretroviral treatment), and a CD4 cell count higher than 200x106/L.Neutropenia, thrombocytopenia, anemia, serum creatinine level highe4r than 1.70 mg/dL, circulating hepatitis B surface antigen positivity, decompensated cirrhosis (defined as biopsy-proved cirrhosis with serum albumin below the lower limit of normal, a prothrombin level <60%, a total bilirubin level higher than the ULN, or a history of ascites, hepatic encephalopathy or esophageal varices), biliary, tumoral, or vascular liver disease, psychiatric disorders, a history of seizures, cardiovascular disease, poorly controlled diabetes mellitus, or autoimmune disorders, or if they had actively injected illicit drugs 3 months before enrollment or reported daily alcohol intake greater than 40 g (women) or 50 g (men). Women not willing to use effective contraception.412Mean age: 39.6
73.79% male
48.1% genotype 1
51.4% genotypes other than 1, 1a, or 1b
peginterferon alfa-2b 1.5 μg
1x /week for 48 weeks
800 mgSVR: 56/205 (27.32%)
ETR: 72/205 (35.12%)
Genotypes 1 or 4:
ETR: 32/125 (25.6%); p<0.001 vs interferon
SR: 21/125 (16.8%); p=0.006 vs interferon
Genotypes 2, 3, or 5:
ETR: 40/80 (50.0%); p<=0.87 vs interferon
SR: 35/80 (43.8%); p=0.88 vs interferon
Histologic response:
Metavir score change was −0.19 in PEG-IFN group vs 0.01 for IFN (p=0.02).
Mean change in Ishak grade was −0.57 for PEG- IFN vs −0.26 for IFN (p=0.24).
Changes in fibrosis did not differ between groups.
interferon alfa-2b
3 million units 3x /week for 48 weeks
800 mgSVR: 41/205 (20%)
ETR: 44/205 (21.46%)
Genotypes 1 or 4:
ETR: 8/129 (6.2%)
SR: 8/129 (6.2%)
Genotypes 2, 3, or 5:
ETR: 36/76 (47.5%)
SR: 33/76 (43.4%)
Chung 2004
US
Adult AIDS Clinical Trials Group A5071
Efficacy quality: Fair
PEG-IFN vs interferonHIVHIV-infected subjects 18 years of age or older with a confirmed diagnosis of hepatitis C, as defined by an HCV RNA level of more than 600 IU per milliliter, and had not previously been treated with interferon alfa; a liver biopsy demonstrating abnormal histologic findings consistent with the presence of chronic hepatitis C was required within 48 weeks before study entry. Subjects with cirrhosis were eligible provided they had no evidence of hepatic decompenstion (i.e., ascites, encephalopathy, jaundice, hypoalbuminemia, or coagulopathy).Clinically significant anemia, neutropenia, or thrombocytopenia, renal disease, positive tests for hepatitis B surface antigen, uncontrolled cardiopulmonary diseaes, poorly controlled psychiatric disease, or an active HIV-related opportunistic infection.133Mean age: 44.5
81.95% male
48% white
33% black
14% Hispanic
5% other
78% genotype 1
22% genotypes other than 1, 1a, or 1b
Treatment naïvepeginterferon alfa-2a
180 μg
1x /week for 48 weeks
600–1000 mgSVR: 18/66 (27.27%)
ETR: 27/66 (40.91%)
Genotype 1:
ETR: 15/51 (29.4%); p NS vs interferon
SR: 7/51 (13.7%); p NS vs interferon
Non-genotype 1:
ETR: 12/15 (80.0%); NS vs interferon
SR: 11/15 (73.3%); p=0.07 vs interferon
Among patients with no virologic response at week 24:
26/37 (70%) patients in PEG-IFN group and 45/57 (79%) in IFN group underwent liver biopsy.
Among this group, histologic response was observed in 35% ot patients in PEG-IFN and 36% of those in IFN group.
Among patients with a virologic response at week 24, 52% had histologic improvement
interferon alfa-2b 3–6 million units
week for 48 weeks
Ribavirin 600–1000 mg dailySVR: 8/67 (11.94%)
ETR: 8/67 (11.94%)
Genotype 1:
ETR: 3/52 (5.8%)
SR: 3/52 (5.8%)
Non-genotype 1:
ETR: 5/15 (33.3%)
SR: 5/15 (33.3%)
Laguno 2004
Spain

Efficacy quality: Fair
PEG-IFN vs interferonHIV subgroupPreviously untreated chronic hepatitis C with HCV RNA positive in plasma, ALT > 1.5fole the ULN and histological modifications in the liver biopsy (fibrosis >1 and/or necroimflammatory activity); control of HIV infection with a viral load <10,000 copies/ml and a CD4 cell count >250 X 106 cells/l, in response to a stable antrretroviral treatment (ART) or without ART if it was not required.Presence of other causes of hepatopathy, decompensated cirrhosis, pregnancy and potential contraindications for interferon or for ribavirin therapy such as hemoglobinopathies, cardiopathy, autoimmune diseases, major depression or other sevee psychiatric pathologies and active illicit drug consumption within the last 12 months.95Mean age: 40
68% male
49% genotype 1
51% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alfa-2b
100–150 μg (weight-based)
1x /week for 48 weeks
800–1200 mgSVR: 23/52 (44.23%)
ETR: 27/52 (51.92%)
Virologic response results by genotype:
ETR, Genotype 1 or 4:
PEG-IFN: 13/32 (41%)
IFN: 3/27 (11%)
p=0.011
ETR, Genotype 2 or 3:
PEG-IFN: 13/19 (68%)
IFN: 10/15 (67%)
p=0.914
SR, Genotype 1 or 4:
PEG-IFN: 12/32 (38%)
IFN: 2/27 (7%)
p=0.007
ETR, Genotype 2 or 3:
PEG-IFN: 10/19 (53%)
IFN: 7/15 (47%)
p=0.730
ALT: SR: 28/52 (53%)
Interferon alpha-2b
3 million units
3x /week for 48 weeks
800–1200 mgSVR: 9/43 (20.93%)
ETR: 13/43 (30.23%)
ALT: SR: 14/43 (33%)
Poizot-Martin 2003
France
Efficacy quality: Poor
PEG-IFN vs interferonHIV subgroupPatients who were treated with a dual therapy protocol consisting of at least 6 monhts and up to 12 months of a combination of interferon (peg or not) plus ribavirin.Not reported.62Median age: 36
range: 34–40 (interquartile range)
67.74% male
1.6% genotype 1
38.7% genotype 1a
14.5% genotype 1b
45.2% genotypes other than 1, 1a, or 1b
Not reportedPeginterferon alfa-2b
180 μg
1x /week for 6–12 months
Described as
"800 mg, two tablets per day" so not clear if 800 or 1600 mg/day.
SVR: 1/20 (5%)
ETR: 4/20 (20%)
Interferon alfa-2b
3 million units
3x /week for 6–12 months
Described as "800 mg, two tablets per day" so not clear if 800 or 1600 mg/day.SVR: 8/42 (%)
ETR: 13/42 (%)
Torriani 2004
Multiple countries
APRICOT
Efficacy quality: Good
PEG-IFN vs interferonHIV subgroupOver age 18, infected with both HIV and HCV, an have anti-HCV antibodies in serum, detactable serum levels of HCV RNA (>600 IU/ml), elevated serum ALT levels documented on 2 or more occasions within the previous 12 months, findings on liver biopsy within the past 15 months that were consistent with the presence of chronic hepatitis C invection, and compensated liver disease (without compromise of lever function or clinically important portal hypertension). Subjects were required either to have been receiving stable antiretroviral therapy for at least six weeks before study entry, with no changes expected for the first eight weeks of the study, or not to have received any antiretroviral therapy for at least eight weeks before randomization and to be able to delay the initiation of antiretroviral therapy for at least six weeks. For the remainder of the study, changes to an existing antiretroviral therapy regimen or initiation of antiretroviral therapy was permitted at the discretion of the investigator.Active HIV-related opportunistic infection or cancer; an absolute neutrophil count below 1500 per cubic millimeter; a platelet count below 70,000 per cubic millimeter; a hemoglobin level below 11 g per deciliter for women, or below 12 g per deciliter for men; a serum creatinine level more than 1.5 times the upper limit of normal; concurrent infection with hepatitis A or B virus; evidence of decompensated liver disease; severe psychiatric disease, especially depression; clinically significant coexisting medical conditions; and, for women, pregnancy or unwillingness to practice contraception.
Participants were also excluded if they had previously received interferon or ribavirin.
860Mean age: 39.9
81.05% male
79% white
10.3% black
0.8% Asian
9.9% other
60.7% genotype 1
39.3% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alfa-2a
180 μg
1x /week for 48 weeks
800 mgSVR: 116/289 (40.14%)
ETR: 136/289 (47.06%)
Results by genotype
ETR:
genotype 1: 67/176 (38.1%)
genotype 2 or 3: 61/95 (64.2%)
SR:
genotype 1: 51/176 (30.0%)
genotype 2 or 3: 59/95 (62.1%) (all groups NS vs IFN + RBV and vs PEG-IFN + placebo)
Peginterferon alfa-2a (no ribavirin)
180 ug
1x /week for 48 weeks
PlaceboSVR: 58/286 (20.28%)
ETR: 90/286 (31.47%)
Results by genotype
ETR:
genotype 1: 37/175 (21.1%)
genotype 2 or 3: 51/90 (56.7%)
SR:
genotype 1: 24/175 (13.7%)
genotype 2 or 3: 32/90 (35.6%)
Interferon alfa-2a
3 million units
3x /week for 48 weeks
800 mgSVR: 33/285 (11.58%)
ETR: 40/285 (14.04%)
Results by genotype
ETR:
genotype 1: 13/171 (7.6%)
genotype 2 or 3: 24/89 (30.0%)
SR:
genotype 1: 12/171 (7.0%)
genotype 2 or 3: 18/89 (20.2%)
Fried 2002
Multiple (US, Europe, Australia, Brazil)
Pegasys International Study Group
Efficacy quality: Fair
PEG-IFN + ribavirin vs PEG-IFN monotherapyAdults with > 2000 copies of HCV RNA by PCR, elevated ALT levels within 6 mo., live biopsy consistent with chronic HCV, no previous interferon treatment.Neutropenia, thrombocytopenia, anemia, r HIC, decomensatied liver disease, serum creatinine > 1.5 x normal, poorly controlled psychiatric disease, alcohol or drug dependence within one year, substantial coexisting medical condition.1121Mean age: 42.5
71.36% male
84.1% white
4.7% black
5.7% Asian
5.4% other
32.6% genotype 1a
30.8% genotype 1b
36.6% genotypes other than 1, 1a, or 1b
Peginterferon alfa-2a
180 units
1x /week for 48 weeks
1000–1200 mgSVR: 254/453 (56.07%)
24 weeks following end of treatment
ETR: 313/453 (69.09%)
SVR by genotype, p vs IFN + RBV:
genotype 1: 138/298 (46.3%), p=0.01
genotype 2 or 3: 106/140 (75.7%), p=0.005
genotype 4: 10/13 (76.9%), p-value not calculated due to small sample size
Body weight of 75 kg or less
Interferon alfa-2b
3 million unit
3x /week for 48 weeks
1000–1200 mgSVR: 195/444 (43.9%)
24 weeks after end of treatment
ETR: 197/444 (44.4%)
SVR by genotype
gentotype 1: 103/285 (36.1%)
gentoype 2 or 3: 88/145 (60.7%)
gentoype 4: 4/11 (36.4%)
Peginterferon alfa-2a (no ribavirin)
180 ug
1x /week for 48 weeks
PlaceboSVR: 65/224 (29%)
24 weeks after end of treatment
ETR: 66/224 (29.5%)
SVR by genotype
gentotype 1: 30/145 (20.7%)
gentoype 2 or 3: 31/69 (44.9%)
gentoype 4: 4/9 (44.4%)
Inati 2005
Lebanon
Efficacy quality: Fair
PEG-IFN + ribavirin vs PEG-IFN monotherapyTransfusion-dependent thalassaemia major patients with chronic HCV infection with at least 2000 copies of HCV RNA/ml of serum by a sensitive polymerase chain reaction (PCR)-based commercial assay . Patients were older than 12 years of age, were infected with genotype 1 or 4 HCV, were treatment naive, and had a liver biopsy consistent with chronic hepatitis C.Patients were excluded if they had neutropenia, thrombocytopenia, hepatitis B virus or human immunodeficiency virus co-infection, decompensated liver disease, serum creatinine greater than 1.5 times the upper limit of normal, poorly controlled psychiatric disease, or absolute contraindication to either drug.20Mean age: 19.6
80% male
75% genotype 1
25% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alfa-2a (plus placebo)
180 μg
1x /week for 48 weeks
PlaceboSVR: 4/12 (33.33%)
ETR: 5/12 (41.67%)
Peginterferon alfa-2a (plus ribavirin)
180 μg
1x /week for 48 weeks
10.6 mg/kgSVR: 5/8 (62.5%)
ETR: 6/8 (75%)
Kamal (A) 2002
Germany
Efficacy quality: Poor
PEG-IFN + ribavirin vs PEG-IFN monotherapyPatients with proven chronic hepatitis C recruited from cohorts participating in 2 trials. Elevated serum ALT value above the upper limit of normal (40 U/L) on 2 occasions during the preceding 6 months, anti–HCV-positive antibody status assessed by second-generation enzyme-linked immunosorbent assay, positive polymerase chain reaction for HCV RNA, lower limit of quantitation of 2000 copies/mL), and had criteria for chronic hepatitis C in the liver biopsy examination performed within the preceding year.No patients with cirrhosis or bridging fibrosis were enrolled and none had previously been treated with IFN therapy. other liver diseases, such as hepatitis A, hepatitis B, autoimmune hepatitis, alcohol-induced liver disease, drug-induced hepatitis, decompensated liver disease, coinfection with human immunodeficiency virus, neutropenia, thrombocytopenia, creatinine concentration greater than 1.5 times the upper limit of normal, serum alpha-fetoprotein concentration greater than 25 ng/mL, organ transplant, neoplastic disease, severe cardiac or pulmonary disease, unstable thyroid dysfunction, psychiatric disorder, current pregnancy or breast feeding, or therapy with immunomodulatory agents within the past 6 months.42Mean age: 42.2
59.52% male
40.48% female
16.7% genotype 1a
69% genotype 1b
14.3% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alfa-2a
180 μg
1x /week for 48 weeks
800–1200 mgSVR: 8/14 (57.14%)
ETR: 11/14 (78.57%)
Of the 16 patients who achieved a SVR, 10 had genoype 1 (4 in the PEG-IFN monotherapy group, 6 in PEG-IFN + RBV group, none in IFN monothrapy group). All 6 patients with genotype non-1 achieved a SVR (2 in IFN monnotherapy group, 2 in PEG-IFN monotherapy group, and 2 in PEG-IFN + RBV group).
Peginterferon alfa-2a
180 μg
1x /week for 48 weeks
NoneSVR: 6/14 (42.86%)
ETR: 10/14 (71.43%)
Interferon alfa-2a
3–6 million units
3x /week for 48 weeks
NoneSVR: 2/14 (14.29%)
ETR: 4/14 (28.57%)
Cargnel 2005
Italy
Italian Co-infection Study (ICOS)
Efficacy quality: Fair
PEG-IFN + ribavirin vs PEG-IFN monotherapyHIVHIV-positive patients with compensated, HCV-related chronic liver disease; males or females, 18–65 years of age; baseline CD4+ =300/mm3; HAART in progress for at least 3 months with positive results (HIV-RNA <400 copies/ml); elevated alanine transferase (ALT) and detectable serum HCV-RNA; liver biopsy within 12 months prior to entry to this protocol consistent with chronic hepatitis C – histological grading and staging were scored according to Knodell and Ishak classification; and haemoglobin values =12 g/dl, leukocyte count >3000/mm3 and platelets >100000/mm3.Previous treatment with IFN, PEG-IFN alone or in combination with RBV; treatment for chronic hepatitis with another antiviral or immunomodulator in the previous 2 years; presence of other causes of liver disease, excluding chronic HCV infection; advanced/decompensated liver disease; presence of serious disease of the central nervous system, cardiovascular system, respiratory tract or retina; haemophilia or other forms of haemoglobinopathy, decompensated diabetes, severe psychiatric disorders, immunomediated diseases or diseases requiring chronic steroid treatment; and drug addiction or alcohol ingestion =80 g/day and/or methadone therapy during the last 2 years.135Mean age: 38.5
82.96% male
17.04% female
43.7% genotype 1
56.3% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alfa-2b (plus ribavirin)
1.5 μg/kg
1x /week for 48 weeks
800 mgSVR: 15/69 (21.74%)
ETR: 20/69 (28.99%)
PEG-IFN + RBV vs monotherapy
Genotype 1–4:
ETR: 6/37 (16.2%) vs 5/34 (14.7%); NS
SVR: 4/37 (10.8%) vs 3/34 (8.8%); p=0.02
Genotype 2–3:
ETR: 14/32 (43.7%) vs 6/32 (18.7%); NS
SVR: 11/32 (34.4%) vs 3/32 (9.4%); p=0.02
Peginterferon alfa-2b monotherapy
1.5 μg/kg
1x /week for 48 weeks
NoneSVR: 6/66 (9.09%)
ETR: 11/66 (16.67%)
Khalili 2005
US
Efficacy quality: Fair
PEG-IFN + ribavirin vs PEG-IFN monotherapyHIVAdult patients (=18 years of age) with treatment-naive chronic HCV, plasma HCV RNA >600 IU/mL, and stable HIV infection. Patients had a liver biopsy within 24 months of enrollment consistent with only chronic HCV disease. Compensated cirrhotics (Child-Pugh grade A) were also included. Patients on HAART had to be on stable therapy for at least 6 weeks prior to HCV therapy, with a CD4 cell count of 200/μL or higher or of 100–99/μL plus a plasma HIV RNA level below 5000 copies/mL.Any chronic liver disease other than HCV, an active HIV-related opportunistic infection and/or malignancy requiring acute systemic therapy, an absolute neutrophil count <750 cells/μL, hemoglobin <10 g/dL in women and <11 g/dL in men, thrombocytopenia (<75,000 platelets/μL), or serum creatinine level >1.5 times the upper limit of normal (ULN). Patients were also excluded if they had a history of severe psychiatric disease, seizure disorder or current anticonvulsant use, an immunologically mediated disease, chronic pulmonary disease, cardiac disease that could be worsened by acute anemia, or poorly controlled thyroid disease.154Mean age: 44.4
81.17% male
59% white
27% black
13% other
76% genotype 1
24% genotypes other than 1, 1a, or 1b
Treatment naïvePeginterferon alfa-2a (plus ribavirin)
180 mg
1x /week for 48 weeks
800 mgSVR: 2/37 (5.41%)
ETR: 4/37 (10.81%)
Peginterferon alfa-2a (plus placebo)
180 mg
1x /week for 48 weeks
PlaceboSVR: 0/39 (0%)
ETR: 1/39 (2.56%)

From: Evidence Tables

Cover of Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection
Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection: Final Report [Internet].
Chou R, Carson S, Chan BKS, et al.
Portland (OR): Oregon Health & Science University; 2007 May.
Copyright © 2007, Oregon Health & Science University, Portland, Oregon.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.