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Kansagara D, Papak J, Pasha AS, et al. Screening for Hepatocellular Cancer in Chronic Liver Disease: A Systematic Review [Internet]. Washington (DC): Department of Veterans Affairs (US); 2014 Jan.
Screening for Hepatocellular Cancer in Chronic Liver Disease: A Systematic Review [Internet].
Show detailsThere is very low strength evidence from which to draw conclusions about the effects of HCC screening on mortality in high-risk patients with chronic liver disease. Screening tests can identify early stage HCC and patients who are selected for surgical treatment often have good long-term survival, but some treatments may be associated with substantial harm. Trials examining the balance of benefits and harms of HCC screening in patients with chronic liver disease should be considered.
Table 2Summary of the evidence on screening for hepatocellular carcinoma in patients with chronic liver disease, and treatment in patients with early-stage hepatocellular carcinoma
| Outcome | For each study design: N studies: N studies by liver disease etiology; N=combined number of participants | Findings | Strength of Evidence* | Comments | ||
|---|---|---|---|---|---|---|
| Effects of screening | ||||||
| Screening vs no screening | Mortality | 2 RCT: 2 HBV; N=19200 16 NRCS: 1 HBV; 3 HCV; 7 HBV/HCV; 5 HBV/HCV/EtOH; N =11340 | One high risk of bias trial of US, RR of death due to HCC, 0.63 (95% CI, 0.41-0.98) One unclear risk of bias trial of AFP, Incidence rate all-cause mortality/100 person-years: 1.83 vs 1.79, P = NS | Very low | Numerous methodologic issues in the trials including allocation concealment, outcome assessment, analytic problems, and selective outcome reporting limit conclusions. Methodologic issues in the observational studies including selection bias, as well as lead- and length-time bias similarly limit conclusions. Studies consistently found HCC diagnosed with screening was earlier stage, but impact on overall mortality unclear. Applicability to hepatitis C and alcoholic liver disease populations limited. | |
| Harms: needle track seeding | 1 Meta-analysis of 8 NCS; N=1340 1 NCS; N=3391 | Overall risk of seeding: 2.7% (95% CI, 1.8-4.0%) | Low | Range of seeding 0-5.8%, most recent study not in meta-analysis found risk of 0.12%. Applicability to current practice may be limited as liver biopsy not often used in diagnosis of HCC. | ||
| Harms: other | No studies | -- | No evidence | |||
| Shorter intervals vs longer intervals | Mortality | 2 RCT: 1 HCV/EtOH, 1 HBV/HCV; N=2022 | Shorter screening intervals (3-4 months) offered no advantage over longer intervals (6-12 months) | Moderate | One trial had unclear risk of bias. No evidence comparing 6- to 12-month intervals. | |
| Harms | NA | NA | ||||
| Effects of treatment of screen-detected or early-stage HCC compared to no treatment | ||||||
| TACE | Mortality | 3 RCT: 1 HBV, 2 EtOH; N=217 3 NRCS: 1 HBV, HCV; 1 HBV, EtOH; 1 HBV, HCV, EtOH; N=795 | No difference in 2 trials of EtOH patients. RR of death, 0.49 (95% CI, 0.29-0.81) in one trial of HBV patients. | Low (EtOH) Low (HBV) | Evidence base is limited by poor methods reporting in 2 trials and small sample size. Directness of evidence to screen-detected disease also limited. | |
| Harms | 3 RCT: 1 HBV; 2 EtOH; N=217 | Serious complications in 8-20% patients | Low | Serious complications included GI hemorrhage, treatment-related death, renal failure, and thrombosis. Studies included patients with both early and late-stage disease and applicability to those with early-stage disease is unclear. | ||
| RFA | Mortality | 4 NRCS: 1 HBV, HCV; 1 HBV, EtOH; 2 HBV, HCV, EtOH; N=965 2 NCS: 2 HBV/HCV; N=339 | 5-year survival 27-55% vs 0-30% | Very low | All non-randomized studies in which confounding by indication limits conclusions about impact on mortality | |
| Harms | 1 NRCS: 1 HBV, HCV, EtOH; N=170 2 NCS: 2 HBV/HCV; N=1249 | Serious complications in 1.8-9.9%; needle-track seeding in 3.2% | Low | Complications included peritoneal bleeding, hemothorax, and portal vein thrombosis. Information comes from one large cohort study focused only on needle-track seeding, and 2 small cohort studies. | ||
| OLT | Mortality | 1 NRCS: 1 HBV, HCV; N=278 3 NCS: 2 HBV/HCV, 1 NR; N=12,304 | 4-5 year survival, 53-73% vs 0-30% | Very low | All non-randomized studies in which confounding by indication limits conclusions about impact on mortality | |
| Harms | 0 | -- | No evidence | Poor reporting of harms in studies. | ||
| Resection | Mortality | 3 NRCS: 1 HBV, HCV; 1 HBV, EtOH; 1 NR; N=952 | 5-year survival, 33-75% vs 0-8.3% HR for death, 0.45 (95% CI,0.34-0.59) | Low | No direct evidence examining mortality. Data from one large, well-conducted observational study which did account for some important confounding factors, but was not able to control for patient comorbidities. | |
| Harms: perioperative mortality | 1 systematic review of 23 studies N=3366 | Perioperative mortality 4% | Low | Data up through 2004; applicability to current practice unclear. | ||
| Sorafenib | Mortality | 0 | -- | No evidence | No studies in patients with early-stage disease | |
| Harms | 0 | -- | ||||
Abbreviations: EtOH = ethanol; HBV = hepatitis B virus; HCV = hepatitis C virus; KQ = key question; NCS = non-comparative study; NR = not reported; NRCS = non-randomized comparative study; NS = not specified; RCT = randomized controlled trial; RR = relative risk
- *
GRADE classification: high = further research is very unlikely to change our confidence on the estimate of effect; moderate = further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low = further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low = any estimate of effect is very uncertain.
- CONCLUSIONS - Screening for Hepatocellular Cancer in Chronic Liver Disease: A Sy...CONCLUSIONS - Screening for Hepatocellular Cancer in Chronic Liver Disease: A Systematic Review
- 13796[uid] (1)Taxonomy
- INCLUSION/EXCLUSION CRITERIA - Screening for Hepatocellular Cancer in Chronic Li...INCLUSION/EXCLUSION CRITERIA - Screening for Hepatocellular Cancer in Chronic Liver Disease: A Systematic Review
- flagellar biosynthesis protein FlhF [Xanthomonas oryzae]flagellar biosynthesis protein FlhF [Xanthomonas oryzae]gi|499727958|ref|WP_011408692.1|Protein
- wingless, partial [Propylea dissecta]wingless, partial [Propylea dissecta]gi|1226775451|gb|ASQ15486.1|Protein
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