Table 5.
Summary of clinical studies in statin
| Study | Etiology | Inclusion criteria | Intervention period | Arms (n) | Age (years) | Outcomes | Study design |
|---|---|---|---|---|---|---|---|
| Nelson et al. [12] (2009) | NAFLD | Biopsy-proven NASH | 12 months | Simvastatin 40 mg/day (10) | 52.6±8.6 | · Necroinflammatory activity (mean, 1.4 vs. 1.0; P>0.05) | RCT |
| Control (6) | 52.5±13.0 | · Fibrosis stage (mean, 1.50 vs. 1.0; P>0.05) | |||||
| Dongiovanni et al. [165] (2015) | NAFLD | Patients who underwent liver biopsy for suspected NASH | ≥6 months | Statin (107) | 53±10 | · Lower presence of steatosis (OR, 0.09; 95% CI, 0.01–0.32; P=0.004), NASH (OR, 0.25; 95% CI, 0.13–0.47; P<0.001), F2–F4 fibrosis (OR, 0.42; 95% CI, 0.20–0.80; P=0.017)* in statin group | Cross-sectional study |
| Control (1,094) | 41±16 | ||||||
| Nascimbeni et al. [166] (2016) | NAFLD | Biopsy-proven NAFLD with type 2 DM | NA | Statin (154) | 55 (48–61) | · Lower presence of NASH (OR, 0.57; 95% CI, 0.32–1.01; P=0.055) and significant fibrosis (OR, 0.47; 95% CI, 0.26–0.84; P<0.011) in statin group | Cross-sectional study |
| Control (192) | 52 (42–58) | ||||||
| Ekstedt et al. [167] (2007) | NAFLD | Biopsy-proven NAFLD with elevated ALT and/or AST >41 U/L and/ or elevated ALP >106 U/L | 10.3–16.3 years | Statin (17) | 48.7±9.1 | · Significant reduction of liver steatosis in statin group (20.4% to 11.1%, P=0.001) | Retrospective cohort study |
| Control (51) | 46.3±11.8 | ||||||
| Rallidis et al. [168] (2004) | NAFLD | Biopsy-proven NASH and abnormal liver enzyme | 6 months | Pravastatin 20 mg/day (5) | 40±8 | · Improvement in the grade of inflammation (75%) and steatosis (25%) | Prospective cohort study |
| Hyogo et al. [169] (2008) | NAFLD | Biopsy-proven NASH with lipidemia | 24 months | Atorvastatin 10 mg/day (31) | 52.5 (27–68) | · Significant improvement of steatosis grade (1.6 to 0.8; P<0.001) and NAS (4.1 to 2.9; P<0.001) | Prospective cohort study |
| Hyogo et al. [172] (2011) | NAFLD | Biopsy-proven NASH and hyperlipidemia | 12 months | Pitavastatin 2 mg/day (20) | 50.6 (25–75) | · Change of NAS (6.7 to 6.3) and fibrosis stage (2.3 to 2.1) | Prospective cohort study |
| Nakahara et al. [170] (2012) | NAFLD | Biopsy-proven NASH and hyperlipidemia | 24 months | Rosuvastatin 2.5 mg/day (19) | 46.3 (20–65) | · Change of NAS (3.89 to 3.44) and fibrosis stage (2.33 to 2.00) | Prospective cohort study |
| Kargiotis et al. [171] (2015) | NAFLD | Biopsy-proven NASH and metabolic syndrome and lipidemia | 12 months | Rosuvastatin 10 mg/day (20) | 40.5±5.6 | · Complete resolution of NASH (95%) | Prospective cohort study |
| Lee et al. [278] (2021) | NAFLD | Age ≥20 years who participated the NHIS physical health examination | 72 months | NAFLD (164,856) | 41.4±12.4 | · Reduced risk of NAFLD development in statin group (adjusted OR 0.66; 95% CI, 0.65–0.67) | Retrospective cohort study |
| Control (824,280) | 41.4±12.4 | ||||||
| Zou et al. [175] (2022) | NAFLD | Diabetes or obesity and ICD- 10 codes (K76.0 and K758.1) | 1.92 years | Statin (73,385) | 58.0±12.4 | · Lower risk of HCC development in statin group (HR, 0.47; 95% CI, 0.36–0.60; P<0.001) | Retrospective cohort study |
| Control (199,046) | 50.0±14.9 | ||||||
| Avins et al. [176] (2008) | Mixed | Patients with evidence of liver disease showing elevated AST or ALT levels or diagnosis of liver disease | 28.8 months (12.1–58.2) | Lovastatin (13,491) | 53.9±11.4 | · Lower incidence of liver function test abnormalities in statin group (incident RR 0.28; 95% CI, 0.12–0.55; P=NA) | Retrospective cohort study |
| Control (79,615) | 47.5±13.6 | ||||||
| Hsiang et al. [177] (2015) | HBV | 1.6 years | Statin (1,176) | 58.7±12.4 | · Lower HCC development in statin group (subHR 0.68; 95% CI, 0.48–0.97; P=0.033) | Retrospective cohort study | |
| 4.9 years | Control (52,337) | 37.6±14.1 | |||||
| Huang et al. [178] (2016) | HBV | 4.71±3.21 | Statin (22,544) | 52.87±11.51 | · Lower incidence of cirrhosis (RR, 0.433; 95% CI, 0.344–0.515; P<0.001) and decompensated cirrhosis (RR, 0.468; 95% CI, 0.344–0.637; P<0.001) in stain group | Retrospective cohort study | |
| 4.57±3.20 years | Control (215,802) | 39.73±13.14 | |||||
| Butt et al. [273] (2015) | HCV | Received HCV treatment ≥14 days | >24 months | Statin (3,347) | 53 (49–56) | · Higher SVR rate (OR, 1.44; 95% CI, 1.29–1.61; P<0.0001) in statin group | Retrospective cohort study |
| Control (3,901) | 52 (48–56) | · Cirrhosis development (17.3% vs. 25.2%; P<0.001) | |||||
| · HCC incidence (1.2% vs. 2.6%, P<0.01) | |||||||
| Simon et al. [179] (2015) | HCV | Previous non- response to standard interferon therapies and advanced hepatic fibrosis on liver biopsy | 3.5 years | Statin (29) | 54.2±7.2 | · Lower risk of fibrosis progression in statin group (unadjusted HR, 0.32; 95% CI, 0.10–0.97; P=0.048; adjusted HR, 0.31; 95% CI, 0.10–0.97; P=0.044) | Retrospective cohort study |
| Control (514) | |||||||
| Yang et. el. [180] (2015) | HCV | 2,874,031.7 personyears | Statin (29,204) | Only distribution available | · Incidence rate of cirrhosis (445.5/100,000 person-years vs. 1311.2/100,000 personyears) | Retrospective cohort study | |
| Control (197,652) | |||||||
| Mohanty et al. [181] (2016) | HCV | 2.6 years | Statin (1,323) | 56 (52–60) | · Lower risk of decompensation (HR, 0.22; 95% CI, 0.17–0.28) and death (HR, 0.39; 95% CI, 0.34–0.44) before matching in statin group | Retrospective cohort study | |
| 1.9 years | Control (12,522) | 54 (50–58) | · Lower risk of decompensation (HR, 0.55; 95% CI, 0.39–0.77 and death (HR, 0.56; 95% CI, 0.46–0.69) after matching in statin group | ||||
| Abraldes et al. [182] (2009) | Mixed (mainly alcohol) | Liver cirrhosis patients with severe portal HTN defined as HVPG of ≥12 mmHg | 30±4 days | Simvastatin (28) | 58±10 | · Change in HVPG (mean, -8.3% vs. -1.6%; P=0.041) | RCT |
| Control (27) | 56±10 | ||||||
| Pollo-Flores et al. [183] (2015) | Mixed (mainly HCV) | Cirrhosis with portal HTN | 3 months | Simvastatin (14) | 56.5 (IQR, 8.7) | · Decreased HVPG of at least 20% from baseline or to ≤12 mmHg) (55% vs. 0%; P=0.03) | RCT |
| Control (20) | 58.5 (IQR, 13.5) | ||||||
| Abraldes et al. [184] (2016) | Mixed (mainly alcohol) | Diagnosis of liver cirrhosis, and variceal bleeding within the previous 5–10 days, and plan to start standard prophylactic treatment for variceal bleeding | 371 days | Simvastatin (69) | 57.42±11.31 | · Higher survival (HR, 0.387; 95% CI, 0.152–0.986; P=0.030) in statin group | RCT |
| 382 days | Control (78) | 57.62±10.59 | · Lower rebleeding risk (HR, 0.858; 95% CI, 0.455–1.620, P=0.583) in statin group | ||||
| Kumar et al. [185] (2014) | Mixed (mainly HCV) | Biopsy-proven liver cirrhosis on statin therapy at biopsy and for ≥3 months after biopsy | 36 months | Statin (81) | 59.79±10.91 | · Lower mortality (HR, 0.53; 95% CI, 0.334–0.856; P=0.01) in statin group | Retrospective cohort study |
| 30 months | Control (162) | 59.64±10.60 | · Lowe risk of decompensation (HR, 0.58, 0.34–0.98; P=0.04) in statin group |
Variables are expressed as median (interquartile range) or mean±standard deviation.
NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; RCT, randomized controlled trial; OR, odds ratio; CI, confidence interval; DM, diabetes mellitus; NA, not available; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; NAS, NAFLD activity score; NHIS, National Health Interview Survey; ICD-10, International Classification of Diseases; HCC, hepatocellular carcinoma; HR, hazard ratio; RR, risk ratio; HBV, hepatitis B virus; HCV, hepatitis C virus; SVR, sustained viral response; HTN, hypertension; HVPG, hepatic venous pressure gradient; IQR, interquartile range.
*
These data are after matching.