Subtle Signs of Liver Cancer to Monitor Before It’s Too Late, Experts Advise

[Article déjà publié le 7
août 2025]

Long associated with viral hepatitis or chronic alcoholism, liver cancer today affects increasingly varied profiles. The rise of diabetes, obesity and “metabolic fatty liver” makes it a silent threat, which often progresses without symptoms or effective screening. This type of cancer is one of the deadliest, partly because it is discovered too late, when it is no longer operable. However, tools exist to prevent, detect and treat this complex disease.

The problem has as much to do with the biology of the tumor as with the organization of care. While therapeutic approaches are diversifying – immunotherapy, targeted radiotherapy, “nanomedicine” – inequalities in access to treatments persist. Understanding the causes, the warning signs, the emerging solutions and the persistent obstacles allows us to better understand the real issues of a cancer which continues to gain ground.

A discreet cancer, often spotted too late

Hepatocellular carcinoma (HCC), the main type of primary liver cancer, often progresses quietly. In patients suffering from cirrhosis or chronic liver disease – particularly due to hepatitis B or C – it can develop in an already damaged area, making its evolution all the more difficult to discern. Dr. Nathaniel Scher, Radiotherapist Oncologist at the Île de France Radiotherapy Center, HORG (Hartmann Oncology Radiotherapy Group), contacted by email, recalls that “ HCC often progresses silently. It is therefore rarely symptomatic at an early stage.” However, when they appear, certain clinical signs should attract attention. Namely: unexplained fatigue, pain in the right hypochondrium (under the ribs, on the right side of the abdomen), unintentional weight loss, jaundice (jaundice), even signs of hepatic decompensation in cirrhotics.

The major difficulty remains the too late diagnosis. Liver cancer is frequently discovered incidentally during an imaging assessment or at an advanced stage, when curative treatments are no longer possible. According to the Mayo Clinic, the majority of people with the condition have no symptoms in the early stages, and when they do occur, they are often nonspecific: loss of appetite, nausea, fatigue, or a swollen abdomen.

For patients identified as high risk, strict monitoring is required. “ An ultrasound every six months is recommended », insists Dr Scher, a strategy confirmed by international recommendations. This regular screening can reveal a small, operable tumor before it becomes symptomatic. However, at this early stage, the cure rate can exceed 70% after surgery or transplantation. The issue is therefore as much medical as organizational. It is based on the identification of the right profiles to monitor, and the rigor of monitoring over time.

A rapidly expanding metabolic cause: NASH

Nonalcoholic steatohepatitis (NASH), a severe form of fatty liver disease, is now a major — and growing — cause of liver cancer in industrialized countries. It results from an accumulation of fat in the liver cells, without excessive alcohol consumption, but in a context of metabolic overload. According to Dr. Nathaniel Scher, “
NASH is replacing viral hepatitis as the main cause of liver cancer “. This epidemiological shift is closely correlated with the explosion of obesity, type 2 diabetes and metabolic syndrome, particularly in North America and Europe.

The danger is insidious. Unlike viral or alcoholic forms, NASH can progress to hepatocellular carcinoma (HCC) without going through the cirrhosis stage. This makes screening particularly difficult, because patients do not always meet the usual surveillance criteria. However, according to the Canadian Cancer Society, this asymptomatic progression increases the risk of late diagnosis and incidental discovery at an advanced stage.

Faced with this complexity, new predictive tools are being developed. “Certain scores based on age, sex and platelet count help identify high-risk non-cirrhotic patients », specifies Dr Scher. These models make it possible to extend surveillance to previously excluded profiles. We thus integrate metabolic factors into the assessment of liver risk. This paradigm shift also requires broader awareness among caregivers and patients. Liver cancer is no longer just a disease of chronic drinkers or virus carriers. No, it can strike young, sedentary and overweight individuals — often without prior symptoms.

Towards targeted and personalized medicine

The management of liver cancer is undergoing a radical transformation. For what ? Thanks to targeted therapies, immunotherapy and new molecular biology technologies. Long limited to surgical treatments or conventional chemotherapy, the therapeutic spectrum is broadening. We now find strategies that are more personalized, better tolerated, and often more effective. As Dr. Nathaniel Scher points out, immunotherapy has become a pillar of systemic treatment of advanced hepatocellular carcinoma, particularly in patients ineligible for surgery or local ablation. By combining immunomodulatory antibodies with other molecules, it significantly improves overall survival. let us add that the side effects are less than with standard chemotherapy.

But the revolution is not limited to treatments. Diagnosis has long focused on imaging and conventional serum markers. Today it benefits from cutting-edge technologies. Innovative terbium-based sensors, developed by the Indian Institute of Science, make it possible, for example, to identify the presence of the enzyme β-glucuronidase, a biomarker associated with the early stages of liver cancer, using a simple disk of paper that fluoresces under UV light. Their low cost and ease of use open up interesting prospects for screening in areas with limited resources.

At the same time, the SLY fluorescent probe, developed in South Korea, makes it possible to precisely localize tumor cells thanks to the recognition of specific glycans overexpressed on cancer cells. Finally, research carried out at the University of Las Vegas is paving the way for the use of lipid nanoparticles capable of delivering mRNA to diseased liver cells via vitamin D receptors. This technology, still experimental, could one day transform the way we target the tumor at the cellular level, with unparalleled precision.

Prevention and inequalities

Although it remains formidable, liver cancer is not inevitable. In many cases, it can be prevented or diagnosed at a curable stage. Prevention is firstly based on the treatment of underlying diseases. Modern antiviral drugs now make it possible to control or even eradicate hepatitis B and C, the main historical causes of hepatocellular carcinoma. As Dr. Nathaniel Scher reminds us, “ several measures can effectively prevent this cancer “. Particularly among people already identified as at risk.

Certain lifestyle habits also have a protective effect. Stopping alcohol and tobacco, losing weight, eating a balanced diet and regular physical activity help slow the progression of chronic liver disease. More surprisingly, moderate coffee consumption is associated with a reduced risk of liver cancer, according to the National Institutes of Health (NIH). Medicinal avenues are also being studied. Metformin, used against diabetes, and statins, prescribed against cholesterol, could play a preventive role. However, the evidence remains to be consolidated.

Persistent challenges

Despite these levers, the French healthcare system faces several challenges. Too many at-risk patients, particularly those with NASH without cirrhosis, still escape screening. Delays between detection of a tumor and initiation of treatment may exceed recommended standards. Access to expert centers remains unequal depending on the region. In addition, the shortage of grafts limits the chances of access to a curative strategy.

Finally, sometimes fragmented coordination between the different players in the care pathway hampers the overall effectiveness of care. To reverse the trend, “Lhe key is identifying the right patients at the right time. And to offer them a structured, effective and rapid care pathway», insists Dr Nathaniel Scher. In this race against time, every month counts. Medicine now has the tools to better detect, treat and sometimes cure. The challenge remains collective.