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  • 1
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    Online Resource
    Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 9 ( 2022-04-27), p. 2463-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 9 ( 2022-04-27), p. 2463-
    Abstract: Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9–15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR 〉 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11092463
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 2
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    Long-Term Prediction Model for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Antiviral Therapy: Based on Data from Korean Patients
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 22 ( 2022-11-08), p. 6613-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 22 ( 2022-11-08), p. 6613-
    Abstract: Predicting the development of hepatocellular carcinoma (HCC) is a key clinical issue in patients with chronic hepatitis B (CHB). The aim of this study was to develop a precise and simple HCC risk score for up to 10 years. A total of 1895 CHB patients treated with entecavir or tenofovir disoproxil fumarate were retrospectively recruited and randomized into derivation (n = 1239) and validation cohorts (n = 656). Variables proven to be independent risk factors for HCC in the derivation cohort were used to develop the prediction model. The ACCESS-HCC model included five variables (age, cirrhosis, consumption of ethanol, liver stiffness, and serum alanine aminotransferase). Areas under curves were 0.798, 0.762, and 0.883 for HCC risk at 3, 5, and 10 years, respectively, which were higher than those of other prediction models. The scores were categorized according to significantly different HCC incidences: 0–4, low; 5–8, intermediate; and 9–14, high-risk. The annual incidence rates were 0.5%, 3.2%, and 11.3%, respectively. The performance of this model was validated in an independent cohort. The ACCESS-HCC model shows improved long-term prediction and provides three distinct risk categories for HCC in CHB patients receiving antiviral therapy. Further research is needed for external validation using larger cohorts.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11226613
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 3
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    How Should We Assign Large Infiltrative Hepatocellular Carcinomas for Staging?
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 9 ( 2020-09-10), p. 2589-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 9 ( 2020-09-10), p. 2589-
    Abstract: Infiltrative gross morphology of hepatocellular carcinoma (HCC) is known to be associated with poor prognosis, but this is not considered for staging. A total of 774 HCC patients who underwent curative liver resection were retrospectively reviewed and the prognostic significance of infiltrative type HCC was assessed using the American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) staging systems. Seventy-four patients (9.6%) had infiltrative HCCs with a higher proportion of multifocal tumors, larger tumors, vessel invasion, increased tumor marker levels, and advanced T-stages than those with nodular HCC (all, p 〈 0.01). Infiltrative morphology was independently associated with lower overall survival (OS), but its impact was significant when the tumor size was ≥ 4 cm (p 〈 0.001). Under current AJCC and BCLC staging criteria, these large infiltrative HCCs were associated with significantly worse OS in early AJCC T-stages (T1b/T2, p 〈 0.001) and BCLC stage A/B (both, p 〈 0.01) but not in late AJCC (T3/T4) and BCLC C. The reassignment of this subtype to T3 and T4 increased the discriminatory ability of AJCC T-staging with lower AIC values (3090 and 3088 vs. 3109) and higher c-index (0.69 and 0.69 vs. 0.67), respectively (both, p 〈 0.001). Similarly, the reassignment of large infiltrative HCC to BCLC stages B and C also improved the prognostic performance. Large infiltrative HCCs should be assigned to more advanced stages in current staging systems for their prognostic impact.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12092589
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Diagnostic Efficacy of Serum Asialo α1-Acid Glycoprotein Levels for Advanced Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis B Compared to That in Healthy Subjects: A Prospective Study
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 2 ( 2023-01-16), p. 712-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 2 ( 2023-01-16), p. 712-
    Abstract: Background: Serum asialo α1-acid gycoprotein (AsAGP) is a novel biomarker specific to liver fibrosis. Aim: To evaluate the diagnostic efficacy of serum AsAGP levels in classifying the severity of liver fibrosis and differentiating liver cirrhosis (LC) in patients with chronic hepatitis B (CHB) from healthy controls. Methods: Overall, 206 subjects were prospectively enrolled. LC was diagnosed based on liver stiffness levels ( 〉 11 kPa) measured using transient elastography. Serum AsAGP levels were measured using an antibody-lectin sandwich immunoassay. We investigated the diagnostic performance by comparing serum AsAGP levels among healthy control, CHB, and CHB with LC groups. Sensitivity, specificity, and optimal AsAGP cut-off values were also calculated. Results: Serum AsAGP levels were significantly different between healthy controls, CHB patients, and CHB patients with LC (1.04 ± 0.31 µg/mL, 1.12 ± 0.34 µg/mL, 1.51 ± 0.43 µg/mL respectively; p 〈 0.001). Serum AsAGP levels positively correlated with liver stiffness (r = 0.46, p 〈 0.001). AUROC of healthy control versus CHB with LC was 0.821 (p 〈 0.001, optimal cut-off 1.036 µg/mL). AUROC of healthy control versus CHB was 0.624 (p = 0.049, optimal cut-off level 0.934 µg/mL). AUROC of CHB versus CHB with LC was 0.765, (p 〈 0.001, optimal cut-off 1.260 µg/mL). Conclusions: Serum AsAGP levels in CHB patients with LC were significantly higher than those in healthy controls and CHB patients. AsAGP levels showed good diagnostic performance in predicting advanced fibrosis and cirrhosis, which suggests a potential role as a biomarker for predicting the progression of liver disease in CHB.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12020712
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 5
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    Early Normalization of Alanine Aminotransferase during Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in HBV Patients
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 9 ( 2021-04-23), p. 1840-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 9 ( 2021-04-23), p. 1840-
    Abstract: Potent antiviral agents effectively reduce liver-related events in patients with chronic hepatitis B. This study aimed to determine whether alanine aminotransferase normalization using potent antiviral agents was related to hepatocellular carcinoma development. From 2007 to 2017, we included 610 patients with chronic hepatitis B who received entecavir or tenofovir disoproxil fumarate. The patients were divided into the alanine aminotransferase normalization group (Gr.1) and non-normalization group (Gr.2) within a year of potent antiviral treatment. Liver-related events included hepatic encephalopathy, variceal bleeding, and ascites. The mortality rate and hepatocellular carcinoma incidence were investigated for each group. The patients who showed ALT normalization at 1 year of treatment were 397 (65.1%) of 610. During a median follow-up period of 86 months, 65 (10.7%) patients developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma was significantly lower in Gr.1 than in Gr.2 (p 〈 0.001). Risk factors for alanine aminotransferase non-normalization were body mass index, cholesterol, and liver cirrhosis at baseline. Male sex, age, platelet level, alcohol use, presence of cirrhosis at baseline, and non-normalization after 1 year of treatment were independent risk factors for hepatocellular carcinoma. Alanine aminotransferase normalization within 1 year of initiating antiviral agents reduces the risk of hepatocellular carcinoma development.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10091840
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 6
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    The Influence of Histologic Inflammation on the Improvement of Liver Stiffness Values Over 1 and 3 Years
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 8, No. 12 ( 2019-11-24), p. 2065-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 12 ( 2019-11-24), p. 2065-
    Abstract: Background: Transient elastography is now an indispensable tool for estimating liver fibrosis. Although many clinical factors other than fibrosis itself are known to affect liver stiffness (LS) values, it is still not yet clear what factors are related to improving LS values. The aim of this study was to find out how baseline histologic inflammation influences LS values and how much this inflammation affects improvement in LS values over time, regardless of actual fibrosis content. Methods: This retrospective study included 678 consecutive patients who underwent liver biopsy and sequential LS assessment from 2006 to 2015 at six tertiary hospitals in Korea. Linear regression analysis was used to evaluate how improvement of LS value can be associated with other factors besides fibrosis content. Results: Basal LS values increased with increasing inflammation in the same fibrosis stage. Degree of inflammation influenced the baseline LS value in a proportional manner (beta coefficient (BE), 6.476; 95% confidence interval (CI), 2.24–10.72; p = 0.003). Moreover, histologic inflammation affected the change in LS value significantly. Higher inflammation grade at baseline was a significant predictor for an improvement in LS value, regardless of the fibrosis stage (BE, −8.581; 95% CI, −15.715–−1.447; p = 0.019). In a subgroup analysis of patients who received repeated liver biopsies, the results showed a similar tendency. Conclusions: The LS value is affected by the degree of inflammation even at a low ALT level. Furthermore, baseline histologic inflammation has a significant impact on the improvement of LS values over time. Therefore, baseline inflammation should be taken into consideration when interpreting an improvement in LS value.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm8122065
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
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  • 7
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    Outcome of Intermittent Thoracentesis versus Pigtail Catheter Drainage for Hepatic Hydrothorax
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 23 ( 2022-12-05), p. 7221-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 23 ( 2022-12-05), p. 7221-
    Abstract: Background/Aims: The management of hepatic hydrothorax (HH) remains a challenging clinical scenario with suboptimal options. We investigated the effect and safety of pigtail catheter drainage compared to intermittent thoracentesis. Methods: This multicenter, retrospective study included 164 cirrhotic patients with recurrent pleural effusion from March 2012 to June 2017. Patients with neoplasms, cardiopulmonary disease, and infectious conditions were excluded. We compared the clinical outcomes of pigtail catheter drainage versus thoracentesis for variables including complications related to procedures, overall survival, and re-admission rates. Results: A total of 164 patients were divided into pigtail catheter (n = 115) and thoracentesis (n = 49) groups. During the follow-up period of 6.93 months after discharge, 98 patients died (pigtail; n = 47 vs. thoracentesis; n = 51). The overall survival (p = 0.61) and 30-day mortality (p = 0.77) rates were similar between the pigtail catheter and thoracentesis groups. Only MELD scores were associated with overall survival (adjusted HR, 1.08; p 〈 0.01) in patients with HH. Spontaneous pleurodesis occurred in 59 patients (51.3%) in the pigtail catheter group. Re-admission rates did not differ between the pigtail catheter and thoracentesis groups (13.2% vs 19.6% p = 0.7). A total of five complications occurred, including four total cases of bleeding (one patient in the pigtail catheter group and three in the thoracentesis group) and one case of empyema in the pigtail catheter group. Conclusions: Pigtail catheter drainage is not inferior to that of intermittent thoracentesis for the management of HH, proving it may be an effective and safe clinical option.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11237221
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 8
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    The Role of Urinary N-Acetyl-β-d-glucosaminidase in Cirrhotic Patients with Acute Kidney Injury: Multicenter, Prospective Cohort Study
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 19 ( 2021-09-23), p. 4328-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 19 ( 2021-09-23), p. 4328-
    Abstract: Background and Aims: Currently, it is difficult to predict the reversibility of renal function and to discriminate renal parenchymal injury in cirrhotic patients with acute kidney injury (AKI). The aim of this study is to evaluate whether urine N-acetyl-β-d-Glucosaminidase (NAG) can predict the survival and response to terlipressin in cirrhotic patients with AKI. Methods: Two hundred sixty-two cirrhotic consecutive patients who developed AKI were prospectively enrolled from 11 tertiary medical centers in Korea between 2016 to 2019. AKI was defined as an increase in serum Cr (SCr) of 0.3 mg/dL or a 50% increase in baseline SCr. Patients diagnosed with hepatorenal syndrome (HRS-AKI) were treated with terlipressin plus albumin. Results: The patients were 58.8 ± 12.9 years old on average and were predominantly male (72.5%). The mean MELD score was 25.3 ± 9.1. When classified according to the AKI phenotype, there were 119 pre-renal, 52 acute tubular necrosis, 18 miscellaneous, and 73 HRS-AKI patients. However, the urine NAG was not effective at discriminating AKI phenotypes, except for HRS-AKI. The baseline urine NAG increased as the baseline AKI stage increased (p 〈 0.001). In addition, within the same AKI stage, the urine NAG values were significantly lower in the AKI-resolved group than in the unresolved group. The urine NAG level was significantly lower in living patients compared with those who died or who underwent a liver transplant within 3 months (p = 0.005). In the multivariate analysis, the increased urine NAG was a significant risk factor for the 3-month transplant-free survival (TFS) rate, especially in patients with Child–Pugh class ≤ B or MELD 〈 24. The urine NAG did not predict the response to terlipressin treatment in patients with HRS. Conclusions: Urine NAG is strongly associated with the severity of AKI in patients with liver cirrhosis and is useful for predicting the 3-month TFS.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10194328
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 9
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    Extraintestinal Manifestation of Yersinia pseudotuberculosis Bacteremia as Acute Hepatitis: Case Report and Review of the Literature
    MDPI AG ; 2021
    In:  Pathogens Vol. 10, No. 10 ( 2021-09-28), p. 1255-
    Details
    In: Pathogens, MDPI AG, Vol. 10, No. 10 ( 2021-09-28), p. 1255-
    Abstract: Yersinia pseudotuberculosis is a causative agent of foodborne zoonosis that usually causes self-limiting pseudoappendicitis. Y. pseudotuberculosis infection also causes systemic spread or extraintestinal manifestations in patients with predisposing conditions. Here, we present a case of acute hepatitis with Y. pseudotuberculosis bacteremia in a 30-year-old man. He was previously healthy without significant medical history other than obesity and current smoking. At the time of admission, he presented with high fever accompanied by chills, jaundice, abdominal pain, and watery diarrhea. Laboratory studies revealed leukocytosis and elevated liver function parameters. A stool culture showed no causative pathogens. Empiric antibiotic therapy with ceftriaxone and metronidazole was administered. Y. pseudotuberculosis was later isolated from the initial blood culture performed on the day of admission using MALDI-TOF mass spectrometry. Antibiotic treatment was continued based on the susceptibility testing results from MALDI-TOF MS and VITEk®2, as well as clinical and laboratory improvements. The patient was discharged on the tenth day of admission and remained healthy with no recurrence during the 12-month follow-up. Here, we review the literature on the systemic infection caused by Y. pseudotuberculosis, including extraintestinal manifestations. This case highlights that Y. pseudotuberculosis may be considered a differential causative organism in patients with acute colitis and hepatitis.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    URL: Article
    DOI: 10.3390/pathogens10101255
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2695572-6
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  • 10
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    The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice
    MDPI AG ; 2023
    In:  Pharmaceutics Vol. 15, No. 1 ( 2023-01-09), p. 222-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 15, No. 1 ( 2023-01-09), p. 222-
    Abstract: Uncontrolled chronic inflammation and necrosis is characteristic of inflammatory bowel disease (IBD). This study aimed to investigate the effect of necrosis inhibitor (NI, NecroX-7) on a dextran sulfate sodium (DSS) induced chronic colitis model of mice. DSS was administered on days 1–5, and the NI was administered intraperitoneally (3 mg/kg, 30 mg/kg) on days 1, 3, and 5 as well as every other day during the first five days of a three-week cycle. Three cycles of administration were performed. Colitis was evaluated based on the disease activity index (DAI) score, colon length, and histological score. Reverse transcription polymerase chain reaction testing, the Western blot assay, and immunohistochemical staining were performed to determine inflammatory cytokine levels. The NI reduced body weight change and the DAI score. Colon length and the histological score were longer and lower in the NI-treated groups, respectively. The NI decreased the expression of pro-inflammatory cytokines, particularly in tumor necrosis factor alpha (TNF-α) and phosphorylated nuclear factor kappa B (p-NF-κB). Immunohistochemical staining revealed decreased inducible nitric oxide synthase (iNOS) and high mobility group box 1 (HMGB1) levels. Overall, the NI improved DSS induced chronic colitis by attenuating the mRNA expression of pro-inflammatory cytokines such as TNF-α. Therefore, NI use is a potential, novel treatment approach for IBD.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics15010222
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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