RESUMEN
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here we investigate the prognostic value of HVPG in compensated (cACLD) MASLD. METHODS: This European multicentre study included MASLD-cACLD patients characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: 340 MASLD-cACLD patients [56.2% men; age: 62 (55-68) years; MELD: 8 (7-9); 71.2% diabetes] were included. Clinically significant portal hypertension (CSPH; i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio, SHR:5.13; p<0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (aSHR per mmHg:1.12; p<0.001). Liver-related mortality occurred in 37 patients with a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (aSHR per mmHg:1.20; p<0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. While MASLD-cACLD patients without CSPH show a very low short-term risk of decompensation and liver-related mortality is rare, the presence of CSPH substantially increases both risks. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in MASLD-cACLD patients without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk-stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.
RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The landscape of the systemic treatment for advanced HCC is changing quickly, and recently, the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvalumab regimen. Nivolumab monotherapy has proven to be effective sometimes for advanced HCC and could be a valuable treatment option for patients outside current treatment indications and reimbursement criteria for the standard of care. This is a particular population of interest. AIM: To evaluate the real-world effectiveness of nivolumab monotherapy in patients with advanced HCC who are not eligible for other treatment. METHODS: We conducted a retrospective, multicentric study including 29 patients with advanced HCC from 3 Belgian tertiary hospitals. All patients had had prior chemotherapy or were intolerant or ineligible for treatments. All study subjects received nivolumab 3 mg/kg in monotherapy, administered once every two weeks intravenously. Treatment continued until disease progression, severe adverse events or death. Data were retrieved from patients' medical records. The outcome parameters such as radiological response according to response evaluation criteria in solid tumors (RECIST) criteria, the biological response through the evolution of the alpha-fetoprotein (AFP) level, and clinical response considering both the Child-Pugh (CP) score and the World Health Organization (WHO) performance status (PS) were reported. A safety profile was also reported. Statistical analysis was performed using the SPSS Statistics 27 statistical software package. RESULTS: The radiological overall response rate (defined as complete or partial response according to the immune RECIST and modified RECIST criteria) to nivolumab monotherapy was 24.1%. The biological overall response rate (defined as a decrease of ≥ 25% in AFP blood level) was 20.7%. Radiological and biological responses were significantly associated both with each other (P < 0.001) and with overall survival (P < 0.005 for radiological response and P < 0.001 for biological response). Overall survival was 14.5 mo (+/- 2.1), and progression-free survival was 10.9 mo (+/- 2.3). After 4 mo of treatment, 78.3% of patients remained clinically stable or even showed improvement in WHO PS. Grade 3 adverse events occurred in 17.2% of patients, none had grade 4 adverse events, and no patients ceased nivolumab due to adverse events. CONCLUSION: Nivolumab monotherapy is a good treatment choice in frail patients with HCC who are ineligible for the standard of care or other validated systemic treatments.
