Lenvatinib is a first-line standard treatment for advanced hepatocellular carcinoma (HCC) with better anti-tumor effects than sorafenib, as shown by greater inhibition of the kinases of fibroblast growth factor receptor and vascular endothelial growth factor (VEGF) receptor. This report describes a patient with advanced HCC who experienced perforation of the small intestine 1 month after starting the treatment with lenvatinib. This patient likely had partial necrosis of a metastasis to the small intestine before starting lenvatinib treatment, with subsequent ischemic changes leading to perforation of the small intestine. Although metastasis of HCC to the small intestine is rare, patients with these metastases should be regarded as being at risk for perforation during lenvatinib treatment.

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To evaluate the potential of drug-eluting bead (DEB)-transcatheter arterial chemoembolization (TACE) as a treatment option for patients with refractory to conventional lipiodol-based TACE (c-TACE) especially with decreased liver function. Patients and Methods: We retrospectively evaluated the treatment results of DEB-TACE for 89 HCC nodules in 27 patients with c-TACE refractory according to liver function. Results: Although overall survival was significantly better in Child-Pugh A patients than in Child-Pugh B patients (median survival time, MST: 561 vs 347 days, p=0.031), progressionfree survival was almost similar in both patients between Child-Pugh A and B (MST: 79 vs 87 days, p=0.534). Regarding antitumor response, the objective response rate (ORR) and disease-control rate (DCR) were 5.3/12.5% and 52.7/87.5% in Child-Pugh A/B, respectively. In each 89 HCC nodules, ORR and DCR were almost similar between Child-Pugh A and B (ORR, 20.3 vs 13.3%; DCR, 77.0 vs 73.3%, respectively). Adverse events of DEB-TACE were well-tolerated, and liver function was reserved during DEB-TACE procedures. Conclusion: DEB-TACE could be a therapeutic option for advanced HCC patients with c-TACE refractory and decreased liver function.

Hepatic encephalopathy is a major complication in patients with advanced cirrhosis and is associated with poor prognosis. To evaluate the effectiveness of l-carnitine supplementation in patients with overt hepatic encephalopathy (OHE), outcomes were retrospectively analyzed in patients with OHE who were treated with intravenous branchedchain amino acids (BCAA), with or without intravenous l-carnitine. Twenty-six patients were treated with intravenous BCAA in addition to conventional agents such as lactulose and non-absorbable antibiotics (Group A), and 19 patients were treated with these agents plus intravenous l-carnitine (Group L). Changes in blood ammonia concentrations, hepatic coma grade and the Glasgow Coma Scale (GCS) were compared in the two groups. Recurrence-free survival (RFS) was evaluated in the two groups and in patients who were and were not administered oral l-carnitine supplementation. At baseline, GCS scores were significantly lower and deterioration in liver function greater in Group L. After 3 d of intravenous l-carnitine, however, GCS showed a significantly greater improvement in Group L than in Group A. Blood ammonia levels improved stably over time in Group L. Overall survival and RFS were similar in Group L and Group A, but median RFS was significantly longer in patients who did than did not receive oral l-carnitine supplementation (735 versus 497 d, p50.03). Although these findings are preliminary, l-carnitine supplementation may be a therapeutic option for patients with OHE and disturbed consciousness.

Purpose The purpose of this study was to evaluate the effectiveness and tolerability of “on-demand” combination therapy with sorafenib and hepatic arterial treatments, such as transarterial chemoembolization and hepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma (HCC). Patients and methods Eighty consecutive patients with advanced HCC, 58 administered sorafenib monotherapy and 22 administered on-demand combination therapy, were retrospectively evaluated. Results The disease control rate was significantly higher in the combination group than in the monotherapy group (86.3% vs 51.7%, p =0.01). Elevated alanine aminotransferase levels were significantly more frequent in the combination group (40.9% vs 12.1%, p =0.01), but it was tolerable. Progression-free survival (180 vs 45 days, p =0.045) and overall survival (983 vs 452 days, p =0.004) were significantly longer in the combination group, as was the duration of sorafenib treatment (367 vs 66 days, p <0.001). Multivariate analysis showed that hepatitis C virus infection, disease control, and combination therapy were positive independent prognostic factors for survival, whereas alpha-fetoprotein >400 ng/mL was negatively prognostic. In patients receiving combination therapy, male sex, hepatitis B virus infection, performance status deterioration, Barcelona clinic liver cancer-B, and major vascular invasion were prognostic of survival. Conclusion On-demand combination therapy was tolerated and may be a therapeutic option for patients with advanced HCC.

Background and Aims Although patients with chronic liver disease (CLD) usually show few symptoms, they exhibit decreased health‐related QOL (HRQOL) with occurrence complications including hepatocellular carcinoma (HCC). Health‐related QOL is an important indicator in the management of CLD. The Chronic Liver Disease Questionnaire (CLDQ) was established as a tool for assessment of HRQOL. In this study, we evaluate its usefulness for the management of daily clinical practice. Methods Patients (N = 190, median age 70 years old) treated between 2016 and 2019 were registered and prospectively followed‐up with annual CLDQ. Associations of liver function and development of factors for admission or death were evaluated. Results Of the 190 patients registered, median age 70 years old, 140 were Child‐A, 121 were Fib‐4 index >2.67 and showed 80 HCC. All 6 domains including Systemic Symptoms (SS) were negatively correlated with Child‐Pugh score more than with albumin‐bilirubin score and Fib‐4 index. A hundred four admission events and 49 deaths were found during observation period, and median event‐free survival was 34.3 months. Treatment for HCC was the most frequent cause of admission, and 37 liver‐related deaths were found. Systemic Symptoms score 2 years after registration was decreased in both HCC‐ and non‐HCC cohort. Systemic Symptoms decreased and SS < 4 might be predictive for event occurrence. Conclusions CLDQ is useful to assess HRQOL in patients with CLD and is well correlated with liver function especially Child‐Pugh. Chronic Liver Disease Questionnaire might be useful to predict the prognosis of CLD and can be a tool of management in clinical practice.

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