Publications by authors named "Hidenori Toyoda"

375 Publications

Misunderstanding of hepatitis C virus (HCV) infection status by non-specialized medical doctors in patients who achieved sustained virologic response to anti-HCV therapy.

J Infect Chemother 2022 May 6. Epub 2022 May 6.

Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Introduction: With the increase in the number of patients with sustained virologic response (SVR) in whom hepatitis C virus (HCV) was eradicated by the anti-HCV therapy, there are now many individuals in whom serum HCV RNA is absent despite positive serum HCV antibodies. However, in general clinical practice, HCV infection remains usually screened by measurement of serum HCV antibodies and patients with SVR can be misunderstood regarding HCV infection status.

Methods: In the multicenter study, we conducted interviews with administered questionnaires to SVR individuals who had regular hospital visits after SVR. The prevalence of experiencing an incorrect diagnosis of HCV infection after SVR was assessed. Individuals who experienced this misunderstanding were further asked where they experienced it and how it made them feel.

Results: In a survey of 2,246 SVR individuals, 197 individuals (8.8%) were misunderstood as having persistent HCV infection by medical doctors due to positive HCV antibody, despite the absence of HCV viremia. These misunderstandings occurred most prevalently at a private clinic (55.3%). More than half (53.3%) of these individuals felt anxious about their HCV infection with becoming unsure about their HCV eradication status.

Conclusions: Misunderstanding HCV status is commonly occurred in SVR individuals. Specialists in hepatology and infectious diseases should broadly emphasize the fact that most patients with HCV antibodies are now HCV-free because of the use of anti-HCV therapy.
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http://dx.doi.org/10.1016/j.jiac.2022.04.024DOI Listing
May 2022

Shorter pruritus period and milder disease stage are associated with response to nalfurafine hydrochloride in patients with chronic liver disease.

Sci Rep 2022 May 4;12(1):7311. Epub 2022 May 4.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Nalfurafine hydrochloride, a selective κ-opioid receptor agonist has been approved for pruritus in patients with chronic liver disease. However, not all patients respond to nalfurafine hydrochloride. The aim of this study was to clarify the efficacy of nalfurafine hydrochloride. The subjects were patients with chronic liver disease complicated by pruritus who were treated with nalfurafine hydrochloride between May, 2015, and May, 2021. The degree of pruritus was evaluated based on the Visual Analog Scale (VAS) score and the Kawashima's pruritus score. Nalfurafine hydrochloride 2.5 μg was orally administered once a day for 12 weeks. A decrease in the VAS score of ≥ 25 mm or the Kawashima's pruritus score of ≥ 1 scores was designated as relevant response. The former of ≥ 50 mm or the latter of ≥ 2 scores as remarkable response. The 326 patients who were evaluated the efficacy at 12 weeks. The median time suffering from pruritus to administration of nalfurafine hydrochloride was 4 months. The median VAS score improved from 70.0 mm before administration to 40.0 and 30.0 mm at 4 and 12 weeks of treatment, respectively. On multivariate analysis, shorter itching period and lower FIB-4 index value were extracted as the independent factors related to remarkable responder. On multivariate analysis, shorter itching period was extracted as the only independent factor related to relevant responder. In conclusion, this study suggested nalfurafine hydrochloride treatment markedly improves pruritus in patients with chronic liver disease. A short pruritus period and less-advanced fibrosis were associated with response to nalfurafine hydrochloride.
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http://dx.doi.org/10.1038/s41598-022-11431-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068920PMC
May 2022

Liver Stiffness Measurements by 2D Shear-Wave Elastography: Effect of Steatosis on Fibrosis Evaluation.

AJR Am J Roentgenol 2022 May 4. Epub 2022 May 4.

Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Hepatic steatosis has been shown to not effect liver stiffness measurements (LSM) by MR elastography (MRE). However, the effect of steatosis on LSM by 2D shear-wave elastography (SWE) remains controversial. To evaluate the effect of hepatic steatosis on the diagnostic performance of LSM from 2D SWE (hereafter, LSM2D-SWE) for evaluation of liver fibrosis, using LSM from MRE (hereafter, LSMMRE) as the reference standard. This retrospective study included 888 patients (442 women, 446 men; median age, 67 years) with chronic liver disease who underwent LSM by both 2D SWE and MRE within a 3-month window. Steatosis was also assessed on the ultrasound examinations by ultrasound-guided attenuation parameter (UGAP) and on the MRI examinations by MRI-based proton-density fat fraction (MRI-PDFF). Fibrosis stages and steatosis grades were classified using previously established thresholds. The effect of steatosis on LSM2D-SWE was evaluated using Kruskal-Wallis tests with post hoc tests and ROC analysis. LSM2D-SWE was significantly higher in patients with severe steatosis than no steatosis by MRI-PDFF among patients with F0 fibrosis [5.5 (interquartile range [IQR], 4.7-6.0) vs 4.7 (IQR, 4.2-5.5), p=.009)] and F1 fibrosis [6.3 (IQR, 6.0-7.2) vs 5.9 (IQR, 5.0-6.6), p=.009]. LSM2D-SWE was significantly higher in patients with severe steatosis than no steatosis by UGAP among patients with F1 fibrosis [6.6 (IQR, 5.9-7.3) vs 5.9 (IQR, 5.1-6.5), p=.008)]. Otherwise, LSM2D-SWE did not vary significantly across steatosis grades at a given fibrosis stage (all p>.05). Sensitivity and specificity for ≥F1 fibrosis were 63.8% and 91.5% in patients without, versus 60.4% and 80.9% in patients with, severe steatosis by MRI-PDFF, and were 62.4% and 91.5% in patients without, versus 72.1% and 78.3% in patients with, severe steatosis by UGAP. Severe hepatic steatosis may result in overestimation of LSM2D-SWE in patients with no or mild steatosis, thus reducing specificity for liver fibrosis detection. UGAP performed at the time of 2D SWE may help identify patients in whom LSM2D-SWE should be assessed with caution. In patients with no or mild steatosis by 2D SWE and severe steatosis by UGAP, MRE may help provide a more reliable measure of liver fibrosis.
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http://dx.doi.org/10.2214/AJR.22.27656DOI Listing
May 2022

Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: A multicenter analysis.

Cancer Med 2022 Apr 19. Epub 2022 Apr 19.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

Aim: The safety and efficacy of atezolizumab plus bevacizumab (Atez/Bev) in elderly patients with unresectable hepatocellular carcinoma (HCC) have not been sufficiently investigated.

Methods: A total of 317 patients with HCC treated with Atez/Bev were studied. We compared the survival and frequency of adverse events in elderly versus non-elderly patients with HCC who were treated with Atez/Bev using an analysis of inverse probability weighting (IPW).

Results: Univariate analysis adjusted with IPW showed that being elderly is not associated with worse overall or progression-free survival (hazard ratio [HR], 1.239; 95% confidence interval [CI], 0.640-2.399; p = 0.526 and HR, 1.256; 95% CI, 0.871-1.811; p = 0.223, respectively). Regarding treatment-related adverse events, any grade of fatigue, proteinuria, decreased appetite, hypertension, and liver injury occurred in ≥10% of patients. There were no significant differences in treatment-related adverse events between the elderly and non-elderly groups. In a subgroup analysis of elderly patients aged 75-79, 80-84, or ≥ 85 years, there were no significant differences in cumulative overall or progression-free survival among these age groups (p = 0.960 and 0.566, respectively). In addition, there were no significant differences in treatment-related adverse events among these three age groups, except for proteinuria of any grade. In a subgroup analysis of patients treated with Atez/Bev as first-line systemic therapy, there were no significant differences in cumulative overall or progression-free survival between the elderly and non-elderly groups (p = 0.728 and 0.805, respectively).

Conclusions: Atez/Bev can be used efficaciously and safely in spite of age in patients with unresectable HCC.
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http://dx.doi.org/10.1002/cam4.4763DOI Listing
April 2022

The best predictive model for post-SVR HCC: can it be universal?

Hepatol Int 2022 Apr 8. Epub 2022 Apr 8.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan.

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http://dx.doi.org/10.1007/s12072-022-10336-5DOI Listing
April 2022

Breaking the Child-Pugh Dogma in Hepatocellular Carcinoma.

J Clin Oncol 2022 Mar 28:JCO2102373. Epub 2022 Mar 28.

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.

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http://dx.doi.org/10.1200/JCO.21.02373DOI Listing
March 2022

Mac-2-binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C.

Hepatol Commun 2022 Mar 28. Epub 2022 Mar 28.

Core Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.

Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non-HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non-HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct-acting antiviral (DAA) treatment were analyzed. The cumulative post-SVR incidence of non-HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non-HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac-2-binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post-SVR incidence of non-HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post-SVR incidence of non-HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.
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http://dx.doi.org/10.1002/hep4.1941DOI Listing
March 2022

Global and regional long-term survival following resection for HCC in the recent decade: A meta-analysis of 110 studies.

Hepatol Commun 2022 Mar 2. Epub 2022 Mar 2.

Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.

Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p = 0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p = 0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.
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http://dx.doi.org/10.1002/hep4.1923DOI Listing
March 2022

Artificial intelligence (AI) models for the ultrasonographic diagnosis of liver tumors and comparison of diagnostic accuracies between AI and human experts.

J Gastroenterol 2022 Apr 27;57(4):309-321. Epub 2022 Feb 27.

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.

Background: Ultrasonography (US) is widely used for the diagnosis of liver tumors. However, the accuracy of the diagnosis largely depends on the visual perception of humans. Hence, we aimed to construct artificial intelligence (AI) models for the diagnosis of liver tumors in US.

Methods: We constructed three AI models based on still B-mode images: model-1 using 24,675 images, model-2 using 57,145 images, and model-3 using 70,950 images. A convolutional neural network was used to train the US images. The four-class liver tumor discrimination by AI, namely, cysts, hemangiomas, hepatocellular carcinoma, and metastatic tumors, was examined. The accuracy of the AI diagnosis was evaluated using tenfold cross-validation. The diagnostic performances of the AI models and human experts were also compared using an independent test cohort of video images.

Results: The diagnostic accuracies of model-1, model-2, and model-3 in the four tumor types are 86.8%, 91.0%, and 91.1%, whereas those for malignant tumor are 91.3%, 94.3%, and 94.3%, respectively. In the independent comparison of the AIs and physicians, the percentages of correct diagnoses (accuracies) by the AIs are 80.0%, 81.8%, and 89.1% in model-1, model-2, and model-3, respectively. Meanwhile, the median percentages of correct diagnoses are 67.3% (range 63.6%-69.1%) and 47.3% (45.5%-47.3%) by human experts and non-experts, respectively.

Conclusion:  The performance of the AI models surpassed that of human experts in the four-class discrimination and benign and malignant discrimination of liver tumors. Thus, the AI models can help prevent human errors in US diagnosis.
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http://dx.doi.org/10.1007/s00535-022-01849-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938378PMC
April 2022

Adherence to regular surveillance visits for hepatocellular carcinoma in patients with chronic hepatitis C virus infection who achieved sustained virologic response.

Eur J Gastroenterol Hepatol 2022 Jun 14;34(6):693-697. Epub 2022 Feb 14.

Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Objective: Patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) to anti-HCV therapy, that is the eradication of HCV, are recommended to continue regular hospital visits for the surveillance of hepatocellular carcinoma (HCC) that can develop after SVR. However, it is unclear how well patients with SVR adhere to post-SVR follow-up over the long term. We investigated this adherence and the factors associated with it.

Methods: Medical record data on regular hospital visits were reviewed in 1329 patients with no history of HCC who achieved SVR by anti-HCV therapy. At the time of SVR confirmation, all patients were advised to continue regular visits, and the risk of post-SVR HCC was explained. The adherence rate of post-SVR follow-up and associated factors were analyzed.

Results: Adherence rates decreased continuously over time, as follows: 76.6% at 5 years, 62.4% at 10 years, 48.8% at 15 years, and 35.3% at 20 years after SVR. Adherence rates did not differ based on the degree of baseline liver fibrosis and were significantly lower in patients who achieved SVR by interferon (IFN)-free therapy and those with HCV genotype 2b.

Conclusion: Adherence to post-SVR follow-up decreased over the long term, and rates differed by patient background. Adherence was especially poor in patients who achieved SVR by IFN-free therapy, and therefore, strategies are necessary to encourage these patients to maintain their regular schedule of hospital visits.
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http://dx.doi.org/10.1097/MEG.0000000000002358DOI Listing
June 2022

Neutrophil-lymphocyte ratio predicts early outcomes in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: a multicenter analysis.

Eur J Gastroenterol Hepatol 2022 Jun 14;34(6):698-706. Epub 2022 Feb 14.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo.

Objective: To investigate whether neutrophil-to-lymphocyte ratio (NLR) can predict outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev).

Methods: A total of 249 patients with unresectable HCC treated with Atez/Bev were included. We analyzed survival and discontinuation of this therapy in this cohort.

Results: Cumulative overall survival at 2, 4, 6, and 8 months was 97.6%, 94.9%, 88.9%, and 82.8%, respectively. Cumulative overall survival differed significantly between patients with low (<3.0) versus high (≥3.0) NLR (P = 0.001). Conversely, cumulative progression-free survival did not differ between patients with low versus high NLR. The distribution of response was 1.5% for complete response, 17.1% for partial response, 60.5% for stable disease, and 21.0% for progressive disease. Responses were not different between patients with low and high NLR. Regarding adverse events, immune-related liver injury of any grade and grade of at least 3, decreased appetite of any grade, grade of at least 3 proteinuria, and other adverse events of any grade differed significantly between patients with low and high NLR. There were 56, 18, and 2 patients who discontinued Atez/Bev therapy due to progression of disease, adverse event, and other reasons, respectively. The cumulative discontinuation rate for Atez/Bev therapy due to adverse events differed significantly between patients with low versus high NLR (P = 0.022). Cox proportional hazards modeling analysis with inverse probability weighting showed that NLR of at least 3.0 was significantly associated with overall survival (hazard ratio, 3.369; 95% confidence interval, 1.024-11.080).

Conclusions: NLR can predict outcomes in patients with unresectable HCC treated with Atez/Bev.
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http://dx.doi.org/10.1097/MEG.0000000000002356DOI Listing
June 2022

Identification of the suitable candidates for EOB-MRI with the high risk of the presence of non-hypervascular hypointense nodules in patients with HCV infection.

Eur Radiol 2022 Feb 10. Epub 2022 Feb 10.

Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Objectives: Non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of progressing to hepatocellular carcinoma (HCC). The presence of NHHNs is a strong risk factor for HCC development in patients with chronic hepatitis C virus (HCV) infection after the achievement of sustained virologic response (SVR). However, it is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection. We therefore explored serum markers that potentially indicate the presence of NHHNs.

Methods: Three serum markers, alpha-fetoprotein (AFP), FIB-4 index, and Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi), were measured in 481 patients with HCV infection and no history of HCC who underwent EOB-MRI. The associations between these serum marker levels and the presence of NHHNs were investigated.

Results: All three markers were associated with the presence of NHHNs. M2BPGi predicted the presence of NHHNs more accurately than AFP and FBB-4 index; M2BPGi had the highest area under the receiver operating characteristic curve. Multivariate analysis identified male gender and high M2BPGi as factors associated with the presence of NHHNs. When patients were stratified by the degree of liver fibrosis, M2BPGi increased with the progression of fibrosis. In addition, NHHNs were more prevalently detected in patients with higher M2BPGi (COI > 3.46) in patients with similar fibrosis degree.

Conclusions: M2BPGi is a serum marker that potentially identifies HCV patients with high risk of the presence of NHHNs, for whom EOB-MRI should be considered.

Key Points: • Non-hypervascular hypointense nodule on EOB-DTPA-enhanced MRI is pre-HCC nodule with high likelihood of progressing to HCC, which is a strong predictor for HCC that develops after the eradication of HCV in patients with HCV infection. • It is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection due to limited access, limited availability of MRI equipment, and high costs. • Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi) levels effectively indicate the presence of NHHNs and can be used to identify patients with high risk of their presence, for whom EOB-DTPA-enhanced MRI should be considered.
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http://dx.doi.org/10.1007/s00330-022-08570-4DOI Listing
February 2022

Association of early bevacizumab interruption with efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma: A landmark analysis.

Hepatol Res 2022 May 9;52(5):462-470. Epub 2022 Feb 9.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

Aim: The present study focused on the association of early bevacizumab (Bev) interruption with the clinical outcome of atezolizumab plus bevacizumab.

Methods: This retrospective study included 239 patients with advanced hepatocellular carcinoma receiving atezolizumab/Bev from September 2020 to June 2021 at 16 different institutions in Japan. We conducted a 9-week landmark analysis to investigate the association of Bev interruption due to adverse events with the therapeutic efficacy.

Results: The median age was 73.0 (68.0-80.0) years old, with 195 (81.6%) men. The objective response rate was significantly higher in patients without Bev interruption than in those with it (34.5% vs. 17.3%, p = 0.038). The median progression-free survival (PFS) was 6.5 months (95% confidence interval [CI] 4.5-9.7) and 9.0 months (95% CI 7.1-not applicable) in patients with and without Bev interruption, respectively, with statistical significance (p = 0.021). The 12-month overall survival (OS) rates in patients with and without Bev interruption were 49.4% (CI 27.7%-67.9%) and 82.2% (95% CI 70.3%-89.6%), respectively, showing a significant difference (p = 0.004). The presence of Bev interruption was a significant factor associated with the PFS (p = 0.021) and OS (p = 0.008). A multivariate analysis showed that modified albumin-bilirubin 2b (p < 0.001) and later-line treatment (p = 0.018) were unfavorable factors associated with Bev interruption. Liver injury, appetite loss, protein urea, and ascites or hepatic edema were more frequently found in patients with Bev interruption than in those without it.

Conclusions: Early Bev interruption was an unfavorable factor associated with the PFS and OS. Good liver function and treatment settings may be associated with maintaining Bev treatment.
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http://dx.doi.org/10.1111/hepr.13748DOI Listing
May 2022

Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study.

Clin Gastroenterol Hepatol 2022 Jan 17. Epub 2022 Jan 17.

Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Background & Aims: There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage.

Methods: This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients.

Results: The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality.

Conclusions: Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.
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http://dx.doi.org/10.1016/j.cgh.2022.01.002DOI Listing
January 2022

Impact of switching to tenofovir alafenamide fumarate in patients with entecavir-treated chronic hepatitis B.

Eur J Gastroenterol Hepatol 2021 12;33(1S Suppl 1):e898-e904

Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Background And Aims: Tenofovir alafenamide (TAF), a new tenofovir prodrug, has been developed to circumvent the less favorable safety profile of tenofovir disoproxil fumarate (TDF). We investigated reductions in hepatitis B surface antigen (HBsAg) levels in patients with HBV infection who received continuous entecavir (ETV) monotherapy or sequential therapy with ETV and TAF.

Methods: This retrospective cohort study included 286 patients who were divided into two groups: continuous ETV monotherapy (ETV group, n = 168) and sequential therapy with ETV and TAF (ETV-TAF group, n = 108). Factors associated with a 90% reduction in HBsAg levels were analyzed by a Cox proportional hazards model using a time-dependent covariate in both groups.

Results: In the multivariate Cox proportional hazards model, the ETV-TAF group [adjusted hazard ratio (aHR) 2.750; 95% confidence interval (CI), 1.265-3.405; P = 0.0038] and BMI ≤ 25.0 kg/m2 (aHR 0.520, 95% CI, 0.308-0.875; P = 0.0139) demonstrated a 90% reduction in HBsAg levels. HBsAg levels of patients in the TAF phase in the ETV-TAF group showed greater yearly percent reductions than those in the ETV group and those in the ETV phase in the ETV-TAF group (P = 0.0361 and P = 0.0022, respectively, Steel-Dwass test).

Conclusion: HBsAg levels decreased more rapidly after patients switched from ETV to TAF. Switching to TAF may be an effective treatment option to reduce HBsAg levels.
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http://dx.doi.org/10.1097/MEG.0000000000002292DOI Listing
December 2021

Influence of liver stiffness heterogeneity on staging fibrosis in patients with nonalcoholic fatty liver disease.

Hepatology 2021 Dec 24. Epub 2021 Dec 24.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Background And Aims: Despite that hepatic fibrosis often affects the liver globally, spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness (LS) heterogeneity on concordance between MR elastography (MRE)-based fibrosis staging and biopsy staging in patients with NAFLD.

Approach And Results: We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3 Tesla MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE-based LS measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE-based fibrosis staging of stage 4 (4.43, kPa; AUROC, 0.89) and stage ≥3 (3.93, kPa; AUROC, 0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of <4. In 86.7% of these discordant cases, variability of LSM was classified as heterogeneous. In MRE-based LSM stage ≥3, 88.9% of discordant cases were classified as heterogeneous. Results of the validation cohort were similar to those of the training cohort.

Conclusions: Discordance between biopsy- and MRE-based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE.
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http://dx.doi.org/10.1002/hep.32302DOI Listing
December 2021

Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis.

Dig Dis 2021 Dec 23. Epub 2021 Dec 23.

Introduction: NAFLD is increasingly prevalent in Asia, where people suffer more metabolic comorbidities at a lower body mass index (BMI), suggesting potential differences in their clinical profile. Therefore, we attempted to characterize the clinical profile of Asians with NAFLD via a meta-analytic approach.

Methods: We searched Pubmed, EMBASE, and Cochrane databases from January 1, 2000 to January 17, 2019. Two authors independently reviewed and selected 104 articles (2,247,754 persons) that identified NAFLD in Asians and reported relevant data, especially BMI and ALT, and excluded individuals with other liver disease and excessive alcohol consumption. Individual patient-level data were obtained from seven cohorts in Asia to complement meta-analyzed data.

Results: Overall, the mean age was 52.07 (95%CI:51.28-52.85) years with those from Southeast Asia (42.66, 95%CI: 32.23-53.11) being significantly younger. The mean BMI was 26.2 kg/m2, higher in moderate-severe vs. mild hepatic steatosis (28.3 vs. 25.7) patients and NFS ≥-1.455 vs. <-1.455 (27.09 vs. 26.02), with 34% having non-obese NAFLD. The mean ALT was 31.74 U/L, higher in NFS <-1.455 vs. ≥-1.455 (33.74 vs. 27.83), though no differences were found by obesity or steatosis severity. The majority of males (85.7%) and females (60.7%) had normal to minimally elevated ALT (1-1.5x 95% ULN). Individual patient-level data analysis (N=7,668) demonstrated similar results.

Conclusion: About one-third of Asians with NAFLD were non-obese and the majority did not have markedly elevated ALT. Therefore, abnormal ALT or BMI are not recommended as a criterion for NAFLD screening in this population. Additionally, there were significant differences in the clinical profiles of NAFLD among the different regions of Asia.
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http://dx.doi.org/10.1159/000521662DOI Listing
December 2021

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

Hepatol Res 2022 Mar 17;52(3):235-246. Epub 2021 Dec 17.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

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.
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http://dx.doi.org/10.1111/hepr.13739DOI Listing
March 2022

Simple Scoring System for Predicting TACE Unsuitable among Intermediate-Stage Hepatocellular Carcinoma Patients in the Multiple Systemic Treatment Era.

Oncology 2022 29;100(2):65-73. Epub 2021 Nov 29.

Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan.

Background/aim: With the development of systemic treatment methods for unresectable hepatocellular carcinoma (uHCC), the concept of unsuitable for transcatheter arterial chemoembolization (TACE) has become important. This study aimed to establish a simple predictive scoring system for determining TACE unsuitable status.

Materials/methods: From 1998 to 2015, 196 patients with intermediate-stage uHCC with Child-Pugh A (score 5:6 = 108:88) and given TACE as the initial treatment were enrolled. At the baseline, tumor burden (Milan criteria-out, up-to-7 in/out, and up-to-11 in/out: 0-2 points) and modified albumin-bilirubin grade 1/2a or 2b (0-1 point) were added to determine the score for TACE unsuitable (CITRUS-MICAN score; low <2 and high ≥2). In addition, a previously reported tumor marker (TM) score, in which alpha-fetoprotein (AFP) was ≥100 ng/mL, fucosylated AFP ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL (each 1 point) (total 0, 1, or ≥2 points), was used for additionally evaluating tumor malignancy potential. Prognosis was retrospectively evaluated based on those scores.

Results: Median survival time (MST) was better for low compared to high CITRUS-MICAN score (42.0 vs. 26.4 months) (p = 0.002). A 2-step evaluation using the combination of CITRUS-MICAN and TM scores showed an MST of 43.2 months for low CITRUS-MICAN/TM score 0/1 (rank-A) and 39.6 months for low CITRUS-MICAN/TM score ≥2 (rank-B2), while it was 46.8 months for high CITRUS-MICAN/TM score 0 (rank-B1), 28.8 months for high CITRUS-MICAN/TM score 1 (rank-B2), and 22.8 months for high CITRUS-MICAN/TM score ≥2 (rank-C). For rank-A cases (n = 51), MST was 43.2 months, while it was 46.8 months for rank-B1 (n = 12), 31.2 months for rank-B2 (n = 82), and 22.8 months for rank-C (n = 51) (p = 0.001).

Conclusion: The results showed that rank-C indicates absolute TACE unsuitable status. For rank-A patients, good prognosis with TACE can be expected, while TACE refractoriness status during the clinical course should be carefully evaluated so as to anticipate the appropriate timing for switching to systemic treatment in rank-B1 and -B2 patients.
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http://dx.doi.org/10.1159/000520292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820430PMC
February 2022

Early experience of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma BCLC-B stage patients classified as beyond up to seven criteria - Multicenter analysis.

Hepatol Res 2022 Mar 2;52(3):308-316. Epub 2021 Dec 2.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

Background/aim: Although systemic therapy is recommended for patients with multiple intermediate stage unresectable hepatocellular carcinoma (u-HCC) classified as beyond the up-to-7 criteria (UT-7 out/multiple) as a transcatheter arterial chemoembolization (TACE) unsuitable condition, few reports have examined the therapeutic efficacy of atezolizumab plus bevacizumab combination therapy (Atez/Bev) in such cases. This study aimed to elucidate the therapeutic response of Atez/Bev in u-HCC patients classified as UT-7 out/multiple.

Material/methods: From September 2020 to September 2021, 95 u-HCC Japanese patients classified as UT-7 out/multiple/Child-Pugh A were enrolled from 21 institutions (median age 76 years, males 73, Child-Pugh 5:6 = 68:27, TNM stage II:III = 17:78). Therapeutic response was retrospectively evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1 and modified RECIST (mRECIST).

Results: Atez/Bev was given as first-line treatment to 52 (54.7%). Objective response rate (ORR)/disease control rate (DCR) at six weeks of RECIST and mRECIST were 17.7%/84.7% and 42.5%/86.2%, respectively. Median PFS was 8.0 months (median observation period: 6.0 months). Child-Pugh A/modified Albumin-bilirubin grade (mALBI) 1 and 2a at baseline, 3, 6, and 9 weeks, were 100%/69.4%, 89.8%/57.3%, 94.8%/65.3%, and 91.4%/60.0%, respectively. Among adverse events (any-grade, >10%) during the present observation period, general fatigue was most frequent (23.2%), followed by urine protein (21.1%), appetite loss (20.0%), and hypertension (13.7%).

Conclusion: Atez/Bev treatment showed favorable therapeutic response with less influence on hepatic function, suggesting it as a useful therapeutic option for patients with such condition.
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http://dx.doi.org/10.1111/hepr.13734DOI Listing
March 2022

Utility of Ultrasound-Guided Attenuation Parameter for Grading Steatosis With Reference to MRI-PDFF in a Large Cohort.

Clin Gastroenterol Hepatol 2021 Nov 10. Epub 2021 Nov 10.

Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.

Background & Aims: Ultrasound-guided attenuation parameter (UGAP) is recently developed for noninvasive evaluation of steatosis. However, reports on its usefulness in clinical practice are limited. This prospective multicenter study analyzed the diagnostic accuracy of grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), a noninvasive method with high accuracy, in a large cohort.

Methods: Altogether, 1010 patients with chronic liver disease who underwent MRI-PDFF and UGAP were recruited and prospectively enrolled from 6 Japanese liver centers. Linearity was evaluated using intraclass correlation coefficients between MRI-PDFF and UGAP values. Bias, defined as the mean difference between MRI-PDFF and UGAP values, was assessed by Bland-Altman analysis. UGAP cutoffs for pairwise MRI-PDFF-based steatosis grade were determined using area under the receiver-operating characteristic curve (AUROC) analyses.

Results: UGAP values were shown to be normally distributed. However, because PDFF values were not normally distributed, they were log-transformed (MRI-logPDFF). UGAP values significantly correlated with MRI-logPDFF (intraclass correlation coefficient = 0.768). Additionally, Bland-Altman analysis showed good agreement between MRI-logPDFF and UGAP with a mean bias of 0.0002% and a narrow range of agreement (95% confidence interval [CI], -0.015 to 0.015). The AUROCs for distinguishing steatosis grade ≥1 (MRI-PDFF ≥5.2%), ≥2 (MRI-PDFF ≥11.3%), and 3 (MRI-PDFF ≥17.1%) were 0.910 (95% CI, 0.891-0.928), 0.912 (95% CI, 0.894-0.929), and 0.894 (95% CI, 0.873-0.916), respectively.

Conclusions: UGAP has excellent diagnostic accuracy for grading steatosis with reference to MRI-PDFF. Additionally, UGAP has good linearity and negligible bias, suggesting that UGAP has excellent technical performance characteristics that can be widely used in clinical trials and patient care. (UMIN Clinical Trials Registry, Number: UMIN000041196).
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http://dx.doi.org/10.1016/j.cgh.2021.11.003DOI Listing
November 2021

Development and multicenter validation of FIB-6: A novel, machine learning, simple bedside score to rule out liver cirrhosis and compensated advanced chronic liver disease in patients with chronic hepatitis C.

Hepatol Res 2022 Feb 24;52(2):165-175. Epub 2021 Nov 24.

Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.

Background: Non-invasive tests (NITs), such as Fibrosis-4 index (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI), developed using classical statistical methods, are increasingly used for determining liver fibrosis stages and recommended in treatment guidelines replacing the liver biopsy. Application of conventional cutoffs of FIB-4 and APRI resulted in high rates of misclassification of fibrosis stages.

Aim: There is an unmet need for more accurate NITs that can overcome the limitations of FIB-4 and APRI.

Patients And Methods: Machine learning with the random forest algorithm was used to develop a non-invasive index using retrospective data of 7238 patients with biopsy-proven chronic hepatitis C from two centers in Egypt; derivation dataset (n = 1821) and validation set in the second center (n = 5417). Receiver operator curve analysis was used to define cutoffs for different stages of fibrosis. Performance of the new score was externally validated in cohorts from two other sites in Egypt (n = 560) and seven different countries (n = 1317). Fibrosis stages were determined using the METAVIR score. Results were also compared with three established tools (FIB-4, APRI, and the aspartate aminotransferase-to-alanine aminotransferase ratio [AAR]).

Results: Age in addition to readily available laboratory parameters such as aspartate, and alanine aminotransferases, alkaline phosphatase, albumin (g/dl), and platelet count (/cm ) correlated with the biopsy-derived stage of liver fibrosis in the derivation cohort and were used to construct the model for predicting the fibrosis stage by applying the random forest algorithm, resulting in an FIB-6 index, which can be calculated easily at http://fib6.elriah.info. Application of the cutoff values derived from the derivation group on the validation groups yielded very good performance in ruling out cirrhosis (negative predictive value [NPV] = 97.7%), compensated advance liver disease (NPV = 90.2%), and significant fibrosis (NPV = 65.7%). In the external validation groups from different countries, FIB-6 demonstrated higher sensitivity and NPV than FIB-4, APRI, and AAR.

Conclusion: FIB-6 score is a non-invasive, simple, and accurate test for ruling out liver cirrhosis and compensated advance liver disease in patients with chronic hepatitis C and performs better than APRI, FIB-4, and AAR.
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http://dx.doi.org/10.1111/hepr.13729DOI Listing
February 2022

Hepatocellular Carcinoma Risk Assessment for Patients With Advanced Fibrosis After Eradication of Hepatitis C Virus.

Hepatol Commun 2022 03 22;6(3):461-472. Epub 2021 Oct 22.

Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase < 28 IU/L, alpha-fetoprotein < 4.0 ng/mL, and Fibrosis-4 Index < 4.28) were classified as low-risk and others were classified as high-risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low-risk patients (0.5-1.1 per 100 person-years in the derivation cohort and 0.9-1.1 per 100 person-years in the validation cohort) than in high-risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high-risk to low-risk (HCC incidence: 0.6 per 100 person-years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person-years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.
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http://dx.doi.org/10.1002/hep4.1833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870028PMC
March 2022

Mortality of inactive hepatitis B virus carriers in Japan is similar to that of the general population.

Hepatol Res 2022 Jan 3;52(1):81-92. Epub 2021 Nov 3.

Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

Aims: Data on the long-term outcomes of individuals with hepatitis B virus (HBV) infection who are hepatitis envelope antigen (HBeAg)-negative inactive carriers (ICs) are limited due to small numbers. We compared the long-term prognosis of well-defined ICs with that of age- and gender-matched general population controls.

Methods: A total of 526 HBeAg-negative patients who demonstrated alanine aminotransferase (ALT) level ≤40 U/L and HBV DNA level ≤4.3 log IU/ml at least three times within 1 year after the start of follow-up were enrolled as ICs. Inactive carriers were divided into two groups: Group A (n = 332), whose ALT level was ≤30 U/L and HBV DNA level was ≤3.3 log IU/ml, and Group B (remaining patients, n = 194). We determined the long-term prognosis of ICs and compared it with that of general population controls. We also analyzed factors associated with hepatitis B surface antigen (HBsAg) clearance and phase transition in ICs.

Results: There were no significant differences in hepatocellular carcinoma development or all-cause, liver-related, or non-liver-related mortality between Groups A and B. There was no significant difference in all-cause mortality between ICs and the general population. Low HBsAg level (≤3.0 log IU/ml) and the presence of fatty liver were associated with HBsAg clearance and high alpha-fetoprotein level was associated with phase transition.

Conclusions: The long-term prognosis of well-defined ICs was similar to that of general population controls. In addition, the ICs had a high HBsAg clearance rate and low phase transition rate.
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http://dx.doi.org/10.1111/hepr.13723DOI Listing
January 2022

Immune-related Liver Injury is a Poor Prognostic Factor in Patients with Nonsmall Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Cancer Invest 2022 Feb 29;40(2):189-198. Epub 2021 Nov 29.

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

It remains unclear whether severe liver immune-related adverse events (liver-irAEs) can affect the prognosis in nonsmall cell lung carcinoma (NSCLC) patients. Of the 365 NSCLC patients treated with immune checkpoint inhibitors (ICIs), 19 suffered from severe liver-irAEs (grade ≥3). The median time-to-onset of liver-irAEs was 53 days postinjection of the first ICI. The progression-free survival and overall survival of the liver-irAEs group (median 69 and 262 days, respectively) were significantly worse than the nonliver-irAEs group (128 and 722 days;  = 0.010 and  = 0.007; respectively). In conclusion, liver-irAEs were associated with poor prognosis in NSCLC patients.
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http://dx.doi.org/10.1080/07357907.2021.1994586DOI Listing
February 2022

Safety, feasibility, and comfort of hepatic angiography and transarterial intervention with radial access for hepatocellular carcinoma.

JGH Open 2021 Sep 30;5(9):1041-1046. Epub 2021 Jul 30.

Department of Nursing Gifu Kyoritsu University Ogaki Japan.

Background And Aim: Hepatic angiography procedures such as transarterial chemoembolization (TACE) are essential procedures for managing patients with hepatocellular carcinoma (HCC), and are usually performed with femoral access. However, femoral access causes patient discomfort and may be associated with the risk of hematoma or pseudoaneurysm at puncture site. We evaluated the safety, feasibility, and patient comfort of hepatic angiography procedures performed with radial access.

Methods: In this single-institution, retrospective, time-frame study, a total of 206 patients who underwent hepatic angiography procedures with radial access, which were first used on October 2017 at our institution, were compared with 240 patients who underwent the same procedures with femoral access before this period. Several measures were assessed, including procedure time and safety. In addition, a questionnaire was used to compare the access types regarding procedure-associated discomfort.

Results: Hepatic angiography procedures performed with radial access, including TACE, were completed in all patients without complications. The procedure time was comparable between radial access and femoral access. Most patients preferred radial to femoral access. Patients taking anticoagulants were able to complete the procedures without discontinuing these drugs.

Conclusions: Hepatic angiography procedures with radial access resulted in less discomfort than those with femoral access, and the two approaches showed similar feasibility and safety. Radial access can be introduced as a routine technique for hepatic angiography procedures.
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http://dx.doi.org/10.1002/jgh3.12628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454468PMC
September 2021

A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C.

PLoS One 2021 10;16(9):e0257166. Epub 2021 Sep 10.

Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan.

Evaluating liver fibrosis is crucial for disease severity assessment, treatment decisions, and hepatocarcinogenic risk prediction among patients with chronic hepatitis C. In this retrospective multicenter study, we aimed to construct a novel model formula to predict cirrhosis. A total of 749 patients were randomly allocated to training and validation sets at a ratio of 2:1. Liver stiffness measurement (LSM) was made via transient elastography using FibroScan. Patients with LSM ≥12.5 kPa were regarded as having cirrhosis. The best model formula for predicting cirrhosis was constructed based on factors significantly and independently associated with LSM (≥12.5 kPa) using multivariate regression analysis. Among the 749 patients, 198 (26.4%) had LSM ≥12.5 kPa. In the training set, multivariate analysis identified logarithm natural (ln) type IV collagen 7S, ln hyaluronic acid, and ln Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-Mac-2 BP) as the factors that were significantly and independently associated with LSM ≥12.5 kPa. Thus, the formula was constructed as follows: score = -6.154 + 1.166 × ln type IV collagen 7S + 0.526 × ln hyaluronic acid + 1.069 × WFA+-Mac-2 BP. The novel formula yielded the highest area under the curve (0.882; optimal cutoff, -0.381), specificity (81.5%), positive predictive values (62.6%), and predictive accuracy (81.6%) for predicting LSM ≥12.5 kPa among fibrosis markers and indices. These results were almost similar to those in the validated set, indicating the reproducibility and validity of the novel formula. The novel formula scores were significantly, strongly, and positively correlated with LSM values in both the training and validation data sets (correlation coefficient, 0.721 and 0.762; p = 2.67 × 10-81 and 1.88 × 10-48, respectively). In conclusion, the novel formula was highly capable of diagnosing cirrhosis in patients with chronic hepatitis C and exhibited better diagnostic performance compared to conventional fibrosis markers and indices.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257166PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432856PMC
November 2021

Long-term persistence of hepatocarcinogenic potential of a non-hypervascular hypointense nodule on EOB-MRI after the eradication of hepatitis C virus.

Hepatol Res 2022 Jan 17;52(1):128-132. Epub 2021 Sep 17.

Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.

Non-hypervascular hypointense nodules (NHHNs) on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of hypervascularization progressing to typical hypervascular hepatocellular carcinoma (HCC). NHHNs that were present before the start of anti-hepatitis C virus (HCV) therapy is a risk marker for HCC development after achieving sustained virologic response (SVR). In this report, we show a patient without a previous history of HCC in whom HCC developed by hypervascularization of NHHN after SVR. This patient achieved SVR more than 8 years before NHHN developed into HCC, and during this time NHHN had been present but had remained unchanged in size and imaging features as shown by repeated EOB-MRI. Hepatocarcinogenic potential of NHHNs persist for a long time after SVR, despite the eradication of HCV.
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http://dx.doi.org/10.1111/hepr.13707DOI Listing
January 2022

GALAD Score Detects Early-Stage Hepatocellular Carcinoma in a European Cohort of Chronic Hepatitis B and C Patients.

Pharmaceuticals (Basel) 2021 Jul 27;14(8). Epub 2021 Jul 27.

Department of Gastroenterology and Hepatology, University Hospital Essen, 45147 Essen, Germany.

Despite vaccination programs and direct antiviral treatments, the incidence of virus-related hepatocellular carcinoma (HCC) remains high, while ultrasound-based detection rates for early-stage HCC is continuously low. To address this insufficiency, we set out to characterize whether the GALAD score, which incorporates gender, age, and serum levels of AFP, AFP isoform L3 (AFP-L3), and des-gamma-carboxy-prothrombin (DCP), can improve early-stage HCC detection in a Caucasian HBV/HCV cohort. In a retrospective German single-center study, 182 patients with HBV, 223 with HCV and 168 with other etiology (OE) of chronic liver disease (CLD) were enrolled. HCC was confirmed in 52 HBV, 84 HCV and 60 OE CLD patients. The diagnostic performance of the single biomarkers in HCC detection was compared to the GALAD model. At initial diagnosis, most patients were at (very) early BCLC 0 ( = 14/7%) or A ( = 56/29%) or intermediate stage BCLC B ( = 93/47%) HCC in all three subgroups. In the BCLC 0/A cohort, GALAD exhibited an AUC of 0.94 discriminating HCC from non-HCC, surpassing AFP (AUC 0.86), AFP-L3 (AUC 0.83) and DCP (AUC 0.83). In the HBV population, GALAD achieved an AUC of 0.96, in HCV an AUC of 0.98 and in OE an AUC of 0.99, clearly superior to the biomarkers alone. Furthermore, in HCV patients GALAD showed a significantly higher specificity (89%) versus AFP (64%) alone. In chronic viral hepatitis, the GALAD model showed superior performance in detection of early-stage HCC, while exhibiting higher specificity in HCV patients compared to AFP alone. We conclude that the GALAD score shows potential for HCC surveillance in Caucasian HBV/HCV patients.
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http://dx.doi.org/10.3390/ph14080735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401792PMC
July 2021

Diagnostic Accuracy of Two-Dimensional Shear Wave Elastography for Liver Fibrosis: A Multicenter Prospective Study.

Clin Gastroenterol Hepatol 2022 Jun 20;20(6):e1478-e1482. Epub 2021 Aug 20.

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.

Chronic liver disease (CLD) leads to the development of hepatocellular carcinoma, which is one of the leading causes of cancer-related deaths globally. Liver fibrosis is the most important prognostic factor for hepatocellular carcinoma development and prognosis in CLD, and accurate staging of liver fibrosis is pivotal in clinical practice. Although liver biopsy is the gold standard for evaluating liver fibrosis, liver biopsy has several limitations including invasiveness, sampling error, and intraobserver and interobserver reproducibility. To resolve these problems, several noninvasive methods for evaluating liver fibrosis have been developed using serum fibrosis markers, ultrasound-based modalities, and magnetic resonance imaging-based modalities..
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http://dx.doi.org/10.1016/j.cgh.2021.08.021DOI Listing
June 2022
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