OBJECTIVES In Greece, there are insufficient data regarding the presence of non-organ and liver-related autoantibodies in hepatitis C patients. This study in a consecutive cohort of 39 such patients ...from central Greece investigates (1) the prevalence of non-organ and liver-related autoantibodies, and (2) the reactivity of anti-liver–kidney microsomal type 1 antibodies (in the case of positivity with at least one of the methods used) against their molecularly defined antigens.
DESIGN All serum samples were tested by standard and molecular assays for the presence of anti-nuclear antibodies, smooth muscle antibodies, anti-liver–kidney microsomal type 1 antibodies, antibodies against parietal cells, anti-CYP2A6, anti-CYP1A2 and anti-CYP2D6 autoantibodies.
METHODS Indirect immunofluorescence, competitive enzyme-linked immunosorbent assays, immunoblotting and novel radioligand assays based on immunoprecipitation of S-methionine labelled recombinant CYP2A6, CYP1A2 and CYP2D6 His-taq fusion proteins produced by in vitro transcription/translation were used.
RESULTS Seven out of 39 patients (17.9%) tested positive for smooth muscle antibodies, 2/39 (5.1%) tested positive for anti-nuclear antibodies, 1/39 (2.5%) tested positive for parietal cell antibodies, and 4/39 (10.3%) were found to be anti-liver–kidney microsomal positive (with at least one of the methods used). All sera were negative for anti-CYP2A6 and anti-CYP1A2 autoantibodies. Three out of four anti-liver–kidney microsomal positive samples had the typical liver–kidney microsomal staining pattern shown by indirect immunofluorescence. However, none tested positive for anti-CYP2D6 autoantibodies using the competitive CYP2D6 enzyme-linked immunosorbent assay, the specific CYP2D6 radioligand assay, and western blot using either human microsomes or recombinant CYP2D6. The fourth patient tested negative for anti-liver–kidney autoantibodies by either indirect immunofluorescence or the competitive enzyme-linked immunosorbent assay, but was repeatedly positive for anti-CYP2D6 autoantibodies by the sensitive and specific radioligand assay. Western blot experiments using human microsomes in this patient serum revealed two bands of 50 kDa and 55 kDa that documented as anti-CYP2D6 and anti-uridine triphosphate glucuronosyltransferase autoantibodies when recombinant CYP2D6 and recombinant uridine triphosphate glucuronosyltransferase autoantigens were used for immunoblot, respectively.
CONCLUSIONS A relatively high incidence of anti-liver–kidney microsomal autoantibodies (10.3%) was found in a consecutive sample of Greek patients with hepatitis C. The expanded panel of assays, however, failed to document CYP2D6 as the target autoantigen of anti-liver–kidney microsomal autoantibodies in most patients. We report for the first time the detection of parietal cell antibodies and both anti-CYP2D6 (anti-liver–kidney microsomal type 1) and anti-uridine triphosphate glucuronosyltransferase (anti-liver–kidney microsomal type 3) autoantibodies in patients who were hepatitis C positive/hepatitis D negative. Further studies are needed to confirm our findings and to determine whether these preliminary results have a clinical importance or not.
Giant cell hepatitis (GCH) is commonly reported in neonatal and infantile liver diseases but rarely in adults where the term postinfantile GCH (PIGCH) is used. PIGCH is associated with many diseases, ...including drugs toxicity, viruses, and autoimmune liver diseases, with autoimmune hepatitis (AIH) being the most prevalent. We present a case of PIGCH in a 76-year-old female without known history of liver disease who suffered from an acute severe episode of hepatitis. After careful exclusion of other hepatitis causes by imaging, virological, immunological, and microbiological investigations, a diagnosis of acute severe AIH (AS-AIH) was established. The patient was started on corticosteroids but she did not respond and died 3 days later because of advanced acute liver failure. Postmortem liver biopsy showed typical PIGCH lesions. Physicians must keep this catastrophic entity in mind in cases of unexplained acute liver injury as, contrary to our case, prompt rescue therapy with corticosteroids may be life-saving.
Full text
Available for:
FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known ...about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. Design We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. Results We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07x10(-9)). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. Conclusion We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.
Monotherapy with standard or pegylated interferon (PegIFN) remains the first-line treatment for HCV infection in patients with thalassemia major (βTM), although its long-term impact is still unknown. ...We aimed to assess the efficacy of IFN-a2b/PegIFN-a2b (one or multiple treatment sessions) and the predictors for sustained virological response (SVR) in HCV-infected βTM patients.
Between 11/1992 and 12/2013 median follow-up: 165.5 months (8-237), 48 βTM HCV-infected patients 19 males, median age: 22 years (12-45), received IFN-a2b (n=34) or PegIFN-a2b (n=14). Twenty-three patients (47.9%) had a previous splenectomy; 13/40 (32.5%) patients had Ishak stage >/=4 and 21/40 (52.5%) had siderosis grade 3-4. HCV-genotype was available in 36 patients (genotype 1: 47.2%, 2: 5.6%, 3: 25%, and 4: 22%). IL28B genotype was determined in 37 patients by means of in-house real-time PCR (CC: 27%, CT: 62.2%, TT: 10.8%).
Totally, 15/48 (31.3%) achieved SVR following the first treatment and 18/48 (37.5%) after multiple courses. Splenectomy (p=0.01) and fibrosis grade >/=4 (p<0.05) were negative predictors for SVR (first course), whereas splenectomy (p<0.05) and age >18 (p<0.02) for SVR after multiple courses. In HCV-genotype 1/4 (n=25), none of the patients with CT or TT IL28B genotype achieved SVR compared to 50% of the CC patients (p=0.004).
Interferon is an effective therapeutic option in HCV-infected βTM patients. IL28B genotype was a strong predictor for SVR, together with splenectomy, age and fibrosis.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This article presents a comprehensive review of nanoparticle-assisted treatment approaches for soft tissue sarcoma (STS). STS, a heterogeneous group of mesenchymal-origin tumors with aggressive ...behavior and low overall survival rates, necessitates the exploration of innovative therapeutic interventions. In contrast to conventional treatments like surgery, radiotherapy (RT), hyperthermia (HT), and chemotherapy, nanomedicine offers promising advancements in STS management. This review focuses on recent research in nanoparticle applications, including their role in enhancing RT and HT efficacy through improved drug delivery systems, novel radiosensitizers, and imaging agents. Reviewing the current state of nanoparticle-assisted therapies, this paper sheds light on their potential to revolutionize soft tissue sarcoma treatment and improve patient therapy outcomes.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
