Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-1-antitrypsin is a glycoprotein which inactivates proteolytic enzymes, especially neutrophil elastase. Infants deficient in this enzyme commonly develop neonatal hepatitis. In adults, the deficiency typically results in emphysema. Only rarely will an adult manifest liver disease. We present a case of adult liver cirrhosis due to Alpha-1-antitrypsin deficiency in a 63-year-old man. Manifestations of alpha-1-antitrypsin deficiency and liver disease are discussed.
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PMID:Alpha-1-antitrypsin deficiency: rare cause of adult cirrhosis--a case report. 842 51

We have established reference ranges for the concentrations of hyaluronic acid in serum from 397 infants and children and measured serum hyaluronic acid at presentation and 1 year follow-up in 37 infants who presented with hepatobiliary disease in the first 6 months of life. In health, hyaluronic acid concentrations fell progressively from median (10-90 percentile) values of 93 micrograms/l (49-153) at 1-3 months of age to 20 micrograms/l (9-40) at 2-3 years and 16 micrograms/l (6-32) at 4-18 years. In patients at presentation, the hyaluronic acid concentration was raised in 11 of 15 with biliary atresia, 6 of 11 with alpha-1 antitrypsin deficiency and 6 of 11 with cryptogenic hepatitis of infancy. One year later, the 9 patients who developed progressive liver disease showed 2-6-fold increases in hyaluronic acid concentration while no increase was observed in the 28 with undetectable or mild disease. Increases in serum hyaluronic acid concentration appeared to be a better indicator of progressive liver disease in infancy than standard laboratory tests.
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PMID:Serum hyaluronic acid in healthy infants and children and its value as a marker of progressive hepatobiliary disease starting in infancy. 851 66

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The majority of patients who develop HCC have underlying cirrhosis, which suggests that cirrhosis itself represents a preneoplastic condition. Nevertheless, whereas patients with cirrhosis of any origin are at increased risk of developing HCC, those with chronic hepatitis B or C infection seem to be at greatest risk. Patients with cirrhosis resulting from chronic alcohol use, hemochromatosis, autoimmune hepatitis, or alpha-1 antitrypsin deficiency have less risk of developing this cancer, and some hepatic diseases, such as primary biliary cirrhosis and Wilson's disease, do not predispose affected persons to an appreciable risk of developing HCC. Certain histological features, such as liver cell dysplasia and macroregenerative nodules, may represent preneoplastic alterations of hepatocytes, but these changes do not seem to be a necessary step in the evolution of liver cancer. The pathogenesis of HCC is unclear, but seems to involve several steps. Hepatitis B virus infection may result in the malignant transformation of hepatocytes by some directly oncogenic mechanism, whereas other necroinflammatory conditions probably predispose to the development of HCC through the introduction of genetic alterations coupled with a reduction of genetic repair functions. Screening patients at risk for the development of HCC using alpha fetoprotein measurements and ultrasonography is widely practiced despite inconclusive evidence of efficacy. If screening is performed, the program used should be tailored to the perceived risk for a particular patient.
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PMID:Preneoplastic conditions of the liver. 870 61

Even at an early stage, hepatocellular carcinoma (HCC) in patients with cirrhosis is often deemed unresectable because of limited liver reserve. In these circumstances, liver transplantation (LTx) offers some hope for palliation or cure. The results of LTx for selected cirrhotic patients with HCC were analysed. The outcomes were compared with those of patients who underwent LTx for other forms of hepatic malignancy and those who underwent LTx for non-malignant conditions. Four hundred and eighty LTx were performed in 441 patients between January 1986 and December 1998. Twenty-eight LTx recipients (25 males, 3 females) of mean age 51 (14 63) yr had cirrhosis and HCC. Twenty-seven patients had underlying predisposing conditions (11 had hepatitis B, 10 had hepatitis C, 2 had hepatitis B and C, 1 had haemochromatosis, 1 had autoimmune hepatitis, 1 had alcoholic cirrhosis and 1 had alpha-1 antitrypsin deficiency). In 22 patients, HCC was diagnosed pre-LTx, and in 6 patients, the cancers were discovered incidentally. The average tumour size and number were 2.8 (0.4-11.5) cm and 1.3 (1-4), respectively. Two patients with known HCC died during and shortly after the LTx operation. Of the other patients, 3 died; 1 died of HCC recurrence 18 months post-LTx, 1 died of graft failure from recurrent hepatitis C and 1 died of fungal sepsis. Twenty-three (82%) patients survived to 22.5 (0.5-96) months post-LTx without HCC recurrence and with 1- and 3-yr actuarial patient survival rates of 87 and 76%, respectively. Equivalent survival rates of patients who underwent LTx for other malignancies (n = 11) were 82 and 46% (p = NS), and for those who underwent LTx for benign causes (n = 402), they were 77 and 73% (p = NS). All 15 patients with known HCC, who met the selection criteria now in use, survived. LTx can result in prolonged. cancer-free survival in a good proportion of patients with cirrhosis and HCC, particularly when the cancers are incidental, or when diagnosed pre-LTx, conforming to established selection criteria. An active LTx programme for this group of patients is justified.
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PMID:An active liver transplant programme for hepatocellular carcinoma in cirrhotic patients: is it justified? 1061 45

Hepatocyte injury and necrosis from many causes may result in pediatric liver disease. Influenced by other cell types in the liver, by its unique vascular arrangements, by lobular zonation, and by contributory effects of sepsis, reactive oxygen species and disordered hepatic architecture, the hepatocyte is prone to injury from exogenous toxins, from inborn errors of metabolism, from hepatotrophic viruses, and from immune mechanisms. Experimental studies on cultured hepatocytes or animal models must be interpreted with caution. Having discussed general concepts, this review describes immune mechanisms of liver injury, as seen in autoimmune hepatitis, hepatitis B and C infection, the anticonvulsant hypersensitivity syndrome, and autoimmune polyendocrinopathy. Of the monogenic disorders causing significant liver injury in childhood, alpha-1 antitrypsin deficiency and Niemann-Pick C disease demonstrate the effect of endoplasmic or endosomal retention of macromolecules. Tyrosinemia illustrates how understanding the biochemical defect leads to understanding cell injury, extrahepatic porphyric effects, oncogenesis, pharmacological intervention, and possible stem cell therapy. Pathogenesis of cirrhosis in galactosemia remains incompletely understood. In hereditary fructose intolerance, phosphate sequestration causes ATP depletion. Recent information about mitochondrial disease, NASH, disorders of glycosylation, Wilson's disease, and the progressive familial intrahepatic cholestases is discussed.
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PMID:Mechanisms of liver injury relevant to pediatric hepatology. 1189 Feb 7

Based on data reported to the OPTN/UNOS Liver Transplant Registry between 1988-2004: 1. There was a very small difference in 5-year graft survival rates comparing living and deceased donors in adult (4.3%) and pediatric patients (2.4%). 2. Although graft survival rates of split liver transplants were lower than whole liver grafts before 1998, 5-year graft survival results of more recent split grafts (65.8%) have become comparable to those of whole liver grafts (66.5%). Among recipients in good condition, split (67.7%) and whole grafts (70.0%) yielded equivalent survival rates. 3. Lower graft survival rates were noted in ABO incompatible grafts, non-heartbeating donors, regrafted patients, and recipients who were in the ICU before transplantation. 4. There was no recipient gender effect on liver transplant outcome. 5. Primary disease distributions were different for different races. Among adult patients, the largest fraction of white patients had alcoholic cirrhosis. Among Asians, Type B cirrhosis was most frequent. Among pediatric patients, biliary atresia constituted the majority of patients. Most of the patients with alpha-1 antitrypsin deficiency were white. Autoimmune hepatitis was most frequently found among black patients. 6. Although 5-year graft survival of black patients (60.2%) was lower than whites (68.1%), Hispanics (67.6%), and Asians (68.0%), black recipients with PBC (73.3%) and PSC (69.9%) had graft survival rates similar to those of whites (78.1%) (73.6%) and Hispanics (75.3%) (77.1%). 7. Zero HLA-A,-B,-DR mismatched livers had very rapid early failures. HLA matching correlated with graft survival in autoimmune hepatitis patients, but not in cirrhosis patients. 8. Short-term graft survival for liver transplants has improved steadily since 1990. However, long-term graft survival after the first year actually declined over time. 9. In adult transplants, 5-year graft survival of autoimmune-related diseases, PBC (77.3%), PSC (73.3%), AIH (74.2%) yielded higher graft survival rates than those of hepatitis B (71.5%) and C (63.2%). 10. In pediatric patients, 5-year survival of biliary atresia (75.4%), autoimmune cirrhosis (70.8%), and alpha-1-antitrypsin deficiency (85.0%) had high graft survival rates, except for acute liver failure (61.6%). 11. Hepatitis C recurrence is now one of the major causes of graft failure in adults. Thrombosis is a major factor in graft failure for pediatric transplants.
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PMID:An analysis of the OPTN/UNOS Liver Transplant Registry. 1670 60

Alpha-1 antitrypsin deficiency is an inherited disease affecting the lung and liver. The typical pulmonary manifestation is chronic obstructive pulmonary disease and emphysema. Severe chronic obstructive pulmonary disease may occur in young adulthood, and terminal respiratory insufficiency causes premature death in many patients. In the liver, alpha-1 antitrypsin deficiency may manifest as benign neonatal hepatitis syndrome; a small percentage of adults develop liver fibrosis, with progression to cirrhosis and hepatocellular carcinoma. The alpha-1 antitrypsin molecule is a serine protease inhibitor that is predominantly produced in the liver. Its most important physiologic functions are the protection of pulmonary tissue from aggressive proteolytic enzymes and regulation of pulmonary immune processes. Diagnosis of alpha-1 antitrypsin deficiency can be established by measurement of the serum alpha-1 antitrypsin concentration or by genetic analysis. Treatment is similar to the usual treatment for patients with chronic obstructive pulmonary disease. A further option is substitution therapy with human alpha-1 antitrypsin. The targets of treatment are the prevention of the accelerated decline of pulmonary function, reduction of lung infections, and improvements in exercise capacity.
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PMID:Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment. 1850 Dec 15

Primary hemochromatosis, alpha-1-antitrypsin (AAT) deficiency, and Wilson's disease are the most common hereditary causes of unclear hepatopathy. Classical primary hemochromatosis (type I) on the basis of a homozygous mutation of the HFE gene, usually presents in adults with increasing hepatocellular siderosis and chronic progressive necroinflammatory liver disease. Homozygous AAT deficiency type PiZZ becomes manifest in newborns as a giant cell hepatitis or findings similar to bile duct atresia, in adults as chronic hepatitis or "cryptogenic cirrhosis". The heterozygous PiZ mutation can lead to PAS-positive hepatocellular AAT deposits increasing over the life time. Immunohistochemical detection of AAT deposits by specific PiZ antibodies is a highly sensitive and specific supplementary method. Molecular analysis of AAT and HFE genes in paraffin-embedded tissue or blood can confirm the diagnosis and allows the zygosity status to be defined. Wilson's disease has to be considered in children and young adults with unexplained histologic findings of chronic hepatitis or steatohepatitis. Rhodanin staining is the most effective histochemical method to detect free copper deposits, but negative staining results do not exclude Wilson's disease. In cases suspected of Wilson's disease further clinical exploration must be initiated. The diagnosis is based on a combination of clinical and biochemical findings, which can be supplemented by mutation analysis of the ATP7B gene.
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PMID:[Hereditary hemochromatosis, alpha-1-antitrypsin deficiency and Wilson's disease. Pathogenesis, clinical findings and pathways to diagnosis]. 1821 Jan 10

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave.
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PMID:Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. 1856 11

Biliary atresia is a rare pediatric disorder that results in obstructive jaundice in early infancy. Liver biopsies are characterized histologically by cholestasis, portal inflammatory infiltrate, and marked bile ductular proliferation. We studied the distribution of neutrophils in biliary atresia in patients who have undergone the Kasai procedure. Thirteen different liver biopsies were accompanied by hilar section in eight cases. Control liver specimens were from two patients with choledochal cysts, three patients with neonatal hepatitis, and three patients with alpha-1 antitrypsin deficiency. We also studied the expression of CAP37, an antimicrobial protein present in neutrophils, using immunohistochemistry in biopsy and hilar sections. Neutrophils were present in the portal tracts in all cases and widely distributed in the parenchyma in nine cases. In six cases, infiltration of neutrophils was associated with discrete foci of liver cell necrosis. There was a significantly higher number of portal tract neutrophils in biliary atresia and choledochal cyst cases than in neonatal hepatitis and alpha-1 antitrypsin deficiency (p<0.05). All neutrophils stained diffusely and strongly with CAP37. Medium staining was also seen in the proliferating portal bile ductules in six cases. This study confirms the wide distribution of neutrophils in biliary atresia, occurring as a result of bile duct obstruction. Infiltrating neutrophils are better highlighted with CAP37 immunostain. Proliferating bile ductules may play a role in the inflammatory response in biliary atresia through expression of CAP37.
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PMID:Neutrophils in biliary atresia. A study on their morphologic distribution and expression of CAP37. 2039 25


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