- Risk factors for Burkitt lymphoma: a nested case-control study in the UK Clinical Practice Research Datalink. [Journal Article]
- BJBr J Haematol 2018 Apr 20
- Burkitt lymphoma (BL) occurs as three subtypes: endemic BL, immunosuppression-related BL and sporadic BL. Descriptive studies of BL age-specific incidence patterns have suggested multimodal peaks nea...
Burkitt lymphoma (BL) occurs as three subtypes: endemic BL, immunosuppression-related BL and sporadic BL. Descriptive studies of BL age-specific incidence patterns have suggested multimodal peaks near 10, 40 and 70 years of age, but the risk factors for BL at different ages are unknown. We investigated risk factors for BL in the United Kingdom among 156 BL cases and 608 matched BL-free controls identified in the Clinical Practice Research Datalink (CPRD) between 1992 and 2016. Associations with pre-diagnostic body mass index, cigarette smoking, alcohol consumption, hepatitis, Epstein-Barr virus (EBV), human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), malaria, allergic and autoimmune conditions, and prednisone use were evaluated. Overall, we identified inverse associations between smoking and BL risk, and positive associations between prior EBV infection, HIV/AIDS and prescription or use of prednisone with BL risk. In age-group stratified analyses, BL was associated with malaria exposure (vs. no exposure, odds ratio [OR] 8·00, 95% confidence interval [CI] 1·46-43·7) among those aged 20-59 years old and with hepatitis infection (vs. no infection, OR 3·41, 95% CI 1·01-11·5) among those aged 60+ years old. The effects of EBV, malaria, HIV/AIDS, prednisone and hepatitis on BL remained significant in mutually-adjusted age-group-specific analyses. No risk factors were associated with childhood BL. We report novel associations for BL in non-endemic settings.
- Ranitidine-Associated Autoimmune Hepatitis. [Journal Article]
- AJAm J Ther 2018 Apr 10
- Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models. [Journal Article]
- CPCell Physiol Biochem 2018 Apr 16; 46(3):1241-1251
- CONCLUSIONS: This model [ConA (20 mg/kg for 12 h)] provides a valuable tool for studying AIH immunopathogenesis and rapidly assessing novel therapeutic approaches.
- A patient presenting with isolated hematuria and renal dysfunction as rare manifestation of cryoglobulinemic glomerulonephritis in the course of autoimmune diseases including Sjögren's syndrome. [Journal Article]
- CCCEN Case Rep 2018 Apr 18
- Autoimmune diseases are sometimes associated with immune-mediated renal diseases and cryoglobulinemia is one of the causes. Cryoglobulinemia and cryoglobulinemic glomerulonephritis associated with pr...
Autoimmune diseases are sometimes associated with immune-mediated renal diseases and cryoglobulinemia is one of the causes. Cryoglobulinemia and cryoglobulinemic glomerulonephritis associated with primary Sjögren's syndrome are most frequent condition among non-hepatitis C virus-related condition. Its typical renal manifestation shows high amount of proteinuria with microscopic hematuria and renal insufficiency. We describe a case of 72-year-old woman with Hashimoto disease, autoimmune hepatitis, Sjögren's syndrome, and immune-related pancytopenia complicated by cryoglobulinemic glomerulonephritis. Before kidney biopsy, tubulointerstitial nephritis probably due to Sjögren's syndrome was suspected because of persistent hematuria without significant proteinuria and developing mild renal dysfunction over 6 months. The developing renal dysfunction associated with isolated hematuria is uncommon in glomerular diseases. Kidney biopsy, however, revealed established membranoproliferative glomerulonephritis with subendothelial deposits consisting of tubular structures with IgM, IgG, and C3 staining. Corticosteroids plus mycophenolate mofetil therapy successfully normalized renal function. Physician should not overlook cryoglobulinemic glomerulonephritis, which is potentially poor prognosis, even if urinalysis shows only persistent isolated hematuria in patients with autoimmune diseases.
- Under-Evaluated or Unassessed Pathogenic Pathways in Autoimmune Hepatitis and Implications for Future Management. [Review]
- DDDig Dis Sci 2018 Apr 18
- Autoimmune hepatitis is a consequence of perturbations in homeostatic mechanisms that maintain self-tolerance but are incompletely understood. The goals of this review are to describe key pathogenic ...
Autoimmune hepatitis is a consequence of perturbations in homeostatic mechanisms that maintain self-tolerance but are incompletely understood. The goals of this review are to describe key pathogenic pathways that have been under-evaluated or unassessed in autoimmune hepatitis, describe insights that may shape future therapies, and encourage investigational efforts. The T cell immunoglobulin mucin proteins constitute a family that modulates immune tolerance by limiting the survival of immune effector cells, clearing apoptotic bodies, and expanding the population of granulocytic myeloid-derived suppressor cells. Galectins influence immune cell migration, activation, proliferation, and survival, and T cell exhaustion can be induced and exploited as a possible management strategy. The programmed cell death-1 protein and its ligands comprise an antigen-independent inhibitory axis that can limit the performance of activated T cells by altering their metabolism, and epigenetic changes can silence pro-inflammatory genes or de-repress anti-inflammatory genes that affect disease severity. Changes in the intestinal microbiota and permeability of the intestinal mucosal barrier can be causative or consequential events that affect the occurrence and phenotype of immune-mediated disease, and they may help explain the female propensity for autoimmune hepatitis. Perturbations within these homeostatic mechanisms have been implicated in experimental models and limited clinical experiences, and they have been favorably manipulated by monoclonal antibodies, recombinant molecules, pharmacological agents or dietary supplements. In conclusion, pathogenic mechanisms that have been implicated in other systemic immune-mediated and liver diseases but under-evaluated or unassessed in autoimmune hepatitis warrant consideration and rigorous evaluation.
- miR-203 Inhibits Alcohol-Induced Hepatic Steatosis by Targeting Lipin1. [Journal Article]
- FPFront Pharmacol 2018; 9:275
- Alcoholic liver disease (ALD) is a global liver disease which characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Alcohol abuse is one of the main reasons for l...
Alcoholic liver disease (ALD) is a global liver disease which characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Alcohol abuse is one of the main reasons for liver disease. Alcoholic fatty liver (AFL) disease is the early stage of ALD and associated with the excessive lipids accumulation in hepatocytes as well as oxidative stress. MicroRNA-203 (miR-203) is known to suppress the proliferation and metastasis of hepatocellular carcinoma, but the role in the progression of alcoholic liver disease is not clear and is warranted for further investigation. In the present study, we have found the expression of miR-203 is down-regulated in Gao-Binge alcoholic mice model and ethanol-induced AML-12 cell lines in vitro. Furthermore, over-expression of miR-203 decrease the lipids accumulation in liver and ethanol-induced AML-12 cells. Mechanistically, we identified that Lipin1 is a key regulator of hepatic lipid metabolism, and acts as a downstream target for miR-203. In summary, our results suggested that over-expression of miR-203 inhibited the liver lipids accumulation and the progression of AFL by targeting Lipin1.
- A study on the etiology of cirrhosis of liver in adults living in the Hills of Himachal Pradesh, India. [Journal Article]
- TGTrop Gastroenterol 2016 Jan-Mar; 37(1):37-41
- CONCLUSIONS: The study identified alcohol as the leading cause of cirrhosis among people in the state. Measures for taking care of preventable risk factors are desired.
- Opposing actions of developmental trichloroethylene and high-fat-diet co-exposure on markers of lipogenesis and inflammation in autoimmune-prone mice. [Journal Article]
- TSToxicol Sci 2018 Apr 12
- Trichloroethylene (TCE) is a widespread environmental pollutant associated with immunotoxicity and autoimmune disease. Previous studies showed that mice exposed from gestation through early life demo...
Trichloroethylene (TCE) is a widespread environmental pollutant associated with immunotoxicity and autoimmune disease. Previous studies showed that mice exposed from gestation through early life demonstrated CD4+ T cell alterations and autoimmune hepatitis. Determining the role of one environmental risk factor for any disease is complicated by the presence of other stressors. Based on its known effects, we hypothesized that developmental overnutrition in the form of a moderately high fat diet (HFD) consisting of 40% kcal fat would exacerbate the immunotoxicity and autoimmune-promoting effects of low-level (<10 μg/kg/day) TCE in autoimmune-prone MRL+/+ mice over either stressor alone. When female offspring were evaluated at 27 weeks of age we found that a continuous exposure beginning at 4 weeks pre-conception in the dams until 10 weeks of age in offspring that TCE and HFD promoted unique effects that were often antagonistic. For a number of adiposity endpoints, TCE significantly reversed the expected effects of HFD on expression of genes involved in fatty acid synthesis/insulin resistance, as well as mean pathology scores of steatosis. While none of the animals developed pathological signs of autoimmune hepatitis, the mice generated unique patterns of anti-liver antibodies detected by western blotting attributable to TCE exposure. A majority of cytokines in liver, gut, and splenic CD4+ T cells were significantly altered by TCE, but not HFD. Levels of bacterial populations in the intestinal ileum were also altered by TCE exposure rather than HFD. Thus, in contrast to our expectations this co-exposure did not promote synergistic effects.
- The Impact of Autoimmune Hepatitis and its Treatment on Health Utility. [Journal Article]
- HepHepatology 2018 Apr 17
- CONCLUSIONS: Our data show evidence of HRQOL impairment in a large cohort of AIH patients compared to the general population. Furthermore, corticosteroid use is strongly associated with decreased HRQOL, independent of remission status. This highlights the need for better corticosteroid-free therapy approaches and emphasizes the need for future novel therapeutic trials in AIH. This article is protected by copyright. All rights reserved.
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- Stratifying Mortality in a Model for End-Stage Liver Disease Waiting List: A Brazilian Single-Center Study. [Journal Article]
- TPTransplant Proc 2018; 50(3):758-761
- CONCLUSIONS: Patients with NASH and alcoholic liver disease had higher mortality while on the waiting list, whereas patients with viral and autoimmune hepatitis had higher transplantation rate. Outcomes were not influenced by PVT.