Hepatology Research最新文献

Aim: To assess whether non-invasive test cutoffs recommended in Western guidelines appropriately identify treatment-eligible fibrosis (F2-3) in Japanese patients with MASLD.

Methods: We analyzed Japanese patients with biopsy-proven MASLD who underwent FIB-4 screening, followed by VCTE or ELF testing. Patients with FIB-4 < 1.3 at age < 65 years or < 2.0 at age ≥ 65 years were excluded, leaving 838 patients in the VCTE cohort and 657 in the ELF cohort. Receiver operating characteristic (ROC) analyses were used to derive cohort-specific cutoffs.

Results: For predicting F2-4, a VCTE cutoff of 8 kPa yielded sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 83.7%/61.2%/80.2%/66.7%. For predicting F4, a VCTE cutoff of 15 kPa yielded 88.1%/76.8%/22.3%/98.8%. For ELF, a cutoff of 9.2 for predicting F2-4 yielded 94.7%/23.1%/66.5%/73.1%. For predicting F4, a ELF cutoff of 10.5 yielded 80.0%/58.4%/9.9%/98.1%. Using ROC-derived cutoffs (VCTE 9.5 and 15 kPa; ELF 10.3 and 10.8), the performance for predicting F2-4 was 74.0%/75.6%/85.1%/60.8% for VCTE and 66.2%/73.9%/80.6%/57.1% for ELF, whereas the performance for predicting F4 was 88.1%/76.8%/22.3%/98.8% for VCTE and 77.1%/69.8%/12.6%/98.2% for ELF. Among test-positive patients, the distribution of F0-1/F2-3/F4 was 28.7%/69.2%/2.1% for VCTE 8-15 kPa and 47.8%/49.8%/2.4% for ELF 9.2-10.5.

Conclusions: Western guideline-recommended VCTE and ELF cutoffs showed high sensitivity in Japanese patients and can be used to exclude cirrhosis. Because the likelihood of cirrhosis increases with VCTE > 15 kPa or ELF > 10.5, treatment eligibility should be determined in conjunction with other clinical information, and confirmatory assessment should be considered when appropriate.

Aim: The creatinine-to-cystatin C ratio (CCR) is considered a convenient surrogate marker for muscle mass, although its evidence in cirrhotic populations is limited. This study investigated the significance of CCR as a marker of sarcopenia in patients with cirrhosis.

Methods: Handgrip strength (HGS) and skeletal muscle mass index (SMI) were assessed in 195 patients with cirrhosis, divided into the sarcopenia (n = 70) and nonsarcopenia (n = 125) groups. Risk factors associated with sarcopenia were identified through multivariable logistic regression analyses.

Results: Sarcopenia was diagnosed in 70 out of 195 patients (35.9%). Patients with sarcopenia were significantly older, with lower body mass index (BMI), serum creatinine, and CCR, as well as higher albumin-bilirubin scores. Age ≥ 65 years, BMI < 25, and low CCR (< 0.63 in women, < 0.68 in men) were independently associated with sarcopenia on both univariable and multivariable analyses. The predictive accuracy of CCR for sarcopenia was comparable to that of a multivariable model combining age and BMI. On Kaplan-Meier analysis, overall survival was significantly lower in patients with low CCR (< 0.66) versus those with high CCR (≥ 0.66). Furthermore, HGS, SMI, and sarcopenia had comparable diagnostic value.

Conclusions: CCR is a simple, noninvasive biomarker for the diagnosis and prognosis of sarcopenia in patients with LC.

Background: Complications associated with the Fontan circulation have become evident in recent years. Fontan-associated liver disease (FALD) has attracted particular attention. However, many aspects of this condition including FALD-associated hepatocellular carcinoma (FALD-HCC) remain unclear.

Patients and methods: Since 2018, 12 liver resections for FALD-HCC were performed in 9 patients at our institution. These 12 procedures were reviewed, and 9 cases of primary HCC were compared with 216 cases of primary HCC resection performed during the same period in non-FALD patients in terms of short- and long-term outcomes.

Results: Among 12, nine were initial and three were recurrences. Approaches included open (n = 6), laparoscopic (n = 4), and robotic surgery (n = 2). Compared with non-FALD patients, FALD group was younger (37 vs. 69 years, p < 0.0001), had lower BMI (19.0 vs. 24.1, p = 0.0002) and showed advanced fibrosis/cirrhosis (F3-4) more frequently (p = 0.03). Intraoperative blood loss was greater in the FALD group (1695 vs. 520 mL, p = 0.0003). Factors associated with blood loss > 1000 mL included CVP > 12 mmHg, tumor size > 2 cm, tumor depth > 3 cm from the liver surface. Among nine patients under regular post-Fontan imaging surveillance, tumors tended to be smaller and blood loss lower. With a mean follow-up period of 32.1 months in the FALD group, recurrence-free survival did not differ between the groups.

Conclusion: Long-term outcomes seem comparable between FALD and non-FALD HCC. In particular, FALD-HCC ≤ 2 cm and close to the liver surface with CVP ≤ 12 mmHg could be potential candidates for surgical resection, including minimally invasive approaches. Post-Fontan surveillance may be crucial.

Aim: Among mass-forming (MF) type intrahepatic cholangiocarcinoma (ICC), approximately 20%-30% are hypervascular on imaging and are associated with improved prognosis. However, the molecular background based on gene expression of this entity remains unclear.

Methods: We retrospectively analyzed 109 patients with MF-type ICC resected at the National Cancer Center Hospital, Japan. Preoperative dynamic computed tomography (CT) images were available for 48 cases. Based on the late-arterial-phase enhancement area (EA) and the relative enhancement ratio (RER), 17 were classified as hypervascular ICC (H-ICC, EA ≥ 50%), 21 as hypovascular ICC (h-ICC, EA < 50%, RER ≥ 1), and 10 as nonvascular ICC (N-ICC, EA < 50%, RER < 1). We compared group-wise arterial vessel density (AVD), then profiled angiogenesis genes to identify a suitable immunohistochemical marker.

Results: The H-ICC group had a better prognosis than h-ICC (P = 0.024) and N-ICC (P = 0.002). H-ICC also had a higher AVD than other groups (P < 0.001). Among the angiogenesis-related genes, vascular endothelial growth factor A (VEGFA) exhibited the strongest correlation with EA (P = 0.012), and H-ICC exhibited higher VEGF positivity than other groups (P = 0.022). The survival and immunostaining profiles of h-ICC closely resembled those of N-ICC. ROC analysis revealed that a VEGF staining positivity of 70% was the optimal cut-off for identifying H-ICC.

Conclusions: H-ICC is characterized by hyperenhancement occupying ≥ 50% of the tumor area on dynamic CT, high AVD, and elevated VEGFA expression. These findings support a distinct clinicopathological subset identifiable by LAP enhancement and VEGF immunostaining.

Aim: Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, is a standard treatment for hormone receptor-positive and HER2-negative breast cancer. However, liver dysfunction induced by abemaciclib is a significant clinical issue.

Methods: We report three cases of drug induced liver injury caused by abemaciclib with characteristic liver atrophy. Case 1: A woman in her seventies developed acute liver failure 2 months after initiation of letrozole and abemaciclib for breast cancer and bone metastases. A contrast-enhanced CT (CECT) scan revealed liver atrophy accompanied by Chilaiditi syndrome. Despite steroid pulse therapy, she progressed to coma. Her liver failure improved, but she died due to worsening of the underlying disease. Case 2: A woman in her seventies developed liver dysfunction 2 months after initiation of anastrozole and abemaciclib to prevent recurrence. A CECT scan revealed liver atrophy and Chilaiditi syndrome. After admission, she progressed to acute liver failure and coma, and steroid pulse therapy was initiated. Hepatic encephalopathy improved with conservative treatment, and liver failure resolved with continued steroid administration. Case 3: A woman in her fifties. After breast cancer surgery, tamoxifen and abemaciclib were started as adjuvant therapy. Blood tests revealed liver dysfunction 2 months later. A CECT scan revealed liver atrophy and Chilaiditi syndrome, which improved with liver support therapy alone without progressing to liver failure.

Results and conclusion: This report is the first highlighting the imaging characteristics of rapid-onset hepatic atrophy associated with abemaciclib-induced liver injury. These findings may provide useful insights for distinguishing abemaciclib-induced liver injury from other etiologies.

Background: The recent reclassification of nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease reflects the central role of metabolic dysfunction in its pathogenesis. Obesity underlies metabolic perturbations; however, liver health risks are not exclusive to individuals with a higher BMI and some individuals with obesity have favorable metabolic health (MH). Thus far, there has been limited examination of liver health indicators among metabolically healthy and unhealthy phenotypes, which is the aim of this study.

Methods: A cross-sectional sample of 2040 middle- to older-aged adults were classified as metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy nonobese (MHNO), and metabolically unhealthy nonobese (MUNO), according to three MH definitions (MeigsA, MeigsB, and Wildman). Liver biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured, and the fatty liver index (FLI) was calculated. Crude and adjusted logistic regression models examined associations between liver function indicators and MH phenotypes.

Results: In fully adjusted models, higher FLI scores were consistently associated with lower likelihood of MHO and MHNO (odds ratios and 95% confidence intervals for MHO: 0.947 (0.934, 0.961) [MeigsA], 0.952 (0.938, 0.966) [MeigsB] and 0.945 (0.931, 0.959) [Wildman] and for MHNO: 0.957 (0.950, 0.964) [MeigsA], 0.950 (0.942, 0.958) [MeigsB] and 0.961 (0.955, 0.968) [Wildman] (all p < 0.001)). Higher ALT and GGT concentrations were inversely associated with MHO, and AST additionally with MHNO, in all models across the three definitions.

Conclusions: Liver function indicators are linked with MH status in middle- to older-aged adults.

Introduction: Recurrent hepatocellular carcinoma (HCC) after hepatectomy remains a major clinical challenge, necessitating effective prognostic stratification. The oncological resectability criteria recently proposed by the Japan Liver Cancer Association and the Japanese Society of Hepato-Biliary-Pancreatic Surgery have not yet been validated in recurrent settings. This study aimed to evaluate the prognostic utility of these criteria in patients with recurrent HCC after hepatectomy.

Methods: This retrospective study included 505 patients with recurrent HCC following initial hepatectomy. Patients were classified into three groups-resectable (R), borderline resectable 1 (BR1), and borderline resectable 2 (BR2)-based on the oncological resectability criteria. Post-recurrence survival was evaluated using the Kaplan-Meier method, and multivariate analysis was performed to identify clinical factors associated with post-recurrence survival.

Results: Among the 505 patients, 248 patients were classified as R, 80 as BR1, and 177 as BR2. The median post-recurrence survival was 73.4 months for the R group, 33.6 months for the BR1 group, and 12.4 months for the BR2 group (p < 0.001). Multivariate analysis identified BR1/BR2 classification (p < 0.001), modified albumin-bilirubin grade 2b or 3 (p < 0.001), and recurrence within 1 year (p = 0.004) as independent predictors of poor post-recurrence survival.

Conclusions: The oncological resectability criteria effectively stratified post-recurrence survival in patients with recurrent HCC. These findings suggest that a multidisciplinary approach may benefit patients with BR1 or BR2 recurrence. Further studies are warranted to explore optimal treatment strategies for recurrent HCC.