Materiały źródłowe

• #1 Prognostic factors and survival in patients with hereditary hemochromatosis and cirrhosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2659901/

  The survival of treated, noncirrhotic patients with hereditary hemochromatosis is similar to that of the general population. Less is known about the outcome of cirrhotic hereditary hemochromatosis patients. The present study evaluated the survival of patients with hereditary hemochromatosis and cirrhosis. […] Cumulative survival for all patients was 88% at one year, 69% at five years and 56% at 20 years. Factors associated with death on multivariate analysis included advanced Child-Pugh score and hepatocellular carcinoma. […] Patients with hereditary hemochromatosis and cirrhosis are at significant risk of developing hepatocellular carcinoma. These patients are older when diagnosed with carcinoma and may have poorer survival following transplantation than patients with other causes of liver disease. Early diagnosis and treatment of hereditary hemochromatosis by preventing the development of cirrhosis may reduce the incidence of hepatocellular carcinoma in the future.

• #1 HFE-Related Hemochromatosis – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1440/

  Prognosis. Individuals diagnosed and treated prior to the development of cirrhosis have a normal life expectancy. Those diagnosed after the development of cirrhosis have a decreased life expectancy even with iron depletion therapy, primarily due to the 10%-30% risk of primary liver cancer (e.g., hepatocellular carcinoma, cholangiocarcinoma). Failure to deplete iron stores after 18 months of treatment is a poor prognostic sign that reflects iron overload severity in most individuals and insufficient phlebotomy therapy in other individuals. With iron depletion, dysfunction of some organs (liver and heart) can improve. Arthropathy and endocrinopathy improve in ~20% of treated individuals. Death in individuals with clinical HFE HC is often caused by liver failure, primary liver cancer, extrahepatic cancers, congestive heart failure, or arrhythmia.

• #1 Correlation of genotype and phenotype in 32 patients with hereditary hemochromatosis in China | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-02020-y

  Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%) […] Cases with type 2A HH have an earlier age at diagnosis (p=0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p=0.01). […] None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p=0.011), cardiac involvement (p=0.042), diabetes (p=0.035) and hypogonadism (p=0.020) was statistically significant in the four groups. […] This study suggested variants in non-HFE genes were the main pathogenic genes in Chinese HH patients. Cases with HJV-related HH had an earlier age at diagnosis and the more severe iron load, whereas more cases with SLC40A1 HH had cirrhosis and diabetes. SUGP2 and DENND3 were likely pathogenic variants for HH in China.

• #1 Prognostic factors and survival in patients with hereditary hemochromatosis and cirrhosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2659901/

  The presence of hepatocellular carcinoma and Child-Pugh score were found to be associated with shorter survival duration. […] The survival curve of 76 nonhepatocellular carcinoma patients was compared with 19 hepatocellular carcinoma-affected patients. The rate of survival was lower in patients with hepatocellular carcinoma. […] Hepatocellular carcinoma occurs in approximately 20% of hemochromatosis patients with cirrhosis and is one of the most common causes of death.

• #1 Epidemiology, Clinical Spectrum and Prognosis of Hemochromatosis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4615-2554-7_31

  Prognosis: Survival analysis in the 251 patients showed that in the absence of cirrhosis and diabetes iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. […] However, patients with massive and long-lasting iron overload had a worse prognosis than patients with less severe iron excess. […] During a mean followup of 13.4 years 69 deaths occurred in the 251 patients. In 19 patients death was due to liver cancer, in 14 due to liver cirrhosis, in 5 due to cardiomyopathy, and in 3 due to diabetes mellitus (all causes significantly more frequent than expected for the general population). […] All liver cancers were seen in cirrhotic livers, but often occurred many years or even decades after complete iron removal. Further strategies have to evaluate the design of screening programs in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• #1

  https://www.nhs.uk/conditions/haemochromatosis/

  If the condition is diagnosed and treated early on, haemochromatosis does not affect life expectancy and is unlikely to result in serious problems. […] But if it’s not found until it’s more advanced, the high iron levels can damage parts of the body. […] This can lead to potentially serious complications, such as liver problems including scarring of the liver (cirrhosis) or liver cancer.

• #1 EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH) | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2015128

  Data from controlled and uncontrolled family studies demonstrate that the majority of p.C282Y homozygotes detected by screening of first-degree relatives of homozygous patients have elevated iron parameters more commonly in men than in women. […] Data from uncontrolled family studies indicate that morbidity in p.C282Y homozygous family members of HH patients is considerable, with up to 42% of them having fibrosis or cirrhosis. […] It is recognized that early treatment to normalize iron stores increases the likelihood that the potential serious complications of the disease are effectively prevented, morbidity and mortality are reduced, and quality of life is increased. […] Moreover, it was recently shown in a cohort of 1086 p.C282Y homozygous patients treated at early stages that they have a long-term survival superior to the general population, with a decreased number of deaths by cardiovascular disease or extra-hepatic cancer, further supporting the benefit of sustained phlebotomy treatment of iron overload in HH.

• #1 EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH) | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2015128

  Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. […] The diseases penetrance is low, affecting predominantly males between 40 and 60 years of age. Despite the remarkable genetic homogeneity of HFE-related HH, the clinical expression is variable, and 75-85% of p.C282Y homozygous individuals do not develop the disease. […] This low penetrance of the genotype emphasizes the need to better define genetic modifiers and environmental factors which contribute to iron overload and to severe clinical expression in these individuals. […] Epidemiology, clinical diagnosis, management and treatment of HH was recently reviewed and discussed in several published practice guidelines and reports.

• #1 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #2 HFE-Related Hemochromatosis – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1440/

  Prognosis. Individuals diagnosed and treated prior to the development of cirrhosis have a normal life expectancy. Those diagnosed after the development of cirrhosis have a decreased life expectancy even with iron depletion therapy, primarily due to the 10%-30% risk of primary liver cancer (e.g., hepatocellular carcinoma, cholangiocarcinoma). Failure to deplete iron stores after 18 months of treatment is a poor prognostic sign that reflects iron overload severity in most individuals and insufficient phlebotomy therapy in other individuals. With iron depletion, dysfunction of some organs (liver and heart) can improve. Arthropathy and endocrinopathy improve in ~20% of treated individuals. Death in individuals with clinical HFE HC is often caused by liver failure, primary liver cancer, extrahepatic cancers, congestive heart failure, or arrhythmia.

• #2 Epidemiology, Clinical Spectrum and Prognosis of Hemochromatosis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4615-2554-7_31

  Prognosis: Survival analysis in the 251 patients showed that in the absence of cirrhosis and diabetes iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. […] However, patients with massive and long-lasting iron overload had a worse prognosis than patients with less severe iron excess. […] During a mean followup of 13.4 years 69 deaths occurred in the 251 patients. In 19 patients death was due to liver cancer, in 14 due to liver cirrhosis, in 5 due to cardiomyopathy, and in 3 due to diabetes mellitus (all causes significantly more frequent than expected for the general population). […] All liver cancers were seen in cirrhotic livers, but often occurred many years or even decades after complete iron removal. Further strategies have to evaluate the design of screening programs in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• #2 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #2 Prognostic factors and survival in patients with hereditary hemochromatosis and cirrhosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2659901/

  The presence of hepatocellular carcinoma and Child-Pugh score were found to be associated with shorter survival duration. […] The survival curve of 76 nonhepatocellular carcinoma patients was compared with 19 hepatocellular carcinoma-affected patients. The rate of survival was lower in patients with hepatocellular carcinoma. […] Hepatocellular carcinoma occurs in approximately 20% of hemochromatosis patients with cirrhosis and is one of the most common causes of death.

• #2 Correlation of genotype and phenotype in 32 patients with hereditary hemochromatosis in China | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-02020-y

  Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%) […] Cases with type 2A HH have an earlier age at diagnosis (p=0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p=0.01). […] None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p=0.011), cardiac involvement (p=0.042), diabetes (p=0.035) and hypogonadism (p=0.020) was statistically significant in the four groups. […] This study suggested variants in non-HFE genes were the main pathogenic genes in Chinese HH patients. Cases with HJV-related HH had an earlier age at diagnosis and the more severe iron load, whereas more cases with SLC40A1 HH had cirrhosis and diabetes. SUGP2 and DENND3 were likely pathogenic variants for HH in China.

• #2 An efficient machine learning-based approach for screening individuals at risk of hereditary haemochromatosis | Scientific Reports

  https://www.nature.com/articles/s41598-020-77367-6

  Hereditary haemochromatosis (HH) is an autosomal recessive disease, where HFE C282Y homozygosity accounts for 80-85% of clinical cases among the Caucasian population. HH is characterised by the accumulation of iron, which, if untreated, can lead to the development of liver cirrhosis and liver cancer. […] These complications can be prevented by phlebotomy therapy if diagnosis is made before any organ damage occurs. Thus, it is of utmost importance to identify individuals at risk of iron overload in order to maximise on early prevention and/or early intervention measures, reduce treatment costs and improve HH individuals life expectancy. […] Current approaches employed to assess HH risk or HFE C282Y homozygosity are very simplistic and utilise methods such as Cox or logistic regression analysis. Even though they have shown promising results, more robust and accurate risk prediction models are necessary.

• #2 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  The outlook for hemochromatosis depends on the timing of diagnosis and treatment. If not caught and addressed early, severe hemochromatosis can cause serious problems. These complications can include organ damage and possible death. […] But hemochromatosis is also a manageable disease. With early detection and treatment, you can survive and live a normal, healthy life. Sometimes organ damage can even be reversed.

• #2 EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH) | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2015128

  Data from controlled and uncontrolled family studies demonstrate that the majority of p.C282Y homozygotes detected by screening of first-degree relatives of homozygous patients have elevated iron parameters more commonly in men than in women. […] Data from uncontrolled family studies indicate that morbidity in p.C282Y homozygous family members of HH patients is considerable, with up to 42% of them having fibrosis or cirrhosis. […] It is recognized that early treatment to normalize iron stores increases the likelihood that the potential serious complications of the disease are effectively prevented, morbidity and mortality are reduced, and quality of life is increased. […] Moreover, it was recently shown in a cohort of 1086 p.C282Y homozygous patients treated at early stages that they have a long-term survival superior to the general population, with a decreased number of deaths by cardiovascular disease or extra-hepatic cancer, further supporting the benefit of sustained phlebotomy treatment of iron overload in HH.

• #2 EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH) | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2015128

  Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. […] The diseases penetrance is low, affecting predominantly males between 40 and 60 years of age. Despite the remarkable genetic homogeneity of HFE-related HH, the clinical expression is variable, and 75-85% of p.C282Y homozygous individuals do not develop the disease. […] This low penetrance of the genotype emphasizes the need to better define genetic modifiers and environmental factors which contribute to iron overload and to severe clinical expression in these individuals. […] Epidemiology, clinical diagnosis, management and treatment of HH was recently reviewed and discussed in several published practice guidelines and reports.

• #3 EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH) | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2015128

  Data from controlled and uncontrolled family studies demonstrate that the majority of p.C282Y homozygotes detected by screening of first-degree relatives of homozygous patients have elevated iron parameters more commonly in men than in women. […] Data from uncontrolled family studies indicate that morbidity in p.C282Y homozygous family members of HH patients is considerable, with up to 42% of them having fibrosis or cirrhosis. […] It is recognized that early treatment to normalize iron stores increases the likelihood that the potential serious complications of the disease are effectively prevented, morbidity and mortality are reduced, and quality of life is increased. […] Moreover, it was recently shown in a cohort of 1086 p.C282Y homozygous patients treated at early stages that they have a long-term survival superior to the general population, with a decreased number of deaths by cardiovascular disease or extra-hepatic cancer, further supporting the benefit of sustained phlebotomy treatment of iron overload in HH.

• #3 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #3 Correlation of genotype and phenotype in 32 patients with hereditary hemochromatosis in China | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-02020-y

  Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%) […] Cases with type 2A HH have an earlier age at diagnosis (p=0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p=0.01). […] None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p=0.011), cardiac involvement (p=0.042), diabetes (p=0.035) and hypogonadism (p=0.020) was statistically significant in the four groups. […] This study suggested variants in non-HFE genes were the main pathogenic genes in Chinese HH patients. Cases with HJV-related HH had an earlier age at diagnosis and the more severe iron load, whereas more cases with SLC40A1 HH had cirrhosis and diabetes. SUGP2 and DENND3 were likely pathogenic variants for HH in China.

• #3 Epidemiology, Clinical Spectrum and Prognosis of Hemochromatosis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4615-2554-7_31

  Prognosis: Survival analysis in the 251 patients showed that in the absence of cirrhosis and diabetes iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. […] However, patients with massive and long-lasting iron overload had a worse prognosis than patients with less severe iron excess. […] During a mean followup of 13.4 years 69 deaths occurred in the 251 patients. In 19 patients death was due to liver cancer, in 14 due to liver cirrhosis, in 5 due to cardiomyopathy, and in 3 due to diabetes mellitus (all causes significantly more frequent than expected for the general population). […] All liver cancers were seen in cirrhotic livers, but often occurred many years or even decades after complete iron removal. Further strategies have to evaluate the design of screening programs in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• #3 HFE-Related Hemochromatosis – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1440/

  Prognosis. Individuals diagnosed and treated prior to the development of cirrhosis have a normal life expectancy. Those diagnosed after the development of cirrhosis have a decreased life expectancy even with iron depletion therapy, primarily due to the 10%-30% risk of primary liver cancer (e.g., hepatocellular carcinoma, cholangiocarcinoma). Failure to deplete iron stores after 18 months of treatment is a poor prognostic sign that reflects iron overload severity in most individuals and insufficient phlebotomy therapy in other individuals. With iron depletion, dysfunction of some organs (liver and heart) can improve. Arthropathy and endocrinopathy improve in ~20% of treated individuals. Death in individuals with clinical HFE HC is often caused by liver failure, primary liver cancer, extrahepatic cancers, congestive heart failure, or arrhythmia.

• #3 An efficient machine learning-based approach for screening individuals at risk of hereditary haemochromatosis | Scientific Reports

  https://www.nature.com/articles/s41598-020-77367-6

  Hereditary haemochromatosis (HH) is an autosomal recessive disease, where HFE C282Y homozygosity accounts for 80-85% of clinical cases among the Caucasian population. HH is characterised by the accumulation of iron, which, if untreated, can lead to the development of liver cirrhosis and liver cancer. […] These complications can be prevented by phlebotomy therapy if diagnosis is made before any organ damage occurs. Thus, it is of utmost importance to identify individuals at risk of iron overload in order to maximise on early prevention and/or early intervention measures, reduce treatment costs and improve HH individuals life expectancy. […] Current approaches employed to assess HH risk or HFE C282Y homozygosity are very simplistic and utilise methods such as Cox or logistic regression analysis. Even though they have shown promising results, more robust and accurate risk prediction models are necessary.

• #3 EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH) | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2015128

  The question remains, however, as to whether preventive treatment should or not be recommended to all unaffected but genetically confirmed individuals because there is no evidence that all of these subjects will necessarily develop iron overload-related morbidity. […] In conclusion, there is enough evidence to support the notion that iron indices may progress in some p.C282Y homozygotes or p.C282Y/p.H63D heterozygotes, supporting the recommendation for a biochemical follow-up. There is no evidence, however, to support a specific follow-up time or schedule.

• #3

  https://www.nhs.uk/conditions/haemochromatosis/

  If the condition is diagnosed and treated early on, haemochromatosis does not affect life expectancy and is unlikely to result in serious problems. […] But if it’s not found until it’s more advanced, the high iron levels can damage parts of the body. […] This can lead to potentially serious complications, such as liver problems including scarring of the liver (cirrhosis) or liver cancer.

• #4 Prognostic factors and survival in patients with hereditary hemochromatosis and cirrhosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2659901/

  The survival of treated, noncirrhotic patients with hereditary hemochromatosis is similar to that of the general population. Less is known about the outcome of cirrhotic hereditary hemochromatosis patients. The present study evaluated the survival of patients with hereditary hemochromatosis and cirrhosis. […] Cumulative survival for all patients was 88% at one year, 69% at five years and 56% at 20 years. Factors associated with death on multivariate analysis included advanced Child-Pugh score and hepatocellular carcinoma. […] Patients with hereditary hemochromatosis and cirrhosis are at significant risk of developing hepatocellular carcinoma. These patients are older when diagnosed with carcinoma and may have poorer survival following transplantation than patients with other causes of liver disease. Early diagnosis and treatment of hereditary hemochromatosis by preventing the development of cirrhosis may reduce the incidence of hepatocellular carcinoma in the future.

• #4 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #4 Correlation of genotype and phenotype in 32 patients with hereditary hemochromatosis in China | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-02020-y

  Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%) […] Cases with type 2A HH have an earlier age at diagnosis (p=0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p=0.01). […] None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p=0.011), cardiac involvement (p=0.042), diabetes (p=0.035) and hypogonadism (p=0.020) was statistically significant in the four groups. […] This study suggested variants in non-HFE genes were the main pathogenic genes in Chinese HH patients. Cases with HJV-related HH had an earlier age at diagnosis and the more severe iron load, whereas more cases with SLC40A1 HH had cirrhosis and diabetes. SUGP2 and DENND3 were likely pathogenic variants for HH in China.

• #4 Epidemiology, Clinical Spectrum and Prognosis of Hemochromatosis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4615-2554-7_31

  Prognosis: Survival analysis in the 251 patients showed that in the absence of cirrhosis and diabetes iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. […] However, patients with massive and long-lasting iron overload had a worse prognosis than patients with less severe iron excess. […] During a mean followup of 13.4 years 69 deaths occurred in the 251 patients. In 19 patients death was due to liver cancer, in 14 due to liver cirrhosis, in 5 due to cardiomyopathy, and in 3 due to diabetes mellitus (all causes significantly more frequent than expected for the general population). […] All liver cancers were seen in cirrhotic livers, but often occurred many years or even decades after complete iron removal. Further strategies have to evaluate the design of screening programs in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• #4 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  The outlook for hemochromatosis depends on the timing of diagnosis and treatment. If not caught and addressed early, severe hemochromatosis can cause serious problems. These complications can include organ damage and possible death. […] But hemochromatosis is also a manageable disease. With early detection and treatment, you can survive and live a normal, healthy life. Sometimes organ damage can even be reversed.

• #4 An efficient machine learning-based approach for screening individuals at risk of hereditary haemochromatosis | Scientific Reports

  https://www.nature.com/articles/s41598-020-77367-6

  In this study we aim to develop a new risk stratification model for HH based on the family study data from the HEIRS cohort, and will investigate the following hypotheses: (1) the integration of family health history, demographic, clinical and genomic data should improve the accuracy of risk assessment models, (2) ML models enable the integration of large scale heterogeneous data and the extraction of valuable knowledge, thereby improving the performance of predictive models. […] The best found model was benchmarked against the IRON score using two approaches and we demonstrated that our risk score model (AUCROC=0.94±0.02) outperforms it. […] To conclude, the HH screening model proposed in this work has a higher performance when compared to the IRON score.

• #4 EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH) | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2015128

  The question remains, however, as to whether preventive treatment should or not be recommended to all unaffected but genetically confirmed individuals because there is no evidence that all of these subjects will necessarily develop iron overload-related morbidity. […] In conclusion, there is enough evidence to support the notion that iron indices may progress in some p.C282Y homozygotes or p.C282Y/p.H63D heterozygotes, supporting the recommendation for a biochemical follow-up. There is no evidence, however, to support a specific follow-up time or schedule.

• #5 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #6 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #7 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #8 Epidemiology, Clinical Spectrum and Prognosis of Hemochromatosis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4615-2554-7_31

  Prognosis: Survival analysis in the 251 patients showed that in the absence of cirrhosis and diabetes iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. […] However, patients with massive and long-lasting iron overload had a worse prognosis than patients with less severe iron excess. […] During a mean followup of 13.4 years 69 deaths occurred in the 251 patients. In 19 patients death was due to liver cancer, in 14 due to liver cirrhosis, in 5 due to cardiomyopathy, and in 3 due to diabetes mellitus (all causes significantly more frequent than expected for the general population). […] All liver cancers were seen in cirrhotic livers, but often occurred many years or even decades after complete iron removal. Further strategies have to evaluate the design of screening programs in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• #8 Hereditary Hemochromatosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0900/p263.html

  Patients with the clinical hereditary hemochromatosis phenotype have been shown to have higher in-hospital mortality (relative risk = 2.45; 95% CI, 2.27 to 2.64; 857 deaths) and out-of-hospital mortality (relative risk = 1.15; 95% CI, 1.00 to 1.33; 216 deaths) compared with control groups. […] The presence of cirrhosis or a ferritin level greater than 2,000 ng per mL (2,000 mcg per L) at the time of diagnosis or in treated patients is associated with higher mortality, mostly liver-related deaths (standardized mortality ratio = 23.9; 95% Cl, 13.9 to 38.2). […] Increased age, diabetes, alcohol consumption, and hepatic fibrosis are independent prognostic factors for death. […] One study suggested that 20% of patients with hereditary hemochromatosis and cirrhosis will develop hepatocellular carcinoma. […] Patients with diabetes have a twofold to sixfold increased risk of premature death if they have increased transferrin saturation or the HFE genotype.

• #9 HFE-Related Hemochromatosis – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1440/

  Prognosis. Individuals diagnosed and treated prior to the development of cirrhosis have a normal life expectancy. Those diagnosed after the development of cirrhosis have a decreased life expectancy even with iron depletion therapy, primarily due to the 10%-30% risk of primary liver cancer (e.g., hepatocellular carcinoma, cholangiocarcinoma). Failure to deplete iron stores after 18 months of treatment is a poor prognostic sign that reflects iron overload severity in most individuals and insufficient phlebotomy therapy in other individuals. With iron depletion, dysfunction of some organs (liver and heart) can improve. Arthropathy and endocrinopathy improve in ~20% of treated individuals. Death in individuals with clinical HFE HC is often caused by liver failure, primary liver cancer, extrahepatic cancers, congestive heart failure, or arrhythmia.

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