Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Digital clubbing is characterized by bulbous enlargement of the distal phalanges due to an increase in soft tissue. It has been associated with a variety of conditions including cyanotic heart disease, neoplasms and infections of the lungs, bronchiectasis, liver cirrhosis, and inflammatory bowel disease. We conducted an observational study at an urban Veterans Affairs Medical Center outpatient HIV clinic to confirm our clinical impression that clubbing is common in HIV-infected patients and to identify factors that might be associated with it. Clinical, laboratory, and physical examination data including measurement of the circumference of the nail bed and distal phalanx of each finger were obtained on 78 HIV-infected patients seen for their routine care over a 3-month period. A digital index (DI), the ratio of the nail bed:distal phalanx circumference was determined for each patient. Clubbing was found in 28 patients (36%). Clubbed patients did not differ from nonclubbed patients with respect to most patient characteristics; CD4 cell counts and quantitative HIV RNA were similar in both groups. Clubbed patients had a significantly higher DI than controls (1.03 versus 0.96, p < 0.001), were younger (45 versus 49 years, p = 0.04), and had longer duration of HIV disease (48 versus, 42 months, p = 0.03). HIV infection should be considered in the differential diagnosis of acquired digital clubbing.
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PMID:Digital clubbing in HIV-infected patients: an observational study. 1904 21

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct infiltration and destruction) and/or lesions suggesting chronic cholangitis as well (bile duct paucity and/or proliferation, periductal sclerosis). Small bile ducts damage may be associated, at onset or in the following years, with lesions of larger bile ducts with duct wall irregularities, strictures, dilations, and beading resulting in the characteristic ''bead-on-a-string'' appearance. The ''small duct'' (autoimmune) sclerosing cholangitis is also called autoimmune cholangitis. PSC is strictly associated to a particular form of inflammatory bowel disease (IBD) which shows features not typical of ulcerative colitis neither of Crohn's disease. Symptoms related to IBD often are present at onset (abdominal pain, weight loss, bloody stools) but the liver disease is frequently asymptomatic and it may be discovered fortuitously. Treatment of PSC is particularly challenging. In case of ''small duct'' SC or in case of evidence active inflammation on liver biopsy, immunosuppressive treatment is probably useful while in case of large bile ducts non inflammatory sclerosis, immunosuppression is probably uneffective. Ursodeoxycholic acid, however, may leads to an improvement of liver biochemistry even if there's no evidence that it may alter the course of disease. Thus, liver transplantation, is often necessary in the long term follow-up, even with a risk of disease recurrence. In adjunction to these two main disorders, many patients show an''overlap'' disease with features of both AIH and PSC. In such disorders the immune-mediated damage concerns both the hepatocyte and the cholangiocyte with a continuous clinical spectrum from AIH with minimal bile ducts lesions and PSC with portal inflammation and active inflammatory liver damage.
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PMID:Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood. 1921 8

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB01*03 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease.
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PMID:The immunobiology of primary sclerosing cholangitis. 1946 33

Stem cells therapies represent a new field of biomedical science which could provide in the future the cure for diseases until now incurable. The present paper reviews current knowledge on key biological properties of stem cells with focus on hepatic and gastrointestinal stem cells and current applications of stem cells therapies in gastrointestinal and liver diseases. Potential clinical applications for stem cells therapies have been suggested from animal model trials in acute liver failure, inherited metabolic liver disease and endstage liver disease (cirrhosis). Hematopoietic autologous stem cells transplantation has already been successfully performed in patients with severe inflammatory bowel disease or patients with refractory celiac disease with aberrant T cells. Future stem cells therapies for gastrointestinal postoperative or Crohn's disease fistulas are currently under investigation. More research is needed for perfecting stem cells harvesting protocols from different sources, in vitro expansion and differentiation protocols which can be used in phase II and III clinical trials.
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PMID:Stem cells therapies for gastrointestinal and liver diseases. 1949 55

We raised a set of monoclonal antibodies (mAb) against recombinant human ADAMTS13, constructed the first antigen test fully based on mAbs and compared ADAMTS13 antigen and enzymatic activity levels in a large set of plasma samples collected from different patients and healthy controls. Assessing both ADAMTS13 antigen and activity helps to understand whether or not the protease is fully active in pathological conditions, e.g. liver cirrhosis, inflammatory bowel disease, cardiac surgery, pregnancy and oral contraceptive intake, in the neonatal state and in normal individuals. Our ADAMTS13 antigen assay showed less variability than the collagen binding-based activity assay. Antigen values correlated well with activity in normal individuals, but differed to various degrees in neonates, pregnancies at later maternal age and cardiac surgery. No discrepancies were noted in liver cirrhosis and inflammatory bowel disease, which were both associated with low plasma levels of ADAMTS13. In conclusion, parallel measurement of ADAMTS13 activity and antigen provides a new tool for understanding the behavior of the VWF-cleaving protease in health and disease.
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PMID:ADAMTS13 in health and disease. 1950 65

Human Glyco_18 domain-containing proteins constitute a family of chitinases and chitinase-like proteins. Chitotriosidase and AMCase are true enzymes which hydrolyse chitin and have a C-terminal chitin-binding domain. YKL-40, YKL-39, SI-CLP and murine YM1/2 proteins possess solely Glyco_18 domain and do not have the hydrolytic activity. The major sources of Glyco_18 containing proteins are macrophages, neutrophils, epithelial cells, chondrocytes, synovial cells, and cancer cells. Both macrophages and neutrophils use the regulated secretory mechanism for the release of Glyco_18 containing proteins. Glyco_18 containing proteins are established biomarkers for human diseases. Chitotriosidase is overproduced by lipid-laden macrophages and is a major marker for the inherited lysosomal storage Gaucher disease. AMCase and murine lectin YM1 are upregulated in Th2-environment, and enzymatic activity of AMCase contributes to asthma pathogenesis. YKL proteins act as soluble mediators for the cell proliferation and migration, and are also involved in rheumatoid arthritis, inflammatory bowel disease, hepatic fibrosis and cirrhosis. Chitotriosidase and YKL-40 reflect the macrophage activation in atherosclerotic plaques. Serum level of YKL-40 is a diagnostic and prognostic marker for numerous types of solid tumors. YKL-39 is a marker for the activation of chondrocytes and the progression of the osteoarthritis in human. Recently identified SI-CLP is upregulated by Th2 cytokine IL-4 as well as by glucocorticoids. This unique feature of SI-CLP makes it an attractive candidate for the examination of individual sensitivity of patients to glucocorticoid treatment and prediction of side effects of glucocorticoid therapy. Human chitinases and chitinase-like proteins are found in tissues and circulation, and can be detected by non-invasive technologies.
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PMID:Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. 1966 98

The Hepatitis B virus (HBV) is a causative agent of acute chronic hepatitis, cirrhosis, and hepatocarcinoma. The Hepatitis B virus X protein (HBx) has pleiotypic functions in the regulation of proliferation and apoptosis. It has been suggested that the anti-inflammatory drug sulfasalazine, which is commonly used to treat rheumatoid arthritis and inflammatory bowel disease, inhibits nuclear factor NF-kappaB and induces cell death in HBx-expressing liver cells. In this study, we demonstrate that sulfasalazine induces cell death via apoptosis in HBx-expressing liver cells, as evidenced by characteristic changes in nuclear morphology, cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-9, and activation of caspase-3. We also demonstrate that inhibition of NF-kappaB by siRNA fails to induce apoptosis of HBx-expressing liver cells, indicating that sulfasalazine modulates apoptosis of HBx-expressing cells in an NF-kappaB-independent manner.
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PMID:Sulfasalazine induces apoptosis of HBx-expressing cells in an NF-kappaB-independent manner. 1985 96

To determine the relative frequencies of gastrointestinal diseases (GI) in patients admitted to Samtah General Hospital, Gizan, the records of 2,442 adults admitted to the medical and surgical services for gastrointestinal diseases during the period 1413 to 1416 were analyzed retrospectively. 1,028 patients had acute appendicitis. The remaining 1,414 patients were admitted for various other GI diseases. In these 1,414 patients the commonest diseases were gastrointestinal infections (36.4%), peptic ulcer disease (19%), gall bladder disease (18.5%), viral hepatitis and its sequelae (20.7%). Despite the high prevalence of cholelithiasis, acute pancreatitis was uncommon (0.1 %). Inflammatory bowel disease was rare. There was no gender - related difference in the prevalence of gastrointestinal infections, peptic ulcer disease and carcinoma of the stomach. Males were significantly more afflicted than females with viral hepatitis (p< 0.0001), cirrhosis of the liver (p< 0.0001), hepatocellular carcinoma (p< 0.0005), variceal bleeding (p< 0.0005), and peptic ulcer bleeding (p< 0.005). As a large proportion of our patients had preventable diseases, it is expected that immunization and other public health measures will reduce the frequency of these diseases in the future.
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PMID:Pattern of gastrointestinal diseases in adult patients admitted to Samtah General Hospital, Gizan region, Saudi Arabia. 1986 48

Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). However, the morphology of precursor lesions and the prevalence of biliary dysplasia among patients undergoing liver transplantation for PSC are incompletely defined, and the earlier studies using relatively small number of cases have yielded conflicting results. We retrospectively evaluated 100 consecutive formalin-fixed PSC liver explants (including 30 with CCA) by randomly sampling the hilar and large intrahepatic bile ducts (10 additional tissue cassettes submitted per case). The following histologic features were evaluated and quantitated according to the number of ducts involved: mucinous metaplasia, pyloric metaplasia, intestinal metaplasia, pancreatic acinar metaplasia, and biliary dysplasia [low-grade vs. high-grade (biliary intraepithelial neoplasia-2 or neoplasia-3), papillary vs. flat]. Using Fisher exact test and t test, these features were correlated with the presence or absence of CCA and with the following clinical parameters: sex, age, PSC duration, cirrhotic-stage liver disease, and inflammatory bowel disease at the time of transplant. We found high frequencies of mucinous metaplasia (77%), pyloric metaplasia (73%), and pancreatic acinar metaplasia (10%), which did not differ between CCA and non-CCA livers. However, livers with CCA were more likely to harbor intestinal metaplasia (43% vs. 19%, P=0.013), dysplasia (of any grade) (83% vs. 36%, P<0.0001), and high-grade dysplasia (60% vs. 11%, P<0.0001), and also contained greater numbers of dysplastic ducts than non-CCA cases (P<0.0001). The relative frequency of papillary (44%) versus flat (56%) dysplasia did not differ between CCA and non-CCA cases. Overall, intestinal metaplasia was a significant predictor of bile duct dysplasia (P=0.0005) and CCA (P=0.013), low-grade dysplasia predicted high-grade dysplasia (P<0.0001) and CCA (P=0.0004), and high-grade dysplasia predicted CCA (P<0.0001). Among the clinical parameters, there were no significant differences in age, sex, history of inflammatory bowel disease, or PSC duration, but patients transplanted for CCA were less likely to have cirrhosis (60% vs. 86%, P=0.008). These data strongly support a metaplasia-low-grade dysplasia-high-grade dysplasia-carcinoma sequence in PSC-associated CCA, and underscore the known lack of relationship between patient age and PSC duration in the development of CCA. Even in the absence of CCA, bile duct dysplasia is still a relatively frequent finding, seen at least focally in 36% of benign end-stage PSC explants. Dysplasia, however, is generally confined to large and septal-size bile ducts and its presence may not be recognized unless multiple sections specifically targeted to the biliary tree are examined.
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PMID:Precancerous bile duct pathology in end-stage primary sclerosing cholangitis, with and without cholangiocarcinoma. 1989 28

Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated.
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PMID:Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. 2019 12


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