Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
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The liver has a central role in the detoxication and elimination of toxic substances which enter the body as lipid-soluble compounds. Their transformation into polar watersoluble metabolites, termed biotransformation, is bound to the membranes of the smooth endoplasmatic reticulum. The oxidating enzyme in biotransformation can be induced by certain toxins and drugs. The chronic induction of enzymes by DDT and the consequences of this process of adaptation, particularly in regard to the metabolism of calcium is discussed. The protective effect of biotransformation and induction of enzymes against carcinogens, especially aflatoxin, are briefly reviewed. As examples of the chronic influence of vasotoxic substances, mention is mode of the veno-occlusive disease caused by the alkaloid phlorrhizidin found in plants, and the vinyl-chloride disease occurring in workers handling PVC. The first leads to portal hypertension of the post-sinusoidal type, while the second leads to pre- or intrasinusoidal portal hypertension and, after years of exposure, to hemangioendotheliosarcoma of the liver. The same tumor has been observed after arsenic intoxication. Arsenic may also lead to non-cirrhotic portal hypertension. The present opinions about environmentally induced gastrointestinal diseases are widely hypothetical. The high frequency of gastric carcinoma in Japan. and the varying occurrence of carcinoma of the colon in the civilized world in comparison with the rural population of tropical regions, is emphasized. The explanation for these facts is probably to be sought in differences of nutrition.
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PMID:[Effects of the environment on the liver and gastrointestinal tract]. 125 20

Abnormal liver biochemical tests are present in up to 30% of patients with inflammatory bowel disease (IBD), and therefore become a diagnostic challenge. Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn's disease and ulcerative colitis (UC), and typically do not correlate with intestinal activity. Primary sclerosing cholangitis (PSC) is the most common hepatobiliary manifestation of IBD, and is more prevalent in UC. Approximately 5% of patients with UC develop PSC, with the prevalence reaching up to 90%. Cholangiocarcinoma and colon cancer risks are increased in these patients. Less common disorders include autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cirrhosis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, liver abscess, and non-alcoholic fatty liver disease. Hepatitis B reactivation during immunosuppressive therapy is a major concern, with screening and vaccination being recommended in serologically negative cases for patients with IBD. Reactivation prophylaxis with entecavir or tenofovir for 6 to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen (HBsAg) positive, independently from viral load. HBsAg negative and anti-HBc positive patients, with or without anti-HBs, should be closely monitored, measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy, and should be treated if the viral load increases. On the other hand, immunosuppressive therapy does not seem to promote reactivation of hepatitis C, and hepatitis C antiviral treatment does not influence IBD natural history either. Most of the drugs used for IBD treatment may induce hepatotoxicity, although the incidence of serious adverse events is low. Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant. Methotrexate-related hepatotoxicity has been described in 14% of patients with IBD, in a dose-dependent manner. Liver biopsy is not routinely recommended. Biologics-related hepatotoxicity is rare, but has been shown most frequently in patients treated with infliximab. Thiopurines have been associated with veno-occlusive disease, regenerative nodular hyperplasia, and liver peliosis. Routine liver biochemical tests are recommended, especially during the first month of treatment. All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement. Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.
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PMID:Hepatobiliary manifestations in inflammatory bowel disease: the gut, the drugs and the liver. 2425 64