Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 57-year-old man was admitted with pruritus and jaundice following treatment for fatigue with the herbal medicine Hochuekkito. The patient was prescribed prednisolone and ursodeoxycholic acid, but he developed progressive cholestasis that required intravenous methylprednisolone pulse therapy. After treatment with plasma exchange for prolonged prothrombin time, the patient recovered; however, his liver function deteriorated because of liver injury induced by trimethoprim-sulfamethoxazole for pneumocystis pneumonia. After reduction of trimethoprim-sulfamethoxazole, his liver function almost returned to normal by day 130 of admission. It has remained normal for 10 months since then. Therefore, when prescribing Hochuekkito, the possibility of drug-induced liver injury should be taken in account.
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PMID:[Liver injury and hepatic encephalopathy induced by the herbal medicine Hochuekkito]. 2489 95

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease caused by diffuse inflammation and fibrosis that can involve the entire biliary tree. It is a progressive disorder which can ultimately lead to biliary cirrhosis, portal hypertension and hepatic failure. PSC is a complex genetic disorder with male predominance. Environmental predisposing factors include non-smoking. It is closely associated with inflammatory bowel disease (IBD), particularly ulcerative colitis, which occurs in about two thirds of PSC cases. Recent studies have suggested that PSC-IBD is a separate disease entity from IBD alone with distinctive genetic and phenotypic characteristics. Most PSC patients are asymptomatic at presentation; clinical symptoms include fatigue, jaundice, weight loss, right upper quadrant pain and pruritis. Serum biochemical tests indicate cholestasis, and diagnosis is usually established by cholangiography. In symptomatic patients, median survival from presentation to death or liver transplantation is about 12 years. It is a premalignant condition, and the majority of deaths are from malignancy, particularly cholangiocarcinoma or colonic cancer. PSC has no curative treatment. Medical treatment with ursodeoxycholic acid may slow progression of the disease and reduce colonic dysplasia, though trials lack statistical significance. Liver transplantation is the only option in young patients with PSC and advanced liver disease.
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PMID:Primary sclerosing cholangitis. 2496 92

Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease characterised by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells (BEC) lining the small intrahepatic bile ducts. This leads to bile duct injury and the retention of hydrophobic bile acids which cause further BEC injury leading to a self-sustaining cycle of bile duct injury. Initially the BEC respond to injury via a homeostatic response including through proliferation. Ultimately they become senescent; an active process with accompanying release of inflammatory cytokines ('the senescent secretome') which contributes to the process of interface hepatitis which is a feature of high-risk and treatment-unresponsive disease. This model for pathogenesis of PBC has implications for potential therapy approaches in targeting both the 'upstream' immune injury and 'downstream' BEC response to the immune injury. Fatigue is the commonest reported symptom in PBC and has a negative impact on patients' perceived quality of life, often through social isolation. It is unrelated to the severity of liver disease and appears unresponsive to current therapies, including ursodeoxycholic acid and transplantation. Fatigue in PBC is complex, with numerous associated peripheral and CNS features. Initially, cholestasis causes degenerative CNS change affecting areas of the brain regulating autonomic dysfunction and sleep, and these changes lead directly to some manifestations of fatigue and the associated cognitive impairment. In addition to this, the anti-mitochondrial antibody has direct muscle level metabolic effects leading to over-utilisation of anaerobic metabolism. Autonomic dysfunction contributes to the impact of this metabolic change by limiting the capacity of the muscle to respond through increased proton/lactate efflux from cells and outflow from tissues. The model has a number of implications for potential therapy approaches.
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PMID:Pathogenesis of primary biliary cirrhosis and its fatigue. 2503 96

The observational study was aimed at assessing the effectiveness and tolerability of Heptral (brand of ademetionine 1,4-butane disulfonate) in Indian patients presenting with intrahepatic cholestasis (IHC) due to chronic Non alcoholic liver disease (NALD). The study also aimed at understanding the prescribing practices of physicians as well as the profile of patients being prescribed Heptral. This Prospective observational study included 250 patients across 23 sites in India. The assessments of health-economic parameters, liver biochemistry, signs and symptoms of IHC (fatigue, jaundice, and pruritus) were performed at two visits, i.e., at baseline and after six weeks of Ademetionine treatment. Ademetionine was prescribed as part of the routine medical treatment as per the local label and not as a study intervention. Full analysis set (FAS) population included 244 patients. The mean age was 43.75 +/- 11.14 years and 75.5% (184/244) patients were males. 30.7% (75/244) of FAS population presented with cirrhosis. Concomitant medications were recommended to 44.4% (108/243) patients. Ademetionine treatment resulted in statistically significant reduction (p < 0.0001) in burden of disease parameters (number of days off work and number of visits to doctor), levels of biochemical markers and signs and symptoms of IHC. Physicians had favourable opinion for effectiveness and tolerability of Ademetionine for majority of the patients. Administration of Heptral in patients with NALD and IHC resulted in significant improvement in burden of disease, laboratory markers, signs and symptoms of cholestasis. The treatment was well tolerated.
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PMID:Heptral (ademetionine) in patients with intrahepatic cholestasis in chronic liver disease due to non-alcoholic liver disease: results of a multicentre observational study in India. 2515 64

Sickle cell intrahepatic cholestasis is a relatively uncommon complication of homozygous sickle cell anemia, which may lead to acute hepatic failure and death. Treatment is mainly supportive, but exchange transfusion is used as salvage therapy in life threatening situations. We describe a case of a 16-year-old female with homozygous sickle cell anemia who presented to the emergency room with fatigue, malaise, dark urine, lower back pain, scleral icterus and jaundice. She was found to have marked hyperbilirubinemia, which persisted after exchange transfusion. Because of the concomitant presence of gallstones and choledocholithiasis, the patient underwent endoscopic ultrasound and laparoscopic cholecystectomy followed by endoscopic retrograde cholangiography and sphincterotomy.
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PMID:Acute liver function decompensation in a patient with sickle cell disease managed with exchange transfusion and endoscopic retrograde cholangiography. 2517 68

Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.
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PMID:Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome. 2582 40

Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.
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PMID:Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy. 2595 76

We report a case of severe hepatic failure caused by gemcitabine hydrochloride (GEM) monotherapy after pancreaticoduodenectomy for advanced pancreatic cancer. A 73-year-old woman received GEM as an adjuvant chemotherapy. She suffered from progressive edema, fatigue, and jaundice after the third GEM administration. Severe liver dysfunction and elevation of bilirubin was observed. A computed tomography scan and magnetic resonance imaging showed diffuse liver swelling suggesting severe hepatic edema with fat accumulation. Needle biopsy of the liver revealed remarkable cholestasis and fat deposition with mild damage of hepatocytes. Drug-induced liver failure was suspected. GEM-stimulated lymphocyte test was negative, but antinuclear antibody was elevated with a marked inflammatory response. She improved to an almost normal condition by steroid and liver protective therapies within a week. Although the frequency of liver failure induced by GEM monotherapy is very rare, it could be fatal. It is important to distinguish it from other causes of liver dysfunction following pancreaticoduodenectomy. Early detection and appropriate drug therapy can improve the prognosis.
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PMID:Severe cholestatic liver failure associated with gemcitabine adjuvant monotherapy for pancreatic cancer. 2618 42

Fatigue is a significant problem in approximately 50% of primary biliary cirrhosis (PBC) patients, with 20% of all patients experiencing significant or life-altering fatigue. Large-scale population studies show that fatigue has a major impact on quality of life (QoL) in PBC, and that it disproportionately affects younger patients. The presence of social dysfunction that accompanies fatigue appears to be a major factor in determining whether fatigue of a particular severity impacts on QoL. The pathogenesis of fatigue in PBC remains unclear, although it is unrelated to the severity of underlying disease and is unresponsive to ursodeoxycholic acid. Perhaps, unsurprisingly, it appears to be complex in origin, probably multifactorial in the majority of patients and associated with depression, autonomic dysfunction and sleep disturbance. Clinically, fatigue has both central and peripheral components. The central component is associated with cognitive impairment and sleep disturbance and characterised by neurophysiological abnormalities of activation and facilitation, together with CNS changes. Peripheral fatigue is associated with muscle dysfunction and an inability to sustain exercise. One hypothesis is that the central processes result directly from cholestasis, which impacts autonomic centres in the brain; these processes then regulate peripheral muscle perfusion, leading to systemic peripheral effects. At present, there is no specific drug therapy for fatigue in PBC and no significant improvement following transplantation. In managing patients with fatigue, understanding their situation is crucial and advice regarding pacing and maintaining social interactions is critical. Most important of all is an understanding of the impact this symptom has on patients' lives and an empathetic clinical interaction.
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PMID:Fatigue in Primary Biliary Cirrhosis: Prevalence, Pathogenesis and Management. 2664 84

We present a rare cause of iridocyclitis in a patient with vitiligo and type 1 diabetes who showed poor metabolic control, and suffered from remitting fever, weight loss, fatigue, diffuse arthralgias and reduced visual acuity. Mild systemic symptoms coupled with increased cholestasis enzymes, insulin resistance, mild inflammation and a functioning adrenal gland focused our clinical work-up on granulomatous causes of iridocyclitis. Specific tests confirmed syphilis, with no involvement of the central nervous system. Ocular syphilis, despite being unusual, can be the only manifestation of the disease. The work-up of any unexplained ocular inflammation should include testing for syphilis so as to not delay the diagnosis.
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PMID:Syphilis iridocyclitis in a patient with type 1 diabetes. 2718 Jul 31


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