CONCLUSIONS

Devan Kansagara; Joel Papak; Amirala S Pasha; Maya O'Neil; Michele Freeman; Rose Relevo; Ana Quinones; Makalapua Motu'apuaka; Janice H Jou

CONCLUSIONS

There 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 2

Summary of the evidence on screening for hepatocellular carcinoma in patients with chronic liver disease, and treatment in patients with early-stage hepatocellular carcinoma.

Publication Details

Copyright

Publisher

Department of Veterans Affairs (US), Washington (DC)

NLM Citation

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. CONCLUSIONS.

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.