MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis

Abstract

Background & aims: Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic livers remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort.

Methods: A total of 354 cases of MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018 were included in the study. Data were extracted from the meetings' databases and from the French Birth and Death Registry.

Results: Of HCC cases, 35% occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Patients without cirrhosis were older, had a greater tumor burden, but also better liver function than patients with cirrhosis. Patients without cirrhosis showed better overall survival than those with cirrhosis (p = 0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Patients without cirrhosis underwent surgery more frequently than patients with cirrhosis (41% vs. 11%, p <0.001), even in cases where the largest tumors were ≥5 cm (42% vs. 14%, p = 0.002) or there were four or more lesions (19% vs. 2%, p = 0.024). Among the patients (with/without cirrhosis) who underwent surgery, survival was not significantly different. The cirrhosis/no cirrhosis ratio remained stable over the study period.

Conclusions: In MASLD-related HCC, patients without cirrhosis account for 35% of cases and have poor prognostic factors (higher age and larger tumors) but also better liver function, resulting in more aggressive management of advanced tumors and better survival compared to patients with cirrhosis.

Impact and implications: The incidence of hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) is projected to increase by 47% to 130% by year 2030 with one-third of cases occurring in non-cirrhotic livers, making them inaccessible to screening and therefore more likely to be diagnosed at an advanced stage. Our study shows that survival in patients with MASLD-related HCC depends on age, tumor burden and underlying liver function and the preserved liver function of these non-cirrhotic patients allows them to be managed surgically. A better understanding of the pathophysiological processes driving HCC occurrence in patients with non-cirrhotic MASLD will help guide the screening and early management of these patients.

Keywords: NAFLD; hepatocarcinoma; steatotic liver disease; survival.

Graphical abstract

Fig. 1

Overall survival according to cirrhosis status. Statistical comparison between patients with and without cirrhosis was conducted using the log-rank test.

Fig. 2

Overall survival as a function of BCLC stages (A) and alpha-foetoprotein serum level (B). Statistical comparison between the groups was conducted using the log-rank test. BCLC, Barcelona Clinic Liver Cancer.

Fig. 3

Treatment modalities for HCC as a function of cirrhosis status (A), and as a function of both cirrhosis status and BCLC stages (B). Statistical comparisons between the groups were performed using the Mann-Whitney U test (for quantitative variables) or the Fisher’s exact test (for qualitative variables). BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; TARE, transarterial radioembolization.

Fig. 4

Treatment modalities for HCC as a function of cirrhosis status and the size of the largest lesion or the number of lesions. Statistical comparisons between the groups were performed using the Fisher’s exact test. (A) In cases where the largest lesion was ≥5 cm, surgery was performed in 42% of the patients without cirrhosis vs. 14% of those with cirrhosis (p = 0.002). In cases with largest lesion between 3–5 cm and those with largest lesion <3 cm, surgery was performed respectively in 54% vs. 17% (p = 0.002) and 47% vs. 6% (p <0.001). (B) In case of ≥4 lesions, surgery was performed in 19% of the patients without cirrhosis vs. 2% of those with cirrhosis (p = 0.024). Among patients with 2–3 lesions and those with one lesion, surgery was performed respectively in: 25% vs. 12% (p = 0.183) and 54% vs. 13% (p <0.001). BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; TARE, transarterial radioembolization.

Fig. 5

Trends in the number of MASLD-related hepatocellular carcinomas presented at the multidisciplinary liver tumor meetings (A) and in the cirrhosis/no cirrhosis ratio over the study period (B). In (B) the number of MASLD-related hepatocellular carcinomas is indicated with the dashed curve, and the blue line represents the regression line of the ratio cirrhosis/no cirrhosis. MASLD, metabolic dysfunction-associated steatotic liver disease.