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BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma (HCC) is a common situation. The only therapeutic options in France are two broad-spectrum tyrosine kinase inhibitors (TKIs), regorafenib (REG) and cabozantinib (CBZ), but no comparative real-life studies are available. AIM To evaluate the progression-free survival (PFS) of patients treated with REG or CBZ, we investigated the disease control rate (DCR), overall survival (OS), and safety of both drugs. To identify the variables associated with disease progression over time. METHODS A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers (Avignon, Marseille, and Nice) between January 2017 and March 2021 using propensity score matching. PFS and OS were assessed using the Kaplan-Meier method. Multivariate analysis (MA) of progression risk factors over time was performed in matched-pair groups. RESULTS Fifty-eight patients 68 (62-74) years old with HCC, Barcelona clinic liver cancer (BCLC) B/C (86%), Child-Pugh (CP)-A/B (24%) received REG for 3.4 (1.4-10.5) mo as second-line therapy. Twenty-eight patients 68 (60-73) years, BCLC B/C (75%), CP-A/B (25%) received CBZ for 3.7 (1.8-4.9) mo after first-line treatment with sorafenib [3 (2-4) (CBZ) vs 4 (2.9-11.8) mo (REG), P = 0.0226]. Twenty percent of patients received third-line therapy. After matching, PFS and DCR were not significantly different after a median follow-up of 6.2 (2.7-11.7) mo (REG) vs 5.2 (4-7.2) mo (CBZ), P = 0.6925. There was no difference in grade 3/4 toxicities, dose reductions, or interruptions. The OS of CP-A patients was 8.3 (5.2-24.8) vs 4.9 (1.6-11.7) mo (CP-B), P = 0.0468. The MA of risk factors for progression over time identified C-reactive protein (CRP) > 10 mg/L, neutrophil-to-lymphocyte ratio (NLR) > 3, and aspartate aminotransferase (AST) > 45 IU as predictive factors. CONCLUSION This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC. Elevated levels of inflammatory markers (CRP and NLR) and AST were associated with non-control of TKIs over time. A 2-mo online progression risk calculation is proposed.

Background and Aim: The prevalence and the role of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) remain unclear, as the literature provides heterogeneous information on the subject. The aim of this study was to determine the prevalence of SIBO in IBS and to assess the correlation between methane and hydrogen levels measured during breath tests and the severity of IBS. Method: Two-hundred and forty-seven patients with IBS were prospectively included. A glucose breath test (GBT) measured H 2 and CH 4 production to diagnose SIBO. A test was positive when H 2 values exceeded 12 ppm in the first 90 min and/or when a CH 4 value exceeded 10 ppm at any time. IBS severity (IBS-SSS), quality of life (GIQLI), and anxiety and depression (HAD) were assessed to investigate the correlation with H 2 and CH 4 production. Results: The prevalence of SIBO in IBS was 36.4% (9.7% with H 2 , 26.7% with CH 4 ). CH 4 levels were significantly higher in the predominantly constipated patients (P = 0.00), while H 2 levels were significantly higher within the diarrheal phenotype (P = 0.01). IBS severity was not correlated with either H 2 levels (r = 0.02; P = 0.84) or CH 4 levels (r = 0.05; P = 0.64). H 2 production was inversely correlated with the quality of life (r = À0.24; P = 0.03) and significantly correlated with the HAD scale (r = 0.22; P = 0.03). The pain and discomfort experienced during GBT was not correlated with methane levels (r = À0.09, P = 0.40), hydrogen levels (r = À0.01, P = 0.93), or sum of both (r = 0.06, P = 0.58), but significantly associated with IBS severity (r = 0.50, P <0.00). Conclusion: SIBO has a high prevalence in IBS but does not increase its severity. Individual susceptibility to pain may have a greater influence on the severity of IBS.

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