Kinya Okada, Yoshikazu Nakayama, Jennings Xu, Yang Cheng, Junko Tanaka
Aim: Hepatitis B surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitis B virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long-term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real-world setting.
Methods: A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression.
Results: In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitis B (CHB) cohort. Among the CHB cohort with an average observational period of 5.19 ± 3.87 years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p < 0.01) and cirrhosis (aHR 0.361, p < 0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100 IU/mL and ≥100 IU/mL), patients with a lower baseline level of HBsAg (<100 IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p < 0.01; cirrhosis aHR 0.618, p < 0.05).
Conclusions: These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long-term outcomes of patients with CHB in the Japanese population.
{"title":"A nation-wide medical record database study: Value of hepatitis B surface antigen loss in chronic hepatitis B patients in Japan.","authors":"Kinya Okada, Yoshikazu Nakayama, Jennings Xu, Yang Cheng, Junko Tanaka","doi":"10.1111/hepr.14056","DOIUrl":"https://doi.org/10.1111/hepr.14056","url":null,"abstract":"<p><strong>Aim: </strong>Hepatitis B surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitis B virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long-term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real-world setting.</p><p><strong>Methods: </strong>A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression.</p><p><strong>Results: </strong>In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitis B (CHB) cohort. Among the CHB cohort with an average observational period of 5.19 ± 3.87 years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p < 0.01) and cirrhosis (aHR 0.361, p < 0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100 IU/mL and ≥100 IU/mL), patients with a lower baseline level of HBsAg (<100 IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p < 0.01; cirrhosis aHR 0.618, p < 0.05).</p><p><strong>Conclusions: </strong>These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long-term outcomes of patients with CHB in the Japanese population.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: This study aimed to determine the value of the drainage fluid volume and direct bilirubin level for predicting significant bile leakage (BL) after hepatectomy and establish novel criteria for early drain removal.
Methods: Data from 351 patients who underwent hepatic resection at Gunma University in Japan between October 2018 and March 2022 were retrospectively analyzed. Clinical characteristics and surgical outcomes of patients with and without significant BL were compared. Criteria for early drain removal were determined and verified.
Results: Bile leakage occurred in 27 (7.1%) patients; 8 (2.3%) had grade A leakage and 19 (5.4%) had grade B leakage. The optimal cut-off value for the drainage fluid direct bilirubin level on postoperative day (POD) 2 was 0.16 mg/dL, which had the highest area under the curve and negative predictive value (NPV). Patients with BL had significantly larger drainage volumes on POD 2. The best cut-off value was 125 mL because it had the greatest NPV. Patients in both the primary and validation (n = 90) cohorts with bilirubin levels less than 0.16 mg/dL and drainage volumes less than 125 mL did not experience leakage.
Conclusions: A drainage fluid volume less than 125 mL and direct bilirubin level less than 0.16 mg/dL on POD 2 are criteria for safe early drain removal after hepatectomy.
{"title":"Early drain removal after hepatectomy based on bile leakage prediction using drainage fluid volume and direct bilirubin level.","authors":"Ryo Muranushi, Norifumi Harimoto, Takaomi Seki, Kei Hagiwara, Kouki Hoshino, Norihiro Ishii, Mariko Tsukagoshi, Takamichi Igarashi, Akira Watanabe, Kenichiro Araki, Ken Shirabe","doi":"10.1111/hepr.14055","DOIUrl":"https://doi.org/10.1111/hepr.14055","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to determine the value of the drainage fluid volume and direct bilirubin level for predicting significant bile leakage (BL) after hepatectomy and establish novel criteria for early drain removal.</p><p><strong>Methods: </strong>Data from 351 patients who underwent hepatic resection at Gunma University in Japan between October 2018 and March 2022 were retrospectively analyzed. Clinical characteristics and surgical outcomes of patients with and without significant BL were compared. Criteria for early drain removal were determined and verified.</p><p><strong>Results: </strong>Bile leakage occurred in 27 (7.1%) patients; 8 (2.3%) had grade A leakage and 19 (5.4%) had grade B leakage. The optimal cut-off value for the drainage fluid direct bilirubin level on postoperative day (POD) 2 was 0.16 mg/dL, which had the highest area under the curve and negative predictive value (NPV). Patients with BL had significantly larger drainage volumes on POD 2. The best cut-off value was 125 mL because it had the greatest NPV. Patients in both the primary and validation (n = 90) cohorts with bilirubin levels less than 0.16 mg/dL and drainage volumes less than 125 mL did not experience leakage.</p><p><strong>Conclusions: </strong>A drainage fluid volume less than 125 mL and direct bilirubin level less than 0.16 mg/dL on POD 2 are criteria for safe early drain removal after hepatectomy.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huiyul Park, Mimi Kim, Hye‐Lin Kim, Seon Cho, Eileen L. Yoon, Dae Won Jun
AimsWe aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction‐associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB‐4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort.MethodsThis retrospective cross‐sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n = 6740).ResultsThe prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n = 80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB‐4 (0.824 in NAFLD vs. 0.818 in MASLD, p = 0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p = 0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB‐4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD.ConclusionsMost patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB‐4 in the MASLD cohort demonstrated satisfactory results.
{"title":"Diagnostic performances of Fibrosis‐4 index and nonalcoholic fatty liver disease fibrosis score in metabolic dysfunction‐associated steatotic liver disease in Asian primary care clinics","authors":"Huiyul Park, Mimi Kim, Hye‐Lin Kim, Seon Cho, Eileen L. Yoon, Dae Won Jun","doi":"10.1111/hepr.14054","DOIUrl":"https://doi.org/10.1111/hepr.14054","url":null,"abstract":"AimsWe aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction‐associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB‐4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort.MethodsThis retrospective cross‐sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (<jats:italic>n</jats:italic> = 6740).ResultsThe prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (<jats:italic>n</jats:italic> = 80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB‐4 (0.824 in NAFLD vs. 0.818 in MASLD, <jats:italic>p</jats:italic> = 0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, <jats:italic>p</jats:italic> = 0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB‐4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD.ConclusionsMost patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB‐4 in the MASLD cohort demonstrated satisfactory results.","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AimAn 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.MethodsPatients 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.ResultsThe 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.ConclusionsIn 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.
{"title":"Kinetics of the hepatitis B core‐related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide","authors":"Norio Itokawa, Masanori Atsukawa, Akihito Tsubota, Toru Ishikawa, Hidenori Toyoda, Koichi Takaguchi, Tsunamasa Watanabe, Chikara Ogawa, Atsushi Hiraoka, Hironao Okubo, Haruki Uojima, Makoto Chuma, Akito Nozaki, Keizo Kato, Shigeru Mikami, Joji Tani, Asahiro Morishita, Toshifumi Tada, Toru Asano, Tomonori Senoh, Tsunekazu Oikawa, Tomomi Okubo, Takashi Kumada, Katsuhiko Iwakiri","doi":"10.1111/hepr.14052","DOIUrl":"https://doi.org/10.1111/hepr.14052","url":null,"abstract":"AimAn 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.MethodsPatients 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.ResultsThe 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 (<jats:italic>p</jats:italic> = 4.53 × 10<jats:sup>−6</jats:sup>). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy.ConclusionsIn 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.","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AimNutritional counseling improves malnutrition, which determines the prognosis of patients with chronic liver disease. In this study, we investigated the effects of nutritional counseling on mortality and the risk of overt hepatic encephalopathy (HE) in patients with alcohol‐associated liver disease.MethodsIn this retrospective cohort study, we included 211 patients with alcohol‐associated liver disease who visited Gifu University Hospital between August 2008 and June 2023. Patients were classified into two groups according to the frequency of nutritional counseling by a registered dietitian. The primary outcomes were all‐cause mortality and overt HE. Propensity score matching analysis was performed to adjust for potential confounders.ResultsAmong the patients (median age 67 years; 88% men; and median Model for End‐Stage Liver Disease score, 9), 86 (39%) were in the high‐frequency (≥2) nutritional counseling group. The high‐frequency group had a significantly higher survival rate (46% vs. 25%) and a lower incidence of overt HE (16% vs. 27%) at 5 years than the low‐frequency group. Nutritional counseling was associated with a reduced risk of mortality (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.36–0.63) and overt HE (HR 0.64; 95% CI 0.42–0.99), independent of hepatocellular carcinoma and liver function reserve. After propensity score matching, nutritional counseling was still associated with a reduced risk of mortality (HR 0.34; 95% CI 0.19–0.59) and overt HE (HR 0.31; 95% CI 0.11–0.87).ConclusionsNutritional counseling effectively improves mortality and prevents overt HE in patients with alcohol‐associated liver disease, thereby proving essential for the management of these patients.
{"title":"Nutritional counseling improves mortality and prevents hepatic encephalopathy in patients with alcohol‐associated liver disease","authors":"Tatsunori Hanai, Kayoko Nishimura, Shinji Unome, Takao Miwa, Yuki Nakahata, Kenji Imai, Atsushi Suetsugu, Koji Takai, Masahito Shimizu","doi":"10.1111/hepr.14053","DOIUrl":"https://doi.org/10.1111/hepr.14053","url":null,"abstract":"AimNutritional counseling improves malnutrition, which determines the prognosis of patients with chronic liver disease. In this study, we investigated the effects of nutritional counseling on mortality and the risk of overt hepatic encephalopathy (HE) in patients with alcohol‐associated liver disease.MethodsIn this retrospective cohort study, we included 211 patients with alcohol‐associated liver disease who visited Gifu University Hospital between August 2008 and June 2023. Patients were classified into two groups according to the frequency of nutritional counseling by a registered dietitian. The primary outcomes were all‐cause mortality and overt HE. Propensity score matching analysis was performed to adjust for potential confounders.ResultsAmong the patients (median age 67 years; 88% men; and median Model for End‐Stage Liver Disease score, 9), 86 (39%) were in the high‐frequency (≥2) nutritional counseling group. The high‐frequency group had a significantly higher survival rate (46% vs. 25%) and a lower incidence of overt HE (16% vs. 27%) at 5 years than the low‐frequency group. Nutritional counseling was associated with a reduced risk of mortality (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.36–0.63) and overt HE (HR 0.64; 95% CI 0.42–0.99), independent of hepatocellular carcinoma and liver function reserve. After propensity score matching, nutritional counseling was still associated with a reduced risk of mortality (HR 0.34; 95% CI 0.19–0.59) and overt HE (HR 0.31; 95% CI 0.11–0.87).ConclusionsNutritional counseling effectively improves mortality and prevents overt HE in patients with alcohol‐associated liver disease, thereby proving essential for the management of these patients.","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AimThis study aimed to compare the effects of the molecular targeted drugs, sorafenib and lenvatinib, on the survival, invasion, and angiogenesis of hepatocellular carcinoma cells. Additionally, we investigated the involvement of transforming growth factor beta (TGF‐β) signaling in their molecular mechanisms.MethodsTo investigate the effects of sorafenib and lenvatinib, we conducted cell viability, invasion, and angiogenesis assays, as well as western blotting analyses.ResultsIn human hepatocellular carcinoma cells (HepG2), sorafenib demonstrated potent inhibitory effects on cell proliferation, but induced cell invasion similar to TGF‐β. In contrast, lenvatinib showed weaker cytotoxicity compared with sorafenib, but suppressed cell invasion induced by TGF‐β. The actions of these two molecular targeted drugs were suggested to involve the regulation of the TGFβR2/ERK pathway. Moreover, in human umbilical vein endothelial cells, Sorafenib showed weaker cytotoxicity and enhanced the effects of TGF‐β on angiogenesis. Conversely, lenvatinib showed potent cytotoxic abilities and suppressed angiogenesis induced by TGF‐β. The actions of these two molecular targeted drugs were suggested to involve the regulation of the crosstalk between TGF‐β signaling and vascular endothelial growth factor signaling.ConclusionsOur findings indicate that both sorafenib and lenvatinib possess anticancer abilities by inducing the cytotoxicity of hepatocellular carcinoma cells. Furthermore, they show opposing effects on TGF‐β‐induced cell invasion and angiogenesis, thereby enhancing the understanding of the multifaceted functions of molecular targeted drugs in treating hepatocellular carcinoma.
{"title":"Comparative analysis of sorafenib and lenvatinib on HepG2 cells and human umbilical vein endothelial cells: Involvement of transforming growth factor‐β signaling in their molecular effects","authors":"Ting Wang, Yasuhiro Takikawa, Kazuyuki Suzuki, Hidekatsu Kuroda, Keisuke Kakisaka, Toshimi Chiba","doi":"10.1111/hepr.14045","DOIUrl":"https://doi.org/10.1111/hepr.14045","url":null,"abstract":"AimThis study aimed to compare the effects of the molecular targeted drugs, sorafenib and lenvatinib, on the survival, invasion, and angiogenesis of hepatocellular carcinoma cells. Additionally, we investigated the involvement of transforming growth factor beta (TGF‐β) signaling in their molecular mechanisms.MethodsTo investigate the effects of sorafenib and lenvatinib, we conducted cell viability, invasion, and angiogenesis assays, as well as western blotting analyses.ResultsIn human hepatocellular carcinoma cells (HepG2), sorafenib demonstrated potent inhibitory effects on cell proliferation, but induced cell invasion similar to TGF‐β. In contrast, lenvatinib showed weaker cytotoxicity compared with sorafenib, but suppressed cell invasion induced by TGF‐β. The actions of these two molecular targeted drugs were suggested to involve the regulation of the TGFβR2/ERK pathway. Moreover, in human umbilical vein endothelial cells, Sorafenib showed weaker cytotoxicity and enhanced the effects of TGF‐β on angiogenesis. Conversely, lenvatinib showed potent cytotoxic abilities and suppressed angiogenesis induced by TGF‐β. The actions of these two molecular targeted drugs were suggested to involve the regulation of the crosstalk between TGF‐β signaling and vascular endothelial growth factor signaling.ConclusionsOur findings indicate that both sorafenib and lenvatinib possess anticancer abilities by inducing the cytotoxicity of hepatocellular carcinoma cells. Furthermore, they show opposing effects on TGF‐β‐induced cell invasion and angiogenesis, thereby enhancing the understanding of the multifaceted functions of molecular targeted drugs in treating hepatocellular carcinoma.","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140800970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background and aims: Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort.
Methods: The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study.
Results: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001).
Conclusion: The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.
{"title":"Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease.","authors":"Kazuhiro Nouso, Miwa Kawanaka, Hideki Fujii, Kazuya Kariyama, Hidenori Toyoda, Michihiro Iwaki, Hideki Hayashi, Satoshi Oeda, Hideyuki Hyogo, Asahiro Morishita, Kensuke Munekage, Kazuhito Kawata, Tsubasa Tsutsumi, Koji Sawada, Tatsuji Maeshiro, Hiroshi Tobita, Yuichi Yoshida, Masafumi Naito, Asuka Araki, Shingo Arakaki, Takumi Kawaguchi, Hidenao Noritake, Masafumi Ono, Tsutomu Masaki, Satoshi Yasuda, Eiichi Tomita, Masato Yoneda, Akihiro Tokushige, Yoshihiro Kamada, Hirokazu Takahashi, Shinichiro Ueda, Shinichi Aishima, Yoshio Sumida, Atsushi Nakajima, Takashi Kumada, Takeshi Okanoue","doi":"10.1111/hepr.14039","DOIUrl":"https://doi.org/10.1111/hepr.14039","url":null,"abstract":"<p><strong>Background and aims: </strong>Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort.</p><p><strong>Methods: </strong>The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study.</p><p><strong>Results: </strong>The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001).</p><p><strong>Conclusion: </strong>The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard Belmonte, Maël Silva‐Rodriguez, Françoise Barbé, Mouni Bensenane, Vincent Haghenejad, Isabelle Vrillon, Asma Alla, Adrien Flahault, Raphael Kormann, Alice Corbel, Zakia Aitdjafer, Didier Quilliot, Laurence Derain‐Dubourg, Farès Namour, Jean‐Louis Guéant, Jean‐Pierre Bronowicki, Abderrahim Oussalah
AimRenal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers.MethodsWe conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43‐multiparametric renal function assessment between January 1, 2021, and June 30, 2023.ResultsAll patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte‐free water clearance <0.4 mL/min, or tubular maximum phosphate reabsorption capacity <0.8 mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14 mL/min/1.73 m2 (95% CI 6–29) and +9 mL/min/1.73 m2 (95% CI 2–15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease ‐ Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate‐ and measured creatinine clearance‐based assessments.ConclusionsThis study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute‐free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.
{"title":"Multiparametric renal function assessment in cirrhotic patients shows high prevalence of medically actionable changes in multiple modules","authors":"Richard Belmonte, Maël Silva‐Rodriguez, Françoise Barbé, Mouni Bensenane, Vincent Haghenejad, Isabelle Vrillon, Asma Alla, Adrien Flahault, Raphael Kormann, Alice Corbel, Zakia Aitdjafer, Didier Quilliot, Laurence Derain‐Dubourg, Farès Namour, Jean‐Louis Guéant, Jean‐Pierre Bronowicki, Abderrahim Oussalah","doi":"10.1111/hepr.14050","DOIUrl":"https://doi.org/10.1111/hepr.14050","url":null,"abstract":"AimRenal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers.MethodsWe conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43‐multiparametric renal function assessment between January 1, 2021, and June 30, 2023.ResultsAll patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte‐free water clearance <0.4 mL/min, or tubular maximum phosphate reabsorption capacity <0.8 mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14 mL/min/1.73 m<jats:sup>2</jats:sup> (95% CI 6–29) and +9 mL/min/1.73 m<jats:sup>2</jats:sup> (95% CI 2–15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease ‐ Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate‐ and measured creatinine clearance‐based assessments.ConclusionsThis study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute‐free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AimAdvanced fibrosis has a strong influence on the occurrence of liver‐related events in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver‐related events.MethodsA total of 282 patients with liver biopsy‐proven MASLD were included. Liver‐related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child–Pugh class B and C, as well as treatment‐eligible esophageal and gastric varices.ResultsMultivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver‐related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver‐related events, including the occurrence of HCC and complications of liver cirrhosis.ConclusionsWhile the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver‐related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.
{"title":"Combined effect of histological findings and diabetes mellitus on liver‐related events in patients with metabolic dysfunction‐associated steatotic liver disease","authors":"Akihito Shiomi, Teruki Miyake, Shinya Furukawa, Bunzo Matsuura, Osamu Yoshida, Takao Watanabe, Ayumi Kanamoto, Masumi Miyazaki, Hironobu Nakaguchi, Yoshio Tokumoto, Masashi Hirooka, Masanori Abe, Yoichi Hiasa","doi":"10.1111/hepr.14049","DOIUrl":"https://doi.org/10.1111/hepr.14049","url":null,"abstract":"AimAdvanced fibrosis has a strong influence on the occurrence of liver‐related events in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver‐related events.MethodsA total of 282 patients with liver biopsy‐proven MASLD were included. Liver‐related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child–Pugh class B and C, as well as treatment‐eligible esophageal and gastric varices.ResultsMultivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver‐related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver‐related events, including the occurrence of HCC and complications of liver cirrhosis.ConclusionsWhile the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver‐related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140800969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AimMyostatin is a myokine involved in muscle mass regulation. The associations between circulating myostatin levels and clinical characteristics in patients with acute liver failure (ALF) and late‐onset hepatic failure (LOHF) are unclear.MethodsIn this retrospective study, 51 patients with ALF or LOHF were included. Serum myostatin was measured using an enzyme‐linked immunosorbent assay.ResultsMyostatin levels were significantly lower in patients with ALF and LOHF than in controls (ALF/LOHF: 2522 pg/mL, controls: 3853 pg/mL, p = 0.003). The prevalence of low myostatin in deceased patients was significantly higher than that in spontaneous survivors and patients who underwent liver transplantation. Patients with low myostatin levels had a high incidence of complications. There was a positive correlation between the psoas muscle index and serum myostatin levels. Patients with low myostatin levels had shorter 1‐year transplant‐free survival and shorter 1‐year overall survival than patients with high myostatin levels. Low serum myostatin levels were associated with poor prognosis independent of the Japanese scoring system for ALF ≥3, King's College criteria, or model for end‐stage liver disease score >30.5. The combination of serum myostatin levels and prognostic models for ALF significantly stratified patients according to 1‐year prognosis.ConclusionsLow serum myostatin levels were associated with a low psoas muscle index, complication rate, and poor prognosis in patients with ALF and LOHF. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with ALF and LOHF.
{"title":"Circulating myostatin levels as a prognostic biomarker in patients with acute liver failure and late‐onset hepatic failure","authors":"Manabu Hayashi, Kazumichi Abe, Tatsuro Sugaya, Yosuke Takahata, Masashi Fujita, Atsushi Takahashi, Hiromasa Ohira","doi":"10.1111/hepr.14051","DOIUrl":"https://doi.org/10.1111/hepr.14051","url":null,"abstract":"AimMyostatin is a myokine involved in muscle mass regulation. The associations between circulating myostatin levels and clinical characteristics in patients with acute liver failure (ALF) and late‐onset hepatic failure (LOHF) are unclear.MethodsIn this retrospective study, 51 patients with ALF or LOHF were included. Serum myostatin was measured using an enzyme‐linked immunosorbent assay.ResultsMyostatin levels were significantly lower in patients with ALF and LOHF than in controls (ALF/LOHF: 2522 pg/mL, controls: 3853 pg/mL, <jats:italic>p</jats:italic> = 0.003). The prevalence of low myostatin in deceased patients was significantly higher than that in spontaneous survivors and patients who underwent liver transplantation. Patients with low myostatin levels had a high incidence of complications. There was a positive correlation between the psoas muscle index and serum myostatin levels. Patients with low myostatin levels had shorter 1‐year transplant‐free survival and shorter 1‐year overall survival than patients with high myostatin levels. Low serum myostatin levels were associated with poor prognosis independent of the Japanese scoring system for ALF ≥3, King's College criteria, or model for end‐stage liver disease score >30.5. The combination of serum myostatin levels and prognostic models for ALF significantly stratified patients according to 1‐year prognosis.ConclusionsLow serum myostatin levels were associated with a low psoas muscle index, complication rate, and poor prognosis in patients with ALF and LOHF. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with ALF and LOHF.","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140800962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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