Hepatology Research最新文献

Aim: Refractory ascites from portal hypertension can be managed with regular large-volume paracentesis (LVP) or transjugular intrahepatic portosystemic shunt (TIPS). Large-volume paracentesis is clinically unsatisfactory and many patients are ineligible or relatively contraindicated for TIPS or Denver shunt. Proximal splenic artery embolization (PSAE) using coils or plugs reduces but does not completely stop splenic arterial inflow, differing from distal splenic artery embolization techniques. By reducing splenic arterial inflow, splenic vein outflow is also decreased, lowering portal pressure and thus treating refractory ascites.

Methods: In this institutional review board-approved single-center retrospective study, electronic medical records were reviewed to obtain demographics and baseline clinical and laboratory data, paracentesis data before and after PSAE, PSAE procedural details, and follow-up imaging up to 12 months post-PSAE. Mixed-effects models were used for statistical analysis.

Results: Ten patients with LVP-dependent ascites meeting inclusion criteria underwent PSAE for refractory ascites from 2017 to 2024. Prior to PSAE, four patients had TIPS, three had liver transplants, and the remaining three were neither TIPS nor transplant candidates. In the month before PSAE, patients averaged 3.8 ± 1.7 paracentesis sessions, draining a total of 20.84 ± 10.39 L of fluid monthly. Post-PSAE, the number of paracentesis sessions decreased to 2.1 ± 2.7, 1.0 ± 1.7, 0.4 ± 1.1, and 0.0 ± 0.0 at 1, 3, 6, and 12 months, respectively (p = 0.03). Corresponding ascitic volume drained decreased to 8.7 ± 10.3, 2.7 ± 6.4, 2.0 ± 5.4, and 0.0 ± 0.0 L (p = 0.01). Over the 12-month follow-up period, 6 of 10 patients became LVP-independent.

Conclusion: Proximal splenic artery embolization can improve refractory ascites in certain patients with portal hypertension, thus providing safe and effective treatment as an alternative to TIPS.

Aim: Some patients undergoing liver resection for hepatocellular carcinoma (HCC) have poor outcomes. Therefore, we aimed to propose a new resectability classification for patients with HCC.

Methods: We classified patients into three categories: resectable (R), borderline resectable (BR), and unresectable (UR). Patients (n = 409) who underwent hepatectomy for HCC were assigned to the non-UR (R and BR classes combined; n = 285) and UR-HCC classes (n = 68; training cohort). Patient characteristics in the BR-HCC and R-HCC groups were compared. The new criteria were tested in a validation cohort (n = 295).

Results: Of the 285 patients, 229 and 56 were classified into the R- and BR-HCC classes, respectively, using macrovascular invasion, tumor size, and future liver remnant/modified albumin-bilirubin scores. Patients with BR-HCC demonstrated significantly worse progression-free and overall survival (p < 0.0001 and p < 0.0001, respectively) than patients with R-HCC in the training cohort. Similar results were observed in the validation cohort. Multivariate analysis of the non-UR-HCC group in the training cohort revealed that the tumor number and BR-HCC were independent predictive factors for poor overall survival.

Conclusions: This classification can help select patients with BR-HCC for preoperative treatment before considering surgery.

Background: The aim of this study was to evaluate the newly established oncological criteria of resectability of hepatocellular carcinoma (HCC) for selecting suitable candidates for systemic and combination therapy.

Methods: The data of 156 consecutive HCC patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The patients were classified into three groups according to the novel oncological criteria for resectability (R, resectable; BR1, borderline resectable 1; and BR2, borderline resectable 2). The prognostic ability and clinical utility for selecting this population to receive combined use of multiple systemic sequential and locoregional therapy was then evaluated. Combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while systemic sequential therapy only and repeated locoregional treatment was defined as a single treatment procedure (STP).

Results: Patients classified as R and BR1 had significantly better overall survival (OS) compared with BR2 (R vs. BR2, p = 0.012; BR1 vs. BR2, p = 0.004). However, there was no significant difference between R and BR1 (p = 1.000), in spite of significantly worse oncological status in the BR1 patients. Following a R0 resection and MCT, the BR1 patients had significantly better OS compared with those receiving STP or no additional treatment (median OS, not reached vs. 25.2 months and 20.1 vs. 11.3 months, respectively; p = 0.034).

Conclusions: In patients with advanced HCC with intrahepatic target nodules the BR1 category is one of the favorable candidates for selecting those to be treated with MCT strategies.

Aim: The unique feature of Fontan circulation is elevated central venous pressure, which causes Fontan-associated liver disease (FALD). FALD is associated with a high incidence of hepatocellular carcinoma (HCC). Performing biopsies in patients with FALD is difficult as a result of warfarinization; gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), a noninvasive examination, is useful for characterizing liver disease and detecting HCC. However, few studies have reported the detailed features of Gd-EOB-DTPA MRI, and the association between these findings and prognosis. Thus, this study aimed to investigate the utility of Gd-EOB-DTPA MRI to predict HCC development in patients with FALD.

Methods: This study enrolled 44 patients with FALD (mean age 25 years) who underwent Gd-EOB-DTPA MRI. The hepatobiliary phase images were scored semiqualitatively, and the patients were classified into the mild (0-1 point) or severe group (≥2 points). The endpoint was HCC, and event-free survival was analyzed using Kaplan-Meier and log-rank tests.

Results: The severe group included 19 patients. During a mean follow-up of 58 months, HCC developed in six patients. Kaplan-Meier analysis revealed that patients in the severe group had a significantly poorer prognosis than those in the mild group (p = 0.0053). The Fibrosis-4 index and liver-to-spleen ratio of patients with HCC were moderate.

Conclusions: Gd-EOB-DTPA MRI can be used to classify disease severity and predict the prognosis of patients with FALD.

Aim: The role of the zinc fingers and homeoboxes family (ZHX1-3), transcriptional repressors, through their subcellular localization in hepatocellular carcinoma (HCC), is not fully understood. The present study aimed to examine the differential nuclear and cytoplasmic expression of ZHXs in HCC tissues.

Methods: Immunohistochemistry was utilized to detect the expression of ZHXs in 54 liver tissues from HCC (n = 33), hepatitis C (n = 16), and the normal liver tissue surrounding hepatic metastasis of colorectal cancer (n = 5). Next-generation sequencing and digital polymerase chain reaction identified gene mutations associated with HCC. Kaplan-Meier curves were constructed to evaluate the relationship between ZHX expression and survival. The results were validated using data from The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were undertaken to identify independent prognostic factors.

Results: High nuclear expression of ZHX1 was associated with poor overall survival (OS), while high nuclear expression of ZHX2 correlated with higher recurrence. Conversely, patients with high cytoplasmic expression of ZHX3 had lower recurrence and better OS. Hepatitis B virus-associated HCC was related to high cytoplasmic expression of ZHX1, which was marginally related to telomerase reverse transcriptase (TERT) promoter mutation-negative HCC. In contrast, low nuclear expression of ZHX3 was associated with TERT promoter mutation-positive HCC and HCC patients over 70 years old.

Conclusions: These results suggest that the expression and localization of different ZHXs may be related to HCC progression, potentially inferring genetic backgrounds such as TERT promoter mutation. Further studies on the relationship between HCC and ZHXs will enhance our understanding and control of HCC.

Aim: Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment.

Methods: Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed.

Results: Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p = 0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders.

Conclusion: Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.