Hepatocellular carcinoma in SA

Dr Leanne Prodehl unpacks the current standings of hepatocellular carcinoma (HCC) in SA.

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Hepatocellular carcinoma (HCC), more commonly known as liver cancer, is the sixth most common cancer and the third cause of cancer mortality globally. HCC is associated with a high mortality with mortality rates almost equivalent to incidence.

Risk factors of hepatocellular carcinoma

Hepatitis B, a virus, is transmitted vertically (mother to child), or horizontally through body fluids. In Sub-Saharan Africa (SSA), horizontal transmission usually occurs in childhood through play. 

Ten to 25% of people with chronic hepatitis B will develop HCC. Notable as more than 350 million people globally are infected and 80 to 90% are unaware of their diagnosis. The WHO has declared that hepatitis B should be eradicated by 2030.

Hepatitis C is similarly transmitted, but there are no vaccines. Antiviral treatment can cure more than 90% of patients, which decreases the HCC risk by up to 70%.

Metabolic dysfunction associated fatty liver disease (MDAFLD) is the fastest growing cause of HCC, and the most common liver disease globally. Up to one fifth of patients with MDAFLD will develop steatohepatitis and of those a quarter will develop cirrhosis. 

The risk factors for cirrhosis include increased age, higher BMI, Type 2 diabetes, hypertension, dyslipidaemia, and cardiovascular disease. The only treatment is intensive lifestyle modification such as weight loss. Treatments such as metformin should be discussed.

Alcohol and HCC is stronger when there is increased consumption; the association increases 10 times if cirrhosis is present. Alcohol-associated HCC has poorer outcomes, based on poor performance status and impaired liver function.

Aflatoxin B is a fungal toxin which infects maize and groundnuts. It’s predominant in SSA, Southeast Asia, and China.

HCC usually develops on the basis of chronic liver disease and cirrhosis with up to 8% of patients with hepatosteatosis developing HCC over time.

Treatment forhepatocellular carcinoma

Treatment is complex and best done through a multi-disciplinary team. When making decisions, the team looks at the number of lesions, their size, location, and underlying liver function.

Surgery is the only modality which offers a chance of cure. It’s often limited by the number and size of lesions or poor underlying liver function.

When patients can’t be resected but the disease is limited then local treatment is given. HCCs are primarily supplied by the hepatic artery, which allows treatment to be given directly to the tumour as well as decreasing the blood supply. This is done with a combination of embolization, chemotherapy, or radiation.

Local ablation involves applying heat, cold, or alcohol to the tumour. These treatments are limited by the size of the lesion. External radiation is also an option but is often reserved for palliation.

HCC is relatively resistant to traditional chemotherapy and until 2007 systemic treatment was limited. A targeted therapy drug changed the outcome for patients with advanced disease and was the best option until about 2017. There are now a number of agents available for systemic treatment. The treatment of choice is a combination of a targeted therapy drug and immunotherapy.

The best treatment is liver transplantation, treating both the tumour and the underlying liver. The number of patients who are appropriate for transplantation are also limited by the scarcity of organs.

It’s important to remember, that the majority of South Africans with HCC present at a late stage and treatment options are limited.

The SSA challenge

Hepatitis infection as a cause of HCC highlights global differences, with 85% of HCC secondary to viral hepatitis occurring in the global south. Most 

HCC occurs in low resource countries with SSA and East Asia accounting for 80% of cases. SSA also has the youngest patients with the median age at presentation being 45 vs 60 – 70 in higher income countries.

In SSA, hepatitis B is responsible for 40 to 55% of HCC and co-infection with HIV leads to faster progression of disease. Survival from HCC is poor in SSA, with overall survival 2.5 months vs six to 10 months elsewhere. This is related to late presentation, lack of surveillance programmes, and dearth of access to treatment. 

In high-income countries, 40% of patients present with early disease with a five-year survival of 70%. In low-income countries, 95% of patients present with advanced or terminal disease.

Prevention

The primary prevention is dependent on the eradication and amelioration of risk factors. One of the most effective mechanisms is universal hepatitis B vaccination. 

In Taiwan, where hepatitis B is endemic, the rate of HCC was decreased by 80% by the introduction of universal hepatitis B vaccination. Unfortunately, the rate of vaccination especially the birth dose is suboptimal particularly in SSA.

HCC was the legacy project for the International Hepato-Pancreato-Biliary Association meeting in Cape Town 2024. A declaration was issued with the following recommendations:

Introducing hepatitis B birth dose vaccination: To prevent mother-to-child transmission.

Enhancing hepatitis B vaccination coverage: Strengthening national immunisation programmes to achieve 90% coverage.

Improving linkages to care: Providing antiviral treatments for chronic hepatitis B and C.

Establishing screening programmes: Implementing early diagnosis and surveillance for at-risk populations.

Expanding treatment capacity: Increasing resources for systemic therapies and palliative care.

It’s important that SSA, which has one of the greatest burdens of viral liver disease, acknowledges viral hepatitis as a public health threat and responds to the 2016 WHO call for elimination. This will require capacity and infrastructure development while acknowledging the challenges of those living with hepatitis and HCC.

This article is brought to you by Eisai Pharmaceuticals Africa.

Header image by Freepik