Zespół gilberta – Rokowania, prognozy i postęp choroby

Zespół gilberta
Rokowania, prognozy i postęp choroby

Zespół Gilberta to łagodne, dziedziczne zaburzenie charakteryzujące się niekonjugowaną hiperbilirubinemią, najczęściej związane z wariantem UGT1A1*28. Rokowanie jest doskonałe, a pacjenci zwykle prowadzą zdrowe życie bez poważnych powikłań. Istotne jest rozróżnienie zespołu Gilberta od innych chorób wątroby, aby uniknąć błędnej interpretacji podwyższonego poziomu bilirubiny. Epidemiologiczne dane wskazują na niższe wskaźniki śmiertelności, szczególnie z powodu chorób sercowo-naczyniowych, u osób z tym zespołem, co sugeruje potencjalny efekt ochronny. Jednak analizy genetyczne podważają przyczynową rolę bilirubiny w ochronie przed chorobami sercowo-naczyniowymi i innymi schorzeniami, co ogranicza jej znaczenie jako celu terapeutycznego.

Rokowanie w zespole Gilberta

Ogólne rokowanie
Wskaźniki śmiertelności
Ochrona sercowo-naczyniowa – kontrowersje
Długość telomerów i potencjalne implikacje dla długowieczności
Potencjalne ryzyko związane z zespołem Gilberta
Rzadkie powikłania i współwystępowanie z innymi schorzeniami

Podsumowanie rokowań w zespole Gilberta

Kolejne rozdziały

Rokowanie w zespole Gilberta

Zespół Gilberta jest łagodnym, dziedzicznym zaburzeniem charakteryzującym się łagodną hiperbilirubinemią niekonjugowaną, związaną z genetycznymi wariantami w regionie promotora genu UGT1A1, z których UGT1A1*28 jest najbardziej powszechny wśród rasy kaukaskiej¹². Rokowanie w zespole Gilberta jest przedmiotem intensywnych badań naukowych, które wskazują na złożone powiązania między tym stanem a długoterminowym zdrowiem.

Ogólne rokowanie

Ogólne rokowanie dla osób z zespołem Gilberta jest doskonałe. Pacjenci z tym schorzeniem mogą prowadzić długie, zdrowe życie bez doświadczania długoterminowych problemów zdrowotnych wynikających z choroby³. Co więcej, zespół Gilberta jest stanem łagodnym, który nie powoduje poważnych powikłań ani problemów zdrowotnych w dłuższej perspektywie⁴. Istotne znaczenie kliniczne zespołu Gilberta leży w możliwości błędnego zinterpretowania łagodnej hiperbilirubinemii jako objawu choroby wątroby, co podkreśla znaczenie dokładnej diagnozy i edukacji pacjenta⁵.

Wskaźniki śmiertelności

Interesujące jest to, że osoby z zespołem Gilberta mogą charakteryzować się niższymi wskaźnikami śmiertelności w porównaniu do populacji ogólnej. Badania epidemiologiczne wskazują, że osoby z tym zespołem mają wskaźniki śmiertelności prawie o połowę niższe niż osoby bez tego schorzenia, co sugeruje potencjalny efekt ochronny przed śmiertelnością ogólną w populacji ogólnej⁶. Dodatkowo, u osób z zespołem Gilberta zaobserwowano opóźnioną śmiertelność z jakiejkolwiek przyczyny, szczególnie z powodu chorób sercowo-naczyniowych⁷.

Ochrona sercowo-naczyniowa – kontrowersje

Istnieją sprzeczne doniesienia dotyczące potencjalnej roli ochronnej zespołu Gilberta w chorobach sercowo-naczyniowych. Niektóre badania epidemiologiczne wskazują na silny związek między podwyższonym poziomem bilirubiny w surowicy a zmniejszoną częstością występowania chorób sercowo-naczyniowych związanych z wiekiem⁸. Ponadto, badacze zaobserwowali niewielkie zwiększone ryzyko zdarzeń sercowo-naczyniowych w populacji kontrolnej w porównaniu do populacji z zespołem Gilberta⁹.

Jednak nowsze analizy danych genetycznych sugerują, że bilirubina nie ma prawdopodobnie przyczynowej roli w ochronie przed chorobami sercowo-naczyniowymi, przewlekłą obturacyjną chorobą płuc lub innymi kluczowymi wynikami opieki zdrowotnej, a zatem stanowi słaby cel interwencji terapeutycznej dla tych schorzeń¹⁰. Ta rozbieżność w wynikach badań podkreśla potrzebę dalszych badań w celu wyjaśnienia dokładnej roli zespołu Gilberta i poziomu bilirubiny w chorobach sercowo-naczyniowych.

Długość telomerów i potencjalne implikacje dla długowieczności

Interesującym odkryciem jest to, że osoby z fenotypem zespołu Gilberta mają średnio dłuższe telomery w porównaniu do osób dopasowanych pod względem wieku i płci z grupy kontrolnej¹¹. Różnica ta wydaje się być bardziej wyraźna wraz z wiekiem, co sugeruje zmniejszone lub wolniejsze skracanie telomerów w zespole Gilberta¹². Obserwacja ta może stanowić kolejne ogniwo łączące zespół Gilberta, a potencjalnie także niekonjugowaną bilirubinę, z długowiecznością, ze szczególnym naciskiem na zdrowe starzenie się¹³.

Potencjalne ryzyko związane z zespołem Gilberta

Mimo ogólnie dobrego rokowania, nosiciele genotypu homozygotycznego rs887829-T (charakterystycznego dla zespołu Gilberta) mają skromne zwiększenie szans na rozwój patologii dróg żółciowych i łupieżu różowego¹⁴. Należy jednak zauważyć, że tylko 3% uczestników, którzy są homozygotami rs887829-T, ma zdiagnozowany zespół Gilberta w dokumentacji medycznej¹⁵, co sugeruje, że wiele przypadków może pozostawać niezdiagnozowanych lub być klinicznie bezobjawowych.

Rzadkie powikłania i współwystępowanie z innymi schorzeniami

W rzadkich przypadkach, szczególnie gdy zespół Gilberta współwystępuje z innymi schorzeniami, mogą wystąpić poważniejsze komplikacje. Na przykład, w opisanym przypadku chińskiej rodziny, gdzie zespół Gilberta współwystępował z zespołem Dubina-Johnsona (rzadki zespół charakteryzujący się hiperbilirubinemią konjugowaną), u probanda w wieku 50 lat rozwinęły się wysięki opłucnowe i wodobrzusze, pogrubienie osierdzia, rozszerzenie wewnątrzwątrobowych i zewnątrzwątrobowych dróg żółciowych oraz powiększenie pęcherzyka żółciowego¹⁶. U brata probanda wystąpił rak wątrobowokomórkowy w wieku 46 lat¹⁷.

Warto jednak podkreślić, że te powikłania wystąpiły w kontekście podwójnego zespołu (Gilberta i Dubina-Johnsona) oraz innych czynników ryzyka, takich jak kamica żółciowa i nadciśnienie¹⁸. Te przypadki są rzadkie i wymagają dalszych badań w celu potwierdzenia bezpośredniego związku z zespołem Gilberta¹⁹.

Podsumowanie rokowań w zespole Gilberta

Mimo że poziom bilirubiny jest podwyższony u osób z zespołem Gilberta, rokowanie jest doskonałe, bez długoterminowych następstw²⁰. Badania sugerują nawet potencjalny efekt ochronny związany z łagodnie podwyższonym poziomem niekonjugowanej bilirubiny, szczególnie w odniesieniu do długowieczności i zdrowia komórkowego²¹.

Chociaż niektóre dane sugerują związek między zwiększonym poziomem bilirubiny a zmniejszoną częstością występowania chorób metabolicznych i sercowo-naczyniowych związanych z wiekiem²², analizy genetyczne podważają przyczynową rolę bilirubiny w tych potencjalnych korzyściach zdrowotnych²³.

W praktyce klinicznej najważniejszym aspektem jest dokładna diagnoza i edukacja pacjenta, aby uniknąć niepotrzebnych badań i niepokoju związanego z błędnym zinterpretowaniem łagodnej hiperbilirubinemii jako objawu poważniejszej choroby wątroby²⁴.

Kolejne rozdziały

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Materiały źródłowe

#1 Gilbertâs syndrome: The good, the bad and the ugly
https://www.wjgnet.com/1948-5182/full/v17/i2/98503.htm
Gilberts syndrome is a benign hereditary disorder characterized by mild hyperbilirubinemia. […] The prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] In fact, individuals with GS have been reported to have mortality rates that are nearly half those of individuals without the syndrome, suggesting a potential protective effect against all-cause mortality in the general population. […] Despite the presence of elevated bilirubin levels, the prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] The clinical significance of GS lies in the potential for mild hyperbilirubinemia to be mistaken for a sign of liver disease highlighting the importance of accurate diagnosis and patient education.
#2 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Gilberts Syndrome is associated with genetic variations in the UGT1A1 gene promoter region, of which the so-called UGT1A1*28 is the most common among Caucasians. […] Epidemiological studies indicate a strong association between increased serum BR and decreased incidence of age-related metabolic and cardiovascular diseases. […] In addition, individuals with GS have been found to exhibit delayed all-cause mortality, especially that from CVDs. […] Our findings reveal a novel characteristic of Gilberts Syndrome, potentially related to a chronic exposure to moderately increased unconjugated serum bilirubin. We show that individuals with a GS phenotype have on average longer telomeres compared to age- and gender-matched controls. This difference appears to be more pronounced with age, suggesting a reduced or slower telomere attrition in GS.
#3 Gilbert’s Syndrome: Symptoms, Causes, Tests & Treatment
https://my.clevelandclinic.org/health/diseases/17661-gilberts-syndrome
People with Gilbert’s syndrome can lead long, healthy lives. They dont experience long-term health problems from the disease. […] Gilbert’s syndrome is a mild condition. It doesnt cause long-term complications or serious health problems.
#4 Gilbertâs syndrome: The good, the bad and the ugly
https://www.wjgnet.com/1948-5182/full/v17/i2/98503.htm
Gilberts syndrome is a benign hereditary disorder characterized by mild hyperbilirubinemia. […] The prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] In fact, individuals with GS have been reported to have mortality rates that are nearly half those of individuals without the syndrome, suggesting a potential protective effect against all-cause mortality in the general population. […] Despite the presence of elevated bilirubin levels, the prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] The clinical significance of GS lies in the potential for mild hyperbilirubinemia to be mistaken for a sign of liver disease highlighting the importance of accurate diagnosis and patient education.
#5 Gilbertâs syndrome: The good, the bad and the ugly
https://www.wjgnet.com/1948-5182/full/v17/i2/98503.htm
Gilberts syndrome is a benign hereditary disorder characterized by mild hyperbilirubinemia. […] The prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] In fact, individuals with GS have been reported to have mortality rates that are nearly half those of individuals without the syndrome, suggesting a potential protective effect against all-cause mortality in the general population. […] Despite the presence of elevated bilirubin levels, the prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] The clinical significance of GS lies in the potential for mild hyperbilirubinemia to be mistaken for a sign of liver disease highlighting the importance of accurate diagnosis and patient education.
#6 Gilbertâs syndrome: The good, the bad and the ugly
https://www.wjgnet.com/1948-5182/full/v17/i2/98503.htm
Gilberts syndrome is a benign hereditary disorder characterized by mild hyperbilirubinemia. […] The prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] In fact, individuals with GS have been reported to have mortality rates that are nearly half those of individuals without the syndrome, suggesting a potential protective effect against all-cause mortality in the general population. […] Despite the presence of elevated bilirubin levels, the prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] The clinical significance of GS lies in the potential for mild hyperbilirubinemia to be mistaken for a sign of liver disease highlighting the importance of accurate diagnosis and patient education.
#7 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Gilberts Syndrome is associated with genetic variations in the UGT1A1 gene promoter region, of which the so-called UGT1A1*28 is the most common among Caucasians. […] Epidemiological studies indicate a strong association between increased serum BR and decreased incidence of age-related metabolic and cardiovascular diseases. […] In addition, individuals with GS have been found to exhibit delayed all-cause mortality, especially that from CVDs. […] Our findings reveal a novel characteristic of Gilberts Syndrome, potentially related to a chronic exposure to moderately increased unconjugated serum bilirubin. We show that individuals with a GS phenotype have on average longer telomeres compared to age- and gender-matched controls. This difference appears to be more pronounced with age, suggesting a reduced or slower telomere attrition in GS.
#8 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Gilberts Syndrome is associated with genetic variations in the UGT1A1 gene promoter region, of which the so-called UGT1A1*28 is the most common among Caucasians. […] Epidemiological studies indicate a strong association between increased serum BR and decreased incidence of age-related metabolic and cardiovascular diseases. […] In addition, individuals with GS have been found to exhibit delayed all-cause mortality, especially that from CVDs. […] Our findings reveal a novel characteristic of Gilberts Syndrome, potentially related to a chronic exposure to moderately increased unconjugated serum bilirubin. We show that individuals with a GS phenotype have on average longer telomeres compared to age- and gender-matched controls. This difference appears to be more pronounced with age, suggesting a reduced or slower telomere attrition in GS.
#9 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Although it is tempting to propose a strong intracellular immune-modulatory effect of UCB, there is no data on uptake of bilirubin by immune cells in vivo. […] While increased UCB levels are so far the only identified outcome in Gilberts Syndrome, we cannot exclude that UGT1A1 mutations might exhibit other effects on human health. […] The present study aimed to investigate differences between healthy individuals with no history or present indication of a CVD. Even though we could identify a mildly increased risk for cardiovascular events in the control population compared to the GS population, we could not attribute the observed difference to either UCB or telomere length differences. […] In conclusion, we could observe a further link between Gilberts Syndrome, and possibly unconjugated bilirubin, and longevity, with emphasis on healthy aging. This work is important when considering bilirubin as a natural therapeutic in fighting cardio-metabolic diseases, as it emphasizes a long-term benefit on a cellular and molecular level.
#10 Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations | BMJ Medicine
https://bmjmedicine.bmj.com/content/2/1/e000467
Only 3% of participants who are homozygous for rs887829-T have a recorded diagnosis of Gilbert syndrome. […] Carriers of this genotype have modest increases in the odds of developing biliary pathology and pityriasis rosea. […] Evidence from the analyses of genetic data suggests that bilirubin has no likely causal role in protection from cardiovascular disease, chronic obstructive pulmonary disease, or other key healthcare outcomes and therefore represents a poor target for therapeutic intervention for these outcomes.
#11 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Gilberts Syndrome is associated with genetic variations in the UGT1A1 gene promoter region, of which the so-called UGT1A1*28 is the most common among Caucasians. […] Epidemiological studies indicate a strong association between increased serum BR and decreased incidence of age-related metabolic and cardiovascular diseases. […] In addition, individuals with GS have been found to exhibit delayed all-cause mortality, especially that from CVDs. […] Our findings reveal a novel characteristic of Gilberts Syndrome, potentially related to a chronic exposure to moderately increased unconjugated serum bilirubin. We show that individuals with a GS phenotype have on average longer telomeres compared to age- and gender-matched controls. This difference appears to be more pronounced with age, suggesting a reduced or slower telomere attrition in GS.
#12 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Gilberts Syndrome is associated with genetic variations in the UGT1A1 gene promoter region, of which the so-called UGT1A1*28 is the most common among Caucasians. […] Epidemiological studies indicate a strong association between increased serum BR and decreased incidence of age-related metabolic and cardiovascular diseases. […] In addition, individuals with GS have been found to exhibit delayed all-cause mortality, especially that from CVDs. […] Our findings reveal a novel characteristic of Gilberts Syndrome, potentially related to a chronic exposure to moderately increased unconjugated serum bilirubin. We show that individuals with a GS phenotype have on average longer telomeres compared to age- and gender-matched controls. This difference appears to be more pronounced with age, suggesting a reduced or slower telomere attrition in GS.
#13 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Although it is tempting to propose a strong intracellular immune-modulatory effect of UCB, there is no data on uptake of bilirubin by immune cells in vivo. […] While increased UCB levels are so far the only identified outcome in Gilberts Syndrome, we cannot exclude that UGT1A1 mutations might exhibit other effects on human health. […] The present study aimed to investigate differences between healthy individuals with no history or present indication of a CVD. Even though we could identify a mildly increased risk for cardiovascular events in the control population compared to the GS population, we could not attribute the observed difference to either UCB or telomere length differences. […] In conclusion, we could observe a further link between Gilberts Syndrome, and possibly unconjugated bilirubin, and longevity, with emphasis on healthy aging. This work is important when considering bilirubin as a natural therapeutic in fighting cardio-metabolic diseases, as it emphasizes a long-term benefit on a cellular and molecular level.
#14 Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations | BMJ Medicine
https://bmjmedicine.bmj.com/content/2/1/e000467
Only 3% of participants who are homozygous for rs887829-T have a recorded diagnosis of Gilbert syndrome. […] Carriers of this genotype have modest increases in the odds of developing biliary pathology and pityriasis rosea. […] Evidence from the analyses of genetic data suggests that bilirubin has no likely causal role in protection from cardiovascular disease, chronic obstructive pulmonary disease, or other key healthcare outcomes and therefore represents a poor target for therapeutic intervention for these outcomes.
#15 Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations | BMJ Medicine
https://bmjmedicine.bmj.com/content/2/1/e000467
Only 3% of participants who are homozygous for rs887829-T have a recorded diagnosis of Gilbert syndrome. […] Carriers of this genotype have modest increases in the odds of developing biliary pathology and pityriasis rosea. […] Evidence from the analyses of genetic data suggests that bilirubin has no likely causal role in protection from cardiovascular disease, chronic obstructive pulmonary disease, or other key healthcare outcomes and therefore represents a poor target for therapeutic intervention for these outcomes.
#16 Concurrence of novel mutations causing Gilbertâs and DubinâJohnson syndrome with poor clinical outcomes in a Han Chinese family | Journal of Human Genetics
https://www.nature.com/articles/s10038-022-01086-1
The proband developed into pleural effusions and ascites, pericardial thickening, intrahepatic and extrahepatic biliary duct dilatation, and enlarged gallbladder at age 50. […] Hepatocellular carcinoma occurred in the proband’s brother at age 46. […] The proband in our study had 50 years of dual jaundice yet did not develop into severe liver-related disease. The proband’s brother, who had a long medication history, hypertension, and cholelithiasis, developed into hepatocellular carcinoma at age 48. […] More similar cases or function verification may reinforce the conclusion. […] The present study illuminates the underpinnings of GS and DJS, and extends mutation profiles and phenotypes of the syndromes.
#17 Concurrence of novel mutations causing Gilbertâs and DubinâJohnson syndrome with poor clinical outcomes in a Han Chinese family | Journal of Human Genetics
https://www.nature.com/articles/s10038-022-01086-1
The proband developed into pleural effusions and ascites, pericardial thickening, intrahepatic and extrahepatic biliary duct dilatation, and enlarged gallbladder at age 50. […] Hepatocellular carcinoma occurred in the proband’s brother at age 46. […] The proband in our study had 50 years of dual jaundice yet did not develop into severe liver-related disease. The proband’s brother, who had a long medication history, hypertension, and cholelithiasis, developed into hepatocellular carcinoma at age 48. […] More similar cases or function verification may reinforce the conclusion. […] The present study illuminates the underpinnings of GS and DJS, and extends mutation profiles and phenotypes of the syndromes.
#18 Concurrence of novel mutations causing Gilbertâs and DubinâJohnson syndrome with poor clinical outcomes in a Han Chinese family | Journal of Human Genetics
https://www.nature.com/articles/s10038-022-01086-1
The proband developed into pleural effusions and ascites, pericardial thickening, intrahepatic and extrahepatic biliary duct dilatation, and enlarged gallbladder at age 50. […] Hepatocellular carcinoma occurred in the proband’s brother at age 46. […] The proband in our study had 50 years of dual jaundice yet did not develop into severe liver-related disease. The proband’s brother, who had a long medication history, hypertension, and cholelithiasis, developed into hepatocellular carcinoma at age 48. […] More similar cases or function verification may reinforce the conclusion. […] The present study illuminates the underpinnings of GS and DJS, and extends mutation profiles and phenotypes of the syndromes.
#19 Concurrence of novel mutations causing Gilbertâs and DubinâJohnson syndrome with poor clinical outcomes in a Han Chinese family | Journal of Human Genetics
https://www.nature.com/articles/s10038-022-01086-1
The proband developed into pleural effusions and ascites, pericardial thickening, intrahepatic and extrahepatic biliary duct dilatation, and enlarged gallbladder at age 50. […] Hepatocellular carcinoma occurred in the proband’s brother at age 46. […] The proband in our study had 50 years of dual jaundice yet did not develop into severe liver-related disease. The proband’s brother, who had a long medication history, hypertension, and cholelithiasis, developed into hepatocellular carcinoma at age 48. […] More similar cases or function verification may reinforce the conclusion. […] The present study illuminates the underpinnings of GS and DJS, and extends mutation profiles and phenotypes of the syndromes.
#20 Gilbertâs syndrome: The good, the bad and the ugly
https://www.wjgnet.com/1948-5182/full/v17/i2/98503.htm
Gilberts syndrome is a benign hereditary disorder characterized by mild hyperbilirubinemia. […] The prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] In fact, individuals with GS have been reported to have mortality rates that are nearly half those of individuals without the syndrome, suggesting a potential protective effect against all-cause mortality in the general population. […] Despite the presence of elevated bilirubin levels, the prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] The clinical significance of GS lies in the potential for mild hyperbilirubinemia to be mistaken for a sign of liver disease highlighting the importance of accurate diagnosis and patient education.
#21 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Although it is tempting to propose a strong intracellular immune-modulatory effect of UCB, there is no data on uptake of bilirubin by immune cells in vivo. […] While increased UCB levels are so far the only identified outcome in Gilberts Syndrome, we cannot exclude that UGT1A1 mutations might exhibit other effects on human health. […] The present study aimed to investigate differences between healthy individuals with no history or present indication of a CVD. Even though we could identify a mildly increased risk for cardiovascular events in the control population compared to the GS population, we could not attribute the observed difference to either UCB or telomere length differences. […] In conclusion, we could observe a further link between Gilberts Syndrome, and possibly unconjugated bilirubin, and longevity, with emphasis on healthy aging. This work is important when considering bilirubin as a natural therapeutic in fighting cardio-metabolic diseases, as it emphasizes a long-term benefit on a cellular and molecular level.
#22 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbertâs Syndrome | Scientific Reports
https://www.nature.com/articles/srep22300
Gilberts Syndrome is associated with genetic variations in the UGT1A1 gene promoter region, of which the so-called UGT1A1*28 is the most common among Caucasians. […] Epidemiological studies indicate a strong association between increased serum BR and decreased incidence of age-related metabolic and cardiovascular diseases. […] In addition, individuals with GS have been found to exhibit delayed all-cause mortality, especially that from CVDs. […] Our findings reveal a novel characteristic of Gilberts Syndrome, potentially related to a chronic exposure to moderately increased unconjugated serum bilirubin. We show that individuals with a GS phenotype have on average longer telomeres compared to age- and gender-matched controls. This difference appears to be more pronounced with age, suggesting a reduced or slower telomere attrition in GS.
#23 Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations | BMJ Medicine
https://bmjmedicine.bmj.com/content/2/1/e000467
Only 3% of participants who are homozygous for rs887829-T have a recorded diagnosis of Gilbert syndrome. […] Carriers of this genotype have modest increases in the odds of developing biliary pathology and pityriasis rosea. […] Evidence from the analyses of genetic data suggests that bilirubin has no likely causal role in protection from cardiovascular disease, chronic obstructive pulmonary disease, or other key healthcare outcomes and therefore represents a poor target for therapeutic intervention for these outcomes.
#24 Gilbertâs syndrome: The good, the bad and the ugly
https://www.wjgnet.com/1948-5182/full/v17/i2/98503.htm
Gilberts syndrome is a benign hereditary disorder characterized by mild hyperbilirubinemia. […] The prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] In fact, individuals with GS have been reported to have mortality rates that are nearly half those of individuals without the syndrome, suggesting a potential protective effect against all-cause mortality in the general population. […] Despite the presence of elevated bilirubin levels, the prognosis for individuals with GS is excellent, with no long-term sequelae reported. […] The clinical significance of GS lies in the potential for mild hyperbilirubinemia to be mistaken for a sign of liver disease highlighting the importance of accurate diagnosis and patient education.