Clinical Research in Hepatology

A topical collection in Journal of Clinical Medicine (ISSN 2077-0383). This collection belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

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Collection Editor
1. Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
2. Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Interests: metabolic and alcoholic associated fatty liver diseases; liver fibrosis; HCC; DILI

Topical Collection Information

Dear Colleagues,

The spectrum of etiologies for liver diseases (LD) is broad and includes toxins, alcohol abuse, infection, autoimmune diseases, and genetic and metabolic disorders. In general, LD accounts annually for approximately 2 million deaths worldwide, due to complications of cirrhosis, liver cancer, or deterioration of liver functions. Besides that, the economic impact is high and the quality of life is low in patients with LD. Though this is sobering, it also highlights an important opportunity to improve public health, given that most causes of liver diseases are preventable. Indeed, over the past 30 years, remarkable progress has been made in basic/clinical research, vaccination programs, drug discovery, and development in the field of hepatology.

In this Topical Collection of JCM, we invite you to contribute original and cutting-edge research articles, reviews, letters, or case studies related to the theme of “Clinical research in hepatology”. We encourage submissions from international contributors and researchers of all specialties that relate to clinical hepatology and liver diseases. Relevant topics include but are not limited to: NASH, NAFLD, ALD, hepatitis, DILI, hepatic fibrosis, steatosis, HCC, cholangiocarcinoma, rare liver diseases, inherited hepatic disorders, treatment and management of LD complications, therapeutic perspectives, and translational aspects in hepatology.

Prof. Dr. Yulia A. Nevzorova
Collection Editor

Manuscript Submission Information

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Keywords

  • NAFLD
  • ALD
  • HCC
  • CCC
  • Hepatitis Cirrhosis
  • DILI
  • Liver transplantation
  • Clinical hepatology

Published Papers (24 papers)

2024

Jump to: 2023, 2022, 2021

15 pages, 1422 KiB  
Article
Efficacy and Safety of a Probiotic Containing Saccharomyces boulardii CNCM I-745 in the Treatment of Small Intestinal Bacterial Overgrowth in Decompensated Cirrhosis: Randomized, Placebo-Controlled Study
by Irina Efremova, Roman Maslennikov, Maria Zharkova, Elena Poluektova, Nona Benuni, Aleksandr Kotusov, Tatyana Demina, Aleksandra Ivleva, Farida Adzhieva, Taisiya Krylova and Vladimir Ivashkin
J. Clin. Med. 2024, 13(3), 919; https://doi.org/10.3390/jcm13030919 - 05 Feb 2024
Cited by 1 | Viewed by 1711
Abstract
(1) Background: The aim was to evaluate the effectiveness of the probiotic containing Saccharomyces boulardii in the treatment of small intestinal bacterial overgrowth (SIBO) in patients with decompensated cirrhosis. (2) Methods: This was a blinded, randomized, placebo-controlled study. (3) Results: [...] Read more.
(1) Background: The aim was to evaluate the effectiveness of the probiotic containing Saccharomyces boulardii in the treatment of small intestinal bacterial overgrowth (SIBO) in patients with decompensated cirrhosis. (2) Methods: This was a blinded, randomized, placebo-controlled study. (3) Results: After 3 months of treatment, SIBO was absent in 80.0% of patients in the probiotic group and in 23.1% of patients in the placebo group (p = 0.002). The patients with eliminated SIBO had decreased frequency of ascites and hepatic encephalopathy, the increased platelets and albumin levels, the decreased blood levels of total bilirubin, biomarkers of bacterial translocation (lipopolysaccharide [LPS]) and systemic inflammation (C-reactive protein), and positive changes in markers of hyperdynamic circulation compared with the state at inclusion. There were no significant changes in the claudin 3 level (the intestinal barrier biomarker) in these patients. No significant changes were observed in the group of patients with persistent SIBO. The serum level of nitrate (endothelial dysfunction biomarker) was lower in patients with eradicated SIBO than in patients with persistent SIBO. One (5.3%) patient with eradicated SIBO and six (42.9%) patients with persistent SIBO died within the first year of follow-up (p = 0.007). (4) Conclusions: SIBO eradication was an independent predictor of a favorable prognosis during the first year of follow-up. Full article
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2023

Jump to: 2024, 2022, 2021

13 pages, 443 KiB  
Article
Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX® as a Screening Tool
by Jordi Sánchez-Delgado, Joaquim Profitós, Marta Arévalo, Alba Lira, Carlos Mármol, Mireia Miquel, Meritxell Casas, Mercedes Vergara, Xavier Calvet, Eugenio Berlanga, Luís del Rio, Oliver Valero, Ester Costa, Marta Larrosa and Enrique Casado Burgos
J. Clin. Med. 2024, 13(1), 188; https://doi.org/10.3390/jcm13010188 - 29 Dec 2023
Viewed by 672
Abstract
Purpose: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a [...] Read more.
Purpose: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. Methods: This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). Results: Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child–Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. Conclusions: The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing. Full article
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10 pages, 939 KiB  
Article
Clinicopathologic Features, Genetics, Treatment, and Long-Term Outcomes in Japanese Children and Young Adults with Benign Recurrent Intrahepatic Cholestasis: A Multicenter Study
by Ken Kato, Shuichiro Umetsu, Takao Togawa, Koichi Ito, Takayoshi Kawabata, Teruko Arinaga-Hino, Naoya Tsumura, Ryosuke Yasuda, Yutaro Mihara, Hironori Kusano, Shogo Ito, Kazuo Imagawa, Hisamitsu Hayashi, Ayano Inui, Yushiro Yamashita and Tatsuki Mizuochi
J. Clin. Med. 2023, 12(18), 5979; https://doi.org/10.3390/jcm12185979 - 15 Sep 2023
Cited by 1 | Viewed by 1336
Abstract
Background: Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients. Methods: We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four [...] Read more.
Background: Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients. Methods: We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four pediatric centers and one adult center between April 2007 and March 2022. Demographics, clinical course, laboratory results, molecular genetic findings concerning ATP8B1 and ABCB11 genes, histopathology, and treatment response were examined retrospectively. Results: Seven Japanese patients with BRIC were enrolled (four male, three female; four BRIC-1 and three BRIC-2). The median age at onset for BRIC-1 was 12 years; for BRIC-2, it was 1 month. Intermittent cholestatic attacks numbered from one to eight during the 11 years of median follow-up. Six patients received a mainstream education; only one patient attended special education. None developed cirrhosis. Three with BRIC-1 showed compound heterozygosity for a variant ATP8B1 gene, while one was heterozygous; two BRIC-2 patients showed compound heterozygosity in ABCB11 and one was heterozygous. Liver biopsy specimens obtained during cholestatic attacks showed fibrosis varying from none to moderate; inflammation was absent or mild. Rifampicin administered to three patients for cholestatic attacks was effective in all, as was cholestyramine in two of three. Conclusions: To our knowledge, this is the first East Asian multicenter study of BRIC patients. Onset age and number of cholestatic attacks varied. Rifampicin and cholestyramine were effective against attacks. No patient developed cirrhosis; most had normal growth and development. The long-term outcomes were satisfactory. Full article
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14 pages, 2156 KiB  
Article
Histological Characteristics and Management of Hepatitis on Immune Checkpoint Inhibitors: A Retrospective Descriptive Study
by Lucia Parlati, Kennie Marcin, Benoit Terris, Anaïs Vallet-Pichard, Marion Corouge, Clémence Hollande, Philippe Sogni, Vincent Mallet and Stanislas Pol
J. Clin. Med. 2023, 12(11), 3751; https://doi.org/10.3390/jcm12113751 - 29 May 2023
Cited by 2 | Viewed by 1255
Abstract
Background and aims: the side effects of immune checkpoint inhibitors (ICI) pose a problem for the clinical management of cancer patients. There is a lack of knowledge of the value of liver biopsy in patients with ICI-related drug-induced liver injury (ICI-DILI). The aim [...] Read more.
Background and aims: the side effects of immune checkpoint inhibitors (ICI) pose a problem for the clinical management of cancer patients. There is a lack of knowledge of the value of liver biopsy in patients with ICI-related drug-induced liver injury (ICI-DILI). The aim of this study was to explore the impact of liver biopsy on clinical management and response to corticosteroids, according to histological findings. Methods: We conducted a retrospective, single-center study to evaluate the biochemical, histological and clinical data of 35 patients with ICI-DILI between 2015 and 2021 in a university hospital in France. Results: Of the 35 patients with ICI-DILI (median [interquartile range] age 62 [48–73] years, 40% males) studied, 20 underwent a liver biopsy. There was no difference in the management of ICI-DILI according to liver biopsy in terms of ICI withdrawal, reduction or rechallenge. According to the histological profile, patients with toxic and granulomatous profiles had a better response to corticosteroids, while patients with cholangitic lesions had the worst response. Conclusion: In ICI-DILI, liver biopsy must not delay patient care but may be useful in identifying patients with a cholangitic profile who have a poorer response to corticosteroids. Full article
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12 pages, 844 KiB  
Article
Clinical Characteristics of Autoimmune Hepatitis in a Middle Eastern Population: A Tertiary Care Center Experience
by Tarek A. Tamimi, Malik Sallam, Deema Rayyan, Randa Farah, Dana Alkhulaifat, Abdallah Al-Ani, Reem Elmusa, Said Sharawi, Omar Tanash and Yaser Rayyan
J. Clin. Med. 2023, 12(2), 629; https://doi.org/10.3390/jcm12020629 - 12 Jan 2023
Cited by 3 | Viewed by 2110
Abstract
Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause, and its manifestations appear to vary by race and ethnicity. The literature on AIH in the Middle East, including Jordan, is scarce; therefore, this study aimed to determine the clinical characteristics [...] Read more.
Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause, and its manifestations appear to vary by race and ethnicity. The literature on AIH in the Middle East, including Jordan, is scarce; therefore, this study aimed to determine the clinical characteristics of AIH in an understudied population. This retrospective chart review study was conducted on AIH patients who presented to Jordan University Hospital over a seven-year period (2014–2020). Retrieved data included sociodemographics, liver function tests, autoimmune serologic markers, viral hepatitis serology, findings on liver biopsies, treatment regimens, post-therapy outcomes and treatment-related complications. The total number of AIH patients included in the study was 30, divided as follows: type 1 AIH (n = 17, 56.7%), type 2 AIH (n = 2, 6.7%), seronegative AIH (n = 9, 30.0%), and two patients who had AIH-primary biliary cirrhosis overlap syndrome (6.7%). The mean age at diagnosis was 44 years (standard deviation: 17 years), with a female predominance (n = 25, 83.3%). Acute presentation was seen among 18 patients (60.0%). Mild to moderate fibrosis (F1 and F2 on METAVIR scoring system) without cirrhosis was observed among patients who underwent liver biopsies (10/19, 52.6%). The majority of patients (73.3%) were initially treated with prednisone, with azathioprine combination in 16.7% of the patients. At 6 months post initial treatment, twenty patients (66.7%) achieved biochemical remission, four patients had incomplete response, two patients failed to improve (one died during the induction of remission period due to AIH-related complications), and four patients were lost to follow-up. This study provided an updated overview of AIH in Jordan. The results showed typical female predominance, and interestingly high rates of acute presentation and seronegative disease. Future longitudinal studies are recommended to address the nature and long-term prognosis of AIH in Jordan. Full article
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2022

Jump to: 2024, 2023, 2021

8 pages, 359 KiB  
Article
Myosteatosis Is Not Associated with Complications or Survival in HCC Patients Undergoing Trans Arterial Embolization
by Chiara Masetti, Nicola Pugliese, Ludovica Lofino, Francesca Colapietro, Roberto Ceriani, Ana Lleo, Dario Poretti, Vittorio Pedicini, Stella De Nicola, Guido Torzilli, Lorenza Rimassa, Alessio Aghemo and Ezio Lanza
J. Clin. Med. 2023, 12(1), 262; https://doi.org/10.3390/jcm12010262 - 29 Dec 2022
Cited by 3 | Viewed by 1775
Abstract
Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. [...] Read more.
Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. We retrospectively analyzed a cohort of 151 cirrhotic patients with unresectable hepatocellular carcinoma (HCC) who underwent their first trans-arterial embolization (TAE) between 1 March 2011 and 1 July 2019 at our Institution. Clinical and biochemical data were collected. Sarcopenia was assessed using the L3-SMI method while myosteatosis with a dedicated segmentation suite (3D Slicer), using a single slice at an axial plane located at L3 and calculating the IMAC (Intramuscular Adipose Tissue Content Index). The sex-specific cut-off values for defining myosteatosis were IMAC > −0.44 in males and >−0.31 in females. In our cohort, 115 (76%) patients were included in the myosteatosis group; 128 (85%) patients had a coexistent diagnosis of sarcopenia. Patients with myosteatosis were significantly older and showed higher BMI than patients without myosteatosis. In addition, male gender and alcoholic- or metabolic-related cirrhosis were most represented in the myosteatosis group. Myosteatosis was not associated with a different HCC burden, length of hospitalization, complication rate, and readmission in the first 30 days after discharge. Overall survival was not influenced by the presence of myosteatosis. Full article
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12 pages, 1321 KiB  
Article
Association of Alpha-1 Antitrypsin Pi*Z Allele Frequency and Progressive Liver Fibrosis in Two Chronic Hepatitis C Cohorts
by Victoria Therese Mücke, Janett Fischer, Marcus Maximilian Mücke, Alexander Teumer, Alexander Koch, Johannes Vermehren, Malin Fromme, Stefan Zeuzem, Christian Trautwein, Christoph Sarrazin, Thomas Berg, Biaohuan Zhou and Karim Hamesch
J. Clin. Med. 2023, 12(1), 253; https://doi.org/10.3390/jcm12010253 - 29 Dec 2022
Cited by 3 | Viewed by 1645
Abstract
(1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant ‘Pi*Z’ emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage (‘Pi*MZ’ genotype) as an additional risk factor in patients with chronic viral hepatitis C [...] Read more.
(1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant ‘Pi*Z’ emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage (‘Pi*MZ’ genotype) as an additional risk factor in patients with chronic viral hepatitis C to develop progressive liver fibrosis. (2) Methods: Two prospectively recruited cohorts totaling 572 patients with therapy-naïve chronic viral hepatitis C (HCV) were analyzed. The Frankfurt cohort included 337 patients and a second cohort from Leipzig included 235 patients. The stage of liver fibrosis was assessed by liver biopsy, AST-to-platelet ratio index (APRI) score and Fibrosis-4 (FIB-4) score (Frankfurt) as well as liver stiffness measurement (LSM) via transient elastography (Leipzig). All patients were genotyped for the Pi*Z variant (rs28929474) of the SERPINA1 gene. (3) Results: In the Frankfurt cohort, 16/337 (4.7%) patients carried the heterozygous Pi*Z allele while 10/235 (4.3%) in the Leipzig cohort were Pi*Z carriers. In both cohorts, there was no higher proportion of Pi*Z heterozygosity in patients with cirrhosis compared to patients without cirrhosis or patients with cirrhosis vs. no liver fibrosis. Accordingly, Pi*Z frequency was not different in histological or serological stages of liver fibrosis (F0–F4) and showed no clear association with LSM. (4) Conclusions: Evaluation in two representative HCV cohorts does not indicate Pi*Z heterozygosity as a clinically relevant disease modifier in chronic HCV infection. However, validation in even larger cohorts with longitudinal follow-up is warranted. Full article
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13 pages, 609 KiB  
Article
Clinical Factors Associated with Non-Obese Nonalcoholic Fatty Liver Disease Detected among US Adults in the NHANES 2017–2018
by Zayd Adnan Razouki, Xiaotao Zhang, Jessica P. Hwang and Natalia I. Heredia
J. Clin. Med. 2022, 11(15), 4260; https://doi.org/10.3390/jcm11154260 - 22 Jul 2022
Cited by 1 | Viewed by 1776
Abstract
NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US [...] Read more.
NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US adults. We aggregated data from the 2017–2018 cycle of NHANES and included adults (age ≥ 20 years) with BMI < 25 kg/m2 with complete data for the survey, medical examination, and VCTE along with controlled attenuation parameter (CAP). We excluded participants with risks of other liver diseases. We considered patients to have non-obese NAFLD if CAP was >285 dB/m, or non-obese NAFLD fibrosis if this CAP criteria was met and liver stiffness was >8.6 kPa. We calculated the adjusted OR and 95% CI for associations with non-obese NAFLD using multivariable logistic regression. The prevalence of non-obese NAFLD was 6.2% and Asian Americans (12.2%) had the highest non-obese NAFLD prevalence. Clinical factors associated with non-obese NAFLD were advanced age and metabolic syndrome (ORadjusted = 6.8, 95% CI 3.0–15.5). In a separate model, we found elevated glucose (ORadjusted = 4.1, 95% CI 2.1–7.9), triglycerides (ORadjusted = 3.8, 95% CI 1.7–8.5), and truncal fat (100-unit increase ORadjusted = 1.07, 95% CI: 1.04–1.10) were associated with higher odds of non-obese NAFLD. Meanwhile, low physical activity (ORadjusted = 2.9, 95% CI 1.2–7.1) was also positively associated with non-obese NAFLD. Non-obese NAFLD is prevalent in the US and is highly associated with metabolic conditions and syndrome. Our results support the importance of considering racial/ethnic differences when investigating NAFLD in a clinical setting. Full article
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13 pages, 1245 KiB  
Article
Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month
by Deok-Gie Kim, Shin Hwang, Jong Man Kim, Je Ho Ryu, Young Kyoung You, Donglak Choi, Bong-Wan Kim, Dong-Sik Kim, Yang Won Nah, Tae-Seok Kim, Jai Young Cho, Geun Hong, Jae Do Yang, Jaryung Han, Suk-Won Suh, Kwan Woo Kim, Yun Kyung Jung, Ju Ik Moon, Jun Young Lee, Sung Hwa Kim, Jae Geun Lee, Myoung Soo Kim, Kwang-Woong Lee and Dong Jin Jooadd Show full author list remove Hide full author list
J. Clin. Med. 2022, 11(14), 4203; https://doi.org/10.3390/jcm11144203 - 20 Jul 2022
Viewed by 1698
Abstract
Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (<60 mL/min/1.73 m2), examining liver recipients with functionally [...] Read more.
Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (<60 mL/min/1.73 m2), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m2, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06–3.53) and infection (HR = 1.44, 95% CI 1.12–1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features (p = 0.013 for recurrent hepatocellular carcinoma, and p = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients’ renal functional reserve. Full article
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11 pages, 617 KiB  
Article
Child–Pugh Score and ABCG2-rs2231142 Genotype Independently Predict Survival in Advanced Hepatoma Patients Treated with Sorafenib
by Po-Han Huang, Jen Yu, Yin-Yi Chu, Yang-Hsiang Lin and Chau-Ting Yeh
J. Clin. Med. 2022, 11(9), 2550; https://doi.org/10.3390/jcm11092550 - 02 May 2022
Cited by 2 | Viewed by 1507
Abstract
Patients with advanced hepatocellular carcinoma (HCC) are treated by immunotherapy and/or targeted agents, such as sorafenib. Several single nucleotide polymorphisms (SNPs) and clinical scores have been proposed as prognostic markers in HCC patients treated with sorafenib. This study aimed to validate the prognostic [...] Read more.
Patients with advanced hepatocellular carcinoma (HCC) are treated by immunotherapy and/or targeted agents, such as sorafenib. Several single nucleotide polymorphisms (SNPs) and clinical scores have been proposed as prognostic markers in HCC patients treated with sorafenib. This study aimed to validate the prognostic values of these markers in a tertiary referral medical center. Two independent cohorts (cohort-1 [n = 97] and cohort-2 [n = 60]) of advanced HCC patients treated with sorafenib monotherapy were enrolled. Univariate followed by multivariate Cox proportional hazard analysis identified Child–Pugh (CP) score (p < 0.001) and renal insufficiency during treatment (p < 0.001) as independent predictors in cohort-1 patients. The same analytic method revealed ascites (p = 0.000), CP score (p = 0.001), infection during treatment (p < 0.001), and ATP-binding cassette subfamily G member 2 (ABCG2)-rs2231142 genotype (p = 0.003) as independent predictors in cohort-2 patients. ABCG2-rs2231142 genotype “CC” was associated with unfavorable overall survival in sorafenib-treated HCC patients. In conclusion, the CP score and ABCG2-rs2231142 genotype served as independent survival predictors for advanced HCC patients receiving sorafenib treatment. Full article
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17 pages, 1067 KiB  
Article
The Utility and Diagnostic Accuracy of Transient Elastography in Adults with Morbid Obesity: A Prospective Study
by Ahmad Hassan Ali, Alhareth Al Juboori, Gregory F. Petroski, Alberto A. Diaz-Arias, Majid M. Syed-Abdul, Andrew A. Wheeler, Rama R. Ganga, James B. Pitt, Nicole M. Spencer, Ghassan M. Hammoud, R. Scott Rector, Elizabeth J. Parks and Jamal A. Ibdah
J. Clin. Med. 2022, 11(5), 1201; https://doi.org/10.3390/jcm11051201 - 23 Feb 2022
Cited by 8 | Viewed by 2164
Abstract
Patients with morbid obesity are at high risk for nonalcoholic fatty liver disease (NAFLD) complicated by liver fibrosis. The clinical utility of transient elastography (TE) by Fibroscan in patients with morbid obesity (body mass index (BMI) ≥ 40 kg/m2) is not [...] Read more.
Patients with morbid obesity are at high risk for nonalcoholic fatty liver disease (NAFLD) complicated by liver fibrosis. The clinical utility of transient elastography (TE) by Fibroscan in patients with morbid obesity (body mass index (BMI) ≥ 40 kg/m2) is not well-defined. We examined the diagnostic accuracy of Fibroscan in predicting significant liver fibrosis (fibrosis stage ≥2) in morbidly obese patients (BMI ≥ 40 kg/m2). Patients scheduled for bariatric surgery were prospectively enrolled. Intraoperative liver biopsy, liver-stiffness measurement (LSM) by Fibroscan (XL probe), and biochemical evaluation were all performed on the same day. The endpoint was significant liver fibrosis defined as fibrosis stage ≥2 based on the Nonalcoholic Steatohepatitis Clinical Research Network. The optimal LSM cutoff value for detecting significant fibrosis was determined by using the Youden Index method. Routine clinical, laboratory, and elastography data were analyzed by stepwise logistic regression analysis to identify predictors of significant liver fibrosis and build a predictive model. An optimal cutoff point of the new model’s regression formula for predicting significant fibrosis was determined by using the Youden index method. One hundred sixty-seven patients (mean age, 46.4 years) were included, of whom 83.2% were female. Histological assessment revealed the prevalence of steatohepatitis and significant fibrosis of 40.7% and 11.4%, respectively. The median LSM was found to be significantly higher in the significant fibrosis group compared to those in the no or non-significant fibrosis group (18.2 vs. 7.7 kPa, respectively; p = 0.0004). The optimal LSM cutoff for predicting significant fibrosis was 12.8 kPa, with an accuracy of 71.3%, sensitivity of 73.7%, specificity of 70.9%, positive predictive value of 24.6%, negative predictive value of 95.5%, and ROC area of 0.723 (95% CI: 0.62–0.83). Logistic regression analysis identified three independent predictors of significant fibrosis: LSM, hemoglobin A1c, and alkaline phosphatase. A risk score was developed by using these three variables. At an optimal cutoff value of the regression formula, the risk score had an accuracy of 79.6% for predicting significant fibrosis, sensitivity of 89.5%, specificity of 78.4%, positive predictive value of 34.7%, negative predictive value of 98.3%, and ROC area of 0.855 (95% CI: 0.76–0.95). Fibroscan utility in predicting significant liver fibrosis in morbidly obese subjects is limited with accuracy of 71.3%. A model incorporating hemoglobin A1c and alkaline phosphatase with LSM improves accuracy in detecting significant fibrosis in this patient population. Full article
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14 pages, 5863 KiB  
Article
Effects of Moderate Alcohol Consumption in Non-Alcoholic Fatty Liver Disease
by Peter Lemmer, Paul Manka, Jan Best, Alisan Kahraman, Julia Kälsch, Ramiro Vilchez-Vargas, Alexander Link, Hsin Chiang, Guido Gerken, Ali Canbay, Lars P. Bechmann and Svenja Sydor
J. Clin. Med. 2022, 11(3), 890; https://doi.org/10.3390/jcm11030890 - 08 Feb 2022
Cited by 10 | Viewed by 2764
Abstract
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have emerged as leading causes of chronic liver diseases worldwide. ALD and NAFLD share several pathophysiological patterns as well as histological features, while clinically, they are distinguished by the amount of alcohol consumed [...] Read more.
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have emerged as leading causes of chronic liver diseases worldwide. ALD and NAFLD share several pathophysiological patterns as well as histological features, while clinically, they are distinguished by the amount of alcohol consumed daily. However, NAFLD coexists with moderate alcohol consumption in a growing proportion of the population. Here, we investigated the effects of moderate alcohol consumption on liver injury, lipid metabolism, and gut microbiota in 30 NAFLD-patients. We anonymously assessed drinking habits, applying the AUDIT- and CAGE-questionnaires and compared subgroups of abstainers vs. low to harmful alcohol consumers (AUDIT) and Cage 0–1 vs. Cage 2–4. Patients who did not drink any alcohol had lower levels of γGT, ALT, triglycerides, and total cholesterol. While the abundance of Bacteroidaceae, Bifidobacteriaceae, Streptococcaceae, and Ruminococcaceae was higher in the low to harmful alcohol drinking cohort, the abundance of Rikenellaceae was higher in the abstainers. Our study suggests that even moderate alcohol consumption has an impact on the liver and lipid metabolism, as well as on the composition of gut microbiota. Full article
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2021

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9 pages, 799 KiB  
Article
Spontaneous Bacterial Peritonitis among Cirrhotic Patients: Prevalence, Clinical Characteristics, and Outcomes
by Naim Abu-Freha, Tal Michael, Liat Poupko, Asia Estis-Deaton, Muhammad Aasla, Omar Abu-Freha, Ohad Etzion and Lior Nesher
J. Clin. Med. 2022, 11(1), 227; https://doi.org/10.3390/jcm11010227 - 31 Dec 2021
Cited by 5 | Viewed by 2031
Abstract
(1) Background: Spontaneous bacterial peritonitis (SBP) is a feared complication of liver cirrhosis. We investigated the prevalence of SBP, positive ascitic fluid cultures, and risk factors for mortality. (2) Methods: A retrospective analysis of all patients with cirrhosis hospitalized or in follow-up in [...] Read more.
(1) Background: Spontaneous bacterial peritonitis (SBP) is a feared complication of liver cirrhosis. We investigated the prevalence of SBP, positive ascitic fluid cultures, and risk factors for mortality. (2) Methods: A retrospective analysis of all patients with cirrhosis hospitalized or in follow-up in a single center between 1996 and 2020. The clinical data, long-term complications, and mortality of SBP patients were compared with those of non-SBP patients. Ascitic fluid positive culture was compared with those without growth. (3) Results: We included 1035 cirrhotic patients, of which 173 (16.7%) developed SBP. Ascitic fluid culture growth was found in 47.4% of the SBP cases, with Escherichia coli bacteria detected in 38%, 24.4% grew ESBL-producing bacteria, and 14.5% displayed multidrug resistance. In a Cox regression model, SBP, male sex, prolonged INR at diagnosis, and hepatocellular carcinoma were found to be risk factors for mortality in cirrhotic patients. The long-term all-cause mortality was 60% in non-SBP and 90% in SBP patients. (4) Conclusions: Only a minority of cirrhotic patients developed SBP, 47.4% of which had positive ascitic fluid cultures with high antibiotic resistance. Growth of ESBL and multidrug resistant organisms is becoming more frequent in the clinical setting, reaching SBP mortality of 90%. Full article
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19 pages, 2180 KiB  
Review
Critical Review of Gaps in the Diagnosis and Management of Drug-Induced Liver Injury Associated with Severe Cutaneous Adverse Reactions
by Marina Villanueva-Paz, Hao Niu, Antonio Segovia-Zafra, Inmaculada Medina-Caliz, Judith Sanabria-Cabrera, M. Isabel Lucena, Raúl J. Andrade and Ismael Alvarez-Alvarez
J. Clin. Med. 2021, 10(22), 5317; https://doi.org/10.3390/jcm10225317 - 15 Nov 2021
Cited by 3 | Viewed by 2598
Abstract
Drug-induced liver injury (DILI) encompasses the unexpected damage that drugs can cause to the liver. DILI may develop in the context of an immunoallergic syndrome with cutaneous manifestations, which are sometimes severe (SCARs). Nevirapine, allopurinol, anti-epileptics, sulfonamides, and antibiotics are the most frequent [...] Read more.
Drug-induced liver injury (DILI) encompasses the unexpected damage that drugs can cause to the liver. DILI may develop in the context of an immunoallergic syndrome with cutaneous manifestations, which are sometimes severe (SCARs). Nevirapine, allopurinol, anti-epileptics, sulfonamides, and antibiotics are the most frequent culprit drugs for DILI associated with SCARs. Interestingly, alleles HLA-B*58:01 and HLA-A*31:01 are associated with both adverse reactions. However, there is no consensus about the criteria used for the characterization of liver injury in this context, and the different thresholds for DILI definition make it difficult to gain insight into this complex disorder. Moreover, current limitations when evaluating causality in patients with DILI associated with SCARs are related to the plethora of causality assessment methods and the lack of consensual complementary tools. Finally, the management of this condition encompasses the treatment of liver and skin injury. Although the use of immunomodulant agents is accepted for SCARs, their role in treating liver injury remains controversial. Further randomized clinical trials are needed to test their efficacy and safety to address this complex entity. Therefore, this review aims to identify the current gaps in the definition, diagnosis, prognosis, and management of DILI associated with SCARs, proposing different strategies to fill in these gaps. Full article
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12 pages, 1411 KiB  
Article
Cessation of Nucleos(t)ide Analogue Therapy in Non-Cirrhotic Hepatitis B Patients with Prior Severe Acute Exacerbation
by Chia-Yeh Lai, Sheng-Shun Yang, Shou-Wu Lee, Hsin-Ju Tsai and Teng-Yu Lee
J. Clin. Med. 2021, 10(21), 4883; https://doi.org/10.3390/jcm10214883 - 23 Oct 2021
Cited by 3 | Viewed by 1650
Abstract
Chronic hepatitis B (CHB) with severe acute exacerbation (SAE) is an urgent problem requiring nucleos(t)ide analogue (NA) therapy. We aim to evaluate the clinical relapse (CR) risk after discontinuing NA in patients with prior SAE. Methods: In this retrospective cohort study, CHB patients [...] Read more.
Chronic hepatitis B (CHB) with severe acute exacerbation (SAE) is an urgent problem requiring nucleos(t)ide analogue (NA) therapy. We aim to evaluate the clinical relapse (CR) risk after discontinuing NA in patients with prior SAE. Methods: In this retrospective cohort study, CHB patients who discontinued NA therapy were screened between October, 2003 and January, 2019. A total of 78 non-cirrhotic patients who had received NA therapy for CHB with SAE, i.e., bilirubin ≥ 2 mg/dL and/or prothrombin time prolongation ≥3 s, (SAE group) were matched 1:2 with 156 controls without SAE (non-SAE group) by means of propensity scores (age, gender, NA categories, NA therapy duration, and HBeAg status). Results: The 5-year cumulative incidences of severe CR, i.e., ALT > 10X ULN, (42.78%, 95% CI: 27.84–57.73% vs. 25.42%, 95% CI: 16.26–34.58%; p = 0.045) and SAE recurrence (25.91%, 95% CI: 10.91–40.91% vs. 1.04%, 95% CI: 0–3.07%; p < 0.001) were significantly higher in the SAE group. Prior SAE history (HR 1.79, 95% CI: 1.04–3.06) was an independent factor for severe CR. The 5-year cumulative incidence of HBsAg seroclearance was significantly higher in the SAE group than that in the non-SAE group (16.82%, 95% CI: 2.34–31.30% vs. 6.02%, 95% CI: 0–13.23%; p = 0.049). Conclusions: Even though it creates a greater chance of HBsAg seroclearance, NA therapy cessation may result in a high risk of severe CR in non-cirrhotic CHB patients with prior SAE. Full article
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13 pages, 755 KiB  
Article
Model of Care for Microelimination of Hepatitis C Virus Infection among People Who Inject Drugs
by Francesco Giuseppe Foschi, Alberto Borghi, Alberto Grassi, Arianna Lanzi, Elvira Speranza, Teo Vignoli, Lucia Napoli, Deanna Olivoni, Michele Sanza, Edoardo Polidori, Giovanni Greco, Paolo Bassi, Francesco Cristini, Giorgio Ballardini, Mattia Altini, Fabio Conti and on behalf of MITH Group
J. Clin. Med. 2021, 10(17), 4001; https://doi.org/10.3390/jcm10174001 - 03 Sep 2021
Cited by 5 | Viewed by 2596
Abstract
Background: People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. Aims: This study aimed to assess the impact of a multidisciplinary [...] Read more.
Background: People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. Aims: This study aimed to assess the impact of a multidisciplinary intervention strategy where HCV screening, treatment and follow-up were performed at the same location on efficacy and safety of DAA-therapy in real-life PWID population. Methods: All HCV-infected PWID referred to five specialized outpatient centers for drug addicts (SerDs) in Northern Italy were prospectively enrolled from May 2015 to December 2019. Hepatologists and SerDs healthcare workers collaborated together in the management of PWID inside the SerDs. Sustained virologic response (SVR), safety of treatment, proportion of patients lost to follow-up and reinfection rate were evaluated. Results: A total of 358 PWID started antiviral treatment. About 50% of patients had advanced fibrosis/cirrhosis, 69% received opioid substitution treatment, and 20.7% self-reported recent injecting use. SVR was achieved in 338 (94.4%) patients. Two patients died during treatment; one prematurely discontinued, resulting in a non-responder; twelve were lost during treatment/follow-up; and five relapsed. No serious adverse events were reported. SVR was lower in recent PWID than in former ones (89.2% vs. 95.8%; p = 0.028). Seven reinfections were detected, equating to an incidence of 1.25/100 person-years. Reinfection was associated with recent drug use (OR 11.07, 95%CI 2.10–58.38; p = 0.005). Conclusion: Our embedded treatment model could be appropriate to increase the linkage to care of HCV-infected PWID. In this setting, DAA regimens are well tolerated and highly effective, achieving a lower rate of reinfection. Full article
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12 pages, 1338 KiB  
Article
Inadequate Ultrasound Examination in Hepatocellular Carcinoma Surveillance: A Systematic Review and Meta-Analysis
by Seung Baek Hong, Dong Hwan Kim, Sang Hyun Choi, So Yeon Kim, Ji Sung Lee, Nam Kyung Lee and Joon-Il Choi
J. Clin. Med. 2021, 10(16), 3535; https://doi.org/10.3390/jcm10163535 - 12 Aug 2021
Cited by 6 | Viewed by 1819
Abstract
We aimed to systematically evaluate the incidence of inadequate US in hepatocellular carcinoma (HCC) surveillance and determine the risk factors. Original studies reporting the incidence or risk factors for inadequate US were identified in MEDLINE, EMBASE, and the Cochrane database. The pooled incidence [...] Read more.
We aimed to systematically evaluate the incidence of inadequate US in hepatocellular carcinoma (HCC) surveillance and determine the risk factors. Original studies reporting the incidence or risk factors for inadequate US were identified in MEDLINE, EMBASE, and the Cochrane database. The pooled incidence of inadequate US was calculated using a random effects model, and subgroup analyses were performed. The pooled odds ratio (OR) was calculated for each risk factor for inadequate US. Six eligible articles were identified from 756 screened articles (4250 patients). The pooled incidence of inadequate US was 21.5%. Significantly higher rates of inadequate US were noted in studies including patients with and without hepatic observations compared with those evaluating only patients with hepatic observations (23.2% vs. 18.8%), studies using US alone compared with US plus alpha-fetoprotein (28.0% vs. 20.8%), and those using pathology and imaging as a reference standard compared with imaging only (23.2% vs. 17.9%). Nonalcoholic steatohepatitis (OR = 2.3 (1.07–4.84)), Child–Pugh B cirrhosis (OR = 2.2 (1.10–4.37)), and high body mass index (OR = 2.2 (1.12–4.24)) were significant risk factors for inadequate US (p ≤ 0.04). In patients at risk of HCC, 21.5% of US surveillance was inadequate. An alternative surveillance modality might be considered in patients with risk factors. Full article
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13 pages, 2133 KiB  
Article
The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis
by Joeri Lambrecht, Mustafa Porsch-Özçürümez, Jan Best, Fabian Jost-Brinkmann, Christoph Roderburg, Münevver Demir, Frank Tacke and Raphael Mohr
J. Clin. Med. 2021, 10(15), 3392; https://doi.org/10.3390/jcm10153392 - 30 Jul 2021
Cited by 15 | Viewed by 2270
Abstract
(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein [...] Read more.
(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population. Full article
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11 pages, 1432 KiB  
Article
A Model Incorporating Serum Alkaline Phosphatase for Prediction of Liver Fibrosis in Adults with Obesity and Nonalcoholic Fatty Liver Disease
by Ahmad Hassan Ali, Gregory F. Petroski, Alberto A. Diaz-Arias, Alhareth Al Juboori, Andrew A. Wheeler, Rama R. Ganga, James B. Pitt, Nicole M. Spencer, Ghassan M. Hammoud, R. Scott Rector, Elizabeth J. Parks and Jamal A. Ibdah
J. Clin. Med. 2021, 10(15), 3311; https://doi.org/10.3390/jcm10153311 - 27 Jul 2021
Cited by 4 | Viewed by 2415
Abstract
We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy [...] Read more.
We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy was performed, and liver histology was evaluated by a pathologist blinded to the patients’ data. The endpoint was significant fibrosis defined as fibrosis stage ≥ 2. Independent predictors of fibrosis were identified by logistic regression. Two hundred ten patients were recruited. Liver histology revealed steatosis in 87.1%, steatohepatitis in 21.9%, and significant fibrosis in 10%. Independent predictors of significant fibrosis were ALP (Odds Ratio (OR) 1.03; 95% Confidence interval (CI), 1.01–1.05), alanine aminotransferase (OR 1.02; 95% CI, 1.01–1.03), HbA1c (OR 1.58; 95% CI, 1.20–2.09), and body mass index (OR 1.06; 95% CI, 1.00–1.13). A tree-based model was developed to predict significant fibrosis, with a receiver operating characteristic (ROC) area of 0.845, sensitivity of 0.857, specificity of 0.836, and accuracy of 0.931. The applicability of serum ALP as an independent biomarker of liver fibrosis should be considered in obesity surgery patients, and in the broader context of obese patients with nonalcoholic fatty liver disease. Full article
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10 pages, 573 KiB  
Article
Long-Term Safety in HBsAg-Negative, HBcAb-Positive Patients with Rheumatic Diseases Receiving Maintained Steroid Therapy after Pulse Therapy
by Ying-Cheng Lin, Yen-Ju Chen, Shou-Wu Lee, Teng-Yu Lee, Yi-Hsing Chen, Wen-Nan Huang, Sheng-Shun Yang and Yi-Ming Chen
J. Clin. Med. 2021, 10(15), 3296; https://doi.org/10.3390/jcm10153296 - 26 Jul 2021
Cited by 5 | Viewed by 2191
Abstract
The risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after glucocorticoid (GC) pulse therapy remains unclear. Aims: Our study aimed to examine the safety of GC pulse therapy in HBsAg-negative, [...] Read more.
The risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after glucocorticoid (GC) pulse therapy remains unclear. Aims: Our study aimed to examine the safety of GC pulse therapy in HBsAg-negative, anti-HBc-positive rheumatic patients. Methods: Medical records of HBsAg-negative, anti-HBc-positive patients receiving GC pulse therapy to treat rheumatic diseases were reviewed. The primary outcome was HBV-associated hepatitis occurring within the first year after GC pulse therapy; the secondary outcome was HBsAg seroreversion occurring during the follow-up period. Results: We identified 5222 HBsAg-negative, anti-HBc-positive patients with rheumatic diseases who had attended Taichung Veterans General Hospital from October 2006 to December 2018. A total of 689 patients had received GC pulse therapy, with 424 patients being analyzed. Hepatitis was noted in 28 patients (6.6%) within the first year after GC pulse therapy, but none had been diagnosed as HBV-associated hepatitis. Three patients (0.7%) later developed HBsAg seroreversion, with a median interval of 97 months from the first episode of GC pulse therapy. These cases concurrently had maintained high dose oral prednisolone (≥20 mg prednisolone daily for over 4 weeks). Conclusions: Amongst the HBsAg-negative, anti-HBc-positive rheumatic patients treated with GC pulse therapy, the risk of HBV-associated hepatitis within the first year was low. HBsAg seroreversion may have developed in the later stage, but only in those patients who had maintained high-dose oral steroid. Full article
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17 pages, 3946 KiB  
Review
Systematic Review with Meta-Analyses: Diagnostic Accuracy of FibroMeter Tests in Patients with Non-Alcoholic Fatty Liver Disease
by Anne-Marieke Van Dijk, Yasaman Vali, Anne Linde Mak, Jenny Lee, Maarten E. Tushuizen, Mohammad Hadi Zafarmand, Quentin M. Anstee, M. Julia Brosnan, Max Nieuwdorp, Patrick M. Bossuyt and Adriaan G. Holleboom
J. Clin. Med. 2021, 10(13), 2910; https://doi.org/10.3390/jcm10132910 - 29 Jun 2021
Cited by 23 | Viewed by 2883
Abstract
Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. [...] Read more.
Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58–0.94); specificity: 91.1% (95%CI 0.89–0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73–0.90); specificity: 84.4% (95%CI 0.62–0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63–0.79); specificity: 82.8% (95%CI 0.71–0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains. Full article
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10 pages, 441 KiB  
Article
The Association between Vitamin D and Nonalcoholic Fatty Liver Disease Assessed by Controlled Attenuation Parameter
by Nam Ju Heo, Hyo Eun Park, Ji Won Yoon, Min-Sun Kwak, Jong In Yang, Su Jin Chung, Jeong Yoon Yim and Goh Eun Chung
J. Clin. Med. 2021, 10(12), 2611; https://doi.org/10.3390/jcm10122611 - 13 Jun 2021
Cited by 10 | Viewed by 2004
Abstract
Background: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). Methods: We conducted a retrospective cohort study of apparently healthy subjects [...] Read more.
Background: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). Methods: We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. Results: Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47–1.00 in Q2 vs. Q1; OR 0.65, 95% CI 0.44–0.94 in Q3 vs. Q1; and OR 0.64, 95% CI 0.44–0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31–0.87 in Q4 vs. Q1). Conclusions: Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD. Full article
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10 pages, 228 KiB  
Article
Association between Administration of Antithrombotics and Intraperitoneal Hemorrhage in Patients Undergoing Percutaneous Interventions for Liver Diseases
by Akira Asai, Keisuke Yokohama, Hideko Ohama, Yusuke Tsuchimoto, Shinya Fukunishi and Kazuhide Higuchi
J. Clin. Med. 2021, 10(11), 2527; https://doi.org/10.3390/jcm10112527 - 07 Jun 2021
Viewed by 1463
Abstract
Currently, percutaneous interventions are essential for diagnosis and treatment of liver diseases. The most frequent complication of percutaneous interventions is intraperitoneal hemorrhage. Recently, the number of patients with liver diseases on antithrombotics has been increasing. This retrospective cohort study aimed to evaluate the [...] Read more.
Currently, percutaneous interventions are essential for diagnosis and treatment of liver diseases. The most frequent complication of percutaneous interventions is intraperitoneal hemorrhage. Recently, the number of patients with liver diseases on antithrombotics has been increasing. This retrospective cohort study aimed to evaluate the risk factors for intraperitoneal hemorrhage in patients after percutaneous interventions for liver diseases. This study included 1025 patients who underwent percutaneous interventions for liver diseases from April 2015 to March 2020. All interventions were performed using an ultrasound-guided approach. The influence of antithrombotic drug administration in patients, who underwent percutaneous interventions according to the guidelines for the American Association for the Study of Liver Disease, was evaluated. Intraperitoneal hemorrhage after percutaneous interventions was detected by computed tomography. Intraperitoneal hemorrhage occurred in nine patients (0.88%); however, these adverse events were not severe. We compared clinical characteristics between the patients with and without intraperitoneal hemorrhage. Although, there was no difference based on the administration of antithrombotics (p = 0.1961), seven of nine patients who showed intraperitoneal hemorrhage received percutaneous treatments (radio frequency ablation or microwave ablation). Therefore, we divided patients who underwent treatments and liver biopsy and then investigated the influence of antithrombotics on the intraperitoneal hemorrhage. After propensity score matching in each patient group, the administration of antithrombotics was not identified as a risk factor for hemorrhage in patients who underwent interventional treatments and patients who underwent liver biopsy. When the antithrombotics were discontinued, according to the guidelines, it may not increase the risk factor for hemorrhage in patients of liver disease who underwent percutaneous interventions. Full article
10 pages, 2818 KiB  
Article
Non-Selective Beta-Blockers Decrease Infection, Acute Kidney Injury Episodes, and Ameliorate Sarcopenic Changes in Patients with Cirrhosis: A Propensity-Score Matching Tertiary-Center Cohort Study
by Tzu-Hao Li, Chih-Wei Liu, Chia-Chang Huang, Yu-Lien Tsai, Shiang-Fen Huang, Ying-Ying Yang, Chang-Youh Tsai, Ming-Chih Hou and Han-Chieh Lin
J. Clin. Med. 2021, 10(11), 2244; https://doi.org/10.3390/jcm10112244 - 21 May 2021
Cited by 4 | Viewed by 1862
Abstract
Background: Cirrhotic complications resulting from portal hypertension can be considerably reduced by non-selective beta-blockers (NSBBs); however, scarce studies have investigated therapeutic agents for other complications. We aimed to investigate the effects of NSBBs on common cirrhotic complications of infection, acute kidney injury (AKI), [...] Read more.
Background: Cirrhotic complications resulting from portal hypertension can be considerably reduced by non-selective beta-blockers (NSBBs); however, scarce studies have investigated therapeutic agents for other complications. We aimed to investigate the effects of NSBBs on common cirrhotic complications of infection, acute kidney injury (AKI), chronic renal function declination, and sarcopenic changes. Methods: Medical records of hospitalization for cirrhosis with at least a 4-year follow-up were analyzed and selected using propensity-score matching (PSM). Generalized estimating equation (GEE) was applied to assess the association of NSBBs with infection requiring hospitalization and AKI. Chronic renal function declination was evaluated by slope of regression lines derived from reciprocal of the serum creatinine level. The covariates of CT-measured skeletal muscle index (SMI) alterations were analyzed by generalized linear mixed model. Results: Among the 4946 reviewed individuals, 166 (83 NSBB group, 83 non-NSBB group) were eligible. Using GEE, Charlson comorbidity index, Child-Pugh score and non-NSBB were risk factors for infection; non-NSBB group revealed a robust trend toward AKI, showed no significant difference with chronic renal function declination of NSBB group, and was negatively associated with SMI alteration. Conclusion: Chronic NSBB use lowered the episodes of infection requiring hospitalization and AKIs, whereas non-NSBB was associated with sarcopenic changes. Full article
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