Hepatology & Internal Medicine & Family Medicine & Medical Genetics
Hereditary hemochromatosis
Hereditary hemochromatosis (HH) is the most common autosomal recessive genetic disease in populations of Northern European origin, characterized by excessive intestinal absorption of dietary iron leading to its progressive accumulation in target organs - liver, pancreas, heart, joints, pituitary gland, skin - and irreversible organ damage if left untreated. The most frequent form is type 1 hemochromatosis, linked to mutations of the HFE gene on chromosome 6p: the C282Y mutation (cysteine → tyrosine substitution at position 282) is responsible for 80-85 % of clinical cases in Caucasian populations, and the H63D mutation constitutes a variant of lower penetrance, clinically significant especially in composite C282Y/H63D heterozygosity. Hemochromatosis is based on dysregulation of hepcidin - a hepatic peptide hormone central to iron metabolism - whose insufficient production or receptor insensitivity prevents regulation of ferroportin, keeping intestinal iron absorption and release from macrophages at inappropriate levels. Clinical penetrance is incomplete: only 10-30 % of C282Y homozygotes develop clinically expressive disease, with women protected by menstrual discharge until menopause. Diagnosis is based on transferrin saturation (TS) - the first marker to rise (>45 %) - and ferritinemia - a marker of iron reserves - confirmed by HFE genotyping. Therapeutic phlebotomy (bloodletting) is the reference treatment: simple, effective, well-tolerated and inexpensive, it normalizes iron reserves and prevents organic complications if started before irreversible lesions set in.
Pathophysiology, genetics, and clinical presentation
- Iron metabolism, role of hepcidin, and mechanism of overload in HH: normal iron metabolism: intestinal absorption (duodenum + proximal jejunum): 1-2 mg/d (compensates for losses) out of 10-20 mg absorbed → transmembrane transport: DMT1 (divalent metal transporter 1) → internalization in enterocyte → ferroportin (FPN1) → export to circulation → oxidation by hephaestine → transferrin binding (apotransferrin → monoferric → diferric transferrin) → storage: intracellular ferritin + hemosiderin → plasma transferrin → transferrin receptor (TfR1) → endocytosis in erythroblasts (erythropoiesis) + hepatocytes → recycling of senescent RBCs by splenic macrophages: 25 mg/d recovered → 95 % of circulating iron comes from macrophagic recycling → intestinal absorption = small fraction; hepcidin - conductor of iron metabolism: 25 amino acid peptide + synthesized by liver → binds to ferroportin → induces its internalization and degradation → blocks iron export from : enterocytes + macrophages + hepatocytes → hepcidin regulation: increased by: iron overload (via BMP6-BMPR/HJV axis) + inflammation (IL-6 → STAT3) → decreased by: iron deficiency + hypoxia (HIF-2α) + increased erythropoiesis (GDF15 + ERFE - erythroferrone) → HH type 1 (HFE) mechanism: normal HFE protein binds transferrin receptor TfR1 and TfR2 → sensing iron saturation → signaling to BMP6/HJV → hepcidin production → in C282Y HH: mutated HFE protein does not normally associate with TfR2 → signaling defect → insufficient hepcidin production → constitutionally active ferroportin → unregulated intestinal absorption → permanent macrophagic release → progressive accumulation of iron → 200-500 mg/year of excess iron → total stores up to 20-50 g (normal: 3-4 g) → oxidative stress damage: Fe²⁺ + H₂O₂ → hydroxyl radicals (Fenton reaction) → lipid peroxidation + DNA damage + fibrosis → cirrhosis + CHC + diabetes + cardiomyopathy; types of hereditary hemochromatosis: type 1 (HFE): C282Y/C282Y (most common in Northern Europe - prevalence 1/200 to 1/300 in subjects of Northern European ancestry) + type 2A (HJV - hemojevelin): juvenile hemochromatosis → severe overload before age 30 + heart disease + hypogonadism → rare + type 2B (HAMP - hepcidin): same juvenile phenotype → very rare + type 3 (TFR2): transferrin receptor 2 mutation → phenotype similar to type 1 but more severe → rare + type 4A/4B (SLC40A1 - ferroportin): autosomal dominant inheritance → type 4A: loss-of-function ferroportin → accumulation in macrophages + few organ complications → type 4B: hepcidin-resistant ferroportin → phenotype similar to type 1
- Epidemiology, HFE mutation genetics, and clinical penetrance: epidemiology: HFE type 1 hemochromatosis: the most common autosomal recessive disease in populations of Celtic (Irish + Scottish + Welsh) + Northern European origin → prevalence of C282Y homozygotes: 1/200-1/400 in Ireland + 1/300-1/400 in Canadian populations of Northern European origin → C282Y heterozygotes: 1/8 to 1/10 → healthy carriers → H63D: widespread (15-20 % of the general population of European ancestry in heterozygosity) → composite C282Y/H63D heterozygosity (2-3 % of the population) → minor clinical phenotype in the majority → S65C: rare mutation + little clinical significance; clinical penetrance of HH C282Y/C282Y: Allen 2008 - NEJM (HealthIron Study - Australia + UK - 31,192 subjects): homozygous C282Y → transferrin saturation elevated in 75 % of men + 60 % of women → ferritin elevated in 75 % of men + 40 % of women → clinically expressive disease (symptoms + organ damage): 28 % of homozygous men + 1 % of homozygous women → conclusion: low clinical penetrance → the vast majority of C282Y homozygotes will never develop symptomatic disease → factors modulating penetrance: sex (women protected by menstrual discharge) + alcohol consumption (potentiates overload + fibrosis) + modifying polymorphisms (SLC11A2 + TFR2 + CYBRD1 + associated hepcidinopathies) + dietary iron intake + frequent blood donations (reduced reserves) + co-morbidities (hepatic steatosis + hepatitis C → accelerated fibrosis); H63D mutations - clinical significance: homozygous H63D/H63D: slight transferrin saturation excess → very rare clinical overload → does not require specific monitoring if ST normal + composite heterozygous H63D/C282Y: ST often elevated + elevated ferritin possible → mild to moderate disease → clinical overload in <1 % → HFE genotyping + martial workup → MRI if elevated ferritin + single heterozygous H63D: carrier → no significant overload → non-systematic family screening required; population screening and family screening: mass screening: not universally recommended (USPSTF → insufficient evidence) → transferrin saturation test if clinical suspicion (unexplained fatigability + incidental elevated ferritin) + family screening: recommended for 1st degree relatives of a C282Y/C282Y proposer → ST + ferritin assay + HFE genotyping → if siblings → 25 % risk of being homozygous C282Y → Health Canada + MSSS: screening of siblings of an index case → family screening program
- Clinical manifestations – target organs and timeline of overload: chronology of accumulation and manifestations: stage 0: genetic predisposition → homozygous C282Y → no overload yet + stage 1: inconsequential iron overload → high ST + normal ferritin → asymptomatic → age: 20-40 years → stage 2: increasing overload → high ferritin → nonspecific symptoms → stage 3: organic overload → hepatic + articular + endocrine involvement → hepatic fibrosis → stage 4: irreversible complications → cirrhosis + diabetes + cardiomyopathy + hypogonadism → age: >40-50 years; clinical manifestations by organ: liver (most affected organ): hepatomegaly (1st clinical sign) → moderate hepatic cytolysis (ALT/AST 2-4× normal) → progressive fibrosis → cirrhosis → CHC (risk ×20 to 200 vs. general population in cirrhosis on HH) → Kowdley 2005 - Gastroenterology: HCC in 30 % of untreated homozygous C282Y cirrhotics + HCC risk persists even after normalization of iron stores if cirrhosis is already established; joints (chondrocalcinosis arthropathy): affected in 40-75 % of symptomatic cases → metacarpophalangeal joints (MCP) 2 and 3 +++ («painful handshake») → pathognomonic when bilateral + early + calcium pyrophosphate deposits (CPDD) → radiological chondrocalcinosis → hip + knee + lumbar → chronic joint pain → arthropathy is poorly reversible under phlebotomy → panaceas; pancreas: «hemochromatosis» type diabetes (bronze diabetes) → iron deposits in β cells + acinar cells → endocrine insufficiency (diabetes + hyperglycemia) + exocrine (malabsorption) → iron is directly toxic to β cells → partial improvement under phlebotomies if not cirrhotic; heart: dilated cardiomyopathy + rhythm disorders (AF + AV block) + heart failure → iron deposits in cardiomyocytes → systolic and diastolic dysfunction → Strohmeyer 1988 - Medicine: cardiac involvement in 15 % of symptomatic HH → reversible under treatment if started before decompensation; endocrine glands: hypogonadotropic hypogonadism (pituitary deposits → gonadotropic insufficiency → LH + FSH deficiency → secondary hypogonadism → impotence + amenorrhea + testicular atrophy + osteoporosis) + hypothyroidism (thyroid deposits) + adrenal insufficiency (rare) + skin: melanoderma - tanned or slate-gray complexion (melanin deposits + hemosiderin → melanocyte activation) → «coppery» complexion → classic triad: cirrhosis + diabetes + tanning = Trousseau's «diabète bronzé» (1865) but late stage avoided if detected early
Biological diagnostics, imaging, and treatment
| Step / processing | Methodology and Interpretation | Evidence and follow-up |
|---|---|---|
| Biological iron assessment — transferrin saturation and ferritin ST >45 % — ferritin — serum iron — transferrin — fasting — diagnostic algorithm |
Transferrin saturation (ST) - first warning marker: ST = (serum iron / CTLF) × 100 = (serum iron / transferrin × 25.1) × 100 → represents filling of transferrin binding sites → normal: male 20-45 % + female 16-45 % → HH warning threshold: ST ≥45 % fasting (in the morning, before any meal) → ST is the best early marker of HH → rises before ferritin (stage 1) → sensitivity for C282Y/C282Y: 90-95 % → limited specificity (false positives: alcoholic cirrhosis + acute hepatitis + hemolytic anemia) → sampling condition: fasting in the morning → serum iron increases by 20-30 % postprandially → false positives reduce; ferritinemia: marker of total iron stores → normal: male 30-300 µg/L + female 15-200 µg/L → elevated ferritin in HH: correlates approximately with hepatic iron stores → ferritin >1,000 µg/L → high risk of significant hepatic fibrosis (Guyader 1998 - Gastroenterology) + ferritin >2,000-3,000 µg/L → frequent cirrhosis → BUT: ferritin is an acute-phase reagent → very numerous false positives: inflammatory syndrome + metabolic syndrome + NAFLD/NASH + alcoholism + hepatic cytolysis → isolated elevated ferritin without elevated ST often points to inflammatory syndrome or fatty liver rather than HH → recommended diagnostic algorithm (EASL 2010 + CASL 2018 + SCC): step 1: fasting ST + ferritin + CBC + liver workup → if ST ≥45 % → step 2: HFE genotyping (C282Y + H63D) → if C282Y/C282Y or C282Y/H63D → complete workup + treatment decision → if non-HFE and ST elevated → liver MRI + liver biopsy if indication → other biochemical markers of martial workup: serum iron (normal 10-28 µmol/L) + CTLF (total iron binding capacity → normal 45-80 µmol/L → decreases in overload) + saturation coefficient = serum iron / CTLF × 100 → glycosylated ferritin (used in some centers - glycosylated fraction <20 % → iron overload; normal ≥50 %) → erythrocyte zinc protoporphyrin (ZPP): increases in iron deficiency → normal in HH (iron available for erythropoiesis) → useful for differentiating HH from martial deficiency in case of doubt; complete hepatogram before treatment: ALT + AST + GGT + total and conjugated bilirubin + PT + albumin + CBC (thrombocytopenia → portal hypertension?) + creatinine + blood glucose + HbA1c + TSH + lipid panel | Interpretation of results in clinical practice - common situations: ST ≥45 % + elevated ferritin + C282Y/C282Y → confirmed HFE hemochromatosis → organ involvement workup → phlebotomy treatment → ST ≥45 % + elevated ferritin + C282Y/H63D → composite heterozygosity → liver MRI to quantify iron → if CHI (hepatic iron concentration) elevated → treatment + ST ≥45 % + normal ferritin + C282Y/C282Y → early stage 1 → annual monitoring + avoidance of aggravating factors + normal ST + elevated ferritin → systemic inflammation or NAFLD/metabolic syndrome much more likely than HH → inflammatory workup (CRP + fibrinogen) + liver workup + insulin resistance index → eliminate secondary cause as a priority + elevated ST + non-C282Y → non-HFE hemochromatosis → liver MRI → biopsy if necessary → genetics (HJV + HAMP + TFR2 + SLC40A1) → referral to internal medicine or hepatology ; indications for liver biopsy in HH (EASL 2010): indications: ferritin >1,000 µg/L + elevated ALT + doubt about cirrhosis → PURPOSE: liver MRI has largely replaced biopsy for iron quantification → biopsy still useful for: assess degree of fibrosis (Metavir) + identify liver comorbidity (NASH + alcohol + HCV) + if non-HFE with inconclusive genetics → Brunt 2008 - American Journal of Gastroenterology: Perls index (Prussian blue staining) + Deugnier score for histological quantification of liver iron |
| Liver MRI - Non-invasive quantification of liver iron R2* — T2* — CHI — FibroScan — biopsy replacement |
Hepatic MRI for iron quantification - non-invasive reference method: physical principle: iron is paramagnetic → disturbs the local magnetic field → shortens T2 and T2* relaxation time → hypointense (black) MRI signal on T2* sequences → quantification: R2* (= 1/T2*) → correlates with hepatic iron concentration (CHI) → reliable, reproducible measurement; sequences and methods used: R2* MRI (FerriScan or equivalent): reference method → CHI calculated in mg Fe/g dry liver → normal: 7 mg Fe/g → correlates with ferritinemia but more precise (not influenced by inflammation) → Gandon 2004 - Lancet : validation of R2 MRI* vs liver biopsy → excellent correlation (r = 0.93) → R2 MRI (Ferriscan method - FerriScan SA): FDA cleared + Health Canada → used as reference in clinical trial protocols + splenic and pancreatic involvement: iron accumulates in the liver and pancreas in HH but NOT in the spleen (the spleen accumulates iron in diseases with macrophagic overload - thalassemia + transfusions → in HH: absence of splenic overload is a distinctive sign of primary vs. secondary overload by transfusion); indication for liver MRI in HH: if C282Y/C282Y or C282Y/H63D + ferritin >300 µg/L in men or >200 µg/L in women → quantify CHI + assess fibrosis + rule out HCC → if ferritin <300 µg/L → MRI not essential → start phlebotomies directly → if non-HFE genotype with confirmed overload → MRI essential to distinguish: non-HFE HH + secondary transfusion overload (splenic + medullary involvement) + metabolic syndrome (moderate overload + steatosis); hepatic elastography (FibroScan) in HH: measures hepatic stiffness in kPa → assesses fibrosis → BUT: iron overload itself increases stiffness → usual FibroScan thresholds less reliable if CHI very high → interpret with caution → maximum value under treatment (after iron depletion) more reliable for assessing residual fibrosis | HCC screening in hemochromatosis - risk and surveillance: HCC risk in HH: Kowdley 2005 - Gastroenterology: C282Y/C282Y cirrhotics → HCC in 30 % over 10 years → risk ×20-200 × general non-cirrhotic population → HCC in HH occurs almost exclusively in cirrhotics → iron depletion prior to cirrhosis reduces risk → HCC risk persists after depletion if cirrhosis is established → HCC screening recommended (EASL + AASLD + SCC): in all cirrhotic HH → abdominal ultrasound + AFP → every 6 months → even if ferritin normalized by phlebotomies + if non-cirrhotic + normalized ferritin + C282Y/C282Y → very low HCC risk → less intensive monitoring + HCC aggravating factors on HH: alcohol + HCV + HBV + steatosis + diabetes → treat simultaneously; cardiac repercussions - initial assessment: ECG (rhythm disorders + BAV) + transthoracic echocardiography: LVEF + diastole + dilated cardiomyopathy → if severe cardiac involvement → cardiac MRI: quantification of myocardial iron → cardiac T2* <20 ms → significant cardiac overload → priority treatment (risk of sudden death) → in HH type 1: cardiac involvement less severe than in juvenile hemochromatoses type 2 + endocrine repercussions: hormone assessment if symptoms: testosterone + LH + FSH + TSH + basal cortisol → replacement therapy if hypogonadism + osteoporosis (DXA) + arthropathy: hand X-rays (chondrocalcinosis + MCP 2-3 joint pinching) |
| Therapeutic phlebotomy — standard treatment Phlebotomy — 450 mL = 200–250 mg Fe — induction phase — maintenance phase — targets — monitoring |
Principle and rationale of phlebotomies: each 450 mL bloodletting removes 200-250 mg of iron (contained in RBCs) → production of new RBCs mobilizes iron from hepatic reserves and macrophages → progressive depletion of iron reserves → 1 phlebotomy/week → depletion of 1-2 g Fe/month → for a patient with 20-30 g excess iron reserves → duration of induction phase: 2-3 years → protective mechanism: reduction in hepatic oxidative stress → slowing or regression of fibrosis → reduced risk of HCC → improvement in cardiomyopathy and diabetes if not irreversible; induction phase (depletion): weekly 450 mL phlebotomies → monitoring: ferritin every 4-6 bleeds → CBC before each phlebotomy (hemoglobin ≥11-12 g/dL before each bleed) → end-of-induction goal: ferritin ≤50 µg/L (some centers aim for ≤20-30 µg/L) → transferrin saturation <45 % → variable duration depending on initial reserves: ferritin 500 µg/L → ~6-12 months + ferritin 3,000 µg/L → ~2-4 years → Brissot 2011 - European Journal of Gastroenterology and Hepatology: reversibility of lesions under phlebotomy: fibrosis (early stages) → improvement or regression + cardiomyopathy → often reversible if not advanced + diabetes → partial improvement + arthropathy → LITTLE reversible (least improved by treatment) + melanoderma → slow improvement + hypogonadism → partially reversible + CHC → reduced risk if cirrhosis prevented; maintenance phase: once ferritin ≤50 µg/L → reduce phlebotomy frequency → 4-6 times/year → often 1 phlebotomy every 2-3 months → for life (disease is genetic + absorption remains excessive) → maintenance monitoring: ferritin + CBC + ST → every 3 months for the first year → then semi-annually → maintenance ferritin target: 50-100 µg/L (some guides: 50-150 µg/L) → do not aim for martial deficiency (ferritin <12 µg/L) → risk of anemia + tolerance of phlebotomies: generally excellent → rare side effects: mild post-phlebotomy fatigue + lipothymia → prevent with hydration before and after + in some centers → therapeutic blood donation: phlebotomies can be performed in blood banks (Héma-Québec) → blood can be used for transfusion under certain conditions («autologous» blood or pool according to local rules) | Evidence on the efficacy of phlebotomies and prognosis under treatment: Niederau 1996 - NEJM: cohort of 251 patients with HH treated with phlebotomies × 14 years → normal survival in non-cirrhotic, non-diabetic patients treated before complications → reduced survival in cirrhotics → conclusion: early treatment before cirrhosis = excellent prognosis + Falize 2006 - Gastroenterology: phlebotomies → histological improvement of fibrosis in 30 % of early cirrhotics → no improvement in advanced cirrhosis → Adams 2010 - Journal of Hepatology: iron depletion → 59 % reduction in HCC risk vs. untreated patients in an Australian cohort + Beaton 2019 - Hepatology Communications: phlebotomies → improvement in liver stiffness (FibroScan) over 2 years; HCC on hemochromatosis - management: monitoring of HH cirrhotics → if HCC detected at early stage (BCLC 0-A) → surgical resection or radiofrequency ablation → liver transplantation if decompensated cirrhosis ± HCC → transplantation definitively corrects iron overload (transplanted liver produces normal hepcidin) → monitor recurrent post-transplant hyperferritinemia if C282Y/C282Y recipient + wild-type donor; contraindications or difficulties with phlebotomies: severe anemia (<10 g/dL) + decompensated cardiomyopathy → alternative erythrocytapheresis (removes RBCs without plasma loss → more effective per session) + iron chelators (IV deferoxamine or PO deferasirox): reserved for patients intolerant of phlebotomy → less effective than phlebotomy → high cost → side effects (deferasirox nephrotoxicity + deferoxamine ocular/auditory toxicity) → treatment of comorbidities: total alcohol abstinence (potentiates fibrosis + HCC) + treatment of diabetes + treatment of hypogonadism (TRT if indicated) + management of arthropathy (NSAIDs + infiltrations + orthopedic surgery if severe) + vitamin C supplementation not recommended at high doses (vitamin C mobilizes iron from deposits → risk of abrupt release of unbound iron → acute oxidative stress → arrhythmias) → dietary advice: avoid iron supplements → avoid excess red meat → alcohol: total abstinence if liver damage → avoid vitamin C supplements → strong tea: natural iron chelator (tannins) → may slightly reduce absorption → no strict diet but avoid excesses |
| Differential diagnosis - non-HH hyperferritinemia and secondary forms NAFLD — alcohol — inflammation — transfusions — aceruloplasminemia — African iron overload |
Hyperferritinemia - non-genetic causes (most frequent in practice): inflammatory syndrome (ferritin = acute phase reagent): CRP elevated + fibrinogen + ferritin elevated + ST normal → do not genotype if CRP very high → wait for resolution of inflammation + metabolic syndrome and NAFLD/NASH: most frequent cause of hyperferritinemia in clinical practice → abdominal obesity + insulin resistance + hepatic steatosis → elevated ferritin (up to 1,000-2,000 µg/L) + normal or moderately elevated ST (25-40 %) → non-HFE → treatment: weight loss + exercise + treatment of T2DM → ferritin decreases without phlebotomy → Bacon 2011 - Gastroenterology: NAFLD + elevated ferritin → accelerated hepatic fibrolysis but moderate intrahepatic iron → no HH → chronic alcoholism: hepatic cytolysis → release of cellular ferritin + stimulation of synthesis by ethanol → ferritin up to 5,000-10,000 µg/L + ST often elevated by hepatocyte damage → distinguish from HH → HFE genotyping + abstinence 3-6 months → reassessment → hemolysis and intravascular hemolysis: hemolysis → hemoglobin release → catabolism → iron + ferritin → hemolytic anemia + elevated LDH + collapsed haptoglobin + bilirubin + acute hepatic cytolysis (fulminant hepatitis + hepatic ischemia): massive release of ferritin → ferritin >50,000-100,000 µg/L → diagnosis evident in clinical picture + multiple transfusions: transfusional hemosiderosis → iron in splenic + hepatic macrophages → MRI: splenic + hepatic overload + no HFE mutation + aceruleoplasminemia (very rare): CPL mutation → absence of ceruloplasmin → defect in Fe²⁺ oxidation → intracellular accumulation → very high ferritin + low ceruloplasmin + microcytic anemia + neurological involvement → MRI: iron in basal ganglia + cerebellum + liver + pancreas + hyperferritinemia-cataract syndrome (HHCS): mutation of the IRE gene of the L-ferritin gene → no iron overload → ferritin elevated in serum BUT normal in tissues → normal ST → early bilateral cataract → no martial therapy required → important: do not treat hyperferritinemia of inflammatory or metabolic origin with phlebotomies. | Non-HFE forms - rare genetic hemochromatoses: juvenile hemochromatosis (type 2A - HJV + type 2B - HAMP) : severe overload before age 30 → cardiomyopathy + arrhythmias + severe hypogonadism + early cirrhosis → non-HFE genotype + T2* cardiac MRI + complete hormonal workup → intensive phlebotomies (2-3/week initially) + if severe cardiomyopathy → emergency IV deferoxamine + hemochromatosis type 3 (TFR2): similar to type 1 but often more severe + hemochromatosis type 4 (SLC40A1 - ferroportin disease): type 4A: accumulation in macrophages + high ferritin + normal ST + anemia on phlebotomies (poor tolerance) → type 4B: similar to type 1 → hepcidin resistance + iron accumulation disease in macrophages (Type 4A): phlebotomies are more difficult (rapid anemia) → less frequent bleeding; heminoplasmin and new treatments under evaluation for severe non-HFE forms: minihepcidin (peptide analogues of hepcidin): in phase 2 → reduce iron absorption → potential in refractory juvenile hemochromatosis + matriptase 2 inhibitors (TMPRSS6): increase endogenous hepcidin production → clinical trials underway + siRNAs targeting ferroportin: in development → no approved treatment yet beyond phlebotomy and chelation therapy in severe forms |
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Fasting transferrin saturation is the first marker to rise in hereditary hemochromatosis: A repeated fasting transferrin saturation (TSAT) of ≥45% %, in the absence of acute inflammation, should trigger HFE genotyping. Ferritin alone, often elevated for inflammatory or metabolic reasons, is not sufficient for diagnosis. If genotyping confirms C282Y/C282Y, phlebotomy should be started even in an asymptomatic patient, as early treatment before cirrhosis reduces mortality to that of the general population.
Situations requiring urgent medical assessment
Acute heart failure + severe arrhythmias (rapid AFib + complete AV block) in a man under 40 with no known heart disease + very high ferritin Juvenile hemochromatosis type 2 or HFE hemochromatosis with advanced cardiomyopathy → Urgent hospitalization → Emergency cardiac MRI (cardiac T2*) → IV deferoxamine if T2* <10 ms → Delayed phlebotomies until cardiac stabilization → Heart transplantation as a last resort.
Discovery of a liver nodule ≥1 cm on surveillance ultrasound in a known cirrhotic with HH → Suspected HCC → Emergency hepatic MRI with gadolinium contrast (wash-in + wash-out) → if HCC confirmed BCLC 0–A → multidisciplinary discussion (resection + ablation + transplantation) → do not delay characterization imaging.
Ferritin >5,000 µg/L + ST >70 % + severe hepatic cytolysis (ALT >10x normal) + decreased TP + elevated bilirubin + confusion → acute liver failure due to severe iron overload or decompensated HH cirrhosis → urgent hospitalization → liver failure assessment + transplant center contact + treatment of encephalopathy + absolute abstinence from alcohol + evaluation for liver transplant indication (MELD ≥15–20).
Siblings of a C282Y/C282Y proposer with detected TS ≥60 % + asymptomatic ferritin 3000 µg/L → Unexplained advanced overload → Not an immediate life-threatening emergency, but rapid evaluation by hepatology → Hepatic MRI (iron overload + fibrosis) + organ evaluation → Start phlebotomies without delay → The earlier the management, the more reversible the lesions are.
Consult at Clinique Omicron
Clinique Omicron physicians prescribe and interpret the complete iron panel — transferrin saturation, ferritin — for the screening and monitoring of hereditary hemochromatosis, coordinate HFE genotyping, manage the initial treatment and follow-up of therapeutic phlebotomies, and refer patients to hepatology or internal medicine for complex cases or those with significant organ damage. Consultations are available at several service points in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for informational purposes only and does not substitute for medical advice from a physician or hepatologist. Any persistent hyperferritinemia or elevated transferrin saturation requires a comprehensive medical evaluation to determine the cause before considering treatment.
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