Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide.

AIM: An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels. METHODS: Patients were treated with TAF monotherapy for 96 weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1 log IU/mL from baseline) were evaluated. RESULTS: The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7 log IU/mL. The median change in HBcrAg from baseline was -1.1 log IU/mL at 96 weeks after treatment. The HBcrAg response rate at 96 weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96 weeks of treatment (p = 4.53 × 10-6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy. CONCLUSIONS: In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment.

Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study.

AIM: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy. METHODS: This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy. RESULTS: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. CONCLUSIONS: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis.

Impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of lenvatinib in patients with hepatocellular carcinoma.

This prospective study examined the impact of genetic polymorphisms on the pharmacokinetics and clinical efficacy and safety of lenvatinib, a substrate of ATP-binding transporters, in a cohort of 48 Japanese patients with hepatocellular carcinoma (HCC). Pharmacokinetic studies were performed at the start of lenvatinib therapy (day 1) and on day 15. The coefficients of variation in AUC0-24h of lenvatinib on days 1 and 15 were 44.0% and 52.4%, respectively. Although the ABCB1 3435C > A, 1236C > T, and 2677G>T/A polymorphisms did not influence pharmacokinetic parameters, the AUC0-24h values on days 1 and 15 of the ABCG2 C/A or A/A group were approximately 1.1-fold and 1.4-fold that in the ABCG2 C/C group (P = 0.164 and 0.024). There were no significant differences in AUC0-24h on days 1 and 15 between the responders (complete or partial response) and non-responders (stable or progressive disease). The AUC0-24h on day 15 in those developing anorexia of any grade was significantly higher than that without such development (P = 0.017). In multivariate analysis, ABCG2 421C > A C/A or A/A was significantly associated with the development of anorexia (odds ratio 9.009, P = 0.009). ABCG2 421C > A polymorphism could affect exposure to lenvatinib and the development of anorexia.

Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis.

AIM: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.

Marked heterogeneity in the diagnosis of compensated cirrhosis of patients with chronic hepatitis C virus infection in a real-world setting: A large, multicenter study from Japan.

BACKGROUND AND AIM: The presence of cirrhosis is an important factor for the management of patients with hepatitis C virus (HCV) infection and it determines the duration of treatment for HCV with the direct-acting antiviral (DAA) regimen of glecaprevir (GLE) and pibrentasvir (PIB), that is, 8 or 12 weeks, if patients do not have a history of DAA failure. However, in real-world settings, determination of cirrhosis depends on the discretion of the attending hepatologists, and it is unclear whether compensated cirrhosis was homogenously diagnosed or not. In this study, we investigated the real-world diagnosis of cirrhosis by characterizing DAA-naïve patients who underwent a 12-week GLE/PIB regimen in whom cirrhosis was diagnosed, comparing their characteristics with those of patients who underwent an 8-week regimen in whom cirrhosis was absent. METHODS: In a large, multicenter cohort study, we compared background characteristics and treatment outcomes among DAA-naïve patients who underwent an 8-week versus a 12-week GLE/PIB regimen. RESULTS: Among 977 patients enrolled, 296 (30.3%) were determined to have cirrhosis and underwent a 12-week regimen. Some patient characteristics largely overlapped between the two groups, including liver fibrosis indices. Sustained viral response rates were similar between groups after adjusting liver fibrosis index with propensity score matching. CONCLUSION: Although adequately diagnosed, the determination of cirrhosis varied widely among institutions or by hepatologists in real-world settings, and the severity of liver fibrosis overlapped significantly between patients in whom compensated cirrhosis was determined to be present and patients in whom cirrhosis was absent. Virologic efficacy was similar after adjusting for the degree of liver fibrosis.

Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema.

BACKGROUND AND AIM: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS: Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.

Real-world experience of 12-week direct-acting antiviral regimen of glecaprevir and pibrentasvir in patients with chronic hepatitis C virus infection.

BACKGROUND: In clinical trials, a pangenotype direct-acting antiviral (DAA) regimen consisting of glecaprevir (GLE) and pibrentasvir (PIB) exhibited high virologic efficacy and tolerability in patients with hepatitis C virus (HCV) infection. This study sought to confirm these findings in real-world settings, focusing on patients with cirrhosis, history of DAA failure, or HCV genotype 3 who were treated with a 12-week regimen in a large multicenter study from Japan. METHODS: In a nationwide multicenter prospective cohort study, we analyzed background characteristics, tolerability, and treatment outcome of patients who underwent a 12-week GLE/PIB regimen. RESULTS: Of 1190 patients, 509 (42.8%) underwent the 12-week regimen, and the remaining patients underwent an 8-week regimen. The rate of sustained virologic response (SVR) of patients treated with the 12-week regimen was 99.0%, comparable with that of patients treated with the 8-week regimen. The adverse events were observed in 29.1% of patients. The main adverse event was pruritus, which was observed in 14.7%. Ten patients (2.0%) discontinued therapy during treatment period. CONCLUSION: The 12-week GLE/PIB regimen was well-tolerated with high virologic efficacy in patients with cirrhosis, experience of DAA, or HCV genotype 3; tolerability and SVR rate were comparable with those of DAA-naïve, non-cirrhotic, non-genotype 3 patients who underwent 8-week regimen.

Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan.

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

Plasma concentration and efficacy of tolvaptan in cirrhotic patients with refractory ascites.

To investigate the relationship between the exposure and efficacy of tolvaptan, we measured pharmacokinetics of total drug at 7 days after repeated doses of 3.75 mg/day tolvaptan in 16 patients with hepatic edema. Nine patients (56.3%) were responders, which were defined as those with body weight reduction of >1.5 kg/week. Serum albumin levels were significantly lower in responders than in non-responders (P = 0.031). However, the pharmacokinetics varied greatly among individuals and was not relevant to the clinical response.

Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study.

PURPOSE: To evaluate safety and efficacy of combining sorafenib with transarterial chemoembolization in patients with advanced stage hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Systemic chemotherapy-naïve patients with a Child-Pugh class A liver profile and advanced stage HCCs were enrolled. Sorafenib therapy (daily dose 800 mg) was initiated within 4 weeks after initial conventional transarterial chemoembolization with an allowance of subsequent on-demand conventional chemoembolization. The primary endpoint was rate of protocol treatment completion, which was defined as sorafenib administration for at least 2 months. Secondary endpoints included objective response rate, disease control rate, overall survival, progression-free survival, and incidence of adverse events. Thirty-one patients (24 men, 7 women; median age, 75 years; vascular invasion, n = 19; extrahepatic metastases, n = 18; both, n = 6) who met the inclusion criteria were enrolled. RESULTS: Protocol treatment was completed in 28 patients (90.3%, 28/31) with median protocol treatment duration of 7.0 months (range, 0.5-30 months) and median of 2 (range, 1-4) transarterial chemoembolization sessions. Objective response rate was 77.4% with median overall and progression-free survival of 17.3 months (95% confidence interval, 11.9-22.6 months) and 5.4 months (95% confidence interval, 4.6-6.2 months), respectively. The most common grade 3 or 4 adverse events were self-limiting elevation of aspartate aminotransferase (54.8%, 17/31) and alanine aminotransferase (45.2%, 14/31). CONCLUSIONS: This combination therapy is feasible and promising in patients with advanced stage HCCs.

Spleen-derived lipocalin-2 in the portal vein regulates Kupffer cells activation and attenuates the development of liver fibrosis in mice.

The liver has an immune tolerance against gut-derived products from the portal vein (PV). A disruption of the gut-liver axis leads to liver injury and fibrosis. The spleen is connected to the PV and regulates immune functions. However, possible splenic effects on liver fibrosis development are unclear. Lipocalin-2 (Lcn2) is an antimicrobial protein that regulates macrophage activation. To clarify the role of the spleen in liver fibrosis development, we induced liver fibrosis in mice after splenectomy, and investigated liver fibrosis development. Liver fibrosis resulted in significantly increased splenic Lcn2 levels, but all other measured cytokine levels were unchanged. Splenectomized mice showed enhanced liver fibrosis and inflammation accompanied by significantly decreased Lcn2 levels in PV. Lipopolysaccharide-stimulated primary Kupffer cells, resident liver macrophages, which were treated with recombinant Lcn2 (rLcn2) produced less tumor necrosis factor-α and Ccl2 and the activation of hepatic stellate cells, the effector cells for collagen production in the liver, was suppressed by co-culture with rLcn2-treated Kupffer cells. In addition, the involvement of gut-derived products in splenectomized mice was evaluated by gut sterilization. Interestingly, gut sterilization blocked the effect of splenectomy on liver fibrosis development. In conclusion, spleen deficiency accelerated liver fibrosis development and decreased PV Lcn2 levels. The mechanism of splenic protection against liver fibrosis development may involve the splenic Lcn2, triggered by gut-derived products that enter the liver through the PV, regulates Kupffer cells activated by the gut-liver axis. Thus, the splenic Lcn2 may have an important role in regulating the immune tolerance of the liver in liver fibrosis development.

Use of finger-piece method for indocyanine green clearance test.

AIM: The indocyanine green (ICG) finger-piece method (FPM), which allows measurement of the ICG concentration by mounting a light sensor onto a finger, is used to assess liver function. We compared the ICG FPM with the conventional ICG blood sampling method (BSM) in patients with liver disorders. METHODS: Ninety consecutive patients simultaneously underwent the ICG BSM and ICG FPM. After ICG administration, blood samples were collected at 5, 10, and 15 min for the ICG BSM. The ICG concentration was measured through the finger piece by an ICG clearance meter. RESULTS: Seventy-one patients (78.9%) had Child-Pugh class A liver disease, and 19 (21.1%) had class B or C. The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values (r = 0.886, P < 0.001). Bland-Altman analysis showed good agreement between the two methods (mean difference, 0.012 ± 0.018). The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values both in patients with Child-Pugh class A liver disease (r = 0.821, P < 0.001) and class B or C liver disease (r = 0.859, P < 0.001). CONCLUSION: The ICG FPM may be an alternative to the ICG BSM for liver function assessment.

Radiofrequency ablation combined with chemolipiodolization in a porcine liver: Comparison of the pharmacokinetic analysis with cisplatin powder and miriplatin.

AIM: To compare the pharmacokinetics of radiofrequency (RF) ablation with chemolipiodolization using cisplatin (CDDP) powder and miriplatin (MPT) in a porcine liver. METHODS: Twelve pigs were divided equally into four groups. After each CDDP powder-lipiodol suspension (n = 6; groups A and B) or MPT-lipiodol suspension (n = 6; groups C and D) was injected into the lateral left artery, one RF ablation was performed at the lateral left lobe of each pig. Six pigs (groups A and C) were killed on the same day as treatment, whereas the other pigs (groups B and D) were killed 7 days after the treatment. The platinum concentrations in venous blood were assayed at 15, 60 and 120 min, and 7 days after treatment. The platinum concentrations in the ablated area and the surrounding liver were also examined. RESULTS: Plasma platinum concentrations of the CDDP group peaked at 15 min, and then gradually diminished over time (µg units), while plasma platinum levels in the MPT group gradually increased over time (ng units). Liver tissue platinum concentrations of the CDDP group were significantly lower in non-ablative areas than in ablated areas at days 0 and 7, while liver concentrations of the MPT group were significantly higher in non-ablative areas than in ablated areas at day 7. CONCLUSION: MPT may be a suitable chemotherapeutic agent to stagnate platinum in the surrounding liver.

ALBI score predicts morphological changes in esophageal varices following direct-acting antiviral-induced sustained virological response in patients with liver cirrhosis.

BACKGROUND: This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis. METHODS: A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy. RESULTS: This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices. CONCLUSIONS: Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices.

Liver function test by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging with consideration of intrahepatic regional differences.

BACKGROUND/AIMS: To accurately quantify liver function using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MR imaging. METHODOLOGY: A total of 105 patients with suspicion of a hepatic tumor (Child­Pugh scores: 5 in 56, 6 in 26, 7 in 20, and 8 in 3) who underwent Gd-EOB-DTPA-enhanced MR imaging and an indocyanine green retention rate at 15 min (ICG-R15) evaluation were retrospectively analyzed. The hepatobiliary images were taken at 20 min after Gd-EOB-DTPA injection. The quantitative liver­spleen contrast ratio (Q-LSC) was measured by calculating the signal intensity of the spleen and 12 intrahepatic points consisting of each central zone (near the porta hepatis) and peripheral zone (near the subcapsular zone) in the two main liver lobes. RESULTS: Each averaged Q-LSC of six points in the central zone or right lobe was significantly higher than that in the peripheral zone or left lobe regardless of hepatic function. The mean Q-LSC of the 12 points was significantly correlated with the ICG-R15 and significantly decreased with elevation of the Child­Pugh score. CONCLUSIONS: The hepatic enhancement by Gd-EOB-DTPA is influenced by zonal and lobar differences. This method with consideration of regional differences is valid for estimation of liver function by Gd-EOB-DTPA-enhanced MR imaging.

Mixed neuroendocrine carcinoma and hepatocellular carcinoma in the liver.

BACKGROUND: Mixed neuroendocrine carcinoma (NEC) and hepatocellular carcinoma (HCC) is extremely rare, thus radiological features have not been fully clarified. CASE: A male patient (age: 70 years) visited our hospital due to a tumor in the liver. Examination using contrast-enhanced computed tomography (CT) revealed a tumor (diameter: 5.0 cm) in hepatic segment 5, with early enhancement of the peripheral area and slight internal heterogeneous enhancement in the arterial and delayed phases, respectively. F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT revealed intratumoral heterogeneity, characterized by increased uptake (standardized uptake value, 12.10) in the corresponding low-density area detected using enhanced CT relative to the surrounding areas of the tumor. On magnetic resonance imaging, diffusion-weighted imaging also showed high intensity in the corresponding low-density area detected using CT. Preoperatively, the patient was diagnosed with HCC and underwent anterior sectionectomy. Pathological findings revealed both HCC and NEC components, and the patient was diagnosed with mixed NEC and HCC. Comparison of component distribution with FDG-PET/CT revealed an increased uptake area was congruent with the NEC component in the tumor. CONCLUSION: In this case, the difference in tumor components affected the uptake in FDG-PET/CT. Such heterogeneous uptake with an enhanced spot may be useful for suspecting the presence of mixed NEC and HCC in patients with atypical HCC.

Endobronchial Watanabe Spigot Placement for Hepatic Abscess and Bronchobiliary Fistula Following Radiofrequency Ablation for Hepatocellular Carcinoma.

A bronchobiliary fistula (BBF) is an uncommon but severe complication after radiofrequency ablation (RFA). However, the definitive salvage methods are controversial. We herein report a patient with hepatocellular carcinoma with hepatic abscess and BBF following RFA. We also review previous reports of BBF after RFA. The patient was a man in his 70s who underwent RFA for recurrent hepatocellular carcinoma in the subphrenic area. Despite percutaneous transhepatic abscess drainage, bilioptysis persisted. Finally, the BBF was occluded with an endobronchial Watanabe spigot under fiber-optic bronchoscopy. Placing an endobronchial Watanabe spigot should be considered as a salvage therapy for refractory BBF following RFA.

L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy.

Lenvatinib is an oral tyrosine kinase inhibitor that acts on multiple receptors involved in angiogenesis. Lenvatinib is a standard agent for the treatment of several types of advanced cancers; however, it frequently causes muscle-related adverse reactions. Our previous study revealed that lenvatinib treatment reduced carnitine content and the expression of carnitine-related and oxidative phosphorylation (OXPHOS) proteins in the skeletal muscle of rats. Therefore, this study aimed to evaluate the effects of L-carnitine on myotoxic and anti-angiogenic actions of lenvatinib. Co-administration of L-carnitine in rats treated with lenvatinib for 2 weeks completely prevented the decrease in carnitine content and expression levels of carnitine-related and OXPHOS proteins, including carnitine/organic cation transporter 2, in the skeletal muscle. Moreover, L-carnitine counteracted lenvatinib-induced protein synthesis inhibition, mitochondrial dysfunction, and cell toxicity in C2C12 myocytes. In contrast, L-carnitine had no influence on either lenvatinib-induced inhibition of vascular endothelial growth factor receptor 2 phosphorylation in human umbilical vein endothelial cells or angiogenesis in endothelial tube formation and mouse aortic ring assays. These results suggest that L-carnitine supplementation could prevent lenvatinib-induced muscle toxicity without diminishing its antineoplastic activity, although further clinical studies are needed to validate these findings.

The Impact of Partial Splenic Embolization on Portal Hypertensive Gastropathy in Cirrhotic Patients with Portal Hypertension.

This study investigated the impact of partial splenic embolization (PSE) on portal hypertensive gastropathy (PHG). We retrospectively analyzed endoscopic findings and the portal venous system of 31 cirrhotic patients with PHG. The improved group was defined as the amelioration of PHG findings using the McCormack classification. Child-Pugh scores of the improved group (18 of 31 patients) were significantly lower compared with those of the non-improved group (p = 0.018). The changes in the diameters of the portal trunk and those of the spleno-portal junction and spleen hilum in the splenic vein of the improved group were significantly larger than those of the non-improved group (p = 0.007, p = 0.025, and p = 0.003, respectively). The changes in the diameters of the portal vein and splenic hilum of the splenic vein showed significant correlations with Child-Pugh score (r = 0.386, p = 0.039; r = 0.510, p = 0.004). In a multivariate analysis of baseline factors related to the improved group, Child-Pugh grade A was significantly associated with the improvement of PHG (odds ratio 6.875, p = 0.033). PSE could be useful for PHG, especially in patients with Child-Pugh grade A, at least in the short term.

Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study.

BACKGROUND: Tricuspid regurgitation pressure gradient (TRPG) measurement by echocardiography is recommended as the most objective examination to detect portopulmonary hypertension (PoPH). This study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a scoring model for identifying patients who are most likely to benefit from echocardiography investigations. RESULTS: A total of 486 patients who underwent echocardiography were randomly allocated to the derivation and validation sets at a ratio of 2:1. Of the patients, 51 (10.5%) had TRPG ≥ 35 mmHg. The median brain natriuretic peptide (BNP) was 39.5 pg/mL. Shortness of breath (SOB) was reported by 91 (18.7%) patients. In the derivation set, multivariate analysis identified female gender, shortness of breath, and BNP ≥ 48.9 pg/mL as independent factors for TRPG ≥ 35 mmHg. The risk score for predicting TRPG ≥ 35 mmHg was calculated as follows: - 3.596 + 1.250 × gender (female: 1, male: 0) + 1.093 × SOB (presence: 1, absence: 0) + 0.953 × BNP (≥ 48.9 pg/mL: 1, < 48.9 pg/mL: 0). The risk score yielded sensitivity of 66.7%, specificity of 75.3%, positive predictive value of 25.5%, negative predict value of 94.3%, and predictive accuracy of 74.4% for predicting TRPG ≥ 35 mmHg. These results were almost similar in the validation set, indicating the reproducibility and validity of the risk score. CONCLUSIONS: This study clarified the characteristics of patients with suspected PoPH and developed a scoring model for identifying patients at high risk of PoPH, which may be used in selecting patients that may benefit from echocardiography.