Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case report is presented of a 43-year-old woman with generalized peliosis hepatitis that developed during longterm use of oral contraceptives (OCs). The patient had been in good health until the last 2 years when she began to experience vague epigastric pains and a feeling of abdominal distension. Several months prior to admission, she had started to complain of itching and fatigue. There was no history of dark urine, white stools, or hepatitis. On physical examination, no jaundice or cutaneous stigmata of chronic liver disease were observed. Laboratory studies showed a normal erythrocyte sedimentation rate and hematological blood count. A radionuclide study of the liver showed hepatomegaly; especially the left lobe was enlarged. A computerized tomographic scan of the liver showed multiple areas of decreased density in both of the enlarged lobes. There was no evidence of a tumor. Selective transfemoral angiography of the celiac artery also showed hepatic enlargement but no signs of a space-occupying lesion. At laparoscopy, the liver was grossly enlarged and had a lumpy appearance, but again there were no signs of a tumor. No evidence of veno-occlusive disease or hepatocellular adenoma was found. The diagnosis was peliosis hepatitis. The OCs were withdrawn, and the patient was discharged. Regular follow-up in the outpatient department showed no decrease in the size of the liver. The alkaline phosphatase level rose. The fatigue became worse, and cholestyramine was prescribed for progressive itching. In September 1980, the patient was admitted for reevaluation. A repeated CT scan and angiography of the liver again yielded no evidence of a tumor. Esophagoscopy showed the presence of varices grade 2. The liver at laparoscopy had the same appearance as it had in 1976. Histological examination of a biopsy specimen showed occasional dilated sinusoids and locally marked periportal and intralobular fibrosis. No regeneration nodules were found. The diagnosis was liver fibrosis. The patient's condition deteriorated gradually in the following years. She experienced increasing fatigue. Steatorrhea developed, and the patient lost weight. She needed increasing doses of cholestyramine and oral supplementation of vitamins A, D, and K. She was admitted for a 3rd time in February 1985. Esophagoscopy revealed varices grade 4. A CT scan of the liver showed no change. The patient successfully underwent an orthotopic liver transplantation in January 1987. The diagnosis of peliosis hepatis was well documented in this patient.
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PMID:Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives. 312 33

A syndrome of intrahepatic cholestasis leading to death in early childhood was studied in 16 Greenland Eskimo children. The pedigrees are compatible with autosomal recessive inheritance. Jaundice, bleeding, pruritus, malnutrition, steatorrhoea, osteodystrophy and dwarfism were typical clinical features. Eight had died between the ages of six weeks and three years due to bleeding or infections. Hyperbilirubinaemia, profound hypoprothrombinaemia, thrombocytosis and elevated alkaline phosphatase levels were evident. Serum calcium, phosphate and parathyroid hormone levels indicated a secondary hyperparathyroidism. Hepatic fibrosis developed with increasing age. Follow-up of the surviving patients was 4 to 30 months. The aetiology of the disease is unknown. The syndrome has some features in common with previously described patients with familial intrahepatic cholestasis. No specific treatment is available. Genetic counselling is essential.
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PMID:Fatal familial cholestatic syndrome in Greenland Eskimo children. 356 58

One hundred and one patients were included in a double-blind controlled trial to determine whether malotilate (diisopropyl 1,3-dithiol-2-ylidene malonate) is therapeutically effective in primary biliary cirrhosis. Fifty-two patients received malotilate (500 mg three times a day) and 49 patients placebo. The mean follow-up time was 28 months (range 6-46 months). The large majority of patients did not have advanced liver disease since only ten patients were in Child-Pugh class B and none in class C, and the median bilirubin and albumin at entry were normal. Malotilate had no clear effect on pruritus. In malotilate recipients the following statistically significant biochemical changes occurred: alkaline phosphatase decreased 21%, AST 20%, ALT 40%, IgA 12% and IgM 26%. In the placebo group no significant changes occurred. Evaluation of entry and 2-year liver biopsies indicated that malotilate diminished plasma cell and lymphocytic infiltrate and piece-meal necrosis, but had no effect on liver fibrosis. There was no difference in survival or in disease progression according to Child-Pugh criteria. In six patients receiving malotilate, but in none on placebo, treatment was discontinued due to suspected side effects. All patients recovered completely. We conclude that malotilate has an immune-modulating, anti-inflammatory but not anti-fibrotic effect in primary biliary cirrhosis. The clinical relevance of the observed benefits, however, appears too slight to recommend malotilate as single drug therapy in primary biliary cirrhosis.
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PMID:The results of a randomized double blind controlled trial evaluating malotilate in primary biliary cirrhosis. A European multicentre study group. 844 37

We report a case of long-lasting MARS therapy as a bridge to liver-kidney transplantation. A 26-month-old girl with congenital tubulointerstitial nephritis and severe liver fibrosis was placed on MARS for an acute-on-chronic liver failure due to sepsis. She underwent two sessions with good tolerance and recovered her previous neurological status. On the basis of pruritus, sleep, and vomiting improvement, repeated MARS sessions were performed to bridge her to combined liver-kidney transplantation. During eight months, 40 sessions were performed with the MARSmini kit and the MARS monitor (Gambro, Lyon, France). The treatment significantly decreased mean pruritus score from 2.2 +/- 0.9 to 0.8 +/- 0.6 night-time awakening and vomiting episodes. Body weight, height, and HC were -3.2, -3.5 and -2.2 SDS before and -1.7, -4.2, -2.0 SDS after eight months on MARS therapy, respectively. The arm circumference/HC ratio increased from 0.28 to 0.31. Mean total bilirubin serum levels were 303 +/- 72 micromol/L before and 214 +/- 42 micromol/L after MARS cycles. Long-lasting MARS dialysis is feasible in children, decreases adverse effects of severe chronic cholestasis, and may help to preserve nutritional status prior to combined liver-kidney transplantation.
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PMID:Long-lasting extracorporeal albumin dialysis in a child with end-stage renal disease and severe cholestasis. 1843 9

Erythema induratum, or nodular vasculitis, was initially described as a type of cutaneous tuberculosis. Currently, it is considered a multifactorial syndrome of lobular panniculitis of unknown cause. An association between erythema induratum and hepatitis C virus (HCV) has been suggested in previous reports. We report the case of a 49-year-old male presenting with a 3-year history of itchy, painful red to violaceous cutaneous nodules and plaques on both legs that had been unresponsive to topical dermatologic treatments. Evaluation of persistent serum transaminase elevations led to a diagnosis of chronic hepatitis C with bridging liver fibrosis. A thorough evaluation to exclude mycobacterial infection was performed, and anti-tuberculosis treatment was started based on a positive QuantiFERON test. There was no improvement in the skin lesions with this treatment. The patient then received standard antiviral therapy with pegylated interferon and ribavirin for 48 weeks. Treatment produced an early virologic response with significant improvement in the skin lesions, pain and pruritus. Six months after antiviral treatment, virologic relapse occurred without recurrence of the cutaneous lesions. There appears to be an association between erythema induratum and hepatitis C infection, probably mediated by circulating immune complexes. Interestingly, lesions improve with antiviral treatment and, as shown in this case, the effect may be sustained after stopping treatment despite virologic relapse.
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PMID:Erythema induratum and chronic hepatitis C infection. 1923 21

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomic-recessive inherited cholestatic disorders that begin in the neonatal period or in the first years of life. There are three types of PFIC defined by different mutations located in the gene responsible for the bile flow through the intrahepatic canalicular transporter system. These disorders usually present in children or young adults and the main clinical manifestations are cholestasis, jaundice and pruritus, and they progress slowly towards liver fibrosis in adult life. PFIC diagnosis is based on clinical suspicion, biochemical findings (that include normal gamma-glutamyl transpeptidase in type 1 and 2, but increased levels in type 3), image techniques that rule-out other disorders, and histological confirmation. Initial treatment consists of symptomatic relief of cholestatic symptoms with choleretic agents (urso-deoxycholic acid). Partial biliary derivation and ileal bypass are intermediate therapeutic options. In case of no response to these treatments, liver transplantation is indicated. We report the case of a neonate with PFIC type 2 presenting as a liver failure.
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PMID:[Progressive familial intrahepatic cholestasis presenting as liver failure]. 1981 57

PFIC 1 is a genetic disorder characterized by hepatic and gastrointestinal disease, often requiring LT during childhood. Extrahepatic symptoms, such as diarrhea and malabsorption, do not improve or may be aggravated after LT, as graft steatosis or steatohepatitis as consequences of the interaction between transplanted liver and native bowel. We describe a patient with PFIC 1 who presented with cholestasis in infancy, who developed intractable pruritus and liver fibrosis. The child underwent living donor LT at 3.6 yr of age, and he early developed severe refractory diarrhea, secondary malabsorption with protein-losing enteropathy, and an early fatty liver disease trough graft steatohepatitis. As the response to cholestyramine was unsatisfactory, we decided to perform an EBD by using the jejunal loop used for the cholangiojejunostomy. Diarrhea resolved rapidly after surgery. He remained well after six months following biliary diversion, with normal stool output and no protein loss. We documented a dramatic improvement of graft steatosis at histology as well as normalization of liver function test. EBD can be considered a valuable treatment option to avoid organ disfunction and loss in PFIC 1 transplanted patients who develop graft steatohepatitis.
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PMID:Recovery of graft steatosis and protein-losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child. 2167 3

6-ethyl-chedeoxycholic acid (6E-CDCA) is a farnesoid X receptor (FXR) ligand endowed with agonistic activity under development for treatment of cholestatic liver diseases including primary biliary cirrhosis (PBC) and liver-related metabolic disorders including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). FXR is a bile sensor that acts in coordination with other nuclear receptors to regulate essential steps of bile acid uptake, metabolism and excretion. 6E-CDCA has been investigated in preclinical models of cholestasis, liver fibrosis and diet-induced atherosclerosis. In a phase II clinical trial in patients with PBC, 6E-CDCA met the primary endpoint of a reduction in alkaline phosphatase levels but safety data indicated that the drug exacerbated pruritus, one of the main symptoms of PBC, suggesting that 6E-CDCA or FXR are mediators of pruritus in humans. Treatment of patients with diabetes and liver steatosis resulted in amelioration of insulin sensitivity despite a reduction a slight reduction in HDL and increased levels of LDL were observed. These side effects on bile acids and lipid metabolism were all predicted by pre-clinical studies, suggesting that potent FXR ligands hold promise but potential side effects might limit their development.
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PMID:Farnesoid X receptor agonist for the treatment of liver and metabolic disorders: focus on 6-ethyl-CDCA. 2170 32

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.
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PMID:Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. 2234 19

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease affecting the intrahepatic and extrahepatic biliary tree leading to bile duct strictures, progressive cholestasis, and development of liver fibrosis and cirrhosis. The pathogenesis of PSC is still elusive; however, both an immune-mediated injury of the bile ducts as well as increased recruitment of intestinal-primed T lymphocytes to the biliary tracts seem to contribute to disease development and progression. TGR5 (Gpbar-1) is a G-protein-coupled receptor responsive to bile acids, which is expressed in cholangiocytes, intestinal epithelial cells, and macrophages of the liver and intestine as well as in CD14-positive monocytes of the peripheral blood. Activation of TGR5 in biliary epithelial cells promotes chloride and bicarbonate secretion, triggers cell proliferation, and prevents apoptotic cell death. In immune cells, stimulation of TGR5 inhibits cytokine expression and secretion, thus reducing systemic as well as hepatic and intestinal inflammation. The expression pattern of TGR5 in the liver and intestine as well as the potential protective functions of TGR5 suggest a role for this receptor in the pathogenesis of PSC. While mutations in the coding region of the TGR5 gene are too rare to contribute to overall disease susceptibility, the expression and localization of the receptor have not been studied in PSC livers. Pharmacological activation of TGR5 in mice promotes protective mechanisms in biliary epithelial cells and reduces hepatic and systemic inflammation; however, it also provokes pruritus. Further studies are needed to predict the potential benefits as well as side effects of TGR5 agonist treatment in PSC patients.
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PMID:TGR5: pathogenetic role and/or therapeutic target in fibrosing cholangitis? 2513 74


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