Prevalence of hepatocellular carcinoma in alpha-1-antitrypsin deficiency

Propst, Theresa; Propst, A; Dietze, Otto; Judmaier, G; Braunsteiner, H; Vogel, Wolfgang

doi:10.1016/s0168-8278(05)80609-9

Cited by 61 publications

(27 citation statements)

References 17 publications

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“…In this study, we tested whether nonsteroidal anti-inflammatory drugs (NSAIDs) could be a comorbid factor in the development of liver injury in ␣ H omozygous (PIZZ) alpha-1-antitrypsin (␣ 1 -AT) deficiency is associated with the development of liver damage and progression to liver failure and transplantation in children and with the development of chronic liver injury, cirrhosis, and hepatocellular carcinoma in adults. [1][2][3][4] The classical form of ␣ 1 -AT deficiency, designated PIZZ, is caused by a homozygous point mutation that results in the substitution of lysine for glutamate 342 . The liver injury in PIZZ deficiency results from the cytotoxicity associated with accumulation of mutant ␣ 1 -ATZ glycoprotein, detected by periodic acid-Schiff base-positive staining, in the endoplasmic reticulum of hepatocytes.…”

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confidence: 99%

“…[1][2][3][4] The classical form of ␣ 1 -AT deficiency, designated PIZZ, is caused by a homozygous point mutation that results in the substitution of lysine for glutamate 342 . The liver injury in PIZZ deficiency results from the cytotoxicity associated with accumulation of mutant ␣ 1 -ATZ glycoprotein, detected by periodic acid-Schiff base-positive staining, in the endoplasmic reticulum of hepatocytes.…”

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confidence: 99%

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Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency

et al. 2006

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Homozygous (PIZZ) alpha-1-antitrypsin (␣ 1 -AT) deficiency is associated with the development of liver damage in children as well as chronic liver injury and hepatocellular carcinoma in adults. The ␣ 1 -AT mutant Z gene encodes a mutant protein that accumulates in the endoplasmic reticulum of hepatocytes rather than being secreted appropriately into serum. Liver injury is caused by the accumulation of ␣ 1 -AT mutant Z protein in hepatocytes, which triggers downstream intracellular injury pathways. However, development of clinical liver disease among PIZZ homozygotes is highly variable, suggesting other genetic or environmental factors contribute to liver injury. In this study, we tested whether nonsteroidal anti-inflammatory drugs (NSAIDs) could be a comorbid factor in the development of liver injury in ␣ H omozygous (PIZZ) alpha-1-antitrypsin (␣ 1 -AT) deficiency is associated with the development of liver damage and progression to liver failure and transplantation in children and with the development of chronic liver injury, cirrhosis, and hepatocellular carcinoma in adults. [1][2][3][4] The classical form of ␣ 1 -AT deficiency, designated PIZZ, is caused by a homozygous point mutation that results in the substitution of lysine for glutamate 342 . The liver injury in PIZZ deficiency results from the cytotoxicity associated with accumulation of mutant ␣ 1 -ATZ glycoprotein, detected by periodic acid-Schiff base-positive staining, in the endoplasmic reticulum of hepatocytes. However, the development of clinical liver injury in PIZZ homozygotes is highly variable. For example, only 10%-15% of PIZZ infants develop clinically overt liver damage. 5 Furthermore, there is wide variation in the severity and progression of liver injury, ranging from patients who are completely asymptomatic to those whose liver damage is severe enough to require transplantation within the first 2 years of life. 1 These observations indicate that other genetic or environmental modifiers must influence the development and progression of liver injury in ␣ 1 -AT deficiency.Several transgenic mouse models expressing the mutant allele of the human ␣ 1 -ATZ gene and recapitulating many features of human liver injury have been described. [6][7][8][9] In the PiZ mouse model of ␣ 1 -AT deficiency Abbreviations: ␣ 1 - AT, PIZZ, NSAID, interleukin 6; PAS, BrdU, bromodeoxyuridine. From the

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Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency

et al. 2006

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“…Cirrhotics patients with autoimmune hepatitis (AIH) [110][111][112][113][114][115] or α 1-antitrypsin deficiency [116][117][118] seem to have an increased HCC risk. However, the HCC incidence is lower than in cirrhotics with viral hepatitis.…”

Section: Hcc Incidence In Cirrhotic Patientsmentioning

confidence: 99%

Surveillance for hepatocellular carcinoma in chronic liver disease: Evidence and controversies

Meer¹

2013

WJG

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Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis, hemochromatosis, primary biliary cirrhosis and non-alcoholic steatohepatitis. Especially cirrhotic patients are at risk of HCC and regular surveillance could enable early detection and therapy, with potentially improved outcome. We here summarize existing evidence for surveillance including ultrasound, other radiological modalities and various serum biomarkers, and current international guideline recommendations for surveillance. Ultrasound and α-fetoprotein (alone or in combination) are most frequently used for surveillance, but their sensitivities and specificities are still far from perfect, and evidence for surveillance remains weak and controversial. Various other potential surveillance tools have been tested, including serum markers as des-carboxyprothrombin, lectin-bound α-fetoprotein, and (most recently) circulating TIE2-expressing monocytes, and radiological investigations such as computed tomography-scan or magnetic resonance imaging-scan. Although early results appear promising, these tools have generally been tested in diagnostic rather than surveillance setting, and in most cases, no detailed information is available on their cost-effectiveness. For the near future, it remains important to define those patients with highest risk of HCC and most benefit from surveillance, and to restrict surveillance to these categories.

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“…Similar considerations apply to cirrhosis due to alpha 1-antitrypsin (AAT) deficiency. 52,53,54 Once more, there is insufficient data to determine whether screening might be beneficial.…”

Section: Cirrhosis Due To Causes Other Than Viral Hepatitismentioning

confidence: 99%

Screening for hepatocellular carcinoma

Sherman

2005

Best Practice & Research Clinical Gastroenterology

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Prevalence of hepatocellular carcinoma in alpha-1-antitrypsin deficiency

Cited by 61 publications

References 17 publications

Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency

Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency

Surveillance for hepatocellular carcinoma in chronic liver disease: Evidence and controversies

Screening for hepatocellular carcinoma

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