Table 2.
Next step to address the top 10 research priorities based on current best evidence (summary)
| Treatment uncertainty (research question) | High-quality systematic review*† | RCTs not included in the systematic review*‡ | Patient-oriented outcomes assessed in trials not included in the systematic review§ | Next step |
| What is the best treatment for people with early or very early hepatocellular carcinoma (HCC)? | 13 | 8 trials | Survival (7 trials), recurrence (5 trials), morbidity (3 trials) | High-quality RCTs of interventions not covered in ongoing trials and comparison of health-related quality (HRQoL) in different treatments |
| What are the best treatments that cure or delay the progression (worsening) of primary sclerosing cholangitis (PSC)? | 14 | 9 trials | None of the trials include survival, HRQoL as outcomes¶ | High-quality RCTs with clinical outcomes (survival, HRQoL) |
| What are the best treatments that cure or delay the progression (worsening) of non-alcohol-related fatty liver disease (NAFLD)? | 15 (Includes only pharmacological interventions) | More than 10 published trials on lifestyle interventions and more than 20 trials on nutritional supplementation with no recent high-quality systematic reviews Pharmacological interventions 44 trials |
Lifestyle interventions and nutritional supplementation Not applicable as there are no high-quality systematic reviews Pharmacological interventions Health-related quality of life (2 trials), resolution of fatty liver disease (11 trials), mortality (2 trials), cirrhosis (2 trials), cardiovascular events (2 trials)¶ |
High-quality systematic reviews on lifestyle interventions (one review) and nutritional supplementation to cure or delay the progression of NAFLD and high-quality RCTs on pharmacological interventions with clinical outcomes (survival, HRQoL) |
| What is the best immunosuppressive regimen in adults undergoing liver transplantation? | 16 (Covers only maintenance immunosuppression) |
Induction immunosuppression: more than 20 published trials Maintenance immunosuppression 4 trials |
Induction immunosuppression Not applicable as there is no high-quality systematic review Maintenance immunosuppression Graft survival (1 trial) Adverse events (1 trial) Hepatocellular carcinoma (1 trial)¶ |
High-quality systematic review on induction immunosuppressive regimen and high-quality RCTs on maintenance immunosuppression with important clinical outcomes (overall survival, HRQoL) |
| Should general public be educated about NAFLD with an aim to reduce the numbers of those that have it? | None | None | - | High-quality RCTs on education to prevent NAFLD |
| What are the best treatments that cure or delay the progression (worsening) of autoimmune hepatitis? | None | 15 trials | Survival (1 trial), health-related quality of life (1 trial)¶ | High-quality RCTs with clinical outcomes (survival, HRQoL) |
| What are the best treatments that cure or delay the progression (worsening) of non-alcohol-related steatohepatitis (NASH)? | The evidence related to this question is covered under NAFLD by performing a subgroup analysis of people with NASH | |||
| Prior to liver transplantation, is it better to transport the donor liver using a machine which pumps blood or preservation solution through the liver (machine perfusion) or is it better to transport it in the standard way of transporting it immersed in cold preservation solution (cold storage)? | None | 5 trials | Overall survival (4 trials), graft survival (5 trials), health-related quality of life (2 trials) | Await results of the RCTs (all expected to complete by the end of 2019) and perform a high-quality systematic review |
| What are the best treatments that cure or delay the progression (worsening) of primary biliary cholangitis? | 17 | 24 trials | Health-related quality of life (5 trials), relief of symptoms (5 trials)¶ | High-quality RCTs with clinical outcomes (survival, HRQoL) |
| Are there any treatments that reverse the liver damage in PSC? | The evidence related to this question is covered under treatments for PSC. The systematic review did not include fibrosis as one of the outcomes. Nine of the trials included in the systematic review reported on fibrosis. Two of the trials not included in the systematic review (and listed above) reported on liver fibrosis | |||
*Numbers indicate the reference number.
†Further well-designed randomised controlled trials (RCTs) using clinical outcomes were recommended by all these systematic reviews.
‡Ongoing trials, unpublished trials or trials published since the search date for the systematic review when a high-quality systematic review based on RCTs exists. If no systematic reviews based on RCTs exist, these are either published trials or ongoing studies.
§This information is reported to find out whether the important patient-oriented outcomes are reported in the trials not covered by high-quality systematic reviews. This is to help with deciding whether new RCTs are necessary on the topic.
¶The remaining trials reported treatment-related adverse events, composite outcomes and surrogate markers.