Professor El-Omar has selected Dr Abid Suddle, Consultant Hepatologist and Transplant Physician, Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, UK to do the next #GUTBlog. Dr Suddle is the first author on this guideline.

The #GUTBlog focusses on the guideline “British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults” which was published in paper copy in GUT in August 2024.

Dr Suddle writes:

“The British Society of Gastroenterology commissioned an update on the guidelines for management of Hepatocellular Carcinoma (HCC) at an opportune juncture. The incidence of and mortality from this cancer is increasing in the United Kingdom, as in other Western nations. Several significant clinical and scientific advances in HCC been made in the last decade. We have many more treatment options than previously, including an increasing repertoire of systemic therapies for those with advanced disease (a group in whom prognosis was previously limited). However, survival after diagnosis of HCC remains suboptimal; with a 5-year survival rate of less than 15%.

I was delighted to be joined by a group of multi-disciplinary and multi-professional national experts to write these guidelines. In making it distinct from the other excellent international guidelines available, we endeavoured to make the content as relevant as possible to the practising professional in the United Kingdom, whilst avoiding being too parochial. The treatment regimens recommended align with those that have regulatory approval for use in the National Health Service. Much of the content of the guideline will have broad relevance.

As in other Western nations, the majority of cases of HCC occur in patients with underlying cirrhosis. The main causes for cirrhosis in the United Kingdom are alcohol related (ARLD) and metabolic dysfunction syndrome related liver disease (MASLD). There is growing literature demonstrating a substantial risk of developing HCC in the context of non cirrhotic MASLD. Chronic liver disease as a consequence of viral hepatitis remains important. Additional risk factors include male sex and increasing age. As with chronic liver disease, HCC incidence is linked to deprivation and ethnicity.

The causal association between chronic liver disease and HCC, and the identification of key risk factors, indicate that HCC should be preventable in a significant portion of patients, at least in principle. It is hoped in the future that national policies will address this and encourage healthy lifestyles to minimise risks of obesity and metabolic syndrome, as well as preventing transmission of viral hepatitis and reducing alcohol misuse. The role for effective antiviral therapy in patients with chronic hepatitis B and hepatitis C infection is established in primary and secondary prevention. There is early and exciting data to suggest a role for immunotherapy based systemic therapy in reducing recurrence of HCC after potentially curative treatment, including surgical resection and thermal ablation. The IM Brave 150 clinical trial provided a promising signal, but further data is required.

We have recommended surveillance for HCC in patients with cirrhosis and certainly subgroups of patients with chronic hepatitis B infection with 6 monthly ultrasound scan and alpha-fetoprotein estimation. On the basis of current data, we cannot recommend surveillance in non- cirrhotic MASLD patients. The importance of discussing the purpose and aims of surveillance, as well as the harms, with each individual patient are emphasised. Surveillance should be restricted to those suitable for anticancer treatment if HCC was diagnosed. The performance of ultrasound and alpha-fetoprotein in identifying early-stage HCC is suboptimal. We discuss the use of imaging techniques such as abbreviated MRI, but further data is required before this can be recommended. The potential role for emerging tools such as blood-based biomarker panels and liquid biopsy are also outlined.

Contrast enhanced axial imaging studies remain the main investigations to diagnose HCC. Both CT and MR can be recommended, each technique has its advantages and disadvantages; and often the choice made will be dependent on institutional experience and patient characteristics. Contrast enhanced ultrasound does have a role, especially in the characterisation of a specific liver lesion. Axial imaging is preferred as the initial investigation due to imaging of the whole liver. The vascular phase characteristics of HCC in a cirrhotic liver are well characterised, but not always fulfilled especially with smaller lesions. Biopsy is required if HCC is suspected in a noncirrhotic liver or if non-invasive criteria are not fulfilled in a cirrhotic liver. The LI-RADS system may help to standardise reporting of imaging studies and help guide further management.

Our recommended treatment algorithm (Figure 1 in the Guideline) differs from that suggested by the Barcelona Cancer Liver Clinic. If the patient has decompensated cirrhosis, the only treatment option that will be associated with survival benefit is liver transplantation. The key question in these patients is if staging of HCC is within accepted criteria for transplant. If not, an understanding of the scope for recompensation of liver function needs to be made, as well as early referral to the palliative care services. In the context of compensated cirrhosis, with good performance status, there are potentially multiple treatment options available. The importance of case discussion within a specialist multidisciplinary team meeting is emphasised. Liver transplant remains the truly ‘curative’ treatment option, although not a panacea, and should be considered in all within accepted criteria. In the case of small solitary HCCs, those 2 cm or less in diameter, resection or ablation should be considered as first-line therapy. These are complimentary rather than directly competitive treatments based upon factors such as liver function and anatomic location tumour. For multinodular HCC beyond transplant criteria, intra-arterial embolic therapy remains a first line treatment. However, optimal results are achieved in patients with relatively limited tumour burden. Systemic treatment may be more suitable for those with large volume bilobar disease. Systemic treatment is definitively the first line therapy for advanced stage HCC. The recommended first, second and potentially third line treatments are outlined in figure 2. Currently, it is difficult to define the place newer treatments such as selective internal radiation therapy and stereotactic radiotherapy should have in the overall treatment algorithm. We do make recommendations, discussion within the MDT is again key. All patients with advanced stage HCC should have early referral to the palliative care services.

The final message in the guidelines, that HCC remains a scourge and a tragedy, may come across as unnecessarily pessimistic but hopefully will act as a call to arms for all those involved in the management of patients. Recent work done by the British Liver Trust in representing patients at the National level has been hugely helpful. Without doubt, it is an exciting time to be involved in the management of HCC, and I would recommend all trainee doctors with an interest in Hepatology consider HCC as a subspecialism.”