Table 1.
General Characteristics of Included Studies*
| Study and Country | Sample Size (n) | % Genotype 1 | Age | % Male | Study Population | |
|---|---|---|---|---|---|---|
| Inclusion criteria/Patient characteristics | Exclusion criteria | |||||
| Predictors of Histologic Progression | ||||||
| Baran 2014 Turkey |
125 | 95 | Mean 45 |
38 | Ishak <4 on initial biopsy >9 portal tracts on liver biopsy Treatment naïve or non-SVR with prior treatment |
HIV co-infected Other chronic liver disease HCC History of immunosuppressive therapy |
| Boccato 2006 Italy |
106 | 62 | Mean 41.6 |
56 | METAVIR F0 or F1 on initial biopsy Biopsy length >15mm and ≥7 portal tracts Minimum 4 yr follow-up Treatment naïve |
|
| Castera 2003 France |
96 | 62 | Mean 41 |
61 | No cirrhosis on initial biopsy Treatment naïve |
HBV or HIV co-infected |
| Colletta 2005 Italy |
40 | 30 | Median 43.5 |
55 | Ishak ≤2 on initial biopsy Serial ALT values < 1.2 times ULN Treatment naïve |
|
| Cross 2009 United Kingdom |
112 | 58 | Median 44 |
66 | Biopsy length >10mm Treatment naïve |
HBV or HIV co-infected Other chronic liver disease Prior liver transplant ETOH intake ≥ 80g/d (male), ≥ 60g/d (female) |
| Fabris 2012 Italy |
93 | 52 | Median 38 |
46 | Ishak ≤1 on initial biopsy Persistently normal or near normal ALT Treatment naïve |
|
| Fartoux 2005 France |
135 | 60 | Mean 38.5 |
59 | METAVIR ≤1 on initial biopsy Biopsy length >10mm Only one known risk factor for HCV infection Treatment naïve |
HBV or HIV co-infected Other chronic liver disease Prothrombin time > 80% Platelets >150,000/mL Hyaluronic acid < 85ug/L |
| Ghany 2003 United States |
123 | 70 | Mean 41 |
63 | Treatment naïve | |
| Khouri 2003 Brazil |
55 | NR | Mean 38 |
58 | Biopsy length >15mm Minimum of 1 year interval between biopsies 18-75 years old Treatment naïve |
HBV or HIV co-infected Immunosuppressed patients Chronic renal failure Using “potentially hepatotoxic drugs” |
| Kurosaki 2008 Japan |
97 | 88 | Median 52 |
51 | No cirrhosis on initial biopsy Treatment with IFN between biopsies without SVR |
HBV or HIV co-infected Other chronic liver disease ETOH consumption >20g/d |
| Levine 2006 Ireland |
167 | 100 | Mean 53 |
0 | Women infected from contaminated immunoglobulin Biopsy length >15mm and ≥5 portal tracts Treatment naïve |
|
| Mummadi 2010 United States |
36 | NR | Median 47 |
75 | No cirrhosis on initial biopsy Minimum of 1 year interval between biopsies |
HBV or HIV co-infected Other chronic liver disease Prior organ transplant ETOH intake >30g/d HCC |
| Perumalswami 2006 United States |
136 | 76 | Mean 44 |
58 | >10 portal tracts on liver biopsy Treatment naïve |
Decompensated cirrhosis HBV or HIV co-infected Other chronic liver disease ETOH ≥60g/d (male), ≥40g/d (female) Malignancy Steroid therapy |
| Ryder 2004 United Kingdom |
214 | 34 | Median 36 |
59 | No cirrhosis on initial biopsy >5 portal tracts on liver biopsy Treatment naïve |
HIV co-infected Coagulation disorder Hemodialysis |
| Tamaki 2013 Japan |
314 | NR | Mean 53.7 |
47 | Minimum of 1.5 year interval between biopsies Biopsy length >15mm IFN between biopsies, without SVR |
HBV or HIV co-infected ETOH ≥40g/d HCC NASH |
| Williams 2011 United Kingdom |
282 | 44 | Mean 37 |
61 | Ishak 0 or 1 on initial biopsy >5 portal tracts on liver biopsy Minimum of 2 year interval between biopsies No treatment during study |
HIV co-infected Coagulation disorder Hemodialysis |
| Predictors of Clinical Outcomes | ||||||
| Bruno 2009 Italy |
324 | 63 | Median 59 |
51.1 | Compensated cirrhosis (Child A) ≤ 70 years old IFN based treatment (55%) without SVR |
HBV or HIV co-infected Other chronic liver disease HCC “unable to attend regular follow-up visits” |
| Ghany 2011 United States |
470 | 94 | Mean 49.8 |
71.3 | HALT-C cohort: Ishak ≥3 on initial biopsy Prior treatment with IFN based therapy without SVR Evaluated control patients without further treatment |
HIV co-infected Other chronic liver disease ETOH abuse within past year CTP score ≥7 History of hepatic decompensation Platelets <75,000 Neutrophil count <1500 Hematocrit <33% HCC or AFP>300 ng/ml Bilirubin >2.5 mg/dl Creatinine >1.5 mg/dl “Serious medical disorder” Use of illicit drugs within past 2 years |
| Giannini 2003 Italy |
63 | NR | Mean 52 |
73 | HBV or HIV co-infected Other chronic liver disease ETOH >40g/d |
|
| Rincon 2013 Spain |
145 | NR | Median 51 |
77 | Compensated cirrhosis Treatment naïve or non-SVR |
Other chronic liver disease Prior liver transplant HCC >3cm or multilobular or vascular invasion |
| Sinn 2008 South Korea |
647 | 71 | Mean 58.2 |
49 | Compensated cirrhosis Minimum of 1 year follow-up Treatment naïve |
HBV or HIV co-infected CTP score >5 HCC |
| Sinn 2013 South Korea |
232 | 62 | Mean 57.2 |
38 | Compensated cirrhosis Minimum of 1 year follow-up ALT< 40 IU/l at baseline Treatment naïve |
HBV or HIV co-infected CTP score >5 HCC |
| VanDerMeer 2012 Europe and Canada |
405 | 76 | Median 48 |
68 | Ishak ≥4 at baseline Prior treatment with IFN based therapy without SVR |
HBV or HIV co-infected |
| Vergniol 2011 France |
1457 | 58 | Mean 51.2 |
53.4 | 52% patients with prior treatment; 38% without SVR 14% SVR with results adjusted for treatment response |
HBV co-infected Other chronic liver disease |
| Predictors of Histologic Progression and Clinical Outcomes | ||||||
| Dienstag 2011 United States |
1050 clinical 622 histologic |
94 | Mean 51 |
71 | HALT-C cohort (See Ghany 2011 above) 517 patients in IFN arm and 533 control arm |
HALT-C cohort (See Ghany 2011 above) |
| Everhart 2009 United States |
985 clinical 557 histologic |
94 | Mean 50.2 |
71 | HALT-C cohort (See Ghany 2011 above) 488 patients from IFN arm and 497 control arm |
HALT-C cohort (See Ghany 2011 above) |
| Fontana 2010 United States |
462 clinical 209 histologic |
94 | Mean 49.5 |
70.3 | HALT-C cohort (See Ghany 2011 above) 49.4% patients in IFN arm |
HALT-C cohort (See Ghany 2011 above) |
| Ghany 2010 United States |
1050 clinical 547 histologic |
94 | Mean 50 |
71 | HALT-C cohort (See Ghany 2011 above) 517 in IFN arm and 533 in control arm |
HALT-C cohort (See Ghany 2011 above) |
| Livingston 2010 United States |
52 | 67 | Median 41 |
51 | Alaska Native and American Indian persons Ishak ≤4 on initial biopsy Treatment naïve |
HBV or HIV co-infected |
AFP= alpha-fetoprotein; ALT= alanine aminotransferase; CTP= Child-Turcotte-Pugh; ETOH= alcohol; HALT-C= hepatitis c antiviral long-term treatment against cirrhosis; HBV=hepatitis B virus; HCC= hepatocellular carcinoma; HCV= hepatitis C virus; HIV= human immunodeficiency virus; IFN= interferon; NASH= non-alcoholic steatohepatitis; PC= analysis of prospectively designed cohort study; RC= retrospective analysis of cohort; SVR= sustained virologic response; ULN= upper limit of normal;
*
For select studies, reported data here reflects only a subset of the total study population based on the patient population and outcome of interest for this systematic review.
aAll studies of histologic progression required patients to undergo at least 2 liver biopsies as the method to evaluate fibrosis progression.