Gene/Protein Disease Symptom Drug Enzyme Compound
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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are chronic progressive cholestatic diseases that frequently lead to biliary cirrhosis. The exact pathogenesis of these diseases remains elusive but is likely immunologically based. Complications range from fatigue and pruritus to end-stage liver disease. The risk of developing hepatocellular carcinoma is low for patients with PBC, whereas cholangiocarcinoma is common in PSC and carries an ominous prognosis. Although ursodeoxycholic acid is effective in slowing the progression of PBC, no effective medical therapy exists for PSC. Liver transplantation is the only option for patients with end-stage liver disease and yields excellent long-term survival in both groups.
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PMID:Biliary tract inflammatory disorders: primary sclerosing cholangitis and primary biliary cirrhosis. 1098 Sep 34

End-stage liver disease due to chronic hepatitis C is the leading indication for orthotopic liver transplantation in the United States. Twenty percent to 30% of hepatitis C patients are at increased risk of developing cirrhosis, and 1% to 4% of cirrhotic patients will develop hepatocellular carcinoma. These findings warrant treatment for hepatitis C virus (HCV)-infected patients. Currently, the mainstay in treatment of HCV is the use of recombinant alpha interferon, or its equivalent, in combination with the oral antiviral agent ribavirin. The major goals of therapy are clearance of the virus, achieving a noninfectious state, and halting the necro-inflammatory process that leads to fibrosis and progression to cirrhosis. End of treatment response (ETR) is biochemical and virological remission-- normalization of serum aminotransferase (ALT) and undetectable levels of HCV RNA, at the end of therapy. Sustained virological response (SVR) is defined as the absence of viremia and persistently normal aminotransferase 6 months off treatment, and is the ultimate goal of therapy. Patients who achieve SVR will have significant and persistent histologic improvement. HCV genotype, pretreatment levels of HCV-RNA (viral load), the presence of advanced fibrosis or cirrhosis, gender, and age are independent predictors of response. Ribavirin is teratogenic, therefore, contraception is mandatory for both males and females during and up to 6 months after therapy. Side effects of combination therapy are dose-dependent and most commonly include symptoms of irritability, depression and fatigue, and laboratory evidences of leukopenia, thrombocytopenia, and hemolytic anemia.
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PMID:Hepatitis C. 1109 32

We report the case of a 66-year-old male with ulcerative colitis diagnosed in 1987, who had been treated with azathioprine (AZA) for the past two years (average dose about 1.6 mg/kg/day). In May 1999 he presented with painless jaundice, fatigue and recent weight loss. Cholestatic enzymes were elevated, alpha-fetoprotein was normal and hepatitis B/C serology negative. After diagnosis of veno-occlusive disease (VOD) and hepatocellular carcinoma (HCC) via biopsy, tumour resection was performed. The histology was typical for a well-differentiated HCC with trabecular and pseudoglandular structures. Neighbouring liver tissue was atrophic, with nodular regenerative hyperplasia (NRH), peliosis-like sinusoidal ectasias and intra-sinusoidal accumulation of blood, associated with peri-sinusoidal fibrosis. Although none of the well-established risk factors for HCC such as cirrhosis, hepatitis B/C, metabolic liver disease or toxins were present, this patient developed HCC. This and previous reports suggest that NRH and/or VOD associated with AZA represent a risk factor for HCC. AZA should therefore not only be stopped in patients with NRH/VOD but patients should also be screened for HCC.
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PMID:Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. 1129 51

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly affects middle-aged women; fatigue and pruritus are the most common symptoms at presentation. Liver function tests are consistent with cholestasis and reveal an elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase with or without elevation of aminotransferase levels. Histologically, PBC is characterized by the destruction of the intrahepatic small bile ducts and subsequently fibrosis. The serological hallmark of the disease is the presence of antimitochondrial antibodies, which are found in 95% of patients with PBC. The antimitochondrial antibodies are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. PBC generally slowly progresses, even over decades, and may lead to liver failure. In symptomatic patients, advanced age, elevated serum bilirubin levels, decreased serum albumin levels, and cirrhosis each correlate with shortened survival. Immunosuppressive and anti-inflammatory drugs have been used in the treatment of PBC based on the presumed autoimmune pathogenesis, but satisfactory agents leading to complete reversal or cure of the disease are not available. At present ursodeoxycholic acid appears to be the only effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving ursodeoxycholic acid still develop progressive disease and require transplantation; transplantation is the only effective therapy at the end stage of the disease.
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PMID:Primary biliary cirrhosis: from induction to destruction. 1135 23

The widespread incidence of hepatitis C (HCV) infection throughout the community is of concern. Although many of those infected will not suffer significantly from their infection, up to one-third will have liver disease, fatigue and oral health problems. General dental practitioners need to be aware of the precautions necessary in treating people with severe liver disease. This paper discusses the issues associated with treating patients who have HCV infection including the importance of preventive programs to reduce dental pathology and maximise oral health.
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PMID:The increasing problem of hepatitis C virus infection. 1169 65

We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra-abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short-term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.
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PMID:Cholangiopathy after short-term administration of piperacillin and imipenem/cilastatin. 1142 85

This study was designed to determine response rate, survival and toxicity associated with combination chemotherapy delivered intra-arterially to liver in patients with hepatic metastases of colorectal origin refractory to standard systemic treatment. A total of 28 patients who failed prior systemic treatment with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment consisting of 5-fluorouracil 700 mg/m(2)/d, leucovorin 120 mg/m(2)/d, and cisplatin 20 mg/m(2)/d for 5 consecutive days. Cycles were repeated at intervals of 5-6 weeks. A major response was achieved in 48% of patients: complete response in 8% and partial response in 40%. The median duration of response was 11.5 months. Median survival was 12 months at a median follow up of 12 months. On multivariate analysis, the only variables with a significant impact on survival were response to treatment and performance status. Toxicity was moderate: grades III-IV neutropenia occurred in 29% of patients. Most of the patients complained of fatigue lasting for a few days following each cycle. There were no cases of hepatobiliary toxicity. These findings indicate that regional intra-arterial treatment should be considered in selected patients with predominantly liver disease following failure of standard treatment.
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PMID:Liver metastases from colorectal cancer: regional intra-arterial treatment following failure of systemic chemotherapy. 1150 87

A 56-year-old man with persistently elevated liver enzyme levels, fatigue, lethargy and a 9.0 kg weight loss over six months underwent a percutaneous liver biopsy that demonstrated multiple granulomas. Screening serologies were positive for histoplasmosis, and he was started on itraconazole treatment. He returned to hospital the same night with coffee-ground emesis and in Addisonian crisis requiring parenteral steroids and intensive care unit support. An abdominal computed tomography scan revealed bilaterally enlarged, nonenhancing adrenal glands suggestive of infarcts, presumed secondary to histoplasmosis. Treatment was initiated with amphotericin B, and Histoplasma capsulatum was cultured from his urine and cerebrospinal fluid. A serum immunodiffusion test was also positive for both H and M bands, indicating active infection with Histoplasmosis species. His serum and urine samples were also weakly positive for the antigen. Despite complications of renal failure, pneumonia and congestive heart failure, he recovered with medical therapy and was discharged home to complete a prolonged course of itraconazole therapy. While hepatic granulomas often reflect an occult disease process, the cause may remain undiscovered in 30% to 50% of patients despite exhaustive investigations. H capsulatum is an uncommon cause of granulomatous liver disease, and with its protean clinical presentation, a high index of suspicion is needed to make the diagnosis and avoid the potentially high fatality rate associated with disseminated infection.
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PMID:A case of Histoplasma capsulatum causing granulomatous liver disease and Addisonian crisis. 1169 4

The best known example of an interaction between the liver and the brain is hepatic encephalopathy. In the 90s a central nervous system origin of the pruritus of cholestatic liver disease and more recently of fatigue of liver disease has been suggested. Hence, three important manifestations of liver disease may be of central origin. Evidence is accumulating that the central opioid system is involved in the development of these manifestations. This short review summarizes current knowledge on the role of the opioid system in development of these liver disease manifestations.
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PMID:The central opioid system in liver disease and its complications. 1172 91

Treatment of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) with ursodeoxycholic acid (UDCA) has been in common use since 1985. In PBC, treatment with UDCA improves laboratory data, liver histology, enables a longer transplantation-free interval and prolongs disease survival. Because UDCA is unable to cure the disease newer drugs or combination therapies are still needed. Studies with UDCA and immunosuppressants such as prednisone, budesonide and azathioprine have shown that in selected patients combination therapy may be superior to UDCA monotherapy. PSC is treated successfully with UDCA and endoscopic dilatation of the bile duct strictures. Treatment of extrahepatic manifestations of cholestatic liver disease such as pruritus, fatigue, osteoporosis and steatorrhea can be problematic and time-consuming.
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PMID:Medical treatment of primary biliary cirrhosis and primary sclerosing cholangitis. 1178 61


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