Liver related topics, abstracts, articles, sites, etc. 
Liver enzymes, cirrhosis, cancer, dysfunction, biopsy & more.
Links pertaining to esophageal varices are also found here.

THE LIVER 

The liver is the major site of iron storage in our bodies, making it susceptible to great damage from excess iron deposition in the condition of Hereditary Hemochromatosis.  

Mild enlargement of the liver may occur early in the disease process with complaint of pain & tenderness occurring under the right rib cage.  Although liver enzymes are often not elevated until the disease is in the advanced stages, ALL abnormal liver function studies should be followed up with an iron profile to rule out HH.  

Fibrosis and cirrhosis occur as a result of the hepatic damage from excess iron, so it is important to diagnose HH before this damage is present.  The cirrhosis from excess iron is similar to that of alcoholic cirrhosis, and many patients are falsely accused of being alcoholics.  While drinking alcoholic beverages does indeed increase iron absorption & should be avoided, cirrhosis may also occur in those who have never drank. Since cirrhosis frequently results in cancer of the liver, anyone who is diagnosed with cirrhosis of the liver should be closely monitored for life for signs of hepatic cancer.  

The following links will direct you to references on liver problems associated with iron overload, as well as articles to help you understand the functions of the liver. Click on the title to read more on these topics.

• A 69-Year-Old Cirrhotic Male Presenting With Diarrhea 
  Interactive Case Challenge from Medscape Gastroenterology 1999   Caroline R. Taylor, MD, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Conn. 

• ABC of diseases of liver, pancreas, and biliary system Other causes of parenchymal liver disease  BMJ 2001;322:290-292 ( 3 February ) Haemochromatosis is the commonest inherited liver disease in the United Kingdom. It affects about 1 in 200 of the population and is 10 times more common than cystic fibrosis.

• Abnormal accumulation of iron in the liver, view of a slide at Michigan State University website

• Abnormalities in estrogen, androgen, and insulin metabolism in idiopathic hemochromatosis.
  Ann N Y Acad Sci 1988  We have concluded that hypogonadism and carbohydrate intolerance are caused by the specific distribution pattern of excess iron in the organism, accompanied by functional impairment of affected parenchymal cells.

• A history of phlebotomy therapy for hemochromatosis.  Crosby WH. Chapman Cancer Center, Joplin, MO Am J Med Sci 1991 Jan  The earlier the disease is discovered, the less risk of morbidity and mortality. Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.

• Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings. Hepatology. 1996 Apr  Hemochromatosis patients with heavy alcohol consumption had a higher prevalence of cirrhosis than hemochromatosis patients without heavy alcohol consumption. Long-term survival was significantly reduced in patients with heavy alcohol consumption.

• A middle aged man with diabetes mellitus and a liver mass. Steven Eliason, M.D., Elizabeth M. Brunt, M.D., Bruce R. Bacon, M.D., Leonard E. Grosso, M.D., Ph.D.  SLUCARE PathLab Case of the Month  

• An autopsy case of hemochromatosis and hepatoma combined with hereditary spherocytosis
  Jpn J Med 1984 Feb Clinical and postmortem examinations suggested that conspicuously enhanced erythropoiesis in the bone marrow and unknown factors may be responsible for an increase in iron absorption from the gut and in the amount of stored body iron, leading to the development of hemochromatosis

• A new syndrome of liver iron overload with normal transferrin saturation. Lancet. 1997 Jan 11 We have found a new non-HLA-linked iron-overload syndrome which suggests a link between iron excess and metabolic disorders. The current diagnostic criteria for genetic haemochromatosis should be reviewed.

• Annals of Internal Medicine SUPPLEMENT DIAGNOSIS AND MANAGEMENT 
  Diagnosis of Hemochromatosis, Annals of Internal Medicine, 1 December 1998. 129:925-931. Lawrie W. Powell, MD; D. Keith George, MD; Sharon M. McDonnell, MD; and Kris V. Kowdley, MD

• Answers to your questions about hereditary hemochromatosis
  from The College of American Pathologists (CAP) Dec 18, 2001

• A Patient's Story Tim Casey: Living with Hemochromatosis  American Liver Foundation Progress Newsletter-Special Double Issue Vol. 17, No. 2/Fall 1995-Winter 1996

• A reappraisal of hepatic siderosis in patients with end-stage cirrhosis: practical implications for the diagnosis of hemochromatosis.  Am J Surg Pathol. 1997 Jun The diagnosis of hemochromatosis in patients with end-stage cirrhosis, even those with a hepatic iron index greater than 1.9, should rely mainly on clinical and histologic data.

• A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload.
  Lab Invest. 1993 Aug   This model will allow the detailed study of the mechanism of iron induced, free radical tissue damage, which is though to be the cause of these lesions and will also be useful in the evaluation of iron chelating therapies to determine whether the hepatic and cardiac pathology of iron overload can be modulated over a long period.

• Biochemical liver profile in hemochromatosis. A survey of 100 patients. 
  J Clin Gastroenterol 1991 Jun; We find that mild abnormalities in the biochemical liver profile are common in hemochromatosis and suggest that patients with an unexplained abnormality in the liver profile should be screened for hemochromatosis with a serum ferritin and transferrin saturation.

• BLOOD TESTS IN LIVER DISEASE by Thomas L. Fabry MD New York, NY 

• Bone and joint involvement in genetic hemochromatosis: role of cirrhosis and iron overload.  J Rheumatol 1997 Sep With multivariate analysis we found that osteoporosis was highly influenced by the degree of iron overload, playing an independent role in accelerating bone loss in patients with GH

• C282Y and H63D mutations of HFE gene in patients with advanced alcoholic liver disease. 
  Rev Esp Enferm Dig 2001 Mar  Our results suggest that H63D mutation of the HFE gene, but not the C282Y mutation, is associated to the risk of developing advanced liver alcoholic disease.

• C282Y and H63D mutations of the haemochromatosis gene in patients with iron overload
  Rev Esp Enferm Dig 2001 [a pdf file]

• Can Cirrhosis be Prevented? 
  By Marilyn Sterling, R.D. From The January 1999 Issue of Nutrition Science News.  The liver truly is remarkable--directly affected by nearly everything a person eats, drinks and breathes, it is still durable and capable of regeneration. Tucked away on the right side of the abdomen, the liver is the human body's largest internal organ, serving as command central for a variety of vital metabolic processes.

• Can large cell change and high proliferative activity predict hepatocellular carcinoma in patients with hereditary hemochromatosis?  Am J Gastroenterol 2000 Oct In hereditary hemochromatosis, the presence of large cell change or high proliferative activity in patients older than 55 yr with cirrhosis should be considered a strong predictor of hepatocellular carcinoma development, especially if hepatitis B virus infection coexists.

• Carcinogenesis of primary liver malignancies Langenbecks Arch Surg 2000 Apr The main risk factors for the development of HCC are viral infections (hepatitis B and C), alcohol use, and the intake of mycotoxins in some areas of the world. In addition to these risk factors, genetic disorders such as hemochromatosis or alpha1-antitrypsin deficiency play a role.

• Cardiac dysfunction because of secondary hemochromatosis caused by congenital non-spherocytic hemolytic anemia. Jpn Circ J. 2001 Feb Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. Liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure.

• Cardiomyopathy as the cause of death in genetic hemochromatosis-.
  Z Gastroenterol. 1996 Mar [article in German] The reports of these two cases underline that hemochromatosis-associated cardiomyopathy is often irreversible if severe congestive heart failure is present. In cardiac decompensation heart transplantation has to be considered as early as possible.

• Chronic iron overload and toxicity: clinical chemistry perspective.
  Clin Lab Sci 2001 Summer; This toxicity involves many organs leading to a variety of serious diseases such as liver disease, heart disease, diabetes mellitus, hormonal abnormalities, dysfunctional immune system, etc. The tissue damage associated with iron overload is believed to result primarily from free radical reactions mediated by iron.

• Cirrhosis of the liver as a precancerous condition 
  Schweiz Rundsch Med Prax 1998 Oct 28 Patients suffering from cirrhosis of the liver due to HBV-, HCV- or HDV-infection and patients with genetic hemochromatosis exhibit a high risk for HCC.

• Cirrhosis patients should be screened for esophageal varices
  Last Updated: 2001-04-09 11:15:44 EDT (Reuters Health)

• Clinical Consequences of New Insights in the Pathophysiology of Disorders of Iron and Heme Metabolism Hematology 2000  The American Society of Hematology The screening strategy could be based on the assessment of serum transferrin saturation in adults aged 18 or more. Genetic testing testing for C282Y would be confined to individuals with transferrin saturation > 45%. This strategy would then avoid the ethical, logistical, and financial problems raised by systematic genetic testing as well as the societal impact of discovering a genetic mutation in asymptomatic persons without a disease. It is, in fact, essential that major changes occur in the attitudes towards unexpressed or slightly expressed HFE homozygosity, especially by insurers and health care administrators, to avoid any adverse genetic discrimination.

• Clinical experience with early hemochromatosis Tidsskr Nor Laegeforen. 1994 Jun [Article in Norwegian] We conclude that fasting serum-iron and transferrin should be determined in all subjects over 40 years of age and in patients with chronic elevation of liver enzymes.

• Clinical Features of Genetic Hemochromatosis in Women Compared with Men 
  Abstracts - August 19, 1997 ANNALS OF INTERNAL MEDICINE  Recognizing the nonspecific nature of presenting symptoms in women is essential for early diagnosis and treatment.

• Clinical management of iron overload.
  Gastroenterol Clin North Am. 1998 Sep HHC is a common inherited disorder, characterized by iron accumulation in the liver, heart, pancreas, and other organs. The clinical consequences of systemic iron loading are diverse and not always improved with iron reduction therapy.

• Clinical spectrum and management of haemochromatosis 
  Baillieres Clin Haematol 1994 Dec Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• Clinical Studies of Haemochromatosis  Queensland Institute of Medical  Research, Hepatocellular Cancer Laboratory, Professor Lawrie Powell   Knowledge of haemochromatosis, its prevention, the type and severity of symptoms it causes, the availability and nature of treatment, ability of sufferers to participate in normal activities, and longevity are relevant issues for community education. Members of an informed public can mobilise support for the early diagnosis of haemochromatosis, encourage people to be tested for the disorder and influence the debate about screening.

• Clinico-morphologic characteristics of primary hemochromatosis
   Arkh Patol. 1995 Nov-Dec 12 autopsy cases of primary hemochromatosis were studied

• Combined orthotopic heart and liver transplantation for genetic hemochromatosis.
  J Heart Lung Transplant. 1997 May Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, 55905, USA.  A 47-year-old man with cirrhotic liver disease complicated by encephalopathy and class IV congestive heart failure caused by genetic hemochromatosis underwent combined orthotopic heart and liver transplantation. The patient remains well, working full time, 4 years after operation. Combined heart and liver transplantation is an effective therapy for selected patients with concurrent heart and liver failure caused by systemic iron overload.

• Common Laboratory Tests in Liver Diseases   Howard J. Worman, M. D.  Division of Digestive and Liver Diseases Departments of Medicine and of Anatomy and Cell Biology College of Physicians & Surgeons Columbia University The purpose of this page is to briefly describe some of the common laboratory tests that may be abnormal in individuals with liver diseases.

• Compound heterozygosity for haemochromatosis gene mutations and hepatic iron overload in allogeneic bone marrow transplant recipients. Pathology 2001 Feb; Iron overload has been proposed as a cause of liver dysfunction after BMT Factors which could be relevant to iron overload include the number of red cell transfusions and mutations within the haemochromatosis gene (HFE).

• Current concepts in rational therapy for haemochromatosis.  
  Drugs. 1991 Jun . Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years).

• Current diagnosis: hereditary metabolic diseases of the liver (primary hemochromatosis, Wilson disease] Schweiz Rundsch Med Prax 1996 Nov [article in German]

• Dermatology and the Liver and the Pancreas:  Hemochromtaosis  Section 6 of 10.  Emedicine journal Sept. 27, 2001.  Hemochromatosis is a disorder of increased iron uptake leading to excess deposition in multiple body organs. The dermatologic manifestation of the disease involves skin hyperpigmentation, which is present in more than 90% of patients at the time of diagnosis. This discoloration has a characteristic metallic gray or bronze-brown color that is generally diffuse, but it may be increased in areas of scars or on the face, neck, extensor surfaces of the arms, or genitalia. Approximately 20% of patients also have pigmentation of the buccal mucosa or the conjunctiva.

• Diabetes and haemochromatosis: current concepts, management and prevention.
  Diabete Metab 1995 Dec Diabetes, a serious complication of haemochromatosis, is frequently associated with cirrhosis which reduces life expectancy

• Diabetes mellitus in hemochromatosis Z Gastroenterol. 1999 Jun  [Article in German] The degree of glucose intolerance and diabetes mellitus in hemochromatosis is closely associated with the stage of iron overload and thus also the stage of the accompanying liver disease. Similar to other liver diseases glucose intolerance due to insulin resistance precedes diabetes mellitus also in hemochromatosis.

• Diagnosis and management of hemochromatosis
  by Dr. Anthony Tavill, Director of the Maurice and Sadie Friedman Center For Digestive Diseases and Liver Disorders, Mathile and Morton J. Stone Professor of Digestive Diseases and Liver Disorders at the Mt. Sinai Medical Center, Professor of Medicine and Nutrition at Case Wetern Reserve University. [Excellent & thorough article of diagnosis & treatment.  This is a pdf file] 

• Diagnosis and management of precirrhotic hemochromatosis Gushurst TP, Triest WE.  Department of Pathology, Cabell Huntington Hospital, West Virginia. W V Med J 1990 Mar  Three cases of hemochromatosis in the precirrhotic stage of the disease are presented. The pathophysiology, clinical and laboratory features and management are discussed. The high gene frequency in the general population warrants routine screening tests in asymptomatic healthy young adults.

• Diagnosis and treatment of genetic hemochromatosis Rev Prat. 2000 May 1 [Article in French]
  Moirand R, Guillygomarc'h A, Brissot P, Deugnier Y. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.

• Diagnosis of liver cirrhosis in children based on colour Doppler ultrasonography with histopathological correlation.  Pediatr Radiol 1998 Nov  Portal vein velocity, arterio-portal vein ratio and hepatic artery visualisation together were reliable in diagnosis of cirrhosis in the paediatric age group.

• Dietary Iron Supplements - Use or not to use?
  Nutrition Today James R. Connor John L. Beard 05-06-1997 There is little reason to support a general need for iron supplementation in the diet at any age. Perhaps this article and review of supplementation pros and cons should conclude with a new interpretation of an old saying: "It is better to wear out than to rust out;" don't expose your system to more iron than it needs.

• Differentiation between heterozygotes and homozygotes in genetic hemochromatosis by means of a histological hepatic iron index: a study of 192 cases. Hepatology. 1993 Jan These data show that the age-dependent nature of iron accumulation can also be accommodated by calculating the histological hepatic iron index and that histological study is an accurate means of predicting the genetic status of hemochromatosis patients when hepatic iron concentration is not available.

• DIGESTIVE TRACT AND REGULATION; REGULATION OF METABOLISM & ENERGY BALANCE   November 13, 1998 (Chap. 17; pp. 602-607)

• Dr. Rose's Peripheral Brain--HEMOCHROMATOSIS

• DRUGS THAT MAY CAUSE LIVER DYSFUNCTION OR DAMAGE The liver is the principal organ that is capable of converting drugs into forms that can be readily eliminated from the body.  This site lists the drugs which require careful monitoring of their effects on the liver.

• Early diagnosis of hepatocellular carcinoma in haemochromatosis influences surgical management Scott Med J 1998 Aug Screening for hepatocellular carcinoma is often not undertaken in patients with haemochromatosis. Survival prospects are poor in patients whose tumour presents symptomatically.

• Effects of Iron Overload  Harvard University website  2-1999

• Effects of iron overload and lindane intoxication in relation to oxidative stress, Kupffer cell function, and liver injury in the rat   Toxicol Appl Pharmacol 2001 Jan 1   These data support the contention that lindane sensitizes the liver to the damaging effects of iron overload by providing an added enhancement to the oxidative stress status in the tissue, and this may contribute to the alteration of the respiratory activity of Kupffer cells and the development of an inflammatory response.

• Effects of iron overload on the immune system. 
  Ann Clin Lab Sci 2000 Oct Department of Pathology, Marshall University and Huntington DVA Medical Center, West Virginia Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.

• Elevated hepatic iron index and end-stage liver disease.
  HEPATOLOGY WATCH, Timely Information for Practicing Physicians.  The authors conclude that iron studies are nonspecific for identifying end-stage liver patients with HHC and that genotyping studies should be utilized. (Cotler SJ, et al. Journal of Hepatology 1998; 29:257-262

• End-stage liver disease without hemochromatosis associated with elevated hepatic iron index. 
  J Hepatol. 1998 Aug;29 Cotler SJ, Bronner MP, Press RD, Carlson TH, Perkins JD, Emond MJ, Kowdley KV.  Department of Medicine, University of Washington, Seattle, USA. (i) Serum transferrin saturation and hepatic iron index lack specificity for hereditary hemochromatosis in end-stage liver disease. (ii) Genotyping for Cys 282 Tyr may provide the best method to identify hereditary hemochromatosis in the setting of end-stage liver disease.

• ESOPHAGEAL VARICES
  Written by Harrriet S. Gilbert, M.D. to MPD-NET Discussion/Support Group 1997

• Evaluation and interpretation of iron in the liver
  Semin Diagn Pathol 1998 Nov  Because homozygosity for the C282Y mutation is diagnostic of the condition regardless of the liver iron concentration-to-age ratio, indication for liver biopsy in C282Y homozygotes is restricted to the assessment of prognostic lesions, such as fibrosis and iron-free-foci.

• Excess iron induces hepatic oxidative stress and transforming growth factor beta1 in genetic hemochromatosis.  Hepatology.  1997 Sep  Houglum K, Ramm GA, Crawford DH, Witztum JL, Powell LW, Chojkier M.  Our data suggest that iron overload increases both lipid peroxidation and TGF-beta1 expression, which together could promote hepatic injury and fibrogenesis.

• Excess Iron Throws Out Welcome Mat to Bacteria 
  Heart, liver, intestines may suffer from over-fortified diet 11/2/2001 News By Serena Gordon HealthScoutNews Reporter (HealthScoutNews) -- Too much iron in the diet could be making people more susceptible to intestinal infections, claims a new study.  And that puts into question whether U.S. food makers need to fortify foods with iron, says one of the nutritionists who conducted the research.

• Factors affecting glucose tolerance in hereditary hemochromatosis
  Clin Invest Med 1997 Apr; These results suggest that iron overload can impair insulin secretion and glucose tolerance early in hereditary hemochromatosis, before cirrhosis occurs.

• Ferritin Physiology Overview of the function of ferritin with a section on hemochromatosis.

• FINAL DIAGNOSES:  A case of Hereditary Hemochromatosis with dilated cardiomyopathy, micronodular cirrhosis, history of chronic alcoholism from Department of Pathology, University of Pittsburgh School of Medicine.  

• FOCUS: ON THE LIVER & CIRRHOSIS
  from the September 94, October 94, and November 94 Focus: On Hepatitis C International newsletters

• Gamna-Gandy bodies of the spleen detected with MR imaging. A case report.   
  Magn Reson Imaging 2001 Nov In this case, MR imaging revealed small siderotic nodules of the spleen, called Gamna-Gandy bodies. These lesions are found in patients with portal vein or splenic vein thrombosis, hemolytic anemia, leukemia, or lymphoma, patients receiving blood transfusions, acquired hemochromatosis, or paroxysmal nocturnal hemoglobinuria.

• Genetic Haemochromatosis:   A guideline on Diagnosis & Therapy compiled on behalf of the Clinical Task Force of the  British Committee for Standards in Haemotology  2/2000 [a pdf file]

• Genetic Health-What Is Hemochromatosis? By Amanda Ewart Toland, PhD  Reviewed by Chris Friedrich, MD, PhD Last updated September 1, 2000

• Haemochromatosis and Diabetes– By Paul Steel.  Paul Steel is a diabetes educator with Manningham Community Health Service in Victoria. He has both a personal and professional interest in haemochromatosis, the most common genetic disorder in Australia, occurring in about one in 300 people.

• Haemochromatosis and HFE gene.
  Acta Gastroenterol Belg. 1999 Oct-Dec The practical management of haemochromatosis has been greatly modified, since liver biopsy is no more necessary for diagnosis in C282Y homozygotes, and is only needed for exclusion of cirrhosis. Family screening has also greatly benefited from genotyping.

• Haemochromatosis may present as exercise related joint pains without arthropathy, early treatment improving outcome, Case reports including x-ray pictures of hips, hands, knees. CLINICAL REVIEW Lesson of the week: Ian McCurdie and J David Perry BMJ 1999

• HCV AND C282Y: A SINISTER SYNERGISM? 
  SELECTED SUMMARY  GASTROENTEROLOGY 1999  The authors conclude that despite only modest increases in iron stores, individuals who are heterozygous for the C282Y mutation develop more fibrosis than homozygous normals with hepatitis C. They speculate that this subgroup of patients may benefit from therapeutic phlebotomy.  The current study supports the hypothesis that even minimal amounts of iron can cause or promote liver injury in the presence of other hepatotoxic conditions, such as alcohol abuse, chronic viral hepatitis, nonalcoholic steatohepatitis, and chronic hepatic porphyria.

• Hemochromatosis: A Common, Rarely Diagnosed Disease
  By Vincent J. Felitti, MD, FACP  Commentary by David Baer, MD, FACP.  Hemochromatosis is the most common, life-threatening genetic disorder in North America, yet most physicians have never personally diagnosed a case: all see an unrecognized case in their offices every two weeks.

• Hemochromatosis: a review.  Clin J Oncol Nurs 2001 Nov-Dec;5(6):257-60   Dolbey CH. Fletcher Allen Health Care, UHC Campus, Arnold 2, 1 South Prospect Avenue, Burlington, VT, 05401, USA. This disorder affects the liver, pancreas, heart, and endocrine systems, and if undetected and untreated, organ damage and death can result.

• Hemochromatosis, A simple genetic trait, Dr. Richard D. Press, Oregon Health Sciences University With the discovery of the causative gene, the disorder stands revealed as America's single most common mendelian disease. Unlike other genetic diseases, it is already curable. Indeed, genetic screening makes it potentially preventable.

• Hemochromatosis at the intersection of classical medicine and molecular biology  
  C R Acad Sci III 2001 Sep

• Hemochromatosis can now be appropriately defined as the presence of two hemochromatosis alleles with or without organ injury, and with or without the presence of iron overload. [I have not been able to retrieve the url to the website from where this came, so if anyone locates it, please let me know!]

• Hemochromatosis:  Conemaugh Health System  
  Hemochromatosis is a condition that develops when too much iron builds up in the body. Excess iron is stored in the organs, such as the kidneys, liver, and heart, and in the joint tissues.

• Hemochromatosis, Cooley Dickinson Hospital  Editor: George R Bowers MD CDH Oncology  January 2000 Volume 4: No. 1.   Hemochromatosis is a common, genetically transmitted disease. The diagnosis of hemochromatosis is sometimes difficult and frequently missed. This issue will review the pathogenesis, diagnosis and treatment of this fascinating disease. Ms. Kathy Fleming will review the management of a most troubling complication of therapy---lymphedema. 

• Hemochromatosis: diagnosis and management. Bacon BR.  Gastroenterology 2001 Feb  HFE mutation analysis has strengthened our ability to diagnose HH accurately and is useful in family studies. HFE mutations may play a contributory role in some patients with PCT, NASH, or chronic HCV.

• Hemochromatosis
  eMedicine Journal, December 7 2001, Volume 2, Number 12, Authored by Sandor Joffe, MD, Section Chief of Abdominal Imaging, Department of Radiology, Beth Israel Medical Center  This article covers the pathophysiology of hemochromatosis as well as the techniques in using ULS, CT & MRI to identify iron deposition in the organs. Pictures & descriptions from scans of the abdomen are shown.

• Hemochromatosis, Front Range Gastroenterology Associates, P.C.  
  2030 Mountain View Avenue, Suite 300, Longmont, CO.  Basic statistics on HH.

• Hemochromatosis  Gale Encyclopedia of Medicine The symptoms of hemochromatosis include fatigue, weight loss, weakness, shortness of breath, heart palpitations, chronic abdominal pain, and impaired sexual performance. The patient may also show symptoms commonly connected with heart failure, diabetes or cirrhosis of the liver. Changes in the pigment of the skin may appear, such as grayness in certain areas, or a tanned or yellow (jaundice) appearance.

• Hemochromatosis: Gastrointestinal Health Hemochromatosis, the most common genetic disease in the United States, results in iron overload and, if left untreated, severe organ damage. 

• Hemochromatosis: genetics helps to define a multifactorial disease 
  Clin Genet, 54(1):1-9 1998 Jul University of Washington, Seattle 98105 wburke@u.washington.edu   Early detection is desirable, because periodic phlebotomy provides effective treatment for iron overload and may prevent complications of the disorder.

• Hemochromatosis:  Genetics, Pathophysiology, Diagnosis and Treatment, "Introduction to Hemochromatosis"  Part I,  by Barton & Edwards.  Except from their book, [a pdf file] This is a large & excellent book covering all areas of hemochromatosis.  Published in 2000, $225.00

• Hemochromatosis in Ireland and HFE. Blood Cells Mol Dis. 1998  The allele frequency of 14% for the C282Y mutation in our control population is the highest reported and supports the hypothesis of a Celtic origin for the hereditary hemochromatosis gene.[pdf file]

• Hemochromatosis:  Life Extension Foundation website.  Disease, Prevention & Treatment 3rd editon.  Dietary & Vitamin recommendations listed here including calcium for blocking of iron absorption.

• Hemochromatosis Mutation Detection, Cys282Tyr and His63Asp  
  Guide to Clinical Laboratory Testing &  Interpretation of genetic testing. 

• Hemochromatosis Presenting as Acute Liver Failure after Iron Supplementation
  The New England Journal of Medicine  July 23, 1998  Vol. 339, Number 4.  We report a case of acute liver failure after iron supplementation in the setting of unrecognized hemochromatosis. 

• Hemochromatosis, Slides of the Liver before Tx.   Also has other slides of the liver in hemochromatosis.

• Hemochromatosis Special  American Liver Foundation newsletter,  ALF Progress, Vol. 21 No. 1, Summer 1999 The ALF newsletter created three scenarios based on the real life ethical, economic and medical quandaries posed by hemochromatosis, and asked three experts from divergent fields to respond with their opinions. The experts are: Bruce R. Bacon, MD [Director, Div. of Gastroenterology & Hepatology, Saint Louis University School of Medicine, St. Louis, M0]; medical ethicist Mark A. Rothstein, Esq. [Director, University of Houston Law Center, Health Law & Policy Institute, Houston, TX] and hemachromatosis patient Gayle Hoffman.

• Hepatic injury in chronic iron overload. Role of lipid peroxidation.   Chem Biol Interact. 1989 Bacon BR, Britton RS. Excess deposition of iron in the parenchymal tissues of several organs (e.g. liver, heart, pancreas, joints, endocrine glands) results in cell injury and functional insufficiency.

• Hepatic iron concentration in hereditary hemochromatosis does not saturate or accurately predict phlebotomy requirements.   Am J Gastroenterol. 1998 Mar  Olynyk JK, Luxon BA, Britton RS, Bacon BR. The phlebotomy requirement for treatment of HH cannot be accurately predicted from the initial HIC or serum ferritin level. Within the range examined, hepatic iron deposition did not saturate in HH.

• Hepatic Pathology Index Images of normal & diseased livers.

• Hepatic stellate cell activation in genetic haemochromatosis. Lobular distribution, effect of increasing hepatic iron and response to phlebotomy. 
  J Hepatol. 1997 Mar   Ramm GA, Crawford DH, Powell LW, Walker NI, Fletcher LM, Halliday JW. This study has demonstrated for the first time in humans a correlation between hepatic iron concentration and stellate cell activation in haemochromatosis, which is reversed by iron removal.

• Hepatic Stellate Cell Behavior During Resolution of Liver Injury

• Hepatic Stellate Cells as a Target for the Treatment of Liver Fibrosis 
  Both articles found in "Seminars in Liver Disease" August 2001 Volume 21, Number 3

• Hepatitis B virus infection markers in genetic haemochromatosis. A study of 272 patients.
  In conclusion, the prevalence of HBV infection markers--especially anti-HBc--is significantly increased in patients with genetic haemochromatosis complicated or not with primary liver cancer. J Hepatol 1991

• Hepatocellular carcinoma arising in non-cirrhotic liver in genetic haemochromatosis. 
  Scand J Gastroenterol 2000 Aug; Recently there have been cases of HCC arising in non-cirrhotic livers, and we report another such case.

• HEPATOCELLULAR CARCINOMA  
  MRI is superior to CT in demonstrating the fibrous capsule seen in 50% of the hepatomas and in delineating the tumor margin and venous invasion.  Images of the liver by CT & MRI.

• Hepatocellular carcinoma in the United States. Prognostic features, treatment outcome, and survival. Cancer 1996 Jun 1 The purpose of this study was to investigate prognostic factors at presentation and the survival of North American patients with hepatocellular carcinoma (HCC

• Hereditary Hemochromatosis and Cancer risk:  More fuel to the fire?  Gastroenterology Vol. 121, No. 5, November 2001  Pg. 1253 [a pdf file]  These data suggest an involvement of iron in carcinogenesis even in heterozygotes for HFE mutations. 

• Hereditary Haemochromatosis and Iron Metabolism, Carlson J, Olsson S, eJIFCC vol 13 no 2, THE JOURNAL OF THE INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY

• Hereditary hemochromatosis.  Ann Clin Lab Sci. 1998 Sep-Oct   Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations.  Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.

• Hereditary Hemochromatosis--A Risk Factor for Cardiovascular Disease The HH mutation is a human genetic model of disturbed iron metabolism, which facilitates research to the mechanism of HH and iron involved in cardiovascular disease. We expect that in the near future, the mechanism of disturbed iron metabolism leading to cardiovascular disease in human will be better understood.

• Hereditary Hemochromatosis 
  CME Activity, Release Date: 2/28/2000 Expiration Date: 2/28/2002 From the February 2000 Issue of Physician Assistant  Objectives: After reading the article, the reader should be able to:
  1. describe the pathophysiology of hereditary hemochromatosis;
  2. recognize the clinical symptoms and signs of hereditary hemochromatosis;
  3. outline screening and evaluation testing; and
  4. provide accurate diagnosis, management, and treatment.

• Hereditary hemochromatosis: diagnosis and treatment in primary care  Tenn Med 1999 Nov With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.

• Hereditary Hemochromatosis FamilyPractice.com  Robert B. Hash, MD, Department of Family Medicine, Mercer University School of Medicine, Macon, Ga. [J Am Board Fam Pract Dec. 2000] Considering the prevalence of the disease, it is important for physicians to consider it in the differential diagnosis when patients complain of the common signs and symptoms. For most patients hereditary hemochromatosis can be successfully treated in the physician's office. Early diagnosis and treatment, before signs of iron toxicity, if possible, can result in improved quality and quantity of life for many patients.

• Hereditary hemochromatosis: impact of molecular and iron-based testing on the diagnosis, treatment, and prevention of a common, chronic disease.  Arch Pathol Lab Med. 1999 Nov Press RD. Department of Pathology, Oregon Health Sciences University, Portland 97201, USA. pressr@ohsu.edu This direct HFE mutation test can now be used not only to confirm the diagnosis of HH in those with symptomatic disease, but also, perhaps more importantly, to detect those with presymptomatic iron overload in whom future disease manifestations may be prevented (with phlebotomy therapy).

• Hereditary hemochromatosis in children, adolescents, and young adults. 
  Am J Pediatr Hematol Oncol. 1988 Spring  Young individuals who should be screened for iron overload include patients with cardiac myopathies, hypogonadism, amenorrhea, loss of libido, diabetes mellitus, other endocrine disorders, cirrhosis of the liver, and arthritis, as well as the siblings, parents, and children of patients with hereditary hemochromatosis or iron loading of unknown cause.

• Hereditary hemochromatosis.  J Fam Pract, 44(3):304-8 1997 Mar  Hereditary hemochromatosis is a genetic disorder of iron metabolism that has an excellent prognosis if diagnosed early.

• Hereditary hemochromatosis: Preventing chronic effects of this underdiagnosed disorder
  Sharon M. McDonnell, MD, MPH; David Witte, MD, PhD VOL 102 / NO 6 / DECEMBER 1997 / POSTGRADUATE MEDICINE.  In this article, Drs McDonnell and Witte discuss the diagnosis and management of this underrecognized problem as well as the various issues involved in screening. An illustrative case of hemochromatosis is also included.

• Hereditary hemochromatosis Rev Med Interne 2000 Nov  At present, any patient admitted with an isolated case of asthenia, or with arthralgia or hypertransaminasemia should be examined via transferrin-saturation testing: if the transferrin saturation coefficient is > 45%, then the presence of the C282Y mutation should be investigated to confirm the diagnosis of hemochromatosis. A liver biopsy is no longer necessary to establish the diagnosis.

• Hereditary Hemochromatosis Since Discovery of the HFE Gene  Clinical Chemistry 2001 [a pdf file] Includes an algorithm for screening and diagnosis of hemochromatosis. This review provides a comprehensive discussion of known mutations in the HFE gene and their phenotypic expression

• Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C.  Hepatology. 1998 Jun  Thus, despite relatively minor increases in iron stores, individuals who are heterozygous for hemochromatosis appear to develop more fibrosis in chronic hepatitis C. Venesection may be useful therapy in this subgroup.

• HFE gene knockout produces mouse model of hereditary hemochromatosis Proc Natl Acad Sci U S A. 1998 Mar.  Xiao Yan Zhou, Shunji Tomatsu, Robert E. Fleming, Seppo Parkkila, Abdul Waheed, Jinxing Jiang, Ying Fei, Elizabeth M. Brunt, David A. Ruddy, Cynthia E. Prass, Randall C. Schatzman, Rosemary O'Neill, Robert S. Britton, Bruce R. Bacon, and William S. Sly  The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload.

• HFE genotype in patients with hemochromatosis and other liver diseases.  Ann Intern Med. 1999 Jun 15 Bacon BR, Olynyk JK, Brunt EM, Britton RS, Wolff RK.   All 66 patients homozygous for the C282Y mutation of HFE had an elevated hepatic iron concentration, but approximately 15% of these patients did not meet a previous diagnostic criterion for hemochromatosis (hepatic iron index > 1.9 mmol/kg per year). Determination of HFE genotype is clinically useful in patients with liver disease and suspected iron overload and may lead to identification of otherwise unsuspected C282Y homozygotes.

• HFE mutations in insulin resistance-associated hepatic iron overload.J Hepatol. 2000 Sep;33;33(3):515-6. No abstract available.

• HFE-PROTEIN IN HEREDITARY HEMOCHROMATOSIS  
  Hereditary hemochromatosis is the most common known autosomal recessive disorder in Caucasians.

• Histological evaluation of iron in liver biopsies: relationship to HFE mutations.  Am J Gastroenterol. 2000 Jul Brunt EM, Olynyk JK, Britton RS, Janney CG, Di Bisceglie AM, Bacon BR.  The use of histological evaluation for iron deposition is simple, assists in expanding information communicated from histopathologic observations, and may be clinically useful in determining the necessity of further evaluation of HFE genotype in subjects with histological evidence of hepatic iron overload.

• Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients.
  Am J Clin Pathol. 2001 Aug The aim of the present study was to describe histologic features of the liver in insulin resistance-associated hepatic iron overload (IR-HIO), defined as the association of metabolic disorders and hepatic iron overload.

• Homozygosity for hemochromatosis: clinical manifestations.  Ann Intern Med. 1980 Oct; Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy.

• Hypogonadism and sexual dysfunction in hemochromatosis: the effects of cirrhosis and diabetes.
  J Clin Endocrinol Metab. 1989 Jul  Sexual dysfunction was a common early complaint in hemochromatosis patients, but these symptoms were frequently overlooked, leading to diagnostic delay.

• Hypothyroidism and hypoparathyroidism in an 11 year old boy with hemochromatosis secondary to aplastic anemia.  Acta Paediatr Jpn. 1995 Aug  This is the first reported case, to our knowledge, of hypoparathyroidism and hypothyroidism due to secondary hemochromatosis with onset during childhood. The patient was a boy with refractory aplastic anemia in whom primary hypothyroidism and hypoparathyroidism became apparent at the age of 10 and 11 years old, respectively.

• Idiopathic hemochromatosis in a 45-year-old infertile man.
  Andrologia. 1987 Sep-Oct The clinical manifestations of primary or idiopathic hemochromatosis include mainly hepatomegaly, diabetes mellitus, and hypogonadism.

• Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people Gastroenterology 1979 Jan;76(1):178-83  The case presented here describes a 26-yr-old woman with problems presenting heart failure, insulin-dependent diabetes, hepatomegaly, and secondary amenorrhea.

• Idiopathic hemochromatosis presenting as amenorrhea and arthritis 
  Am J Med 1987 May A young woman with idiopathic hemochromatosis is described

• Illustrations to Hemochromatosis, Radiology CT scan pictures

• Imaging Diagnosis of Hepatocellular Carcinoma and Premalignant/Borderline Lesions 
  Sem Liver Disease 19(3):297-309, 1999   Early detection of hepatocellular carcinoma (HCC) has improved with recent noninvasive imaging modalities, such as ultrasonography (US), computer tomography (CT), and magnetic resonance imaging (MRI).

• Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease.
  Hepatology 2001 Mar In conclusion, patients with HH are at high risk of both liver cancer and other malignancies, which should be carefully sought during follow-up.

• Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis.  Gastroenterology 1998 Feb The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significant association with hepatic damage in these patients. Heterozygosity for the hemochromatosis gene mutation therefore cannot always be considered benign.  

• Insulin resistance-associated hepatic iron overload Gastroenterology 1999 Nov; This study shows that patients with unexplained hepatic iron overload are characterized by a mild to moderate iron burden and the nearly constant association of an IRS irrespective of liver damage.

• Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma Oncology 2000 Nov In hepatocellular carcinoma (HCC) iron has been implicated as a risk factor primarily in patients with hereditary haemochromatosis (HH) and cirrhosis

• Interrelationships of alcohol and iron in liver disease with particular reference to the iron-binding proteins, ferritin and transferrin  Linda M Fletcher; June W Halliday; Lawrie W Powell   Journal of Gastroenterology and Hepatology 14 (3), 202-214 It is known that the regular consumption of alcohol is responsible for the disruption of normal iron metabolism in humans, resulting in the excess deposition of iron in the liver in approximately one-third of alcoholic subjects.  It is known that the regular consumption of alcohol is responsible for the disruption of normal iron metabolism in humans, resulting in the excess deposition of iron in the liver in approximately one-third of alcoholic subjects.

• IRON AND HFE MUTATIONS IN HCV.  Hemochromatosis gene mutations in chronic hepatitis C virus (HCV) patients.   The authors conclude that HFE gene mutations contribute to hepatic iron overload in chronic HCV patients. (Kazemi-Shirazi L, et al. Gastroenterology 1999; 116: 127-134)

• Iron and liver diseases. Can J Gastroenterol. 2000 Nov; Iron appears to affect the natural history of hepatitis C virus-related chronic liver diseases, alcoholic liver disease and nonalcoholic steatohepatitis by leading to a more severe fibrosis and thus aiding the evolution to cirrhosis.

• Iron catalyzed oxidative damage, in spite of normal ferritin and transferrin saturation levels and its possible role in Werner's syndrome, Parkinson's disease, cancer, gout, rheumatoid arthritis, etc. Med Hypotheses 2000 Sep the disease is often overlooked by physicians, until several organs have been damaged permanently (heart, liver, brain, pancreas, kidneys, spleen, etc.). Moreover, since ferritin, transferrin saturation and hematocrit levels are not directly related to cellular iron levels, and since excess iron can wreak havoc in the cell, we can conclude that there is a need for a better way to evaluate intracellular iron levels and especially the intracellular free iron levels by a non-invasive technique.

• Iron-Containing Compounds in Humans VAMC Pathology Service, Memphis, TN
  
• Iron-induced liver injury
  Clin Liver Dis 2000 May:  Iron, either in the form of heme or non-heme compounds, is essential to life, but it can also pose serious health risks. The liver is a principal target for iron toxicity.

• Iron in the era of molecular biology Pathol Biol (Paris). 1999 Nov Identification of the HFE gene and its C282Y and H63D mutations has improved the classification of iron overload disorders

• Iron is Hot:  An Update on the Pathophysiology of Hemochromatosis: Blood Journal Sept. 15, 1998  Genetic iron overload disorders are prevalent yet poorly understood. [A pdf file.]

• Iron Loading and Disease Surveillance
  Eugene D. Weinberg   Indiana University, Bloomington, Indiana   Emerging Infectious Diseases Journal, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Excessive iron in specific tissues and cells (iron loading) promotes development of infection, neoplasia, cardiomyopathy, arthropathy, and various endocrine and possibly neurodegenerative disorders.

• IRON OVERLOAD AND INSULIN RESISTANCE: Hyperferritinemia with normal transferrin saturation. The increased iron burden should presumably be treated as in genetic hemochromatosis. Whether morbidity and mortality from the associated conditions is modified by such a measure remains to be determined.

• Iron overload and liver fibrosis.  
  Arthur MJ. J Gastroenterol Hepatol 1996 Dec; Unravelling the mechanism of liver fibrogenesis in iron overload states may, therefore, provide important general insights into the pathogenesis of liver fibrosis. The present article reviews current knowledge of this field with emphasis on the role of lipid peroxidation, sideronecrosis of hepatocytes and spillover of iron to Kupffer cells.

• Iron overload and public health
  Bull Acad Natl Med. 2000  Genetic hemochromatosis, due to its frequency (about 300,000 cases in France) and to its severity, must be considered as a public health burden. Its curability--insofar as its diagnosis has been made early--and the disposal of non invasive and reliable phenotypic (transferrin saturation) and genotypic (HFE C282Y mutation) tests make its diagnosis easy.

• Iron Overload Disease due to Hereditary Hemochromatosis  CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection and treatment for this genetic condition can lessen morbidity and mortality, and in some cases prevent the onset of disease. Therefore, early detection of hemochromatosis represents a major chronic disease prevention opportunity.

• Iron Overload Disorder Common and Increases Risk for Heart Attacks  Full Health Nutrition Canada ArterialHealth e-News^© October 1999 A genetic defect that causes iron overload disease is the most common inherited disorder among whites, affecting one in 188 people of northern European descent.

• Iron Overload (Hemosiderosis; Hemochromatosis) The Merck Manual of Diagnosis and Therapy Section 11. Hematology And Oncology Chapter 128. Hemochromatosis is often diagnosed late in the course of disease after significant tissue injury is present because the clinical symptoms are insidious and the extent of organ involvement varies; thus, the full clinical picture evolves slowly

• Iron overload in bone marrow transplant recipients.   
  Bone Marrow Transplant. 1998 Jul Strasser SI, Kowdley KV, Sale GE, McDonald GB.

• Irritable Bowel Syndrome & The Iron Connection
  This booklet written by Dr. Leslie Johnston, mentions a connection between excess iron & IBS, Chronic Fatigue Syndrome [CFS], Fibromyalgia [FM] & many other symptoms and/or diagnoses

• Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis? Am J Gastroenterol 2001 Feb  From this analysis, it appears that a hepatic iron concentration >283 micromol/g is associated with cirrhosis. However, the low sensitivity of this threshold suggests that other cofactors contribute to the development of cirrhosis in hemochromatosis. Early diagnosis is encouraged to initiate iron depletion before the development of cirrhosis.

• Liver biopsy in chronic hepatitis C. Histopathology, molecular diagnostic analysis, and implications for therapeutic management  Pathologe 2001 Nov 22The frequency of chronic hepatitis C necessitates awareness of coinciding liver damage by nutritional or drug toxicity, bile duct diseases, and hereditary hemochromatosis. [Article in German]

• Liver Biopsy 
  National Digestive Diseases Information Clearinghouse 2 Information Way  Bethesda, MD 20892-3570  
  • Liver Biopsy, Preparation, Procedure, Recovery

• Liver fibrosis in genetic hemochromatosis. Respective roles of iron and non-iron-related factors in 127 homozygous patients. J Hepatol. 1992 Sep; These results suggest that the iron overload threshold necessary to induce fibrosis is modulated by non-iron-related factors such as alcoholism, sex and age.

• LIVER, GALL BLADDER, & PANCREAS
  Thomas A. Godwin, M.D.Department of Pathology  1995, Cornell University Medical College  Descriptions of various diseases affecting these organs as well as pathology slides.

• Liver iron accumulation in patients with chronic active hepatitis C:  prevalence & role of hemochromatosis gene mutations and relationship with hepatic histological lesions
  Journal of Hepatology 1999  [a pdf file]

• Liver transplantation for hereditary hemochromatosis. This suggests that regardless of the cause, iron overload may be detrimental in patients undergoing OLT. Liver Transpl 2001 Aug

• Long-term survival analysis in hereditary hemochromatosis.
  Gastroenterology. 1991 Aug Early diagnosis and treatment of hemochromatosis in the precirrhotic stage can lead to long-term survival similar to that in the general population. The presence of cirrhosis significantly increases mortality and is the major clinical factor affecting survival.

• Long-term survival in patients with hereditary hemochromatosis Gastroenterology, Vol 110, 1107-1119, 1996 by American Gastroenterological Association   Prognosis of hemochromatosis and most of its complications, including liver cancer, depend on the amount and duration of iron excess. Early diagnosis and therapy largely prevent the adverse consequences of iron overload.

• Magnetic resonance imaging of the liver: current clinical applications.
  Mayo Clin Proc 1993 Feb.  Magnetic resonance imaging provides excellent anatomic depiction of the liver and important information about focal and diffuse diseases that affect this organ.

• Magnetic resonance iron-free nodules in genetic hemochromatosis.
  Am J Gastroenterol. 1999 Apr  The present data confirm the high prevalence of liver cancer at the time of diagnosis, mainly in cirrhotic patients greater than 45 years of age, and indicate that, when performing MRI for liver iron quantification, a complete hepatic MRI examination is preferable to a simple signal measurement in patients at risk for hepatocellular carcinoma.

• Management of hereditary hemochromatosis. Blood Rev. 1994 Dec Phatak PD, Cappuccio JD. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening.

• Management of hemochromatosis. Hemochromatosis Management Working Group.
  Ann Intern Med. 1998 Dec 1  Barton JC, McDonnell SM, Adams PC, Brissot P, Powell LW, Edwards CQ, Cook JD, Kowdley KV.  The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management.

• Mild liver enzyme abnormalities: eliminating hemochromatosis as cause. David L. Witte Clinical Chemistry. 1997;43:1535-1538 Laboratory-initiated screening programs using 
  unsaturated iron-binding capacity can eliminate symptomatic hemochromatosis. Detection of hemochromatosis
  before development of cirrhosis or diabetes followed by removal of iron by therapeutic phlebotomy is associated
  with length and quality of life identical to age-matched controls.

• Molecular genetics of hemochromatosis 
  Ann Endocrinol (Paris) 1999 Sep Hemochromatosis is a recessive disorder of iron metabolism characterized by progressive iron loading of parenchymal organs, which accounts for clinical complications such as cirrhosis, diabetes mellitus, cardiopathy, endocrine dysfunctions and arthropathy.

• Mutations in the hfe gene and their interaction with exogenous risk factors in hepatocellular carcinoma:   Blood Cells Mol Dis 2001 Mar-Apr; These data indicate that the prevalence of the main mutation associated with hereditary hemochromatosis is significantly higher in cirrhotic Italian patients with hepatocellular carcinoma compared to a normal population and suggest that heterozygotes for HFE mutations exposed to hepatitis virus infections or who had been alcohol abusers could have an increased risk of developing cirrhosis and later liver cancer than people without the mutations exposed to the same risk factors.

• Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis.  J Hepatol. 1999 Sep  : The prevalences of the HFE gene mutations associated with hereditary hemochromatosis are increased among North American subjects with NASH.

• Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging.
  Br J Haematol. 1994 May . It is concluded that MRI based on SIR measurements offers a precise and reproducible non-invasive method for the determination and follow-up of iron overload within a wide range of liver iron concentrations. Our findings may increase the clinical use of MRI in haematological patients with iron overload.

• Noninvasive Prediction of Fibrosis in C282Y Homozygous Hemochromatosis 
  GASTROENTEROLOGY 1998;115:929-936  In C282Y homozygous patients, the diagnosis of severe fibrosis relies on liver biopsy, but absence of severe fibrosis can be accurately predicted in most patients on the basis of simple clinical and biochemical variables.

• Outlook Not Bright for Patients With Bleeding Oesophageal Varices  
  Drug & Ther Perspect 14(8):10-13, 1999   Varices are a complication of cirrhosis...

• Overview on Iron Overload and Hemochromatosis CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection of hemochromatosis is essential because the disease’s potentially serious complications can be prevented by early therapy.

• Pathology Cases for Diagnosis: A 37 year old male is referred to the liver clinic for evaluation of abnormal liver related enzymes.  Includes pictures of biopsy slides. Case 96-19: Liver II Contributed by D. Robert Dufour, M.D., CAPT, MC, USNR-R Date Available: July 22, 1996 - December 31, 1996 

• Population screening in hereditary hemochromatosis   Annu Rev Public Health 2000

• Potential MR pitfall in relying on lesion/liver intensity ratio in presence of hepatic hemochromatosis.  J Comput Assist Tomogr. 1988 Mar-Apr; Mirowitz S, Heiken JP, Lee JK. Department of Radiology, Jewish Hospital of St. Louis, Washington University Medical Center, MO. We present a case of hepatic metastasis studied by magnetic resonance imaging in which a spuriously high lesion/liver intensity ratio (suggestive of cavernous hemangioma) was obtained due to underlying hemochromatosis.

• Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. Witte DL, Crosby WH, Edwards CQ, Fairbanks VF, Mitros FA. College of American Pathologists Clin Chim Acta 1996 Feb. In view of the high prevalence in the American population (prevalence varies with ethnic background), the low cost of diagnosis and treatment, the efficacy of treatment if begun early, and, on the other hand, high costs and low success rate of late diagnosis and treatment, systematic screening for hemochromatosis is warranted for all persons over the age of 20.

• Preventing manifestations of hereditary haemochromatosis through population based screening.
  To evaluate the efficacy of identifying presymptomatic hereditary haemochromatosis through population based screening.  J Med Screen 1994 Jan

• Primary liver cancer in genetic hemochromatosis: a clinical, pathological, and pathogenetic study of 54 cases Gastroenterology 1993 Jan

• Primary liver carcinoma in genetic hemochromatosis reveals a broad histologic spectrum. Hepatocellular carcinoma (HCC) is a well-known complication of genetic hemochromatosis (GH). Am J Clin Pathol 2001 Nov;116

• PULLING IRON OUT OF THE FIRE by Shelly Morrow.  This article appeared in the Sept/Oct 2000 issue of Arthritis Today, published by the Arthritis Foundation, Inc.

• Recognition and management of hereditary hemochromatosis.   Am Fam Physician 2002 Mar 1 65:853-60 Brandhagen DJ, Fairbanks VF, and Baldus W Mayo Medical School, Rochester, Minnesota, USA. The HFE gene test is useful in confirming the diagnosis of hereditary hemochromatosis, screening adult family members of patients with HFE mutations and resolving ambiguities concerning iron overload.

• Recognizing genetic hemochromatosis.  J La State Med Soc. 1994 Dec  This article reviews the disease process hemochromatosis, which is now recognized as one of the most common genetic disorders.  It is imperative that physicians learn to recognize early signs and symptoms of hemochromatosis so that treated patients can expect a normal life span with minimal medical intervention.

• Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis 
  Rev Port Cardiol. 1994 Oct  In this paper, we report a case of a young woman with a eight years evolution of amenorrhea, cardiac failure, diabetes mellitus and increased pigmentation of the skin, associated with biochemical markers of iron overload. It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.

• Relating Genomic Research to Patient Care JAMA 11/2000 Educating health care professionals about the complexities of the genetics of adult disease (in addition to congenital illness) is an important goal, and one disease model that is useful for this purpose involves hemochromatosis.

• Renal Transplantation and Evolution of Hemochromatosis:  A Clinical Case Report
  Despite being one of the world's most frequent autosomal recessive diseases, there are very few cases in the literature concerning hereditary hemochromatosis and renal transplantation. [a pdf file]

• Review article: the screening, diagnosis and optimal management of haemochromatosis.
  Aliment Pharmacol Ther. 1997 Aug   George DK, Powell LW.  Joint Liver Program, Queensland Institute of Medical Research, Brisbane, Australia.  Haemochromatosis is common, occurring in approximately 1 in 300 people in Caucasian populations, and untreated can cause serious morbidity and early death.

• Risk of disease in siblings of patients with hereditary hemochromatosis Digestion 2001

• Safety aspects of iron in food. 
  Ann Nutr Metab 2001;  There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects.

• Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase
  Gut 2000  The association of raised ALT activity and transferrin saturation of >60% could provide a simple, cost effective method for detecting individuals with clinical haemochromatosis.

• Screening for Iron Overload due to Hereditary Hemochromatosis 
  CDC website, Reyes, Michele, PhD and Muin J. Khoury, MD, PhD,  National Center for Chronic Disease Prevention and Health Promotion  Identifying people early with evidence of iron overload represents a major chronic disease prevention opportunity.

• Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance. J Lab Clin Med. 2000 May   We find the benefits of serum ferritin iron measurement to be marginal in patients with iron overload disease.

• Serum increase and liver overexpression of carbohydrate 19.9 antigen in patients with genetic haemochromatosis. Gut. 1994 Aug   In conclusion, this study shows that a mild, reversible, and non-specific increase in serum CA 19.9 is common in genetic haemochromatosis patients and shows that this increase is related to iron excess, directly or through associated liver damage.

• Should all patients with diabetes mellitus be screened for hemochromatosis?   Department of Family Medicine University of California, Los Angeles 924 Westwood Blvd, Suite 650 Los Angeles, CA 90095-1628  West J Med 2002;176:110-114  Enhanced case finding becomes the first stage in a public health response when evidence has emerged for an effective early treatment of a disorder. It means the detection of HHC at the time of early symptoms, and it allows patients to benefit from early phlebotomy.  The implementation of this approach would include adding fasting serum transferrin saturation to the usual workup of patients with newly diagnosed diabetes mellitus, arthritis, and impotence.  The CDC recommends such iron-overload testing in anyone with possible symptoms of hemochromatosis, which includes patients with newly diagnosed diabetes mellitus.

• Slides of the liver with iron involvement

• Surgical treatment of hepatocellular carcinoma in cirrhosis Ann Gastroenterol Hepatol (Paris) 1996 Jan-Feb However the best treatment is the prevention of cirrhosis.

• Survival and causes of death in hemochromatosis.   Observations in 163 patients.
  Ann N Y Acad Sci. 1988  Life expectancy was reduced in patients who presented with cirrhosis or diabetes compared to patients who presented without these complications at the time of diagnosis. Patients who could be depleted of iron during the first 18 months of venesection therapy had a markedly better prognosis compared to those patients who could not be depleted during this time period.

• Testosterone treatment of men with idiopathic hemochromatosis. 
  Clin Investig 1992 Jul  Patients with chronic liver disease usually exhibit low plasma levels of testosterone with loss of libido and potency; this is also valid in male patients suffering from idiopathic hemochromatosis (IHC), in whom nowadays the diagnosis is made at an earlier age. Because of the positive effects on general well-being, liver regeneration capacity, and potency, testosterone should especially be administered to younger subjects suffering from IHC.

• The articular damage of hemochromatosis. A little known aspect Recenti Prog Med 1999 Apr The aim of this report is to underline that the patients with premature osteoarthritis or unexplained chondrocalcinosis must be screened for genetic haemochromatosis in order to formulate the correct diagnosis before the development of severe internal organ involvement.

• The diagnosis of hemochromatosis in the era of the gene
  Ann Endocrinol (Paris). 1999 Sep [article in French] The discovery of the hemochromatosis gene has deeply changed and simplified the diagnosis of the disease. In a given individual, establishing the diagnosis relies, from now on, on a simple blood sample showing the couple: elevated transferrin saturation and homozygous C282Y mutation (= C282Y +/+). Liver biopsy should only be performed when iron overload is massive in order to detect cirrhosis (or bridging fibrosis), i.e. in a prognostic view.

• "The Elusive Hemochromatosis Gene and Other Reports on Iron Metabolism"
  by Bruce R. Bacon,    M.D., Director, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine/Page 2 & Page 13  American Liver Foundation Progress Newsletter-Special Double Issue Vol. 17, No. 2/Fall 1995-Winter 1996 

• THE EVALUATION OF ABNORMAL LIVER FUNCTION TESTS AND JAUNDICE
  Carol Murakami, M.D., Richard Willson, M.D., and Susan Stover-Dalton, M.D. This discussion on the evaluation of abnormal liver function tests relates to the overall prevention of end stage liver disease and the consequent need for liver transplantation.

• The haemochromatosis gene: a co-factor for chronic liver diseases?
  J Gastroenterol Hepatol. 1999 Aug George DK, Powell LW, Losowsky MS  Iron loading of mild to moderate degree due to heterozygosity or homozygosity for the haemochromatosis genetic mutations acts as a significant hepatotoxin aggravating hepatic damage from other causes of liver disease.

• The haemochromatosis gene: a global perspective and implications for the Asia-Pacific region.
  J Gastroenterol Hepatol. 1999 Sep; Epidemiological studies have shown that this gene is more widespread than its phenotypic expression would suggest and that the heterozygous state may be implicated in the expression of other diseases of the liver such as porphyria cutanea tarda, hepatitis C virus infection and non-alcoholic steatohepatitis.

• The Liver: Introduction and Index The liver is the largest gland in the body and performs an astonishingly large number of tasks that impact all body systems. One consequence of this complexity is that hepatic disease has widespread effects on virtually all other organ systems.

• The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology. 1997 Jan The nonspecific nature of the presenting features in patients and the presence of significant clinical symptoms in patients discovered through family investigations underscore the importance of family and population screening for hemochromatosis.  The prevalence of cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue increased as liver iron concentration increased. The most common presentations at diagnosis were fatigue

• The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans Am J Gastroenterol 2001 Aug.  Diabetes mellitus (DM) has been reported to increase the risk of hepatocellular carcinoma (HCC). We carried out a case-control study to examine the role of DM while controlling for several known risk factors of HCC.

• Too much iron can hurt joints, body organs 
  The Albuquerque Tribune. By John Crowe The Associated Press 1/11/00

• Update on Liver Disease Conference Report 35th Annual Meeting of the European Association for the Study of the Liver April 30 - May 3, 2000 Rotterdam, The Netherlands Medscape Gastroenterology  What's New for the Treatment of Esophageal Varices in Patients With Cirrhosis?

• URBANA ATLAS OF PATHOLOGY  Image Number 36 - Liver, cirrhosis, hemochromatosis Hemochromatosis is the accumulation of iron in the cells of the body

• Utility of hepatic iron index in American patients with hereditary hemochromatosis: a multicenter study. Gastroenterology.   1997 Oct Kowdley KV, Trainer TD, Saltzman JR, Pedrosa M, Krawitt EL, Knox TA, Susskind K, Pratt D, Bonkovsky HL, Grace ND, Kaplan MM.   A "threshold" hepatic iron concentration of 71 mumol/g can almost always distinguish patients with HHC from patients with other liver diseases and may be a useful adjunct to the hepatic iron index in the diagnosis of HHC in the diverse U.S. population.

• Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis.  Hepatology. 1986 Jan-Feb It is concluded: that chemical measurement of hepatic iron concentration, when corrected for the age of the subject, reliably distinguishes early hemochromatosis from alcoholic siderosis, and, that there appears to be a threshold level of hepatic iron above which there is a high risk of fibrosis.

• What Are the Major Causes of Cirrhosis? Liver injury that results in cirrhosis also may be caused by a number of inherited diseases such as cystic fibrosis, alfa-1 antitrypsin deficiency, hemochromatosis, Wilson's disease, galactosemia, and glycogen storage diseases.

• What's new in hemochromatosis.  Curr Opin Hematol 2001 Mar  The high correlation of HFE to HHC has caused it to be considered as a candidate gene for population-based genetic testing for diagnosis and detection of predisposition to HHC. 

• Yersinia enterocolitica infection with multiple liver abscesses uncovering a primary hemochromatosis. Scand J Gastroenterol 2001 Feb  In conclusion, severe septic forms of yersiniosis are mainly found in patients with iron overload, due to a handicapped iron metabolism of the Yersinia bacteria. Mortality is high despite treatment.

• Zellweger Syndrome Information Page  
  National Institute of Neurological Disorders and Stroke   The most common features of Zellweger syndrome include an enlarged liver, high levels of iron and copper in the blood, and vision disturbances.

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