Topic Editors

Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan
Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

Liver Fibrosis and Cirrhosis

Abstract submission deadline
closed (31 August 2022)
Manuscript submission deadline
closed (30 November 2022)
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Topic Information

Dear Colleagues,

Liver fibrosis and cirrhosis are caused by a wide range of chronic liver diseases, including hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcoholic-related liver disease, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver diseases. Recent advances in molecular and cellular techniques have succeeded in providing new aspects in the diagnosis and treatment of liver fibrosis and cirrhosis. This Special Issue aims to cover the state-of-the-art researches on the basic and clinical findings in relation to the liver fibrosis and cirrhosis. We invite authors to submit original articles, as well as review articles regarding recent findings about liver fibrosis and cirrhosis. We are particularly interested in molecular approaches for the diagnosis and treatment of chronic liver diseases. Potential topics include, but are not limited to:

  • Biomarkers for liver fibrosis/cirrhosis and their complications
  • Genomic researches for chronic liver diseases and their complications, including gene SNPs (Single Nucleotide Polymorphisms)
  • Molecular mechanisms of liver fibrosis/cirrhosis and their complications
  • Recent advances in the management of liver fibrosis and cirrhosis
  • Molecularly-targeted therapy for liver cancer

Dr. Hirayuki Enomoto
Dr. Tatsuo Kanda
Topic Editors

Keywords

  • biomarker
  • genomic research
  • epigenomic research
  • molecular mechanisms
  • viral hepatitis
  • alcoholic-related liver disease
  • non-alcoholic fatty liver disease
  • autoimmune liver diseases
  • liver cirrhosis
  • hepatocellular carcinoma

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Diagnostics
diagnostics
3.6 3.6 2011 20.7 Days CHF 2600
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900
Journal of Clinical Medicine
jcm
3.9 5.4 2012 17.9 Days CHF 2600
Livers
livers
- - 2021 22 Days CHF 1000
Medicina
medicina
2.6 3.6 1920 19.6 Days CHF 1800

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Published Papers (30 papers)

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11 pages, 1566 KiB  
Article
Splenic Arterial Pulsatility Index to Predict Hepatic Fibrosis in Hemodialysis Patients with Chronic Hepatitis C Virus Infection
by Chen-Hua Liu, Yu-Jen Fang, Chun-Jen Liu, Tung-Hung Su, Shang-Chin Huang, Tai-Chung Tseng, Jo-Hsuan Wu, Pei-Jer Chen and Jia-Horng Kao
J. Clin. Med. 2023, 12(5), 2020; https://doi.org/10.3390/jcm12052020 - 3 Mar 2023
Viewed by 1125
Abstract
The clinical utility of the splenic arterial pulsatility index (SAPI), a duplex Doppler ultrasonographic index, to predict the stage of hepatic fibrosis in hemodialysis patients with chronic hepatitis C virus (HCV) infection remains elusive. We conducted a retrospective, cross-sectional study to include 296 [...] Read more.
The clinical utility of the splenic arterial pulsatility index (SAPI), a duplex Doppler ultrasonographic index, to predict the stage of hepatic fibrosis in hemodialysis patients with chronic hepatitis C virus (HCV) infection remains elusive. We conducted a retrospective, cross-sectional study to include 296 hemodialysis patients with HCV who underwent SAPI assessment and liver stiffness measurements (LSMs). The levels of SAPI were significantly associated with LSMs (Pearson correlation coefficient: 0.413, p < 0.001) and different stages of hepatic fibrosis as determined using LSMs (Spearman’s rank correlation coefficient: 0.529, p < 0.001). The areas under receiver operating characteristics (AUROCs) of SAPI to predict the severity of hepatic fibrosis were 0.730 (95% CI: 0.671–0.789) for ≥F1, 0.782 (95% CI: 0.730–0.834) for ≥F2, 0.838 (95% CI: 0.781–0.894) for ≥F3, and 0.851 (95% CI: 0.771–0.931) for F4. Furthermore, the AUROCs of SAPI were comparable to those of the fibrosis index based on four parameters (FIB-4) and superior to those of the aspartate transaminase (AST)-to-platelet ratio index (APRI). The positive predictive value (PPV) for ≥F1 was 79.5% when the Youden index was set at 1.04, and the negative predictive values (NPVs) for ≥F2, ≥F3, and F4 were 79.8%, 92,6%, and 96.9%, respectively, when the maximal Youden indices were set at 1.06, 1.19, and 1.30. The diagnostic accuracies of SAPI with the maximal Youden index for a fibrosis stage of ≥F1, ≥F2, ≥F3, and F4 were 69.6%, 67.2%, 75.0%, and 85.1%, respectively. In conclusion, SAPI can serve as a good noninvasive index in predicting the severity of hepatic fibrosis in hemodialysis patients with chronic HCV infection. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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15 pages, 1683 KiB  
Article
Assessing Liver Fibrosis Using 2D-SWE Liver Ultrasound Elastography and Dynamic Liver Scintigraphy with 99mTc-mebrofenin: A Comparative Prospective Single-Center Study
by Donatas Jocius, Donatas Vajauskas, Artūras Samuilis, Kipras Mikelis, Skirmante Jokubauskiene, Kestutis Strupas and Algirdas E. Tamosiunas
Medicina 2023, 59(3), 479; https://doi.org/10.3390/medicina59030479 - 28 Feb 2023
Cited by 1 | Viewed by 1601
Abstract
Background and Objectives: Many quantitative imaging modalities are available that quantify chronic liver disease, although only a few of them are included in clinical guidelines. Many more imaging options are still competing to find their place in the area of diagnosing chronic liver [...] Read more.
Background and Objectives: Many quantitative imaging modalities are available that quantify chronic liver disease, although only a few of them are included in clinical guidelines. Many more imaging options are still competing to find their place in the area of diagnosing chronic liver disease. We report our first prospective single-center study evaluating different imaging modalities that stratify viral hepatitis-associated liver fibrosis in a treatment-naïve patient group. Materials and Methods: The aim of our study is to compare and to combine already employed 2D shear wave elastography (2D-SWE) with dynamic liver scintigraphy with 99mTc-mebrofenin in chronic viral hepatitis patients for the staging of liver fibrosis. Results: Seventy-two patients were enrolled in the study. We found that both 2D-SWE ultrasound imaging, with dynamic liver scintigraphy with 99mTc-mebrofenin are able to stratify CLD patients into different liver fibrosis categories based on histological examination findings. We did not find any statistically significant difference between these imaging options, which means that dynamic liver scintigraphy with 99mTc-mebrofenin is not an inferior imaging technique. A combination of these imaging modalities showed increased accuracy in the non-invasive staging of liver cirrhosis. Conclusions: Our study presents that 2D-SWE and dynamic liver scintigraphy with 99mTc-mebrofenin could be used for staging liver fibrosis, both in singular application and in a combined way, adding a potential supplementary value that represents different aspects of liver fibrosis in CLD. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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16 pages, 2906 KiB  
Article
Role of B Cell-Activating Factor in Fibrosis Progression in a Murine Model of Non-Alcoholic Steatohepatitis
by Kozue Kanemitsu-Okada, Masanori Abe, Yoshiko Nakamura, Teruki Miyake, Takao Watanabe, Osamu Yoshida, Yohei Koizumi, Masashi Hirooka, Yoshio Tokumoto, Bunzo Matsuura, Mitsuhito Koizumi and Yoichi Hiasa
Int. J. Mol. Sci. 2023, 24(3), 2509; https://doi.org/10.3390/ijms24032509 - 28 Jan 2023
Cited by 1 | Viewed by 1933
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease all over the world. Therapeutic strategies targeting its multidirectional pathways are required. Particularly, fibrosis is closely associated with its prognosis. We previously found that B cell-activating factor (BAFF) is associated with [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease all over the world. Therapeutic strategies targeting its multidirectional pathways are required. Particularly, fibrosis is closely associated with its prognosis. We previously found that B cell-activating factor (BAFF) is associated with severity of NAFLD. Here, we determined the direct in vivo role of BAFF in the development of liver fibrosis. Histological and biochemical analyses were performed using wild-type and BAFF-deficient mice. We established a murine model of non-alcoholic steatohepatitis (NASH) using carbon tetrachloride injection accompanied by high-fat/high-cholesterol diet feeding. Additionally, in vitro analysis using mouse macrophage-like cell line RAW264.7 and primary hepatic stellate cells was performed. Hepatic steatosis and inflammation, and most importantly, the progression of liver fibrosis, were ameliorated in BAFF-deficient mice compared to those wild-type mice in our model. Additionally, BAFF deficiency reduced the number of CD11c+ M1-type macrophages in the liver. Moreover, BAFF stimulated RAW264.7 cells to secrete nitric oxide and tumor necrosis factor α, which drove the activation of hepatic stellate cells. This indicates that BAFF plays a crucial role in NASH development and may be a promising therapeutic target for NASH. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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12 pages, 1628 KiB  
Article
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
by Yoonseok Lee, Seryun Bae, Ji Hoon Kim, Minjung Kwak, So Yeon Jeon, Taehyung Kim, Sun Young Yim, Young-Sun Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon and Kwan Soo Byun
J. Clin. Med. 2023, 12(2), 712; https://doi.org/10.3390/jcm12020712 - 16 Jan 2023
Cited by 2 | Viewed by 1378
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) [...] Read more.
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. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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16 pages, 467 KiB  
Article
Low-Cost Predictors for Liver Function and Clinical Outcomes after Sustained Virological Response in Patients with HCV-Related Cirrhosis and Thrombocytopenia
by Secil Omer, Adrian Iftime, Ileana Constantinescu and Ion Dina
Medicina 2023, 59(1), 146; https://doi.org/10.3390/medicina59010146 - 11 Jan 2023
Viewed by 1790
Abstract
Background and Objectives: To find low-cost markers that can identify the hepatitis C virus cirrhotic patients that are at risk for long-term severe adverse liver effects (ascites, ascites or upper gastrointestinal bleeding, hepatocellular carcinoma), after treatment. There is established evidence for the [...] Read more.
Background and Objectives: To find low-cost markers that can identify the hepatitis C virus cirrhotic patients that are at risk for long-term severe adverse liver effects (ascites, ascites or upper gastrointestinal bleeding, hepatocellular carcinoma), after treatment. There is established evidence for the benefits of treating hepatitis C virus cirrhotic patients, but there is still some need for clarification concerning the real impact on the long-term evolution after achieving sustained virological response; there is no general consensus in the literature about identifying the patients that do not improve post-treatment. Materials and Methods: Our retrospective analysis investigated the long-term (2 years) evolution of 46 patients with cirrhosis with thrombocytopenia, previously infected with VHC, treated and who obtained an SVR after DAA treatment. Results: Despite the overall improvement, 8.7% patients developed hepatocellular carcinoma and 6.5% patients ascites/upper GI bleeding. We found that FIB-4, MELD and AFP changes at 1 year were the most significant predictors for these outcomes. Additionally, a drop in leukocyte count after 1 year seemed to indicate a risk for hepatocellular carcinoma, but this was not consistent. Conclusions: It might be beneficial to intensify the surveillance for post-treatment adverse liver effects for the patients with these marker changes at 1 year. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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10 pages, 1292 KiB  
Article
Distinct Expression Patterns of Genes Coding for Biological Response Modifiers Involved in Inflammatory Responses and Development of Fibrosis in Chronic Hepatitis C: Upregulation of SMAD-6 and MMP-8 and Downregulation of CAV-1, CTGF, CEBPB, PLG, TIMP-3, MMP-1, ITGA-1, ITGA-2 and LOX
by Leona Radmanić, Petra Korać, Lana Gorenec, Petra Šimičić, Kristian Bodulić, Adriana Vince and Snježana Židovec Lepej
Medicina 2022, 58(12), 1734; https://doi.org/10.3390/medicina58121734 - 27 Nov 2022
Cited by 2 | Viewed by 1656
Abstract
Background and Objectives: The aim of this study was to analyze the expression of genes on transcriptomic levels involved in inflammatory immune responses and the development of fibrosis in patients with chronic hepatitis C. Materials and Methods: Expression patterns of 84 [...] Read more.
Background and Objectives: The aim of this study was to analyze the expression of genes on transcriptomic levels involved in inflammatory immune responses and the development of fibrosis in patients with chronic hepatitis C. Materials and Methods: Expression patterns of 84 selected genes were analyzed with real-time quantitative RT PCR arrays in the peripheral blood of treatment-naive patients with chronic hepatitis C and healthy controls. The panel included pro- and anti-fibrotic genes, genes coding for extracellular matrix (EMC) structural constituents and remodeling enzymes, cell adhesion molecules, inflammatory cytokines, chemokines and growth factors, signal transduction members of the transforming growth factor- beta (TGF-ß) superfamily, transcription factors, and genes involved in epithelial to mesenchymal transition. Results: The expression of SMAD-6 coding for a signal transduction TGF-beta superfamily member as well as MMP-8 coding for an ECM protein were significantly increased in CHC patients compared with controls. Conclusions: Chronic hepatitis C was also characterized by a significant downregulation of a set of genes including CAV-1, CTGF, TIMP-3, MMP-1, ITGA-1, LOX, ITGA-2, PLG and CEBPB encoding various biological response modifiers and transcription factors. Our results suggest that chronic hepatitis C is associated with distinct patterns of gene expression modulation in pathways associated with the regulation of immune responses and development of fibrosis. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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15 pages, 906 KiB  
Review
Liver Fibrosis, Liver Cancer, and Advances in Therapeutic Approaches
by Indu Rajapaksha
Livers 2022, 2(4), 372-386; https://doi.org/10.3390/livers2040028 - 2 Nov 2022
Cited by 2 | Viewed by 2960
Abstract
Chronic liver diseases (CLDs) that lead to hepatic fibrosis, cirrhosis, and/or hepatocellular carcinoma (HCC) have become a major cause of illness and death worldwide. The main causative factors for CLDs are chronic viral infections, excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD), and [...] Read more.
Chronic liver diseases (CLDs) that lead to hepatic fibrosis, cirrhosis, and/or hepatocellular carcinoma (HCC) have become a major cause of illness and death worldwide. The main causative factors for CLDs are chronic viral infections, excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD), and cholestatic diseases. The primary approach to managing cirrhosis should be removing the causative agent, and the secondary approach should address fibrogenesis. Liver cancer is also a leading cause of death worldwide, and many therapeutic approaches exist to treat the disease. However, liver transplantation remains the last treatment option for cirrhosis and liver cancer. Thus, this review discusses the pathophysiology of liver fibrosis, its progression to cirrhosis and HCC, and current therapeutic options available to treat the diseases with potential therapeutic options that will be available in the near future. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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16 pages, 2085 KiB  
Article
Quantitative Assessment of Liver Impairment in Chronic Viral Hepatitis with [99mTc]Tc-Mebrofenin: A Noninvasive Attempt to Stage Viral Hepatitis-Associated Liver Fibrosis
by Donatas Jocius, Donatas Vajauskas, Kipras Mikelis, Skirmante Jokubauskiene, Jolita Jakutiene, Kestutis Strupas and Algirdas E. Tamosiunas
Medicina 2022, 58(10), 1333; https://doi.org/10.3390/medicina58101333 - 23 Sep 2022
Cited by 1 | Viewed by 1927
Abstract
Background and objectives—Chronic viral hepatitis B and C infections are one of the leading causes of chronic liver impairment, resulting in liver fibrosis and liver cirrhosis. An early diagnosis with accurate liver fibrosis staging leads to a proper diagnosis, thus tailoring correct [...] Read more.
Background and objectives—Chronic viral hepatitis B and C infections are one of the leading causes of chronic liver impairment, resulting in liver fibrosis and liver cirrhosis. An early diagnosis with accurate liver fibrosis staging leads to a proper diagnosis, thus tailoring correct treatment. Both invasive and noninvasive techniques are used in the diagnosis and staging of chronic liver impairment. Those techniques include liver biopsy, multiple serological markers (as either single tests or combined panels), and imaging examinations, such as ultrasound or magnetic resonance elastography. Nuclear medicine probes may also be employed in staging liver fibrosis, although the literature scarcely reports this. The purpose of our study was to investigate whether a dynamic liver scintigraphy with [99mTc]Tc-mebrofenin has any value in staging or grading chronic liver damage. Materials and Methods—We prospectively enrolled patients with chronic viral hepatitis B and C infection referred for liver biopsy. All patient underwent dynamic liver scintigraphy with 99mTc-mebrofenin prior to liver biopsy. Dynamic liver scintigraphy was performed immediately after intravenous tracer injection for 30 min scanning time. Multiple scintigraphy parameters were calculated (whole liver lobe and focal area time to peak (TTP), 30 min to peak ratio (30/peak), whole lobe and focal area slope index in 350 s (slope_350). Liver biopsy took place shortly after imaging. Results—We found that many dynamic scintigraphic parameters are positively or negatively associated with different stages of liver fibrosis. The main parameters that showed most value are the ratio between 30 min and the peak of the dynamic curve (30/peak_dex (ratio)), and liver clearance corrected for body surface area and liver area (LCL_m2_dm2 (%/min/m2/dm2)). Conclusions—Our present study proves that conducting dynamic liver scintigraphies with [99mTc]Tc-mebrofenin has potential value in staging liver fibrosis. The benefits of this method, including whole liver imaging and direct imaging of the liver function, provide an advantage over presently used quantitative imaging modalities. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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15 pages, 2712 KiB  
Article
Long-Term Effects of Rifaximin on Patients with Hepatic Encephalopathy: Its Possible Effects on the Improvement in the Blood Ammonia Concentration Levels, Hepatic Spare Ability and Refractory Ascites
by Keiji Yokoyama, Hiromi Fukuda, Ryo Yamauchi, Masashi Higashi, Takashi Miyayama, Tomotaka Higashi, Yotaro Uchida, Kumiko Shibata, Naoaki Tsuchiya, Atsushi Fukunaga, Kaoru Umeda, Kazuhide Takata, Takashi Tanaka, Satoshi Shakado, Shotaro Sakisaka and Fumihito Hirai
Medicina 2022, 58(9), 1276; https://doi.org/10.3390/medicina58091276 - 14 Sep 2022
Cited by 3 | Viewed by 1901
Abstract
Background and Objectives: To investigate the long-term efficacy of rifaximin (RFX) for hyperammonemia and efficacy for refractory ascites in patients with cirrhosis. Materials and Methods: We enrolled 112 patients with liver cirrhosis who were orally administered RFX in this study. Changes [...] Read more.
Background and Objectives: To investigate the long-term efficacy of rifaximin (RFX) for hyperammonemia and efficacy for refractory ascites in patients with cirrhosis. Materials and Methods: We enrolled 112 patients with liver cirrhosis who were orally administered RFX in this study. Changes in the clinical data of patients were evaluated up to 36 months after RFX administration. The primary endpoint was a change in blood ammonia levels. Secondary endpoints included changes in clinical symptoms, Child–Pugh (CP) score, number of hospitalizations, degree of refractory ascites, adverse events, and the relationship between RFX administration and the renin-angiotensin-aldosterone system. Results: An improved rate of overt hepatic encephalopathy (HE) of 82.7% was observed 3 months after RFX administration, which significantly induced a progressive decrease in blood ammonia concentration and an improved CP score up to 36 months. No serious RFX treatment-related adverse events were observed. 36.5% in patients after RFX administration improved refractory ascites. After RFX administration, patients with satisfactory control of hepatic ascites without addition of diuretic had lower renin concentration than those with poor control (p < 0.01). At less than 41 pg/mL renin concentration, the control of refractory ascites was significantly satisfactory (p < 0.0001). Conclusions: RFX reduced blood ammonia concentration and improved hepatic spare ability and the quality of life of patients with long-term HE to up to 36 months. Our study revealed the effects of RFX against refractory ascites, suggesting that renin concentration may be a predictive marker for assessing ascites control. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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11 pages, 1403 KiB  
Article
Skin Autofluorescence Measurement as Initial Assessment of Hepatic Parenchyma Quality in Patients Undergoing Liver Resection
by Maciej Krasnodębski, Marcin Morawski, Jan Borkowski, Karolina Grąt, Jan Stypułkowski, Michał Skalski, Andriy Zhylko, Marek Krawczyk and Michał Grąt
J. Clin. Med. 2022, 11(18), 5341; https://doi.org/10.3390/jcm11185341 - 11 Sep 2022
Viewed by 1443
Abstract
Skin autofluorescence (SAF) can detect advanced glycation end products (AGEs) that accumulate in tissues over time. AGEs reflect patients’ general health, and their pathological accumulation has been associated with various diseases. This study aimed to determine whether its measurements can correlate with the [...] Read more.
Skin autofluorescence (SAF) can detect advanced glycation end products (AGEs) that accumulate in tissues over time. AGEs reflect patients’ general health, and their pathological accumulation has been associated with various diseases. This study aimed to determine whether its measurements can correlate with the liver parenchyma quality. This prospective study included 186 patients who underwent liver resections. Liver fibrosis and/or steatosis > 10% were found in almost 30% of the patients. ROC analysis for SAF revealed the optimal cutoff point of 2.4 AU as an independent predictor for macrovesicular steatosis ≥ 10% with an AUC of 0.629 (95% CI 0.538–0.721, p = 0.006), 59.9% sensitivity, 62.4% specificity, and positive (PPV) and negative (NPV) predictive values of 45.7% and 74.1%, respectively. The optimal cutoff point for liver fibrosis was 2.3 AU with an AUC of 0.613 (95% CI 0.519–0.708, p = 0.018), 67.3% sensitivity, 55.2% specificity, and PPV and NPV of 37.1% and 81.2%, respectively. In the multivariable logistic regression model, SAF ≥ 2.4 AU (OR 2.16; 95% CI 1.05–4.43; p = 0.036) and BMI (OR 1.21; 95% CI 1.10–1.33, p < 0.001) were independent predictors of macrovesicular steatosis ≥ 10%. SAF may enhance the available non-invasive methods of detecting hepatic steatosis and fibrosis in patients prior to liver resection. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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19 pages, 1139 KiB  
Review
Spontaneous Bacterial Peritonitis in Decompensated Liver Cirrhosis—A Literature Review
by Chien-Hao Huang, Chen-Hung Lee and Ching Chang
Livers 2022, 2(3), 214-232; https://doi.org/10.3390/livers2030018 - 6 Sep 2022
Cited by 8 | Viewed by 7624
Abstract
Background: Spontaneous bacterial peritonitis (SBP) is defined as a bacterial infection of the ascitic fluid without a surgically treatable intra-abdominal infection source. SBP is a common, severe complication in cirrhosis patients with ascites, and if left untreated, in-hospital mortality may exceed 90%. However, [...] Read more.
Background: Spontaneous bacterial peritonitis (SBP) is defined as a bacterial infection of the ascitic fluid without a surgically treatable intra-abdominal infection source. SBP is a common, severe complication in cirrhosis patients with ascites, and if left untreated, in-hospital mortality may exceed 90%. However, the incidence of SBP has been lowered to approx. 20% through early diagnosis and antibiotic therapy. Clinical awareness, prompt diagnosis, and immediate treatment are advised when caring for these patients to reduce mortality and morbidity. Aim: To discuss important issues comprising types of SBP, pathogenesis, bacteriology, including the emergence of multidrug-resistant (MDR) microorganisms, prompt diagnosis, risk factors, prognosis, treatment strategies, as well as recurrence prevention through antibiotic prophylaxis until liver transplantation and future trends in treating and preventing SBP in detail. Methods: This article is a literature review and appraisal of guidelines, randomized controlled trials, meta-analyses, and other review articles found on PubMed from between 1977 and 2022. Results: There are three types of SBP. Bacterial translocation from GI tract is the most common source of SBP. Therefore, two thirds of SBP cases were caused by Gram-negative bacilli, of which Escherichia coli is the most frequently isolated pathogen. However, a trend of Gram-positive cocci associated SBP has been demonstrated in recent years, possibly related to more invasive procedures and long-term quinolone prophylaxis. A diagnostic paracentesis should be performed in all patients with cirrhosis and ascites who require emergency room care or hospitalization, who demonstrate or report consistent signs/symptoms in order to confirm evidence of SBP. Distinguishing SBP from secondary bacterial peritonitis is essential because the conditions require different therapeutic strategies. The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Albumin supplementation, especially in patients with renal impairment, is also beneficial. Selective intestinal decontamination is associated with a reduced risk of bacterial infection and mortality in high-risk group. Conclusions: The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Since the one-year overall mortality rates for SBP range from 53.9 to 78%, liver transplantation should be seriously considered for SBP survivors who are good candidates for transplantation. Further development of non-antibiotic strategies based on pathogenic mechanisms are also urgently needed. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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10 pages, 710 KiB  
Article
The Role of Presepsin in Diagnosing Infections in Patients with Liver Cirrhosis and Overt Hepatic Encephalopathy
by Razvan Igna, Irina Gîrleanu, Camelia Cojocariu, Cristina Muzîca, Laura Huiban, Catalin Sfarti, Tudor Cuciureanu, Stefan Chiriac, Ana-Maria Sîngeap, Oana Cristina Petrea, Remus Stafie, Sebastian Zenovia, Robert Năstasă, Ermina Stratina, Adrian Rotaru, Carol Stanciu, Anca Trifan and Mihaela Blaj
Diagnostics 2022, 12(9), 2077; https://doi.org/10.3390/diagnostics12092077 - 27 Aug 2022
Cited by 2 | Viewed by 1422
Abstract
Infections and sepsis represent severe liver cirrhosis (LC) complications and the precipitating factors of hepatic encephalopathy (HE). The early diagnosis and treatment of infections in patients with LC and HE can significantly increase their survival. Presepsin is a serum biomarker evaluated for the [...] Read more.
Infections and sepsis represent severe liver cirrhosis (LC) complications and the precipitating factors of hepatic encephalopathy (HE). The early diagnosis and treatment of infections in patients with LC and HE can significantly increase their survival. Presepsin is a serum biomarker evaluated for the early diagnosis of infections and sepsis in the general and cirrhotic populations. This study aimed to evaluate the role of presepsin in the early diagnosis of infections in patients with LC and HE. This prospective observational study included all consecutive cirrhotic patients admitted to our tertiary university center with overt HE. The patients were follow-up until discharge. In this study, we included 365 patients with a median age of 59 years, of whom 61.9% were male. Infections were diagnosed in 134 patients (36.7%). The presepsin level was higher in patients with infections than those without infections (3167 vs. 500, p < 0.001). The ROC analysis results demonstrated that the best cut-off value for presepsin in infections detection was 980 pg/mL with a sensitivity of 80.17%, specificity of 82.5% (AUROC 0.869, CI 95%: 0.819–0.909, p < 0.001, Youden index J of 0.622), a positive predictive value of 40.63%, and a negative predictive value of 96.53%. In conclusion, in patients with LC and overt HE, presepsin levels >980 pg/mL could enhance the suspicion of bacterial infections. Presepsin may be an adequate non-invasive tool for the early diagnosis of infections in patients with LC and overt HE. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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13 pages, 1685 KiB  
Article
The Effect of Roux-en-Y Gastric Bypass on Non-Alcoholic Fatty Liver Disease Fibrosis Assessed by FIB-4 and NFS Scores—An 11.6-Year Follow-Up Study
by Elfrid Christine Smith Sandvik, Kristin Matre Aasarød, Gjermund Johnsen, Dag Arne Lihaug Hoff, Bård Kulseng, Åsne Ask Hyldmo, Hallvard Græslie, Siren Nymo, Jorunn Sandvik and Reidar Fossmark
J. Clin. Med. 2022, 11(16), 4910; https://doi.org/10.3390/jcm11164910 - 21 Aug 2022
Cited by 5 | Viewed by 1861
Abstract
Severe obesity is a strong risk factor for non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass (RYGB) surgery effectively induces weight loss, but few studies have described the long-term effects of RYGB on NAFLD-related fibrosis. Data from 220 patients with severe obesity operated [...] Read more.
Severe obesity is a strong risk factor for non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass (RYGB) surgery effectively induces weight loss, but few studies have described the long-term effects of RYGB on NAFLD-related fibrosis. Data from 220 patients with severe obesity operated by RYGB in Central Norway were analysed. Variables incorporated in NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4) index and anthropometric data were collected before surgery and a mean of 11.6 years postoperatively. FIB-4 > 1.3 or NFS > 0.675 were used as cut-off values for advanced fibrosis. Proportions with advanced fibrosis decreased from 24% to 14% assessed by FIB-4 and from 8.6% to 2.3% using NFS, with resolution rates of advanced fibrosis of 42% and 73%, respectively. The shift towards lower fibrosis categories was significant (NFS p < 0.0001; FIB-4 p = 0.002). NFS decreased from −1.32 (IQR −2.33–−0.39) to −1.71 (IQR −2.49–−0.95, p < 0.001) 11.6 years after surgery, whereas FIB-4 did not change: 0.81 (IQR 0.59–1.25) to 0.89 (IQR 0.69–1.16, p = 0.556). There were weak correlations between change in fibrosis scores and weight loss. In conclusion, the majority of patients with advanced fibrosis at baseline had improvement after 11.6 years. Factors associated with reduction in fibrosis were not identified. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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17 pages, 1577 KiB  
Article
Circulating microRNAs as Biomarkers of Hepatic Fibrosis in Schistosomiasis Japonica Patients in the Philippines
by Ian Kim B. Tabios, Marcello Otake Sato, Ourlad Alzeus Gaddi Tantengco, Raffy Jay C. Fornillos, Masashi Kirinoki, Megumi Sato, Raniv D. Rojo, Ian Kendrich C. Fontanilla, Yuichi Chigusa, Paul Mark B. Medina, Mihoko Kikuchi and Lydia R. Leonardo
Diagnostics 2022, 12(8), 1902; https://doi.org/10.3390/diagnostics12081902 - 5 Aug 2022
Cited by 2 | Viewed by 2072
Abstract
Host-derived microRNAs (miRNAs) play important regulatory roles in schistosomiasis-induced hepatic fibrosis. This study analyzed selected serum miRNAs among Filipino schistosomiasis japonica patients with ultrasound (US)-detectable hepatic fibrosis. A prospective cohort study design with convenience sampling was employed from 2017 to 2019. The study [...] Read more.
Host-derived microRNAs (miRNAs) play important regulatory roles in schistosomiasis-induced hepatic fibrosis. This study analyzed selected serum miRNAs among Filipino schistosomiasis japonica patients with ultrasound (US)-detectable hepatic fibrosis. A prospective cohort study design with convenience sampling was employed from 2017 to 2019. The study sites were eight endemic barangays in Leyte, Philippines. Eligible chronic schistosomiasis patients with varying severities of hepatic fibrosis were enrolled in the cohort and serially examined at 6, 12, and 24 months from baseline. Baseline serum miR-146a-5p, let-7a-5p, miR-150-5p, miR-122-5p, miR-93-5p, and miR200b-3p were measured using RT-qPCR. A total of 136 chronic schistosomiasis patients were included in this prospective cohort study. Approximately, 42.6% had no fibrosis, 22.8% had mild fibrosis, and 34.6% had severe fibrosis at baseline The serum levels of the antifibrotic miR-146a (p < 0.0001), miR-150 (p = 0.0058), and let-7a (p < 0.0001) were significantly lower in patients with hepatic fibrosis while the profibrotic miR-93 (p = 0.0024) was elevated. miR-146a-5p (AUC = 0.90, 95% CI [0.84, 0.96], p < 0.0001) has the most promising potential to differentiate patients with (n = 78) versus without (n = 58) hepatic fibrosis. The baseline level of serum miR-146-5p was significantly different in patients with progressive fibrosis (n = 17) compared to those who never developed fibrosis (n = 30, p < 0.01) or those who had fibrosis reversal (n = 20, p < 0.01) after 24 months. These findings demonstrate the potential utility of serum miRNAs, particularly of miR-146a, as a supplementary tool for assessing hepatic fibrosis in chronic schistosomiasis japonica patients. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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13 pages, 1781 KiB  
Article
Prognostic Nomograms for Hospital Survival and Transplant-Free Survival of Patients with Hepatorenal Syndrome: A Retrospective Cohort Study
by Yi Song, Yu Wang, Chaoran Zang, Xiaoxi Yang, Zhenkun Li, Lina Wu and Kang Li
Diagnostics 2022, 12(6), 1417; https://doi.org/10.3390/diagnostics12061417 - 8 Jun 2022
Viewed by 1499
Abstract
Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis with a poor prognosis. To develop novel and effective nomograms which could numerically predict both the hospital survival and transplant-free survival of HRS, we retrospectively enrolled a cohort of 149 patients. A backward stepwise [...] Read more.
Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis with a poor prognosis. To develop novel and effective nomograms which could numerically predict both the hospital survival and transplant-free survival of HRS, we retrospectively enrolled a cohort of 149 patients. A backward stepwise method based on the smallest Akaike information criterion value was applied to select the covariates to be included in the Cox proportional hazards models. The Harrell C-index, area under the receiver operating characteristic curve (AUC), Brier score, and Kaplan–Meier curves with the log-rank test were used to assess nomograms. The bootstrapping method with 1000 resamples was performed for internal validation. The nomogram predicting hospital survival included prothrombin activity, HRS clinical pattern, Child–Pugh class, and baseline serum creatinine. The C-index was 0.72 (95% confidence interval (CI), 0.65–0.78), and the adjusted C-index was 0.72 (95% CI, 0.66–0.79). The nomogram predicting transplant-free survival included sex, prothrombin activity, HRS clinical pattern, model for end-stage liver disease–Na score, and peak serum creatinine. The C-index of the nomogram was 0.74 (95% CI, 0.69–0.79), and the adjusted C-index was 0.74 (95% CI, 0.68–0.79). The AUC and Brier score at 15, 30, and 45 days calculated from the hospital survival nomogram and those at 6, 12, and 18 months calculated from the transplant-free survival nomogram revealed good predictive ability. The two models can be used to identify patients at high risk of HRS and promote early intervention treatment. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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11 pages, 1163 KiB  
Article
The Usefulness of the Athens Insomnia Scale for Evaluating Sleep Disturbance in Patients with Chronic Liver Disease Comparing with Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale
by Hideto Kawaratani, Hisamitsu Miyaaki, Atsushi Hiraoka, Kazuhiko Nakao, Yoichi Hiasa, Hitoshi Yoshiji, Kiwamu Okita and Kazuhiko Koike
Medicina 2022, 58(6), 741; https://doi.org/10.3390/medicina58060741 - 30 May 2022
Cited by 4 | Viewed by 2689
Abstract
Background and Objectives: Sleep disturbance due to muscle cramps or hepatic encephalopathy in patients with chronic liver disease (CLD) can lead to a reduced quality of life. The Pittsburgh sleep quality index (PSQI) is commonly used for evaluating sleep disturbance; however, this [...] Read more.
Background and Objectives: Sleep disturbance due to muscle cramps or hepatic encephalopathy in patients with chronic liver disease (CLD) can lead to a reduced quality of life. The Pittsburgh sleep quality index (PSQI) is commonly used for evaluating sleep disturbance; however, this questionnaire is time-consuming owing to the large number of questions. As the usefulness of the Athens insomnia scale (AIS) in patients with CLD is not sufficiently known, the present study aimed to determine whether the AIS and Epworth sleepiness scale (ESS) could be used as simple alternative questionnaires for evaluating sleep disturbances in patients with CLD. Materials and Methods: A total of 117 patients with CLD were retrospectively evaluated. Patients with overt hepatic encephalopathy were excluded. All patients were examined using the AIS, PSQI, and ESS, and their responses to these questionnaires were statistically analyzed. Results: The number of patients diagnosed with sleep disturbance using the AIS, PSQI, and ESS were 39 (33.3%), 37 (31.6%), and 9 (7.7%), respectively. There was no correlation between PSQI and ESS scores (r = 0.011, p = 0.910); in contrast, the AIS scores showed a significant correlation with the PSQI scores (r = 0.689, p < 0.001). When the PSQI was considered as the standard for evaluating sleep disturbance, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AIS were 76.9%, 91.0%, 81.1%, and 88.8%, respectively. In the sleep medication group, the sensitivity, specificity, PPV, and NPV of the AIS were 100%, 70%, 78.6%, and 100%, respectively. Conclusions: This is the first report to indicate that the AIS is an alternative questionnaire to the PSQI and that it can be a useful tool for detecting cirrhosis-related complications in patients with CLD. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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13 pages, 1368 KiB  
Article
Excess Risk of Major Adverse Cardiovascular and Kidney Events after Acute Kidney Injury following Living Donor Liver Transplantation
by Yi-Chia Chan, Cheng-Hsi Yeh, Lung-Chih Li, Chao-Long Chen, Chih-Chi Wang, Chih-Chi Lin, Aldwin D. Ong, Ting-Yu Chiou and Chee-Chien Yong
J. Clin. Med. 2022, 11(11), 3100; https://doi.org/10.3390/jcm11113100 - 30 May 2022
Cited by 3 | Viewed by 1724
Abstract
Acute kidney injury (AKI) is a well-known risk factor for major adverse kidney events (MAKE) and major adverse cardiovascular events (MACE) in nontransplant settings. However, the association between AKI after liver transplantation (LT) and MACE/MAKE is not established. A retrospective cohort analysis including [...] Read more.
Acute kidney injury (AKI) is a well-known risk factor for major adverse kidney events (MAKE) and major adverse cardiovascular events (MACE) in nontransplant settings. However, the association between AKI after liver transplantation (LT) and MACE/MAKE is not established. A retrospective cohort analysis including 512 LT recipients was conducted. The incidence of post-LT AKI was 35.0% (n = 179). In total, 13 patients (2.5%) developed de novo coronary artery disease (CAD), 3 patients (0.6%) diagnosed with heart failure (HF), and 11 patients (2.1%) had stroke. The post-LT AKI group showed a higher incidence of CAD and HF than the no post-LT AKI group (4.5% versus 1.5%, p = 0.042; 1.7% versus 0%, p = 0.018; respectively), while there was no significant difference in the stroke events (2.8% versus 1.8%, p = 0.461). Through Cox regression analysis, history of cardiovascular disease (HR 6.51, 95% CI 2.43–17.46), post-LT AKI (HR 3.06, 95% CI 1.39–6.75), and pre-LT diabetes (HR 2.37, 95% CI 1.09–5.17) were identified as independent predictors of MACE; pre-LT chronic kidney disease (HR 9.54, 95% CI 3.49–26.10), pre-LT diabetes (HR 3.51, 95% CI 1.25–9.86), and post-LT AKI (HR 6.76, 95% CI 2.19–20.91) were risk factors for end-stage renal disease. Post-LT AKI is predictive for the development of MACE and MAKE. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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13 pages, 1221 KiB  
Article
Significant Decrease in the Prevalence of Anxiety and Depression after Hepatitis C Eradication
by Justyna Slonka, Damian Piotrowski, Ewa Janczewska, Arkadiusz Pisula, Joanna Musialik and Jerzy Jaroszewicz
J. Clin. Med. 2022, 11(11), 3044; https://doi.org/10.3390/jcm11113044 - 28 May 2022
Cited by 2 | Viewed by 1714
Abstract
Chronic hepatitis C (CHC) is an ongoing epidemiological problem. The hepatitis C virus (HCV) may infect brain tissue, worsening mental health outcomes. The new era of highly effective oral Direct-Acting Agents (DAA) has brought a chance to eradicate the infection by 2030, however, [...] Read more.
Chronic hepatitis C (CHC) is an ongoing epidemiological problem. The hepatitis C virus (HCV) may infect brain tissue, worsening mental health outcomes. The new era of highly effective oral Direct-Acting Agents (DAA) has brought a chance to eradicate the infection by 2030, however, screening campaigns are urgently needed as the majority of the infected are still undiagnosed. The aim of this study was to assess the prevalence of anxiety and depression among HCV patients, and the correlation with health-related quality of life (HRQoL) in the real-world setting, before and after DAA treatment. Data on anxiety, depression, and HRQoL, were collected by using self-reported questionnaires in a single center in Poland. The study group involved 90 respondents, 50% female, with a mean age of 43.8 years. HCV eradication decreased anxiety prevalence from 30.4% to 19.1% and depression from 35.2% to 18.2%. Significant improvement in 3 out of 4 of the WHOQOL-BREF (TheWorld Health Organization Quality of Life-BREF) domains and 8 out of 10 of the HQLQv.2 domains was obtained. Anxiety diminished the somatic domain scores by 3.5 (p < 0.0001), psychological by 2.3 (p = 0.0062), social by 1.75 (p = 0.0008), and environmental by 2.68 points (p = 0.0029). Depression diminished the somatic domain scores by 3.79 (p < 0.001), psychological by 2.23 (p < 0.001), social by 1.84 (p < 0.001), and environmental by 2.42 points (p = 0.004). In the Hepatitis Quality of Life Questionnaire version 2 (HQLQ v.2), the presence of depression and/or anxiety-impaired mental health, physical health, well-being, and vitality. These results indicate the need for an active search for HCV-infective people, especially among patients in psychiatric and psychological care. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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10 pages, 255 KiB  
Article
Hepatic Steatosis and Fibrosis in Chronic Inflammatory Bowel Disease
by Claudia Veltkamp, Shuai Lan, Eleni Korompoki, Karl-Heinz Weiss, Hartmut Schmidt and Helmut K. Seitz
J. Clin. Med. 2022, 11(9), 2623; https://doi.org/10.3390/jcm11092623 - 6 May 2022
Cited by 6 | Viewed by 2228
Abstract
Background and Purpose: Chronic inflammatory bowel diseases (IBD) frequently affect extraintestinal organs including the liver. Since limited evidence suggests the presence of liver disease in IBD patients, we studied the frequency of hepatic steatosis and fibrosis in these patients and characterized disease-related factors. [...] Read more.
Background and Purpose: Chronic inflammatory bowel diseases (IBD) frequently affect extraintestinal organs including the liver. Since limited evidence suggests the presence of liver disease in IBD patients, we studied the frequency of hepatic steatosis and fibrosis in these patients and characterized disease-related factors. Methods: In this retrospective, cross-sectional, hospital-based, single-center study, consecutive patients with Crohn’s disease (CD) and ulcerative colitis (UC) were included who had undergone routine abdominal ultrasound including transhepatic elastography. Hepatic steatosis was diagnosed by hyperechogenicity on B-mode ultrasound and by measuring controlled attenuation parameter (CAP). Hepatic fibrosis was assumed if transhepatic elastography yielded a stiffness > 7 kPa. Results: 132 patients (60% CD) with a median disease duration of 10 years were included. Steatosis assessed by B-mode ultrasound and CAP correlated well. Of the IBD patients, 30.3% had non-alcoholic fatty liver (NAFL). Factors associated with NAFL were age, BMI, duration of disease, as well as serum activities of aspartate-aminotransferase (AST) and gamma-glutamyl-transpeptidase (GGT). In multivariate analysis, only disease duration was independently associated with hepatic steatosis. Hepatic fibrosis was found in 10 (8%) of all IBD patients, predominantly in patients with CD (10/11). Conclusions: Pure hepatic steatosis is common in both CD and UC, whereas hepatic fibrosis occurs predominantly in CD patients. Association of disease duration with NAFLD suggests a contribution of IBD-related pathogenetic factors. Longitudinal studies are needed to better understand the impact of IBD on hepatic disorders. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
18 pages, 3751 KiB  
Article
Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis
by Aron Park, Seung Joon Choi, Sungjin Park, Seong Min Kim, Hye Eun Lee, Minjae Joo, Kyoung Kon Kim, Doojin Kim, Dong Hae Chung, Jae Been Im, Jaehun Jung, Seung Kak Shin, Byung-Chul Oh, Cheolsoo Choi, Seungyoon Nam and Dae Ho Lee
Int. J. Mol. Sci. 2022, 23(9), 5035; https://doi.org/10.3390/ijms23095035 - 1 May 2022
Cited by 3 | Viewed by 2396
Abstract
We found several blood biomarkers through computational secretome analyses, including aldo-keto reductase family 1 member B10 (AKR1B10), which reflected the progression of nonalcoholic fatty liver disease (NAFLD). After confirming that hepatic AKR1B10 reflected the progression of NAFLD in a subgroup with NAFLD, we [...] Read more.
We found several blood biomarkers through computational secretome analyses, including aldo-keto reductase family 1 member B10 (AKR1B10), which reflected the progression of nonalcoholic fatty liver disease (NAFLD). After confirming that hepatic AKR1B10 reflected the progression of NAFLD in a subgroup with NAFLD, we evaluated the diagnostic accuracy of plasma AKR1B10 and other biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis in replication cohort. We enrolled healthy control subjects and patients with biopsy-proven NAFLD (n = 102) and evaluated the performance of various diagnostic markers. Plasma AKR1B10 performed well in the diagnosis of NASH with an area under the receiver operating characteristic (AUROC) curve of 0.834 and a cutoff value of 1078.2 pg/mL, as well as advanced fibrosis (AUROC curve value of 0.914 and cutoff level 1078.2 pg/mL), with further improvement in combination with C3. When we monitored a subgroup of obese patients who underwent bariatric surgery (n = 35), plasma AKR1B10 decreased dramatically, and 40.0% of patients with NASH at baseline showed a decrease in plasma AKR1B10 levels to below the cutoff level after the surgery. In an independent validation study, we proved that plasma AKR1B10 was a specific biomarker of NAFLD progression across varying degrees of renal dysfunction. Despite perfect correlation between plasma and serum levels of AKR1B10 in paired sample analysis, its serum level was 1.4-fold higher than that in plasma. Plasma AKR1B10 alone and in combination with C3 could be a useful noninvasive biomarker for the diagnosis of NASH and hepatic fibrosis. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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11 pages, 898 KiB  
Article
Concomitant Hepatectomy and Atrial Thrombectomy under Cardiopulmonary Bypass versus Staged Hepatectomy in the Treatment for Hepatocellular Carcinoma with Large Right Atrial Tumor Thrombi
by Wen-Shan Chao, Ching-Hui Shen, Shao-Ciao Luo, Feng-Hsu Wu, Hao-Ji Wei, Chu-Leng Yu, Cheng-Chung Wu, Yun Yen and Fang-Ku P’eng
J. Clin. Med. 2022, 11(8), 2140; https://doi.org/10.3390/jcm11082140 - 12 Apr 2022
Cited by 2 | Viewed by 1695
Abstract
(1) Background: Hepatocellular carcinoma (HCC) with a large right atrium tumor thrombus (RATT) is a rare and critical presentation. Emergency hepatectomy and thrombectomy under cardiopulmonary bypass (CPB) is life-saving and potentially curative. The aim of this study is to propose an appropriate approach [...] Read more.
(1) Background: Hepatocellular carcinoma (HCC) with a large right atrium tumor thrombus (RATT) is a rare and critical presentation. Emergency hepatectomy and thrombectomy under cardiopulmonary bypass (CPB) is life-saving and potentially curative. The aim of this study is to propose an appropriate approach for this condition. (2) Methods: In period A (1998 to 2010, n = 7), hepatectomy and thrombectomy were concomitantly performed, and staged hepatectomy was performed in period B (2011 to 2018, n = 17). (3) Results: The median overall survival time (MOST) in the published studies was 14 months. Moreover, the blood loss, blood transfusion rate, length of ICU stays, and hospital costs were significantly reduced in period B. The MOSTs of patients in period A (n = 6) and period B (n = 17) were 14 vs. 18 months (p = 0.099). The median disease-free survival times (MDFTs) in period A (n = 6) and period B (n = 15) were 8 vs. 14 months (p = 0.073), while the MOSTs in period A and period B were 14 vs. 24 months (p = 0.040). (4) Conclusions: Emergency thrombectomy under CPB and staged hepatectomy 4–6 weeks later may be an appropriate approach for HCC with large RATT. However, the optimal waiting interval requires further investigation. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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10 pages, 1088 KiB  
Article
Impact of Liver Fibrosis on Survival of Patients with Intrahepatic Cholangiocarcinoma Receiving Gemcitabine-Based Chemotherapy
by Maximilian N. Kinzler, Christina Klasen, Falko Schulze, Eva Herrmann, Andreas A. Schnitzbauer, Jörg Trojan, Stefan Zeuzem, Peter J. Wild and Dirk Walter
J. Clin. Med. 2022, 11(7), 2057; https://doi.org/10.3390/jcm11072057 - 6 Apr 2022
Cited by 1 | Viewed by 2041
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the most frequent subtype of cholangiocarcinoma (CCA), and the incidence has globally increased in recent years. In contrast to surgically treated iCCA, data on the impact of fibrosis on survival in patients undergoing palliative chemotherapy are missing. We retrospectively [...] Read more.
Intrahepatic cholangiocarcinoma (iCCA) is the most frequent subtype of cholangiocarcinoma (CCA), and the incidence has globally increased in recent years. In contrast to surgically treated iCCA, data on the impact of fibrosis on survival in patients undergoing palliative chemotherapy are missing. We retrospectively analyzed the cases of 70 patients diagnosed with iCCA between 2007 and 2020 in our tertiary hospital. Histopathological assessment of fibrosis was performed by an expert hepatobiliary pathologist. Additionally, the fibrosis-4 score (FIB-4) was calculated as a non-invasive surrogate marker for liver fibrosis. For overall survival (OS) and progression-free survival (PFS), Kaplan–Meier curves and Cox-regression analyses were performed. Subgroup analyses revealed a median OS of 21 months (95% CI = 16.7–25.2 months) and 16 months (95% CI = 7.6–24.4 months) for low and high fibrosis, respectively (p = 0.152). In non-cirrhotic patients, the median OS was 21.8 months (95% CI = 17.1–26.4 months), compared with 9.5 months (95% CI = 4.6–14.3 months) in cirrhotic patients (p = 0.007). In conclusion, patients with iCCA and cirrhosis receiving palliative chemotherapy have decreased OS rates, while fibrosis has no significant impact on OS or PFS. These patients should not be prevented from state-of-the-art first-line chemotherapy. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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17 pages, 7269 KiB  
Article
Heparanase Inhibition Prevents Liver Steatosis in E0 Mice
by Safa Kinaneh, Walaa Hijaze, Lana Mansour-Wattad, Rawan Hammoud, Hisam Zaidani, Aviva Kabala and Shadi Hamoud
J. Clin. Med. 2022, 11(6), 1672; https://doi.org/10.3390/jcm11061672 - 17 Mar 2022
Cited by 2 | Viewed by 2188
Abstract
Background: Non-alcoholic fatty liver disease affects up to 30% of adults in the USA, and is associated with a higher incidence of chronic liver morbidity and mortality. Several molecular pathways are involved in the pathology of liver steatosis, including lipid uptake, lipogenesis, lipolysis, [...] Read more.
Background: Non-alcoholic fatty liver disease affects up to 30% of adults in the USA, and is associated with a higher incidence of chronic liver morbidity and mortality. Several molecular pathways are involved in the pathology of liver steatosis, including lipid uptake, lipogenesis, lipolysis, and beta-oxidation. The enzyme heparanase has been implicated in liver steatosis. Herein, we investigated the effect of heparanase inhibition on liver steatosis in E0 mice. Methods: In vivo experiments: Male wild-type mice fed with either chow diet (n = 4) or high-fat diet (n = 6), and male E0 mice fed with chow diet (n = 8) or high-fat diet (n = 33) were included. Mice on a high-fat diet were treated for 12 weeks with PG545 at low dose (6.4 mg/kg/week, ip, n = 6) or high dose (13.3 mg/kg/week, ip, n = 7), SST0001 (1.2 mg/mouse/day, ip, n = 6), or normal saline (control, n = 14). Animals were sacrificed two days after inducing peritonitis. Serum was analyzed for biochemical parameters. Mouse peritoneal macrophages (MPMs) were harvested and analyzed for lipid content. Livers were harvested for histopathological analysis of steatosis, lipid content, and the expression of steatosis-related factors at the mRNA level. In vitro experiments: MPMs were isolated from untreated E0 mice aged 8–10 weeks and were cultured and treated with either PG545 or SST0001, both at 50 µg/mL for 24 h, followed by assessment of mRNA expression of steatosis related factors. Results: Heparanase inhibition significantly attenuated the development of liver steatosis, as was evident by liver histology and lipid content. Serum analysis indicated lowering of cholesterol and triglycerides levels in mice treated with heparanase inhibitors. In liver tissue, assessment of mRNA expression of key factors in lipid uptake, lipolysis, lipogenesis, and beta-oxidation exhibited significant downregulation following PG545 treatment and to a lesser extent when SST0001 was applied. However, in vitro treatment of MPMs with PG545, but not SST0001, resulted in increased lipid content in these cells, which is opposed to their effect on MPMs of treated mice. This may indicate distinct regulatory pathways in the system or isolated macrophages following heparanase inhibition. Conclusion: Heparanase inhibition significantly attenuates the development of liver steatosis by decreasing tissue lipid content and by affecting the mRNA expression of key lipid metabolism regulators. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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11 pages, 1275 KiB  
Article
Selecting the Target Population for Screening of Hepatic Fibrosis in Primary Care Centers in Korea
by Huiyul Park, Eileen L. Yoon, Mimi Kim, Seon Cho, Jung-Hwan Kim, Dae Won Jun and Eun-Hee Nah
J. Clin. Med. 2022, 11(6), 1474; https://doi.org/10.3390/jcm11061474 - 8 Mar 2022
Cited by 5 | Viewed by 1702
Abstract
Screening strategies for hepatic fibrosis are heavily focused on patients with fatty liver on sonography in primary care centers. This study aimed to investigate the target population for screening significant hepatic fibrosis in primary care centers. This retrospective cross-sectional cohort study used data [...] Read more.
Screening strategies for hepatic fibrosis are heavily focused on patients with fatty liver on sonography in primary care centers. This study aimed to investigate the target population for screening significant hepatic fibrosis in primary care centers. This retrospective cross-sectional cohort study used data from 13 nationwide centers. A total of 5111 subjects who underwent both abdominal sonography and magnetic resonance elastography as part of their health check-up were included. Subjects with viral hepatitis and/or a history of significant alcohol consumption were excluded. Significant and advanced hepatic fibrosis was defined as ≥3.0 kPa and ≥3.6 kPa in the MRE test, respectively. The prevalence of significant and advanced hepatic fibrosis was 7.3% and 1.9%, respectively. Among the subjects with significant hepatic fibrosis, 41.3% did not have fatty liver. Hepatic fibrosis burden increased according to the number of metabolic risk abnormalities. Nearly 70% of subjects with significant hepatic fibrosis also had two or more metabolic risk abnormalities and/or diabetes. However, the prevalence of fibrosis did not differ between the groups with and without fatty liver. The presence of two or more metabolic risk abnormalities was an independent risk factor for significant hepatic fibrosis regardless of the fatty liver. Therefore, in the setting of primary care centers, screening for hepatic fibrosis would better be extended to subjects with metabolically unhealthy status beyond those with fatty liver. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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10 pages, 285 KiB  
Article
Hyperuricemia Is Associated with Significant Liver Fibrosis in Subjects with Nonalcoholic Fatty Liver Disease, but Not in Subjects without It
by Pei-Chia Yen, Yu-Tsung Chou, Chung-Hao Li, Zih-Jie Sun, Chih-Hsing Wu, Yin-Fan Chang, Feng-Hwa Lu, Yi-Ching Yang, Chih-Jen Chang and Jin-Shang Wu
J. Clin. Med. 2022, 11(5), 1445; https://doi.org/10.3390/jcm11051445 - 7 Mar 2022
Cited by 9 | Viewed by 3100
Abstract
Liver fibrosis is associated with liver-related outcomes, yet often remains underdiagnosed in primary care settings. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD), but the relationship between hyperuricemia and liver fibrosis remains unclear. Data on individuals without NAFLD is also limited. We [...] Read more.
Liver fibrosis is associated with liver-related outcomes, yet often remains underdiagnosed in primary care settings. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD), but the relationship between hyperuricemia and liver fibrosis remains unclear. Data on individuals without NAFLD is also limited. We investigated the association between hyperuricemia and liver fibrosis in subjects with and without NAFLD. This study recruited 11,690 relevant participants from a health-checkup center. NAFLD was based on ultrasonography. Hyperuricemia was defined as serum uric acid > 6.0 mg/dL in women and >7.0 mg/dL in men. Significant liver fibrosis was diagnosed with the aspartate aminotransferase to platelet ratio index ≥0.5. The following were positively associated with significant liver fibrosis: hyperuricemia (p = 0.001), age ≥ 65 years (p < 0.001), male gender (p < 0.001), obesity (p = 0.009), hypertension (p = 0.002), diabetes (p < 0.001), and NAFLD (p < 0.001) in the logistic regression. The positive association of hyperuricemia with significant liver fibrosis remained in subjects with NAFLD (p = 0.001), but not in subjects without NAFLD. In conclusion, hyperuricemia increased the associated risk of significant liver fibrosis. The positively associated risk existed in subjects with NAFLD, but not in those without it. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
13 pages, 971 KiB  
Review
Persistence of Cryoglobulinemic Vasculitis after DAA Induced HCV Cure
by Mahmood Danishwar, Zahid Jamil, Salman Khan, Michael Nakhla, Ishtiaq Ahmad, Muhammad Ashar Ali and Daryl T. Y. Lau
J. Clin. Med. 2022, 11(4), 984; https://doi.org/10.3390/jcm11040984 - 14 Feb 2022
Cited by 8 | Viewed by 2813
Abstract
Treatment with a direct acting antiviral (DAA) has revolutionized HCV therapy, as more than 95% of patients achieve a sustained virological response (SVR). Cryoglobulinemic vasculitis (CryoVas), however, can persist and recur after the HCV cure. In this systematic review, we include data from [...] Read more.
Treatment with a direct acting antiviral (DAA) has revolutionized HCV therapy, as more than 95% of patients achieve a sustained virological response (SVR). Cryoglobulinemic vasculitis (CryoVas), however, can persist and recur after the HCV cure. In this systematic review, we include data from 19 studies that provided information on the persistence and recurrence of CryoVas after the HCV cure with DAAs. A complete clinical response (CR) was reported in 63.7% to 90.2% of the DAA-treated patients after achieving SVR. Relapse of CryoVas symptoms was reported in 4% to 18% of the patients. Neuropathy, nephropathy, and dermatological complications were the most common manifestations of CryoVas. B-cell clones persisted in 31–40% of the patients and could contribute to CryoVas relapse. INFL3-rs12979860, ARNTL-rs648122, RETN-rs1423096, and SERPINE1-rs6976053 were associated with a higher incidence of persistence and recurrence of CryoVas. Prospective multicenter studies with diverse patient populations are needed to validate these findings for the timely and effective management of this challenging condition. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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10 pages, 5274 KiB  
Article
Validation of PH and Varices Risk Scores for Prediction of High-Risk Esophageal Varix and Bleeding in Patients with B-Viral Cirrhosis
by Seunghwan Shin, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn and Beom Kyung Kim
Diagnostics 2022, 12(2), 441; https://doi.org/10.3390/diagnostics12020441 - 9 Feb 2022
Cited by 1 | Viewed by 1434
Abstract
Esophageal varices (EVs) can be accurately predicted using PH and varices risk scores. We aimed to validate their prognostic performances. Methods: We enrolled patients with B-viral cirrhosis as the training cohort (n = 503). Areas under receiver operating characteristic curves (AUROCs) for [...] Read more.
Esophageal varices (EVs) can be accurately predicted using PH and varices risk scores. We aimed to validate their prognostic performances. Methods: We enrolled patients with B-viral cirrhosis as the training cohort (n = 503). Areas under receiver operating characteristic curves (AUROCs) for HEV were calculated for PH (=−5.953 + 0.188 × liver stiffness (LS) + 1.583 × sex (1:male/0:female) + 26.705 × spleen diameter/platelet count ratio) and varices (=−4.364 + 0.538 × spleen diameter −0.049 × platelet count −0.044 × LS + 0.001 × LS × platelet count) risk scores, and compared to LSPS (=LS × spleen diameter/platelet count). An independent cohort was recruited for further validation (n = 222). In the training cohort, the varices risk score showed the highest AUROC (0.926), followed by the PH risk score (0.924) and LSPS (0.924), but without any statistically significant differences. For varices risk scores ≤−1.70 and ≥1.48, a 95.0% negative predictive value (NPV) and 91.2% positive predictive value (PPV) were observed, respectively. At PH risk scores ≤2.25 and ≥7.71, 95.0% NPV and 90.0% PPV were observed, respectively. At LSPS ≤1.73 and ≥13.9, 95.3% NPV and 95.0% PPV were observed, respectively. The EV bleeding (EVB) risk during follow-up increased stepwise and significantly when stratified by PH, varices risk scores, and LSPS (all p < 0.001). In the validation cohort, NPVs were generally similar when stratified by PH (88.2%), varices risk scores (93.2%), and LSPS (88.9%); however, corresponding PPVs were suboptimal. PH and variceal risk scores are reliable for predicting HEV and future EVB. Patients with PH and varices risk scores ≤2.25 and ≤−1.70, respectively, may avoid endoscopy safely. For convenience, LSPS might be a good alternative, with comparable prognostic performance to these two models. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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15 pages, 2506 KiB  
Article
Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis
by Chiara Donadei, Andrea Angeletti, Maria Cappuccilli, Massimiliano Conti, Diletta Conte, Fulvia Zappulo, Alessio De Giovanni, Deborah Malvi, Rita Aldini, Aldo Roda and Gaetano La Manna
J. Clin. Med. 2022, 11(3), 636; https://doi.org/10.3390/jcm11030636 - 27 Jan 2022
Cited by 2 | Viewed by 2036
Abstract
Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, [...] Read more.
Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, an additional mechanism may be hypothesized to explain the renal dysfunction during liver cirrhosis. Recent evidence suggest that such mechanisms may be closely related to obstructive jaundice. Methods: Given the not completely elucidated role of bile acids in kidney tissue damage, this study developed a rat model of AKI with liver cirrhosis induction by carbon tetrachloride (CCl4) inhalation for 12 weeks. Histological analyses of renal and liver biopsies were performed at sacrifice. Organic anion tubular transporter distribution and apoptosis in kidney cells were analyzed by immunohistochemistry. Circulating and urinary markers of inflammation and tubular injury were assayed in 21 treated rats over time (1, 2, 4, 8, and 12 weeks of CCl4 administration) and 5 controls. Results: No renal histopathological alterations were found at sacrifice. Comparing treated rats with controls, organic anion transporters were differentially expressed and localized. High serum bile acid values were detected in cirrhotic animals, while caspase-3 staining was negative in both groups. Increased levels of serum inflammatory and urinary tubular injury biomarkers were observed during cirrhosis progression, with a peak after 4 and 8 weeks of treatment. Conclusions: These findings suggest possible adaptive tubular mechanisms for bile acid transporters in response to cirrhosis-induced AKI. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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12 pages, 1212 KiB  
Article
Diagnostic Value of Non-invasive Scoring Systems in the Prediction of Esophageal Varices in Patients with Liver Cirrhosis—Single Center Experience
by Tijana Glisic, Milica Stojkovic Lalosevic, Tamara Milovanovic, Ivan Rankovic, Marija Stojanovic, Aleksandar Toplicanin, Marko Aleksic, Vladimir Milivojevic, Jelena Martinov Nestorov, Iva Lolic and Dusan D. Popovic
Medicina 2022, 58(2), 158; https://doi.org/10.3390/medicina58020158 - 20 Jan 2022
Cited by 4 | Viewed by 3760
Abstract
Background and Objectives: Upper endoscopy is considered the gold standard for screening and diagnosis of esophageal varices (EV). Non-invasive methods for predicting EV have become a research hotspot in recent years. The aim of this study was to assess the role of [...] Read more.
Background and Objectives: Upper endoscopy is considered the gold standard for screening and diagnosis of esophageal varices (EV). Non-invasive methods for predicting EV have become a research hotspot in recent years. The aim of this study was to assess the role of non-invasive scores in predicting the presence of EV in patients with liver cirrhosis, and to determine the value of these scores in predicting the outcome of patients with cirrhosis presenting with acute variceal bleeding. Materials and Methods: A total of 386 patients with liver cirrhosis were included. The model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), fibrosis-4-index (FIB-4), fibrosis index (FI), King’s Score, albumin-bilirubin (ALBI) score, and platelet-albumin-bilirubin (PALBI) score were calculated. The discriminatory capacities of the examined scores in predicting the presence of esophageal varices were tested using receiver operating characteristic (ROC) curves. Results: The ROC curve analysis showed (area under the curve) AUC values of ALBI and PALBI of 0.603, and 0.606, respectively, for the prediction of EV. APRI, MELD, PALBI, King’s, FIB-4, and ALBI scores showed statistically significant correlation with EV bleeding (p < 0.05). AUC of APRI and MELD for predicting EV bleeding were 0.662 and 0.637, respectively. The AUC value of MELD in short-term mortality was 0.761. Conclusions: ALBI and PALBI scores had modest diagnostic accuracy of EVs in liver cirrhosis. APRI and MELD can be used as a reference index for the EV bleeding, and MELD score is best associated with short-term outcome in cirrhotic patients. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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11 pages, 705 KiB  
Article
Activity of Total Alcohol Dehydrogenase, Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in the Serum of Patients with Alcoholic Fatty Liver Disease
by Blanka Wolszczak-Biedrzycka, Elżbieta Zasimowicz-Majewska, Anna Bieńkowska, Grzegorz Biedrzycki, Justyna Dorf and Wojciech Jelski
Medicina 2022, 58(1), 25; https://doi.org/10.3390/medicina58010025 - 24 Dec 2021
Cited by 3 | Viewed by 2984
Abstract
Background and objectives: The aim of the current study was to assess the use of determinations of total alcohol dehydrogenase and the activity of its isoenzymes as well as aldehyde dehydrogenase in the serum of patients with alcohol liver disease. Materials and [...] Read more.
Background and objectives: The aim of the current study was to assess the use of determinations of total alcohol dehydrogenase and the activity of its isoenzymes as well as aldehyde dehydrogenase in the serum of patients with alcohol liver disease. Materials and Methods: The testing was performed on the serum of 38 patients with alcoholic fatty liver (26 males and 12 females aged 31–75). The total activity of ADH was determined by the colorimetric method. The activity of ADH I and ADH II, as well as ALDH, was determined by the spectrofluorometric method using fluorogenic specific substrates. The activity of isoenzymes of other classes was determined by spectrophotometric methods using substrates. Results: A statistically significantly higher ADH I activity was noted in the serum of patients with alcoholic fatty liver (4.45 mIU/L) compared to the control group (2.04 mIU/L). A statistically significant increase in the activity was also noted for the class II alcohol dehydrogenase isoenzyme (29.21 mIU/L, control group: 15.56 mIU/L) and the total ADH (1.41 IU/L, control group: 0.63 IU/L). Conclusions: The obtained results imply the diagnostic usefulness of the determination of AHD total, ADH I, and ADH II activity in the serum of patients with alcoholic fatty liver. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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