I-Screening
I-Treatment | Include – screening
Include – treatment | | KQ1 –Benefits of screening:
1a. In which subgroups of patients with chronic liver disease have the effects of HCC screening on patient survival been evaluated?
1b. What are the effects of HCC screening on disease-specific and all-cause mortality in these patient subgroups?
1c. Are there particular HCC screening modalities that are more effective on patient survival than others?
KQ2 –Harms of screening:
2. What are the harms of HCC screening among patients with chronic liver disease? | KQ3 – What are the benefits and harms of treating early stage HCC? |
| I-SR | Include – systematic review | | Systematic review or meta-analysis that addresses any of the key questions. Code X9-SR for comparative effectiveness reviews of treatment modalities. |
| X1 | Non-English language | Most foreign language abstracts have been filtered out, but can be retrieved for further review as needed. | | |
| X2 | Not relevant to HCC | | | |
| X3 | Study population is not in scope for either screening or treatment KQs. | Exclude: Patients with prior, advanced, or metastatic HCC; in vitro studies. | Adults with chronic active viral hepatitis, alcohol-related liver disease, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis – all with or without cirrhosis. | Patients with early stage HCC, defined as patients with the equivalent of BCLC Stage A (3 or fewer nodules, <3cm, or 1 nodule <5 cm).
Milan criteria = early stage HCC.
Include studies for which at least a portion of the population is Stage A and B (these studies may be useful for addressing harms). |
| X4 | No primary data, or study design not in scope | Exclude: Non-systematic or narrative reviews, opinions, case studies, case series, quasi-experimental studies, or other excluded study designs. | Include studies that compare screened patients with unscreened patients, using any of the following study designs:
Observational studies, e.g., cohort or case-control designs Controlled studies, e.g., RCT, controlled clinical trial, controlled before/after designs.
Also include: active-controlled/head-to-head trials and observational studies that compare screening modalities or screening intervals.
For cost studies: include primary data collected in U.S. settings. Exclude modeling and simulation studies, and primary studies in non-U.S. settings. | Included study designs:
Randomized, placebo-controlled trials comparing a single treatment or combination of included treatment modalities vs no active treatment/placebo/active screening without treatment (analogous to watchful waiting); Observational studies of a single or combination treatment modality that: - -
include a comparison group of untreated HCC patients, and
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have a sample size ≥ 100 patients (treated plus untreated)
- -
adjust for potential confounders. Studies that do not examine the effects of potential confounders (age, sex, baseline liver disease) are excluded.
Specific exclusions for treatment studies:
Code X9 for head-to-head/active-controlled treatment trials;
X9-SR for comparative effectiveness reviews; add combo (e.g. X9-combo) to indicate multiple treatment modalities.
Use code X10 for observational studies include an untreated comparison group, and contain data on harms of treatment but sample size is <100 treated patients. |
| X5 | Modality used for screening or treatment is not in scope | Excluded screening modalities:
Biomarkers, thrombocytopenia, DNA/ RNA analyses.
Excluded treatment modalities:
Exclude percutaneous alcohol injection (no longer in use, and not in 2010 guidelines). Specify excluded treatments as they occur in the screening process. | Ultrasound, CT, MRI, and/or alpha-fetal protein screening for primary HCC. | Early stage/curative treatments include resection, transplant, radiofrequency ablation, transarterial chemoembolization, and sorafenib. |
| X6 | None of the reported outcomes are in scope | Exclude studies that do not report any of the outcomes of interest.
Exclude diagnostic accuracy studies. | Benefits:
Harms:
Psychological effects (eg, anxiety, stress, depression, labeling) Liver biopsy-related complications (eg, bleeding, infection) Renal insufficiency Overdiagnosis (ie, identifying cancers that would not have caused disease undetected)
• Cost – include primary data collected in U.S. settings. | Benefits:
Harms:
|
| X7 | Other reason: specify | Add comments or keywords as needed. | | |
| X9 | | Exclude head-to-head/active-controlled treatment trials.
Code X9-SR for systematic reviews/ meta-analyses on comparative effectiveness.
X9-combo, where applicable. | | |
| X10 | | Exclude relevant observational studies on treatments with sample size <100 treated patients (we may pull these later if low yield of studies with n≥100). | | |
| X11 | Duplicate publication | Exclude older publications or conference proceedings that have been subsequently published as full-text articles | | |
| Note: Excluded articles should each receive a single X code, according to the order listed. Articles coded for background (‘B’) should also receive an X code. |
| B | Background | Add ‘B’ any of the above X codes (e.g., ‘X6–B’) if the article contains information that may be useful for the introduction, discussion, limitations, future research, or other contextual purposes. Add comments or keywords as needed. | | |