Hideo A Baba's research while affiliated with University of Duisburg-Essen and other places

Publications (309)

Article
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Vibrational spectroscopy can detect characteristic biomolecular signatures and thus has the potential to support diagnostics. Fabry disease (FD) is a lipid disorder disease that leads to accumulations of globotriaosylceramide in different organs, including the heart, which is particularly critical for the patient’s prognosis. Effective treatment op...
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The role of non-parenchymal liver cells as part of the hepatic, innate immune system in the defense against hepatotropic viruses is not well understood. Here, primary human Kupffer cells, liver sinusoidal endothelial cells and hepatic stellate cells were isolated from liver tissue obtained after tumor resections or liver transplantations. Cells wer...
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The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibr...
Article
Background An accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. Aim To identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. Methods 174 LT recipients were enrolled. Liver biopsy, liver functional tests...
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Whether hepatitis B virus (HBV) activates or represses innate immunity continues to be debated. Toll-like receptor (TLR) 2 has been identified to recognize HBV particles in human hepatocytes. The Hippo pathway, known for growth control, is suggested to play a vital role in immune regulation. Here, molecular interactions between HBV-triggered TLR si...
Preprint
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Introduction: Autoimmune hepatitis (AIH) is a rare liver disease with a favorable prognosis following immunosuppression. In this work-up, we present our long-term experience with this patient collective. Patients and Methods: Overall, we were able to retrospectively evaluate data from 535 patients with histologically confirmed AIH over a period of...
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Autopsies (dissections or cadaver dissections) from clinical or forensic indications in cases of unclear, premature (usually <40 years of age, in individual cases also later) or cardiovascular deaths serve, in addition to the definitive clarification of the cause, to identify or distinguish between genetic causes. These are particularly relevant in...
Preprint
Extracellular vesicles (EVs) harvested from cell culture supernatants of human mesenchymal stromal cells (MSCs) suppress acute inflammation in preclinical models of various diseases. Furthermore, they promote regeneration of damaged tissues. Following successful clinical treatment of a steroid-refractory Graft-versus-Host-Disease (GvHD) patient wit...
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Background: Pexidartinib is approved in the U.S. for tenosynovial giant cell tumors (TGCTs). Herein, we assessed the hepatic safety profile of pexidartinib across patients with TGCTs receiving pexidartinib. Materials, and methods: Hepatic adverse reactions (ARs) were assessed by type and magnitude of liver test abnormalities, classified as (a) i...
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Heart failure is often accompanied by titin-dependent myocardial stiffness. Phosphorylation of titin by cGMP-dependent protein kinase I (PKGI) increases cardiomyocyte distensibility. The upstream pathways stimulating PKGI-mediated titin phosphorylation are unclear. We studied whether C-type natriuretic peptide (CNP), via its guanylyl cyclase-B (GC-...
Article
Liver transplantation is an established treatment option for patients with end-stage liver disease. The therapy management of these patients is interdisciplinary and requires pathologists to have both clinical and immunological knowledge. Continuous advances in treatment and increasing clinical experience are accompanied by the further development...
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Alcoholism is one of the leading and increasingly prevalent reasons of liver associated morbidity and mortality worldwide. Alcoholic hepatitis (AH) constitutes a severe disease with currently no satisfying treatment options. Lipoxin A4 (LXA4), a 15-lipoxygenase (ALOX15)-dependent lipid mediator involved in resolution of inflammation, showed promisi...
Article
Fatty liver disease is a rising problem worldwide, particularly due to metabolic syndrome. The current prevalence is 20–30%, but a further increase is expected whereby children will also be increasingly affected. The presence of fat in hepatocytes is known as steatosis or, in the case of nonalcoholic origin, nonalcoholic fatty liver (NAFL). It is b...
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Background: The proteoglycan syndecan-1 is involved in cell proliferation, adhesion and angiogenesis. It was shown to be involved in cancer progression in different tumor entities. So far, the role of syndecan-1 in renal cell carcinoma (RCC), one of the most common diseases in urologic oncology, was little described. Purpose of the present study w...
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Background & Aims Primary sclerosing cholangitis (PSC) is characterized by chronic cholestasis and inflammation, which promotes cirrhosis and an increased risk of cholangiocellular carcinoma (CCA). The transcription factor Krueppel‐like‐factor‐6 (KLF6) is a mediator of liver regeneration, steatosis, and hepatocellular carcinoma (HCC), but no data i...
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Background and aims: To date, conflicting data exist as to whether hepatitis B virus (HBV) has the ability to induce innate immune responses. Here, we investigated cellular changes after the first contact between HBV and primary human hepatocytes (PHH) in vitro and in vivo. Approach and results: The exposure of PHH to HBV particles resulted in n...
Article
Objective: Activated perivascular mast cells (MCs) participate in different cardiovascular diseases. Many factors provoking MC degranulation have been described, while physiological counterregulators are barely known. Endothelial CNP (C-type natriuretic peptide) participates in the maintenance of vascular barrier integrity, but the target cells an...
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Background Intranuclear inclusions (NI) in normal and neoplastic tissues have been known for years, representing one of the diagnostic criteria for papillary thyroid carcinoma (PTC). BRAF activation is involved among others in autophagy. NI in hepatocellular carcinoma contain autophagy-associated proteins. Our aim was to clarify if NI in thyroid ca...
Article
Background: Familial atrial septal defect (ASD) has previously been attributed primarily to mutations in cardiac transcription factors. Here, we report a large, multi-generational family (78 members) with ASD combined with a late-onset dilated cardiomyopathy and further characterize the consequences of mutant α-actin. Methods: We combined a geno...
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Persistent infection with hepatitis C virus (HCV) is a known risk factor for the development of hepatocellular carcinoma (HCC). The lack of the tumor suppressor promyelocytic leukemia protein (PML) in combination with HCV fosters hepatocarcinogenesis via induction of HCC using diethylnitrosamine (DEN) in a rodent model. However, the spontaneous dev...
Data
Current non-invasive scores for assessment of NAFLD severity do not correlate with NAS. In a cohort of 164 obese individuals with NAFLD known non-invasive scores were tested for correlation with the NAS. The APRI (A) and Gholam’s score (B) achieved a reasonable Spearman r of 0.34 and 0.37, respectively. Though, neither the BARD score (C) nor the NA...
Data
Raw data tables for all datasets. (XLSX)
Data
Current non-invasive scores cannot differentiate histological NASH from NAFL. In a cohort of 164 obese individuals with NAFLD AUCs were calculated to assess classification into NAFL or NASH by known non-invasive scores. The APRI score reached an AUC of 0.65 (A) and Gholam’s Score an AUC of 0.7 (B), both significantly better than random guessing. Th...
Data
The new score significantly correlates with SAF score. Using NAS-based classification of NAFLD to generate the new score might be seen as limitation. Thus the score was correlated to the SAF in the training (A) and validation cohort (C), resulting in significant robust correlations. In addition the score was tested to separate NAFL from NASH accord...
Data
Significant correlations of the new score with available parameters in a subgroup of the lifestyle intervention cohort at T0. (PDF)
Data
Significant correlations of the new score with available parameters in a subgroup of the lifestyle intervention cohort at T52. (PDF)
Article
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Background & aims Current non-invasive scores for the assessment of severity of non-alcoholic fatty liver disease (NAFLD) and identification of patients with non-alcoholic steatohepatitis (NASH) have insufficient performance to be included in clinical routine. In the current study, we developed a novel machine learning approach to overcome the cave...
Data
Current non-invasive scores for assessment of NAFLD severity do not correlate with fibrosis stage. In a cohort of 164 obese individuals with NAFLD known non-invasive scores were tested for correlation with the fibrosis stage. None of the tested scores, APRI (A), Gholam’s Score (B), BARD (C), NAFLD fibrosis score (D), or Palekars score (E) were corr...
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For decades, intranuclear inclusions in many normal and neoplastic cells have been considered to be mere invaginations of cytoplasm into the nucleus without any notable function or influence on disease. We investigated such inclusions in 75 specimens of hepatocellular carcinoma (HCC). In this context we demonstrate that these inclusions are true in...
Article
Cardiac functionality is dependent on a balanced protein turnover. Accordingly, regulated protein decay is critical to maintain cardiac function. Here we demonstrate that deficiency of SPRED2, an intracellular repressor of ERK-MAPK signaling markedly expressed in human heart, resulted in impaired autophagy, heart failure, and shortened lifespan. SP...
Article
Tissue protein expression of IMP3 is emerging as a promising prognostic factor in renal cell carcinoma (RCC). The most commonly used immunohistochemical (IHC) antibody has been criticized for its low specificity. In addition, blood levels of IMP3 have not yet been analyzed in RCC. Therefore, we compared the prognostic performance of two different I...
Article
Aim: To assess the diagnostic accuracy of liver maximum capacity (LiMAx®) test compared to transient elastography (TE) and serum biomarkers for the noninvasive detection of different stages of liver fibrosis and cirrhosis. Patients and methods: We retrospectively correlated LiMAx®, TE, aspartate aminotransferase (AST) to alanine aminotransferase...
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The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2...
Article
Background: Although organ shortage is a rising problem, organs from HCV RNA positive donors are not routinely transplanted in HCV negative individuals. Since HCV only infects hepatocytes, other organs such as kidneys are merely contaminated with HCV via the blood. We here established a protocol to reduce HCV virions during the cold ischemic time....
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Background: The current seventh edition of the TNM classification for intrahepatic cholangiocarcinoma (ICC) includes tumor number, vascular invasion, lymph node involvement but no longer the tumor size as compared to the sixth edition. The impact of the seventh edition on stage-based prognostic prediction for patients with ICC was evaluated. Meth...
Article
Background/aims: Autoimmune hepatitis (AIH) is a relatively rare cause of liver dysfunction and may lead in some cases to acute liver failure (ALF). The aim of our study was to evaluate the clinical course and outcome of patients with AIH-induced ALF. Methods: We retrospectively enrolled 32 patients with AIH-induced ALF and 93 age- and sex-match...
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AIM To investigate potential triggering factors leading to acute liver failure (ALF) as the initial presentation of autoimmune hepatitis (AIH). METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients (9.2%) fulfilled the criteria for ALF defin...
Article
Background -Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular tone but the target cells remain controversial. The cGMP-producing guanylyl cyclase-B (GC-B) receptor for CNP is expressed in vascular smooth muscle cells (VS...
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Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. He...
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The hepatocyte nuclear factor (HNF) family regulates complex networks of metabolism and organ development. Human mutations in its prototypical member HNF1A cause maturity-onset diabetes of the young (MODY) type 3. In this study, we identified an important role for HNF1A in the preservation of erythrocyte membrane integrity, calcium homeostasis, and...
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Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF)-1α....
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Controlled oxygenated rewarming (COR) up to 20°C during ex vivo machine perfusion limits reperfusion induced tissue injury upon graft implantation. Rewarming up to normothermia might add further benefits and provide better prediction of post transplantation organ function. The effect of 90 min of oxygenated machine perfusion with Aqix RS-I after co...
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Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond th...
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BACKGROUND Bridging treatments are employed in liver transplant waitlist patients with hepatocellular carcinoma (HCC) because of the risk of tumor progression during the waiting time. Radioembolization is mostly employed in the control of large or multifocal HCCs when other locoregional treatment modalities cannot be applied because of the number o...
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Key Clinical Message To the best of our knowledge, this is the first report of aplastic anemia (AA) preceding autoantibody‐negative autoimmune hepatitis (AIH) with successful treatment of both conditions with the same immunosuppressive regimen, resulting in hematopoietic reconstitution and remission of AIH.
Article
Previous studies have shown that hepatocellular carcinoma (HCC) develops more frequently in hepatitis B virus surface antigen (HBsAg)-transgenic mice (Alb/HBs) than in wild-type (WT) mice. However, the mechanism of this HCC model has not been well documented. Toll-like receptor 4 (Tlr4) signaling probably links innate immunity and HCC progression....
Article
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Objective Alterations in sphingolipid and ceramide metabolism have been associated with various diseases, including nonalcoholic fatty liver disease (NAFLD). Acid sphingomyelinase (ASM) converts the membrane lipid sphingomyelin to ceramide, thereby affecting membrane composition and domain formation. We investigated the ways in which the Asm knocko...
Article
A 49-year-old male patient was referred to our institution for acute liver failure (ALV). Apart from cholestasis, coagulopathy, and hepatic encephalopathy (HE) I°, laboratory studies revealed a significant increase in liver enzymes with an alanine aminotransferase (ALT) level of 4’108 U/L and an aspartate aminotransferase (AST) level of 3’878 U/l (...
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Donor livers marginally acceptable or acceptable according to extended criteria are more frequently transplanted due to the growing discrepancy between demand and availability of donor organs. One type of marginally acceptable graft is a steatotic donor liver, because it is more sensitive to ischemia-reperfusion injury. Thus, quantitative assessmen...
Data
AIF and tissue data. The files contain the time points and the relaxation rate changes of the AIF and the five skeletal muscle regions of the pigs hind limb. (ZIP)
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The purpose of this study was to assess the accuracy of fractional blood volume (vb) estimates in low-perfused and low-vascularized tissue using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The results of different MRI methods were compared with histology to evaluate the accuracy of these methods under clinical conditions. vb was...
Article
Background & aims: Serum ferritin and transferrin have been identified as prognostic markers in patients with chronic diseases. In the present study we investigated if these parameters can predict outcome in patients with acute liver failure. Methods: 102 consecutive patients with acute liver failure were retrospectively analyzed. The patients w...
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Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to reg...