John D Ryan

Beaumont Hospital · Hepatology Unit

Hereditary haemochromatosis (HH) is an autosomal recessive disease resulting in excessive levels of iron. In a recent study, in a US population of 448 patients diagnosed with HH, a positive association between HH and nonmelanoma skin cancers (NMSCs) was observed (Pan CX, Yang K, Lau CB et al. Non-melanoma skin cancer in patients with hereditary hem...

Aims: Patients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is lack of data regarding the biology of HFE-HCC. We compared the course of HFE-HCC with a matched non-HFE-HCC control group and examin...

LINKED CONTENT This article is linked to Gillespie et al paper. To view this article, visit https://doi.org/10.1111/apt.17380

Background: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) h...

Dear Editor, Patients with psoriasis have a sevenfold increased risk of developing nonalcoholic fatty liver disease (NAFLD) and subsequent hepatic fibrosis because of chronic inflammatory processes.¹ This risk is further increased by the concomitant use of methotrexate (MTX), which is recommended as a first-line systemic treatment for the disease.¹...

Objective To determine the impact of minimum unit pricing (MUP) on the primary outcome of alcohol-related hospitalisation, and secondary outcomes of length of stay, hospital mortality and alcohol-related liver disease in hospital. Design Databases MEDLINE, Embase, Scopus, APA Psycinfo, CINAHL Plus and Cochrane Reviews were searched from 1 January...

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron...

BACKGROUND Due to a huge focus of healthcare resources on acute COVID-19 care during the early phase of the pandemic, endoscopy activity worldwide was significantly reduced. This subsequently led to a reduction in the number of Oesophageal and Gastric cancers diagnosed during this period, resulting in delayed diagnosis. AIM To measure the impact o...

Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload b...

Background & aims: Body composition predicts mortality in patients with cirrhosis. The impact of sex on this association is unknown. We investigated the impact of sex on this association in patients with cirrhosis assessed for liver transplantation. Methods: This single centre retrospective cohort study included adults assessed for liver transpl...

Background: Cirrhosis develops in <10% of individuals homozygous for the C282Y variant in the homeostatic iron regulator (HFE) gene. Carriage of PCSK7:rs236918 is associated with an increased risk of cirrhosis in this population. Aim: To determine if genetic variants significantly associated with the risk of alcohol- and NAFLD-related cirrhosis...

Background & Aims Iron reduction by venesection has been the cornerstone of treatment of Hemochromatosis for decades; its reported health benefits are many. Repeated phlebotomy can lead to a compensatory increase in intestinal iron absorption, reducing intestinal iron availability. As most gut bacteria are highly dependent on iron for survival, we...

Hereditary Hemochromatosis is a condition caused by defects in iron‐sensing genes leading to parenchymal iron loading. If diagnosed early and treated appropriately, many of the complications, including liver fibrosis, cirrhosis and liver cancer, arthritis, cardiomyopathy and diabetes, were thought to be avoided. As iron reduction by venesection bec...

Background The development of accurate, non‐invasive markers to diagnose and stage non‐alcoholic fatty liver disease (NAFLD) is critical to reduce the need for an invasive liver biopsy and to identify patients who are at the highest risk of hepatic and cardio‐metabolic complications. Disruption of steroid hormone metabolic pathways has been describ...

Objective: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Steroid hormones and bile acids are potent regulators of hepatic carbohydrate and lipid metabolism. Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile...

Non-alcoholic fatty liver disease (NAFLD) is a globally prevalent health problem, associated in its more severe forms with increased liver-related and cardiovascular-related morbidity and mortality. We established a multidisciplinary metabolic hepatology clinic in 2014 and have analysed the clinical data to evaluate the effectiveness of this servic...

Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted inductio...

Background Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans h...

Exposure of healthy islets with IL-22 does not potentiate GSIS. Insulin secretion in human (donors n = 3) (a, c) and mouse islets (b, d) was measured in the presence of 100 ng/mL IL-22 for 1 h (a, b) or 72 h (c, d) and stimulated with 1 mM (black bars) or 20 mM glucose (grey bars). Data are presented as percentage of basal secretion (mean ± SEM as...

Propionate and bile acids potentiate GSIS in mouse and human islets. (a) Insulin secretion was measured in mouse islets (mice n = 3) treated for 72 h with 1 mM propionate and then stimulated for 1 h with 1 mM (black bars) or 20 mM glucose (grey bars). (b) Insulin secretion was measured in human islets (donors n = 3) stimulated for 1 h with 1 mM (bl...

GLP-1 and insulin concentrations in serum samples before and after bariatric surgery. Total serum GLP-1(a) and insulin (b) in healthy volunteers (n = 20) and in patients before and 6 months after bariatric surgery (n = 25). Data are presented as mean ± SEM. (One-way ANOVA for multiple comparison) ⁎P < 0.05 for indicated comparison.

IL-22 is elevated in rats after gastric bypass and correlates with PYY increase in humans. (a) Plasma IL-22 levels in non-operated (n = 6), sham (n = 7) and RYGB (n = 21) GK rats. Data are presented as mean ± SEM. (One-way ANOVA for multiple comparison) ⁎⁎⁎P < 0.001 for indicated comparison. (b) Correlation between the increase in IL-22 and PYY in...

Introduction Spontaneous Bacterial Peritonitis (SBP) is associated with 30%–50% mortality within 1 year and 70% chance of recurrence. EASL guidelines state prophylactic antibiotics should be given to patients with proven SBP (secondary prophylaxis) and patients with low total protein count (<15 g/L) in ascitic fluid with no prior history of SBP (pr...

HEREDITARY HAEMOCHROMATOSIS (HH) Our aim was therefore to provide an objective, simple, brief, and practical set of recommendations on therapeutic aspects of HH, understandable by patients/citizens without medical training.

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous...

Background and aims: Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinemia i...

MR elastography is a novel method for non-invasive fibrosis assessment, not yet sufficiently validated. In a recent study in 104 patients Park, Gastroenterology 2017; 152: 598-602), MRE was compared to transient elastography for the diagnosis of fibrosis is nonalcoholic fatty liver disease. The current viewpoint critically appraises this study.

Chronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepa...

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an i...

Chronic hepatitis C is associated with health-related quality of life and cognitive impairments, even in mild disease. Recent evidence demonstrating hepatitis C virus (HCV) neurotropism has strengthened a neuropathophysiological hypothesis. However, sample heterogeneity confounds study outcomes. A uniquely homogeneous cohort of Irish women, followi...

Standard medical education dictates that the vast majority of cases of an alanine aminotransferase (ALT) level >1,000 IU/l will be due to acute ischaemia, acute drug-induced liver injury (DILI) (usually paracetamol) or acute viral hepatitis. There are very few references in the literature to other potential causes of an ALT >1,000 IU/l nor to the p...

Background/aims: Innately low hepcidin levels lead to iron overload in HFE-associated hereditary haemochromatosis. Methods: This study compared hepcidin and non-transferrin bound iron (NTBI) levels in untreated iron-loaded and non-iron-loaded C282Y homozygotes to levels in C282Y/H63D compound heterozygotes and individuals with other HFE genotype...

Background Spleen stiffness can be measured by transient elastography. Recent studies have shown that spleen stiffness correlates with hepatic venous pressure gradient and can predict oesophageal varices. Elevated spleen stiffness in cirrhosis has been attributed to splenic tissue hyperplasia and fibrosis, portal hypertension and its consequent hyp...

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastr...

Unlabelled: Pegylated interferon-α (PEG-IFN-α) forms an integral part of the current treatment for hepatitis C virus (HCV) infection. PEG-IFN-α suppresses HCV production by augmenting the innate antiviral immune response. Recent studies have reported the induction of hepcidin, the iron regulatory hormone, by IFN-α in vitro. As hepcidin plays an im...

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Anecdotal reports of poor patient compliance with hepatitis C disease management exist yet little data are available on the true rates of dropout. To examine all referrals made to an urban tertiary care liver centre for hepatitis C virus (HCV) management, track subsequent progress and identify dropout trends. A cross-sectional retrospective review...

Unlabelled: Hereditary hemochromatosis (HH) is a common inherited iron overload disorder. The vast majority of patients carry the missense Cys282Tyr mutation of the HFE gene. Hepcidin, the central regulator of iron homeostasis, is deficient in HH, leading to unchecked iron absorption and subsequent iron overload. The bone morphogenic protein (BMP)...