Cirrhosis in Hemochromatosis: Independent Risk Factors in 368 HFE p.C282Y Homozygotes

Barton, James C.; McLaren, Christine E.; Chen, Wen-Pin; Ramm, Grant A.; Anderson, Gregory J.; Powell, Lawrie W.; Subramaniam, V. Nathan; Adams, Paul C.; Phatak, Pradyumna D.; Gurrin, Lyle; Phillips, John D.; Parker, Charles J.; Emond, Mary J.; McLaren, Gordon D.

doi:10.5604/01.3001.0012.3169

Cited by 33 publications

(30 citation statements)

References 29 publications

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“…Even with inherent selection bias, studies estimate the prevalence of biopsy-proven cirrhosis to be 23%-28% in Caucasians with HH, with most of these also having co-existing contributors to their liver disease. (43,44) Cirrhosis solely due to the effects of iron overload was seen in only 3%. It has also been reported that the lifetime incidence of severe liver disease alone appears to be approximately 9% of male HFE C282Y homozygotes of European ancestry, based on data from prospective cohort studies.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review of the Clinical Outcomes of Iron Reduction in Hereditary Hemochromatosis

et al. 2020

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1470 design, region where study was performed), participant demographics (age, percent male, hemochromatosis diagnosis), iron reduction therapy regimens, and clinical outcomes on mortality, cirrhosis, liver fibrosis, portal hypertension, HCC, liver transplant, arthritis, joint replacement, diabetes, cardiovascular disease, heart failure, erectile dysfunction, hypogonadism, quality of life, fatigue, biochemical iron indices, and liver function tests (Table 2). QUalIty aSSeSSMeNt oF INClUDeD StUDIeS Two authors independently assessed the risk of bias in the included studies (A.P. and T.C.). The ROBINS-I tool (4) or the Cochrane risk of bias tool (5) were used to evaluate the nonrandomized and randomized studies, respectively. Disagreements were resolved by discussion, and a consensus decision was made.

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Section: Discussionmentioning

confidence: 99%

Systematic Review of the Clinical Outcomes of Iron Reduction in Hereditary Hemochromatosis

et al. 2020

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“…In particular, chronic hepatitis C tends to be aggravated by the presence of heterozygous HFE mutations, which leads to a high deposition of hepatic iron and advanced stages of fibrosis [36,37]. In addition to the viral infection, patients with hereditary hemochromatosis tend to display altered responses to other environmental factors, such as alcohol and smoking [38,39]. Among the non-genetic modifiers of hereditary hemochromatosis, reduced consumption of alcoholic beverages and body weight increase can explain decreased long-term iron load in hereditary hemochromatosis, while tobacco smoking may aggravate iron loading [39].…”

Section: Dietary Iron Overloadmentioning

confidence: 99%

Dietary and Sentinel Factors Leading to Hemochromatosis

Moon

2019

Nutrients

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Although hereditary hemochromatosis is associated with the mutation of genes involved in iron transport and metabolism, secondary hemochromatosis is due to external factors, such as intended or unintended iron overload, hemolysis-linked iron exposure or other stress-impaired iron metabolism. The present review addresses diet-linked etiologies of hemochromatosis and their pathogenesis in the network of genes and nutrients. Although the mechanistic association to diet-linked etiologies can be complicated, the stress sentinels are pivotally involved in the pathological processes of secondary hemochromatosis in response to iron excess and other external stresses. Moreover, the mutations in these sentineling pathway-linked genes increase susceptibility to secondary hemochromatosis. Thus, the crosstalk between nutrients and genes would verify the complex procedures in the clinical outcomes of secondary hemochromatosis and chronic complications, such as malignancy. All of this evidence provides crucial insights into comprehensive clinical or nutritional interventions for hemochromatosis.

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“…Most disease-causing strains are associated with gastroenteritis, but can also infect open wounds and cause septicemia [9]. Vibrio infections can be fatal if these conditions are left without prompt treatment and the risk of clinical disease and death increases dramatically in certain conditions, such as immunocompromised states, uncontrolled diabetes, liver cirrhosis, and cancers [12,13]. Cholera, another major life-threatening intestinal infection, is caused by V. cholerae, and affects an estimated 3-5 million people worldwide and causes 28 800-130 000 deaths a year [14,15].…”

Section: Introductionmentioning

confidence: 99%

NAG‐thiazoline is a potent inhibitor of the Vibrio campbellii GH20 β‐N‐Acetylglucosaminidase

et al. 2020

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Vibrio spp. play a vital role in the recycling of chitin in oceans, but several Vibrio strains are highly infectious to aquatic animals and humans. These bacteria require chitin for growth; thus, potent inhibitors of chitin-degrading enzymes could serve as candidate drugs against Vibrio infections. This study examined NAG-thiazoline (NGT)-mediated inhibition of a recombinantly expressed GH20 b-N-acetylglucosaminidase, namely VhGlcNAcase from Vibrio campbellii (formerly V. harveyi) ATCC BAA-1116. NGT strongly inhibited VhGlcNAcase with an IC 50 of 11.9 AE 1.0 lM and K i 62 AE 3 µM, respectively. NGT was also found to completely inhibit the growth of V. campbellii strain 650 with an minimal inhibitory concentration value of 0.5 µM. ITC data analysis showed direct binding of NGT to VhGlcNAcase with a K d of 32 AE 1.2 lM. The observed DG°b inding of À7.56 kcalÁmol À1 is the result of a large negative enthalpy change and a small positive entropic compensation, suggesting that NGT binding is enthalpy-driven. The structural complex shows that NGT fully occupies the substrate-binding pocket of VhGlcNAcase and makes an exclusive hydrogen bond network, as well as hydrophobic interactions with the conserved residues around the À1 subsite. Our results strongly suggest that NGT could serve as an excellent scaffold for further development of antimicrobial agents against Vibrio infections.

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Cirrhosis in Hemochromatosis: Independent Risk Factors in 368 HFE p.C282Y Homozygotes

Abstract: In conclusion, cirrhosis in HFE p.C282Y homozygotes is significantly associated with age, diabetes, daily alcohol intake, and iron removed by phlebotomy, taking into account the effect of other variables.

Cited by 33 publications

References 29 publications

Systematic Review of the Clinical Outcomes of Iron Reduction in Hereditary Hemochromatosis

Systematic Review of the Clinical Outcomes of Iron Reduction in Hereditary Hemochromatosis

Dietary and Sentinel Factors Leading to Hemochromatosis

NAG‐thiazoline is a potent inhibitor of the Vibrio campbellii GH20 β‐N‐Acetylglucosaminidase

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