Publications by authors named "Thomas Berg"

567 Publications

From Screening to Therapy: Anti-HCV Screening and Linkage to Care in a Network of General Practitioners and a Private Gastroenterology Practice.

Pathogens 2021 Dec 2;10(12). Epub 2021 Dec 2.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.

(1) Background: Low rates of hepatitis C virus (HCV) diagnosis and sub-optimal linkage to care constitute barriers toward eliminating the infection. In 2012/2013, we showed that HCV screening in primary care detects unknown cases. However, hepatitis C patients may not receive further diagnostics and therapy because they drop out during the referral pathway to secondary care. Thus, we used an existing network of primary care physicians and a practice of gastroenterology to investigate the pathway from screening to therapy. (2) Methods: HCV screening was prospectively included in a routine check-up of primary care physicians who cooperated regularly with a private gastroenterology practice. Anti-HCV-positive patients were referred for further specialized diagnostics and treatment if indicated. (3) Results: Seventeen primary care practices screened 1875 patients. Twelve individuals were anti-HCV-positive (0.6%), six of them reported previous antiviral HCV therapy, and one untreated patient was HCV-RNA-positive (0.05% of the population). None of the 12 anti-HCV-positive cases showed up at the private gastroenterology practice. Further clinical details of the pathway from screening to therapy could not be analyzed. (4) Conclusions: The linkage between primary and secondary care appears to be problematic in the HCV setting even among cooperating partners, but robust conclusions require larger datasets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens10121570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706228PMC
December 2021

The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis.

Hepatol Commun 2021 Dec 27. Epub 2021 Dec 27.

Precision Medicine-Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1886DOI Listing
December 2021

The Practicability of the Xpert HCV Viral Load Fingerstick Point-of-Care Assay in Primary Care Settings.

Viruses 2021 11 22;13(11). Epub 2021 Nov 22.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.

Linkage to care presents one obstacle toward eliminating HCV, and the current two-step pathway (anti-HCV, followed by HCV-RNA testing) results in the loss of patients. HCV screening was tested in the primary care setting with the fingerstick Xpert HCV viral load point-of-care assay to analyze the practicability of immediate diagnosis. Anti-HCV (Cobas) and HCV-RNA (Cobas Amplicor version 2.0, only performed if anti-HCV was positive) were analyzed centrally as the gold standard. The Xpert assay was performed by 10 primary care private practices. In total, 622 patients were recruited. Five individuals (0.8%) were anti-HCV positive, and one was HCV-RNA positive. The Xpert test was valid in 546/622 (87.8%) patients. It was negative in 544 and positive in 2 cases, both of whom were anti-HCV negative. The HCV-RNA PCR and the Xpert test were both negative in 4/5 anti-HCV-positive cases, and the individual with HCV-RNA 4.5 × 10 IU/mL was not detected by the Xpert test. Primary care physicians rated the Xpert test practicability as bad, satisfactory, or good in 6%, 13%, and 81%, respectively, though 14/29 (48%) bad test ratings were assigned by a single practice. Despite adequate acceptance, interpretability and diagnostic performance in primary care settings should be further evaluated before its use in HCV screening can be recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13112327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623012PMC
November 2021

Multimorbidity, psychoactive substance use and psychological distress among acute medically ill patients: a cross-sectional study.

BMJ Open 2021 11 23;11(11):e052428. Epub 2021 Nov 23.

Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway.

Background: In order to target the complex health needs of patients with multimorbidity using psychoactive substances, knowledge regarding the association between substance use and multimorbidity in an acute setting is needed.

Aims: Examine psychoactive substance use patterns among acute medically ill patients, and determine the association between multimorbidity and substance use, and psychological distress.

Design: Cross-sectional study.

Setting And Participants: 2874 acute medically ill patients admitted to a medical emergency department in Oslo, Norway.

Measurements: Primary outcome: multimorbidity recorded by the presence of ≥2 International Classification of Diseases 10th revision-physical and/or mental health conditions per patient, extracted from medical records. Predictor variables: self-reported data on age, sex, occupational status, psychological distress (Hopkins Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4) and results from blood samples on psychoactive medicinal and illicit drugs.

Findings: Of all patients, 57.2% had multimorbidity. Of these, 62.6% reported psychological distress, 85.5% consumed either alcohol, medicinal and/or illicit drugs and 64.4% combined alcohol with psychoactive medicinal drugs. Patients with risky alcohol use were more likely to have multimorbidity compared with patients with low-risk alcohol use (OR 1.53; 95% CI 1.05 to 2.24). Patients using psychoactive medicinal drugs were more likely to have multimorbidity compared with non-users (OR 1.34; 95% CI 1.07 to 1.67).

Conclusion: Multimorbidity was associated with psychoactive medicinal drug and risky alcohol use, and psychological distress. Substance use was widespread, with alcohol and psychoactive medicinal drugs most frequently combined. Monitoring substance use among multimorbid patients is necessary to develop tailored treatments, and reduce burden on the healthcare system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-052428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611427PMC
November 2021

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

J Hepatol 2021 Nov 14. Epub 2021 Nov 14.

Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, MI, USA; Medicine Service VA Ann Arbor Healthcare System, Ann Arbor, Michigan, MI, USA.

Background & Aims: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction.

Methods: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.

Results: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses.

Conclusions: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.

Lay Summary: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.11.006DOI Listing
November 2021

Reply to: "G-CSF in acute-on-chronic liver failure - Art of 'patient selection' is paramount!"

J Hepatol 2022 Feb 29;76(2):473-475. Epub 2021 Oct 29.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.10.019DOI Listing
February 2022

Predicting eye and hair colour in a Norwegian population using Verogen's ForenSeq™ DNA signature prep kit.

Forensic Sci Int Genet 2022 Jan 24;56:102620. Epub 2021 Oct 24.

Centre for Forensic Genetics, Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Norway.

Prediction of eye and hair colour from DNA can be an important investigative tool in forensic cases if conventional DNA profiling fails to match DNA from any known suspects or cannot obtain a hit in a DNA database. The HIrisPlex model for simultaneous eye and hair colour predictions was developed for forensic usage. To genotype a DNA sample, massively parallel sequencing (MPS) has brought new possibilities to the analysis of forensic DNA samples. As part of an in-house validation, this study presents the genotyping and predictive performance of the HIrisPlex SNPs in a Norwegian study population, using Verogen's ForenSeq™ DNA Signature Prep Kit on the MiSeq FGx system and the HIrisPlex webtool. DNA-profiles were successfully typed with DNA input down to 125 pg. In samples with DNA input < 125 pg, false homozygotes were observed with as many as 92 reads. Prediction accuracies in terms of AUC were high for red (0.97) and black (0.93) hair colours, as well as blue (0.85) and brown (0.94) eye colours. The AUCs for blond (0.72) and brown (0.70) hair colour were considerably lower. None of the individuals was predicted to have intermediate eye colour. Therefore, the error rates of the overall eye colour predictions were 37% with no predictive probability threshold (pmax) and 26% with a probability threshold of 0.7. We also observed that more than half of the incorrect predictions were for individuals carrying the rs12913832 GG genotype. For hair colour, 65% of the individuals were correctly predicted when using the highest probability category approach. The main error was observed for individuals with brown hair colour that were predicted to have blond hair. Utilising the prediction guide approach increased the correct predictions to 75%. Assessment of phenotype-genotype associations of eye colours using a quantitative eye colour score (PIE-score), revealed that rs12913832 AA individuals of Norwegian descent had statistically significantly higher PIE-score (less brown eye colour) than individuals of non-northern European descent. To our knowledge, this has not been reported in other studies. Our study suggests that careful assessment of the target population prior to the implementation of forensic DNA phenotyping to case work is beneficial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsigen.2021.102620DOI Listing
January 2022

Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers.

Cardiovasc Intervent Radiol 2021 Oct 29. Epub 2021 Oct 29.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Liebigstr. 20, 04103, Leipzig, Germany.

Chemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2-6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0-354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153-701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00270-021-02983-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555734PMC
October 2021

Global impact of the first wave of COVID-19 on liver transplant centers: A multi-society survey (EASL-ESOT/ELITA-ILTS).

J Hepatol 2022 02 13;76(2):364-370. Epub 2021 Oct 13.

Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre, Rotterdam, the Netherlands.

Background And Aims: The global impact of SARS-CoV-2 on liver transplantation (LT) practices across the world is unknown. The goal of this survey was to assess the impact of the pandemic on global LT practices.

Method: A prospective web-based survey (available online from 7 September 2020 to 31 December 2020) was proposed to the active members of the EASL-ESOT/ELITA-ILTS in the Americas (including North, Central, and South America) (R1), Europe (R2), and the rest of the world (R3). The survey comprised 4 parts concerning transplant processes, therapy, living donors, and organ procurement.

Results: Of the 470 transplant centers reached, 128 answered each part of the survey, 29 centers (23%), 64 centers (50%), and 35 centers (27%) from R1, R2, and R3, respectively. When we compared the practices during the first 6 months of the pandemic in 2020 with those a year earlier in 2019, statistically significant differences were found in the number of patients added to the waiting list (WL), WL mortality, and the number of LTs performed. At the regional level, we found that in R2 the number of LTs was significantly higher in 2019 (p <0.01), while R3 had more patients listed, higher WL mortality, and more LTs performed before the pandemic. Countries severely affected by the pandemic ("hit" countries) had a lower number of WL patients (p = 0.009) and LTs (p = 0.002) during the pandemic. Interestingly, WL mortality was still higher in the "non-hit" countries in 2020 compared to 2019 (p = 0.022).

Conclusion: The first wave of the pandemic differentially impacted LT practices across the world, especially with detrimental effects on the "hit" countries. Modifications to the policies of recipient and donor selection, organ retrieval, and postoperative recipient management were adopted at a regional or national level.

Lay Summary: The health emergency caused by the coronavirus pandemic has dramatically changed clinical practice during the pandemic. The first wave of the pandemic impacted liver transplantation differently across the world, with particularly detrimental effects on the countries badly hit by the virus. The resilience of the entire transplant network has enabled continued organ donation and transplantation, ultimately improving the lives of patients with end-stage liver disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.09.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511875PMC
February 2022

An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B.

J Hepatol 2022 Feb 2;76(2):311-318. Epub 2021 Oct 2.

Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.

Background & Aims: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk.

Methods: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development.

Results: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up.

Conclusions: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir.

Lay Summary: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.09.025DOI Listing
February 2022

Risks and Benefits of Discontinuation of Nucleos(t)ide Analogue Treatment: A Treatment Concept for Patients With HBeAg-Negative Chronic Hepatitis B.

Hepatol Commun 2021 10 18;5(10):1632-1648. Epub 2021 Jun 18.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.

Systematic discontinuation of long-term treatment with nucleos(t)ide analogues (NAs) is one strategy to increase functional cure rates in patients with chronic hepatitis B e antigen (HBeAg)-negative hepatitis B. Currently, available study results are heterogeneous; however, long-term hepatitis B surface antigen (HBsAg) loss rates of up to 20% have been reported in prospective trials. This review proposes criteria that can be used when considering NA discontinuation in patients with chronic hepatitis B virus (HBV). Discontinuing NA treatment frequently results in a virologic and biochemical relapse that runs through different phases: the lag phase, reactivation phase, and consolidation phase. The HBV-DNA flares observed during the reactivation phase are often transient and most likely represent a trigger for inducing a long-term immune control by specific CD8+ T cells, and therefore do not need immediate interventions but close follow-up evaluation. Low HBsAg levels at the time of treatment cessation predict a positive long-term response to NA discontinuation associated with a higher likelihood of HBsAg clearance. Other host and viral biomarkers are currently under evaluation that may prove to be helpful to further characterize the population that may benefit most from the finite NA treatment concept. Potential harmful biochemical flares during the reactivation phase need to be identified early and can be effectively terminated by reintroducing NA treatment. Hepatic decompensation represents a risk to patients with cirrhosis undergoing NA discontinuation. Therefore, the finite NA approach should only be considered after excluding advanced fibrosis and cirrhosis and if a close follow-up of the patient and supervision by an experienced physician can be guaranteed. Conclusion: For selected patients, NA discontinuation has become a powerful tool to achieve control over HBeAg-negative HBV infections. Its significant effect represents a challenge to novel treatment approaches, but it may also serve as their enhancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485892PMC
October 2021

Hepatocellular Carcinoma Prevention by Aspirin: Are Platelets the Link?

Hepatol Commun 2021 12 7;5(12):2151-2152. Epub 2021 Jul 7.

Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631088PMC
December 2021

Gadoxetic acid uptake as a molecular imaging biomarker for sorafenib resistance in patients with hepatocellular carcinoma: a post hoc analysis of the SORAMIC trial.

J Cancer Res Clin Oncol 2021 Sep 20. Epub 2021 Sep 20.

Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Purpose: Gadoxetic acid uptake on hepatobiliary phase MRI has been shown to correlate with ß-catenin mutation in patients with HCC, which is associated with resistance to certain therapies. This study aimed to evaluate the prognostic value of gadoxetic acid uptake on hepatobiliary phase MRI in patients with advanced HCC receiving sorafenib.

Methods: 312 patients with available baseline hepatobiliary phase MRI images received sorafenib alone or following selective internal radiation therapy (SIRT) within SORAMIC trial. The signal intensity of index tumor and normal liver parenchyma were measured on the native and hepatobiliary phase MRI images, and relative tumor enhancement higher than relative liver enhancement were accepted as high gadoxetic acid uptake, and its prognostic value was assessed using univariate and multivariate Cox proportional hazard models.

Results: The median OS of the study population was 13.4 (11.8-14.5) months. High gadoxetic acid uptake was seen in 51 (16.3%) patients, and none of the baseline characteristics was associated with high uptake. In univariate analysis, high gadoxetic acid uptake was significantly associated with shorter overall survival (10.7 vs. 14.0 months, p = 0.005). Multivariate analysis confirmed independent prognostic value of high gadoxetic acid uptake (HR, 1.7 [1.21-2.3], p = 0.002), as well as Child-Pugh class (p = 0.033), tumor diameter (p = 0.002), and ALBI grade (p = 0.015).

Conclusion: In advanced HCC patients receiving sorafenib (alone or combined with SIRT), high gadoxetic acid uptake of the tumor on pretreatment MRI, a surrogate of ß-catenin mutation, correlates with shorter survival. Gadoxetic acid uptake status might serve in treatment decision-making process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03803-3DOI Listing
September 2021

The Prognostic Effect of Mutations in Non-Small Cell Lung Carcinoma Revisited: A Norwegian Multicentre Study.

Cancers (Basel) 2021 Aug 26;13(17). Epub 2021 Aug 26.

Department of Clinical Pathology, University Hospital of North Norway, N-9038 Tromsø, Norway.

Background: due to emerging therapeutics targeting G12C and previous reports with conflicting results regarding the prognostic impact of and G12C in non-small cell lung cancer (NSCLC), we aimed to investigate the frequency of mutations and their associations with clinical characteristics and outcome. Since mutation subtypes have different preferences for downstream pathways, we also aimed to investigate whether there were differences in outcome according to mutation preference for the Raf, PI3K/Akt, or RalGDS/Ral pathways.

Methods: retrospectively, clinicopathological data from 1233 stage I-IV non-squamous NSCLC patients with known status were reviewed. ' associations with clinical characteristics were analysed. Progression free survival (PFS) and overall survival (OS) were assessed for the following groups: wild type (wt) versus mutated, wt versus G12C versus non-G12C, among mutation subtypes and among mutation subtypes grouped according to preference for downstream pathways.

Results: a total of 1117 patients were included; 38% had mutated tumours, 17% had G12C. Among mutated, G12C was the most frequent mutation in former/current smokers (45%) and G12D in never smokers (46%). There were no significant differences in survival according to status, G12C status, among mutation subtypes or mutation preference for downstream pathways.

Conclusion: status or mutation subtype did not have any significant influence on PFS or OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13174294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428342PMC
August 2021

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B.

Clin Gastroenterol Hepatol 2021 Sep 6. Epub 2021 Sep 6.

Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain.

Background & Aims: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC.

Methods: The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort.

Results: A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26-0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28-0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28-0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00-1.67).

Conclusions: This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.09.001DOI Listing
September 2021

Reply to: Correspondence on 'the times they are a-changing - A refined proposal for finite HBV nucleos(t)ide analogue therapy.'

J Hepatol 2021 12 26;75(6):1499-1501. Epub 2021 Aug 26.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.08.014DOI Listing
December 2021

Experiences from six years of quality assured Model of End Stage Liver Disease (MELD) diagnostics.

PLoS One 2021 26;16(8):e0254219. Epub 2021 Aug 26.

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.

Background: The model of end-stage liver disease (MELD) score was established for the allocation of liver transplants. The score is based on the medical laboratory parameters: bilirubin, creatinine and the international normalized ratio (INR). A verification algorithm for the laboratory MELD diagnostic was established, and the results from the first six years were analyzed.

Methods: We systematically investigated the validity of 7,270 MELD scores during a six-year period. The MELD score was electronically requested by the clinical physician using the laboratory system and calculated and specifically validated by the laboratory physician in the context of previous and additional diagnostics.

Results: In 2.7% (193 of 7,270) of the cases, MELD diagnostics did not fulfill the specified quality criteria. After consultation with the sender, 2.0% (145) of the MELD scores remained invalid for different reasons and could not be reported to the transplant organization. No cases of deliberate misreporting were identified. In 34 cases the dialysis status had to be corrected and there were 24 cases of oral anticoagulation with impact on MELD diagnostics.

Conclusion: Our verification algorithm for MELD diagnostics effectively prevented invalid MELD results and could be adopted by transplant centers to prevent diagnostic errors with possible adverse effects on organ allocation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254219PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389365PMC
November 2021

Current State and Future Possibilities in Liver Transplantation.

Surg Technol Int 2021 08;39:128-134

Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, Germany.

Due to medical and surgical progress, liver transplantation (LT) is is nowadays a routine treatment for terminal liver failure and hepatic malignancies. However, in recent years there has been a change in the indications for LT. Especially in western industrialized countries, the use of LT for chronic hepatis B and hepatitis C cirrhosis is continuously decreasing since the introduction of effective antiviral drugs. Liver cirrhosis due to non-alcoholic steatohepatitis (NASH), alcoholic liver disease and hepatocellular carcinoma (HCC) in cirrhosis are now among the leading indications for LT. Due to tremendous progress in oncology, immunology, and technical aspects, multidisciplinary cancer treatment increasingly includes LT for non-HCC hepatobiliary malignancies. Excellent 5-year survival rates of 75 to 80% can now be achieved after LT. However, in patients with liver cirrhosis, the implementation of a 'sickest first' principle for liver allocation has led to an increasing number of critically ill patients undergoing liver transplantation. This results in an increased morbidity and mortality after liver transplantation. Moreover, donor characteristics have markedly shifted to less ideal grafts due to an increasing shortage of donor organs in many countries. In this context, normothermic machine perfusion with oxygenated blood components using pulsatile flow has been shown to reduce liver damage despite a prolonged preservation time and might be able to provide viability testing for otherwise discarded organs. With favorable donor and recipient conditions, excellent long-term results can be obtained with a 10-year survival rate of close to 70%. However, in patients with a high MELD score (>30), survival rates markedly decrease by 12-18%. Future research should focus on optimization of organ allocation, optimization of immunosuppression including tolerance induction, and on increasing the donor organ pool to further improve and the numbers of successful LT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.52198/21.STI.39.TR1444DOI Listing
August 2021

Copy number variation and expression of exportin-4 associates with severity of fibrosis in metabolic associated fatty liver disease.

EBioMedicine 2021 Aug 11;70:103521. Epub 2021 Aug 11.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia. Electronic address:

Background: Liver fibrosis risk is a heritable trait, the outcome of which is the net deposition of extracellular matrix by hepatic stellate cell-derived myofibroblasts. Whereas nucleotide sequence variations have been extensively studied in liver fibrosis, the role of copy number variations (CNV) in which genes exist in abnormal numbers of copies (mostly due to duplication or deletion) has had limited exploration.

Methods: The impact of the XPO4 CNV on histological liver damage was examined in a cohort comprised 646 Caucasian patients with biopsy-proven MAFLD and 170 healthy controls. XPO4 expression was modulated and function was examined in human and animal models.

Findings: Here we demonstrate in a cohort of 816 subjects, 646 with biopsy-proven metabolic associated liver disease (MAFLD) and 170 controls, that duplication in the exportin 4 (XPO4) CNV is associated with the severity of liver fibrosis. Functionally, this occurs via reduced expression of hepatic XPO4 that maintains sustained activation of SMAD3/SMAD4 and promotes TGF-β1-mediated HSC activation and fibrosis. This effect was mediated through termination of nuclear SMAD3 signalling. XPO4 demonstrated preferential binding to SMAD3 compared to other SMADs and led to reduced SMAD3-mediated responses as shown by attenuation of TGFβ1 induced SMAD transcriptional activity, reductions in the recruitment of SMAD3 to target gene promoters following TGF-β1, as well as attenuation of SMAD3 phosphorylation and disturbed SMAD3/SMAD4 complex formation.

Interpretation: We conclude that a CNV in XPO4 is a critical mediator of fibrosis severity and can be exploited as a therapeutic target for liver fibrosis.

Funding: ME and JG are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant (APP1053206) and Project and ideas grants (APP2001692, APP1107178 and APP1108422). AB is supported by an Australian Government Research Training Program (RTP) scholarship. EB is supported by Horizon 2020 under grant 634413 for the project EPoS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2021.103521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365315PMC
August 2021

Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: A multicenter randomized trial (GRAFT study).

J Hepatol 2021 12 5;75(6):1346-1354. Epub 2021 Aug 5.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany. Electronic address:

Background & Aims: Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF.

Methods: In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period.

Results: Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711-1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697-1.430; p = 0.992 and HR 1.058; 95% CI 0.727-1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation.

Conclusions: In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. CLINICALTRIALS.

Gov Number: NCT02669680 LAY SUMMARY: Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.07.033DOI Listing
December 2021

Common ABCB4 and ABCB11 Genotypes Are Associated with Idiopathic Chronic Cholestasis in Adults.

Dig Dis 2021 Jul 6. Epub 2021 Jul 6.

Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.

Introduction: Pathogenic mutations in genes encoding the hepatocanalicular transporters ATP8B1, ABCB11 and ABCB4 are causative for progressive cholestatic liver disease in children. In adults, less severe variants such as the common ABCB4 c.711A>T polymorphism have been associated with intrahepatic cholestasis in pregnancy and elevated liver enzymes. Hence, our aim was to study the role of common polymorphisms in adult patients with chronic unexplained cholestasis.

Methods: Screening of outpatients of two university hospitals identified a cohort of 94 patients with chronic cholestasis of unknown origin after thorough exclusion of other causes. Genotyping was performed using TaqMan assays, and frequencies for the ABCB4 rs2109505 (c.711A>T), rs1202283 (c.504T>C), ABCB11 rs2287622 (p.A444V) and rs497692 (c.3084A>G) variants of the study cohort were compared to a cohort of 254 healthy controls.

Results: The dominating symptoms of the patients were pruritus and jaundice, though the majority of them did not report symptoms at inclusion. Advanced fibrosis or cirrhosis was present in 11 patients (11.7%) only. Genotyping revealed the presence of the ABCB4 c.711A>T risk variant in 79 patients (84%), a frequency that is significantly (p = 0.037) higher than that in controls (71%). The ABCB11 p.A444V variant was also more frequent in cholestatic patients (p = 0.042).

Conclusion: The common ABCB4 c.711A>T and ABCB11 p.A444V polymorphisms are more prevalent in adult patients with idiopathic cholestasis than in healthy controls and may therefore represent risk factors for the development of chronic cholestatic liver disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000518203DOI Listing
July 2021

Sex-dependent dynamics of metabolism in primary mouse hepatocytes.

Arch Toxicol 2021 09 9;95(9):3001-3013. Epub 2021 Jul 9.

Faculty of Medicine, Rudolf-Schönheimer-Institute of Biochemistry, Leipzig University, Leipzig, Germany.

The liver is one of the most sexually dimorphic organs. The hepatic metabolic pathways that are subject to sexual dimorphism include xenobiotic, amino acid and lipid metabolism. Non-alcoholic fatty liver disease and hepatocellular carcinoma are among diseases with sex-dependent prevalence, progression and outcome. Although male and female livers differ in their abilities to metabolize foreign compounds, including drugs, sex-dependent treatment and pharmacological dynamics are rarely applied in all relevant cases. Therefore, it is important to consider hepatic sexual dimorphism when developing new treatment strategies and to understand the underlying mechanisms in model systems. We isolated primary hepatocytes from male and female C57BL6/N mice and examined the sex-dependent transcriptome, proteome and extracellular metabolome parameters in the course of culturing them for 96 h. The sex-specific gene expression of the general xenobiotic pathway altered and the female-specific expression of Cyp2b13 and Cyp2b9 was significantly reduced during culture. Sex-dependent differences of several signaling pathways increased, including genes related to serotonin and melatonin degradation. Furthermore, the ratios of male and female gene expression were inversed for other pathways, such as amino acid degradation, beta-oxidation, androgen signaling and hepatic steatosis. Because the primary hepatocytes were cultivated without the influence of known regulators of sexual dimorphism, these results suggest currently unknown modulatory mechanisms of sexual dimorphism in vitro. The large sex-dependent differences in the regulation and dynamics of drug metabolism observed during cultivation can have an immense influence on the evaluation of pharmacodynamic processes when conducting initial preclinical trials to investigate potential new drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-021-03118-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380230PMC
September 2021

Influence of gender on cytokine induced depression and treatment: Gender aspects of IFN-α-induced depression.

J Affect Disord 2021 09 23;292:766-772. Epub 2021 Jun 23.

Department of Clinical Psychology and Psychotherapy, Universität Hamburg, Hamburg, Germany; Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Germany. Electronic address:

Background: Cytokine treatment with Interferon-alpha (IFN-α) represents a clinical model of immune associated depression, but it remains unclear if it is of the same entity as major depressive disorder (MDD). The study focuses on possible gender differences in IFN-α induced depression and effects of a pre-emptive antidepressant treatment.

Methods: Data from 181 patients with chronic hepatitis C infection (cHC) without history of mental illnesses undergoing treatment with IFN-α 2a and ribavirin were re-analyzed for gender effects. Patients with a pre-emptive antidepressant therapy with Escitalopram (n = 90, verum group) to prevent IFN-induced depression were compared to patients who received placebo (n = 91). Depressive symptoms before and during HCV-treatment were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), Beck's Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale.

Results: We found significant differences regarding the incidence and severity of depressive symptoms between men and women for patients without antidepressant pre-treatment (placebo group). Significantly more women without pre-emptive antidepressant therapy suffered from clinically relevant depression (MADRS values ≥ 13, p = 0.041) and self-rated depressive symptoms (BDI ≥ 17, p = 0.024). Antidepressant pre-treatment showed comparable effects regarding the reduction of incidence and severity of depression in both women and men.

Conclusions: Compared to MDD, IFN-alpha-induced depression in patients with cHC is also characterized by gender differences with an increased risk for women but no gender difference regarding the effects of an antidepressant pre-treatment is found. Our data strengthens the hypothesis that Interferon-induced depression serves as a clinical model for immune related depressive disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.05.087DOI Listing
September 2021

COVID-19 and the liver - Lessons learned.

Liver Int 2021 06;41 Suppl 1:1-8

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.

Liver involvement, indicated by elevated liver function test results, is common in hospitalized patients with coronavirus disease 2019 (COVID-19) and has been linked to disease severity and outcome. A dual pattern of elevated liver function tests can be observed especially in patients with severe or critical COVID-19, characterized by an increase in aminotransferases early in the course of this disease, followed by an increase in cholestasis-associated biochemistry markers at later stages. This dual pattern is associated with inflammatory response markers and poor outcome. Current notions on the mechanisms of liver injury in COVID-19 include direct cytopathic effects of the virus on hepatocytes and cholangiocytes, ischemic and hypoxic liver damage, drug-induced liver injury, activation of hepatic immune cells by excess cytokine production and exacerbation of pre-existing liver disease. Patients with obesity-related non-alcoholic fatty liver disease and, in particular, patients with cirrhosis are at high risk of liver injury and a fatal outcome from COVID-19. In contrast, individuals receiving stable immunosuppressive medication for autoimmune liver diseases or during long-term follow-up after liver transplantation do not have a higher case-to-infection ratio and have a fairly favourable outcome. The present review describes the epidemiology, characteristics and potential pathological mechanisms of COVID-19-related liver injury. Moreover, the influence of pre-existing liver disease on the susceptibility and severity of liver injury in COVID-19 are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447354PMC
June 2021

Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus.

Adv Sci (Weinh) 2021 06 1;8(11):2004168. Epub 2021 May 1.

Storr Liver Centre Westmead Institute for Medical Research Westmead Hospital and University of Sydney Westmead NSW 2145 Australia.

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202004168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188187PMC
June 2021

A genetic variant in toll-like receptor 5 is linked to chemokine levels and hepatocellular carcinoma in steatohepatitis.

Liver Int 2021 09 27;41(9):2139-2148. Epub 2021 Jun 27.

Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany.

Background & Aims: Bacterial translocation drives liver disease progression. We investigated whether functional genetic variants in toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, affect the risk for hepatocellular carcinoma (HCC).

Methods: Healthy controls (n = 212), patients with alcohol abuse without liver disease (n = 382), and patients from a discovery cohort of alcohol-associated cirrhosis (n = 372 including 79 HCC cases), a validation cohort of alcohol-associated cirrhosis (n = 355 including 132 HCC cases), and a cohort of cirrhosis due to nonalcoholic steatohepatitis (NASH) (n = 145 including 62 HCC cases) were genotyped for the TLR5 rs5744174 and rs5744168 polymorphisms. Chemokine levels were measured by ELISA in patients' sera and supernatants of flagellin-stimulated healthy monocytes.

Results: Frequency of the TLR5 rs5744174 TT genotype was similar in healthy controls (33%), controls with alcohol abuse (34%), and patients with alcohol-associated cirrhosis in the discovery (28%), validation (33%), and NASH cohort (31%). The TT genotype was enriched in patients with versus without HCC in the discovery, validation, and NASH cohort (41% vs 25%; 39% vs 29%; 40% vs 24%; p < .05 each). This genotype remained a risk factor for HCC (OR = 1.9; p = .01) after multivariate correction for age, gender, diabetes, and carriage of the PNPLA3 148M variant. Interleukin-8 induction in monocytes from healthy controls and serum levels of interleukin-8 and CXCL1 from cirrhotic patients with the TT genotype were significantly increased versus C allele carriers.

Conclusion: The TLR5 rs5744174 polymorphism, affecting immune response to flagellin, is linked to occurrence of HCC in cirrhosis caused by steatohepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14980DOI Listing
September 2021

Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B.

JHEP Rep 2021 Jun 20;3(3):100290. Epub 2021 Apr 20.

Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background & Aims: Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC.

Methods: We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively.

Results: HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78-0.82). NPVs were always >99% (99.3-100%), whereas PPV ranged between 13% and 24%.

Conclusions: In NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease.

Lay Summary: Several risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhepr.2021.100290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144729PMC
June 2021

The Current Status of Granulocyte-Colony Stimulating Factor to Treat Acute-on-Chronic Liver Failure.

Semin Liver Dis 2021 08 15;41(3):298-307. Epub 2021 May 15.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.

Patients with acute-on-chronic liver failure (ACLF) have a devastating prognosis and therapeutic options are limited. Granulocyte-colony stimulating factor (G-CSF) mobilizes immune and stem cells and possess immune-modulatory and proregenerative capacities. In this review, we aim to define the current evidence for the treatment with G-CSF in end-stage liver disease. Several smaller clinical trials in patients with different severity grades of end-stage liver disease have shown that G-CSF improves survival and reduces the rate of complications. Adequately powered multicenter European trials could not confirm these beneficial effects. In mouse models of ACLF, G-CSF increased the toll-like receptor (TLR)-mediated inflammatory response which led to an increase in mortality. Adding a TLR4 signaling inhibitor allowed G-CSF to unfold its proregenerative properties in these ACLF models. These data suggest that G-CSF requires a noninflammatory environment to exert its protective properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1723034DOI Listing
August 2021

Three are better than one-increasing HBV seroprotection by a tri-antigenic vaccine.

Lancet Infect Dis 2021 09 11;21(9):1197-1198. Epub 2021 May 11.

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig 04315, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(20)30845-8DOI Listing
September 2021
-->