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)

Chronic biliary tract disease is the third most common indication for orthotopic liver transplantation (OLT) in the United States. Most patients undergoing OLT for chronic biliary tract disease have end-stage liver disease associated with cirrhosis, but a minority are transplanted in the precirrhotic stage for indications that can include poor quality of life (eg, intractable pruritus or fatigue), recurrent ascending cholangitis, or cholangiocarcinoma. A smaller subset of these patients suffer from severe noncirrhotic portal hypertension that can be associated with histologic features of nodular regenerative hyperplasia (NRH) and/or obliterative portal venopathy. We reviewed 306 liver explants performed for chronic biliary tract disease at 2 institutions during 1995 to 2003 to identify patients who were transplanted in the precirrhotic stage. The following clinical data were recorded: age, sex, type of biliary tract disease, radiology, clinical symptoms, signs of portal hypertension, pretransplant shunting procedures, time between diagnosis and OLT, and primary indication for OLT. Histopathologic data included: explant weight, gross appearance, fibrosis stage (1 to 4), cholangitis, bile duct dysplasia, malignancy, portal vein thrombi, presence of NRH, and presence of obliterative portal venopathy. Twenty-six of 306 (8.5%) patients underwent OLT in the precirrhotic stage (12 females: 14 males, mean age of 46 y, age range 12 to 68 y). At explant, fibrosis stage ranged from 1 to 2 (portal and periportal fibrosis) to 3 (multiple bridging fibrosis). Underlying biliary tract disease included primary sclerosing cholangitis (18 cases), primary biliary cirrhosis (5 cases), autoimmune cholangitis (2 cases), and secondary sclerosing cholangitis (1 case). Primary indications for OLT were recurrent cholangitis and/or decreased quality of life (11 cases), complications of portal hypertension (6 cases), portal hypertension plus cholangitis/decreased quality of life (5 cases), and malignancy (4 cases). Of the 11 patients with portal hypertension as a major indication for transplant, 2 had undergone transjugular intrahepatic portal-systemic shunting and 3 others had portal vein thrombi. Histopathologically, NRH was prominent in 8 of these 11 patients (73%) and obliterative portal venopathy in 6 (55%). NRH was also present in 4 of the 15 (27%) patients who were transplanted for other indications. These results indicate that precirrhotic portal hypertension is a predominant or major contributing factor to OLT in a significant minority (11 of 306, 3.3%) of patients with chronic biliary tract disease. The occurrence of NRH in some patients transplanted for other indications suggests it is a histologic pattern that can precede the development of clinically significant portal hypertension.
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PMID:Liver transplantation in precirrhotic biliary tract disease: Portal hypertension is frequently associated with nodular regenerative hyperplasia and obliterative portal venopathy. 1706 88

Schistosomiasis is caused by trematode parasites of one of five species, Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Schistosoma intercalatum, or Schistosoma mekongi, acquired via skin contact with fresh water containing infectious larval cercariae. Between 1 and 8 weeks after exposure, acute schistosomiasis presents as dermatitis, fever, fatigue, or eosinophilia. If untreated, long-term infection may cause anemia or undernutrition and may progress to liver fibrosis, portal hypertension, or hydronephrosis. Schistosomiasis represents a threat to residents and visitors in all endemic areas of Africa, Asia, and South America. Travelers should be made aware of infection risk if they become exposed to untreated fresh water. New immigrants and those returning to high-risk areas to visit friends and family should be screened for signs and symptoms of acute and chronic schistosomiasis. Physicians caring for travelers and immigrants must be familiar with the signs and symptoms of schistosomiasis and must be able to diagnose and treat it correctly.
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PMID:Schistosomiasis in travelers and immigrants. 1837 15

Portopulmonary hypertension is an uncommon but treatable pulmonary vascular consequence of portal hypertension, which can lead to significant morbidity and mortality. Portopulmonary hypertension results from excessive pulmonary vasoconstriction and vascular remodeling that eventually leads to right-heart failure and death if left untreated. Although pulmonary vascular disease in these patients may be asymptomatic or associated with subtle and nonspecific symptoms (dyspnea, fatigue and lower extremity swelling), it should be looked for especially if patients are potential candidates for liver transplantation. Patients with clinical suspicion of portopulmonary hypertension should undergo screening testing, specifically echocardiography. Right heart catheterization remains the gold standard for the diagnosis. The existence of moderate to severe disease poses higher risks and challenges for liver transplantation. The disease has a substantial impact on survival and requires focused pharmacological therapy. New and evolving medical therapies, such as prostanoids (intravenous, inhaled or oral), endothelin receptors antagonists, phosphodiesterases inhibitors, combination therapy and other experimental drugs might change the natural course of the disease. Case reports and cases series have been published regarding the efficacy and safety of pharmacological therapy, but randomized, controlled multicenter trials are urgently needed. Liver transplantation is not the treatment of choice for portopulmonary hypertension, but after optimal hemodynamic and clinical improvement with medical therapy as a bridge, liver transplant can be considered an option in selected patients.
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PMID:Portopulmonary hypertension: state of the art. 1903 31

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis. The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma. Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.
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PMID:New approaches in the therapy of hepatitis C in dialysis patients. 1925 44

Myelofibrosis (either primary or postpolycythemia vera/essential thrombocythemia) is a chronic and debilitating myeloproliferative neoplasm for which there is no well-accepted standard of care. Clinical manifestations of this disease (e.g., cytopenias, splenomegaly, bone marrow fibrosis) and constitutional symptoms (e.g., hypercatabolic state, fatigue, night sweats, fever) create significant treatment challenges. For example, progressive splenomegaly increases the risk for more serious clinical sequelae (e.g., portal hypertension, splenic infarction). Myelofibrosis arises from hematopoietic stem cells or early progenitor cells. However, the molecular mechanisms underlying its pathogenesis and clinical presentation are poorly understood, delaying the development of effective and targeted treatments. Recent studies have implicated mutations that directly or indirectly lead to the deregulated activation of Janus-activated kinase 2 (JAK2). Appreciation for the activation of JAK2 and the importance of increased levels of circulating proinflammatory cytokines in the pathogenesis and clinical manifestations of myelofibrosis has led to novel therapeutic agents targeting JAKs. This review will briefly discuss the origins of the JAK2 hypothesis, the clinical relevance of JAK2 mutations in myelofibrosis, and recent clinical progress in targeting JAKs as a therapeutic intervention for patients with this chronic and debilitating disease.
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PMID:Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis. 2021 35

Drugs used for treating inflammatory bowel disease are known to have a number of gastrointestinal and liver adverse effects. 5-ASA products are relatively safe and have few adverse events. In contrast sulfasalazine has side effects in 11-40% of treated patients including fatigue, nausea, abdominal pain and diarrhoea. Glucocorticoids can induce or propagate peptic ulcers and upper GI bleeding especially in combination with NSAIDs. Thioguanins may have severe gastrointestinal side effects including gastrointestinal complaints (in up to 12%), hepatotoxicity (up to 4%) and pancreatitis (1%). Nodular regenerative hyperplasia (NRH) is an important potential side effect of thiopurine therapy especially in men with Crohn's disease after ileocecal resection. NRH may ultimately lead to portal hypertension. A major concern of methotrexate therapy in IBD besides myelosuppression and pulmonary fibrosis is hepatotoxicity. 5mg of folic acid substitution per week potentially decreases gastrointestinal side effects by 80% without interfering with the efficacy of methotrexate. Besides renal dysfunction, tremor, hirsutism, hypertension and gum hyperplasia cyclosporine is known to have a number of gastrointestinal side effects that occur with less frequency such as diarrhoea (up to 8%) nausea and vomiting (up to 10%) and hepatotoxicity in 1-4%. Rare gastrointestinal adverse events are gastritis and peptic ulcers. Paying attention to these potential deleterious side effects is mandatory for physicians treating IBD patients.
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PMID:Gastrointestinal and liver adverse effects of drugs used for treating IBD. 2022 29

Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension.
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PMID:Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt. 2052 7

Wandering spleen is the displacement of the spleen from its normal location due to the loss or weakening of ligaments that hold the spleen in the left upper quadrant. The possibility of torsion of the spleen is high due to the long and mobile nature of the vascular pedicle. Generally, cases are asymptomatic. Under conditions of delayed diagnosis, symptoms of splenomegaly, left portal hypertension, gastric fundal varices, and hypersplenism may present as a result of development of vascular congestion associated with chronic torsion. There are only a few cases in the literature reporting the association of wandering spleen and fundal varices. We report herein the case of a 55-year-old female who admitted to our clinic with complaints of fatigue and epigastric pain. She was determined to have gastric fundal varices and hypersplenism secondary to the development of left portal hypertension due to chronic splenic torsion.
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PMID:A case of torsion of the wandering spleen presenting as hypersplenism and gastric fundal varices. 2148 Jan 20

Portopulmonary hypertension (PPHT) is a respiratory complication of portal hypertension, defined as an increase in mean pulmonary artery pressure (PAP) of > 25 mmHg with an increase in pulmonary vascular resistance of > 240 dyn.s/cm(-5) and a normal pulmonary capillary wedge pressure ( < 15 mmHg), which often occurs in subjects with liver cirrhosis. Histopathological features of PPHT are endothelial and smooth-muscle cell proliferation and fibrosis leading to luminal obstruction in the resistance arteries. The pathogenesis of PPHT may result from an imbalance between vasoconstrictor and vasodilating factors. The most common pulmonary symptom is exertional dyspnea; fatigue, chest pain and syncope occur more often at an advanced stage. Edema, ascites and prominent jugular veins are signs of both decompensated hepatic cirrhosis and right ventricular failure. Right heart catheterisation is the gold standard for the diagnosis and defines PPHT in mild disease with PAP less than 35 mmHg, moderate disease with PAP between 35 and 45 mmHg, and severe disease with PAP of 45 mmHg or higher. The medical treatment of portopulmonary hypertension is based on the treatment of other forms of pulmonary arterial hypertension, including vasomodulating pharmacologic agents. Liver transplantation is accompanied by high risk of mortality, generally due to acute right ventricular failure and cardiovascular collapse. The prognosis of PPHT is poor with mean survival of 15 months.
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PMID:Portopulmonary hypertension. 2163 86

Abdominal tuberculosis is a rare infectious disease that can involve the peritoneum and lead to portal vein thrombosis and mimic peritoneal carcinomatosis. We report on a 43-year-old male patient with fatigue and progressive weight loss for two years. Ascites was the only pathologic finding in his physical examination and laboratory findings revealed only a mild anaemia with Ca-125 elevation. The ascitic fluid Adenosine deaminase (ADA) level was also elevated. Computed tomography revealed splenomegaly, a mesenteric mass measuring 3.5 cm and intra-abdominal lymphadenopathies at the hepatic hilum. Oesophagogastroduodenoscopy (EGD) revealed oesophageal varices which was also consistent with portal hypertension. Diagnostic laparotomy and biopsies obtained from the omentum and the lymph nodes revealed acid-fast staining tuberculosis bacilli.
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PMID:Abdominal tuberculosis leading to portal vein thrombosis, mimicking peritoneal carcinomatosis and liver cirrhosis. 2271 72


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