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)

Fibrosis of chronic pancreatitis can cause obstructive jaundice by compressing the intrapancreatic portion of the common bile duct. The frequency and clinical manifestations of common bile duct stricture from symptomatic chronic pancreatitis have been evaluated in 26 patients undergoing lateral pancreaticojejunostomy for intractable pain between 1974 and 1980. Four patients (15%) had a stricture with partial obstruction of the common duct in addition to pancreatic duct obstruction. Three of the four strictures were identified prior to operation by ERCP. The fourth developed biliary obstruction six months after pancreaticojejunostomy. Slight elevation of alkaline phosphatase was common and occurred in 12 of 22 patients with chronic pancreatitis without biliary obstruction. Alkaline phosphatase was elevated greater than four times normal in three of the four patients with a biliary stricture. Elevation of total and direct serum bilirubin occurred only in patients with stricture of the distal common duct. A waxing and waning picture of jaundice was seen in these four patients. When a fixed smooth stricture of the common duct is demonstrated in a patient with symptomatic chronic pancreatitis, drainage of the biliary tree should be combined with pancreatic duct drainage in order to prevent cholangitis, biliary cirrhosis, diagnostic confusion with pancreatic carcinoma, and persistence of pain.
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PMID:common duct obstruction in patients with intractable pain of chronic pancreatitis. 711 5

Mastocytosis is a disease of mast cell hyperplasia that may involve several organ systems, including liver. Between 1988 and 1991, we conducted a retrospective-prospective study of 41 patients with mastocytosis and found 61% had evidence of liver disease. Hepatomegaly was detected in 24%, splenomegaly in 41%, and elevated serum alkaline phosphatase, serum aminotransaminases, 5'nucleotidase, or gamma-glutamyltranspeptidase (GGTP) in 54% of the patients. Alkaline phosphatase levels directly correlated with GGTP levels, hepatomegaly, splenomegaly, and liver mast cell infiltration and fibrosis. Elevated alkaline phosphatase levels and splenomegaly were observed more frequently in patients with categories II and III mastocytosis. Five patients in combined disease categories II or III developed ascites or portal hypertension and died of complications of mastocytosis; three had hypoprothrombinemia at the time of death. Thirty-five liver biopsy specimens from 25 patients were examined. Mast cell infiltration was commonly observed in the biopsy specimens, more severe in those patients with either category II or III disease, and correlated with hepatomegaly, splenomegaly, alkaline phosphatase levels, and GGTP levels. Mast cells were often only detected by using special stains (toluidine blue and chloracetate esterase). Increased portal fibrosis was seen in 68% of the biopsy specimens and correlated with mast cell infiltration and portal inflammation. Cirrhosis was not observed. Nodular regenerative hyperplasia, portal venopathy, and venoocclusive disease was observed in eight biopsy specimens and may have been the cause of the portal hypertension or ascites in four patients. These findings demonstrate that liver disease with mast cell infiltration is a common finding in patients with mastocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases. 755 67

Liver injury produced by CCl4 depends on its metabolism by the liver cytochrome P450 enzyme system to a highly reactive intermediate (CCl3.). Cimetidine impairs cytochrome P450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl4-induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl4 plus cimetidine (120 mg kg-1, p.o.) three times a week for 8 weeks; group 3 received CCl4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl4 increased (P < 0.05) serum activities of alkaline phosphatase, gamma-GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co-treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P450. However, it could also stimulate regenerative processes.
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PMID:Cimetidine prevents and partially reverses CCl4-induced liver cirrhosis. 791 3

Non-alcohol-induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH. Forty patients were diagnosed with NASH based on a compatible liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty-four patients received 13 to 15 mg/kg/d of UDCA for 12 months. Sixteen patients with hypertriglyceridemia were placed on clofibrate, 2 g/day for 12 months. Twenty-five women and 15 men entered the study. Six of 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later required liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate, no change from baseline was found in mean ALT, aspartate transaminase (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histological grade of steatosis, inflammation, or fibrosis after 12 months of treatment as compared with entry. Alkaline phosphatase activities decreased significantly from baseline. Despite the known lipid-lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1-year pilot study. However, treatment of NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible benefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial.
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PMID:Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. 867 65

Use of long-term total parenteral nutrition (TPN) is often presumed to be associated with serious hepatic dysfunction. In this retrospective study, we reviewed the complete charts of patients who had received TPN for more than 2.5 years, starting in infancy or childhood, for evidence of liver dysfunction. There were 16 male and 10 female patients with a total of 254.5 patient years on TPN. Seventeen patients have been on TPN since birth or early infancy. Thirteen of 26 patients derive > or = 90% of their calorie intake from TPN. Six patients had hepatomegaly; two of them also had splenomegaly. Twenty-one patients had normal transaminases, nine have had past episodes of raised enzymes ranging from 2.5 to 7.5 times normal. Seventeen patients always had normal bilirubin levels, five had past episodes of hyperbilirubinaemia, while four patients had persistently raised bilirubin levels (range 1.5-20.7 g/dl). Alkaline phosphatase was normal for age in all patients except two. Hepatic synthetic function, as measured by albumin, pre-albumin levels and prothrombin time, was within the normal range in all patients except one. Liver biopsies were performed in eight patients. Two biopsies showed cirrhosis, one showed chronic active hepatitis (CAH) with cholestasis, two patients had fibrosis, one showed cholestasis and two biopsies were normal. One patient with cirrhosis and one with CAH were positive for hepatitis C antibody. Another asymptomatic patient was positive for hepatitis B. Only the patient with CAH had hepatic decompensation. We conclude that clinical hepatic failure is uncommon in our group of patients on long-term TPN for 2.5 years or more. Cirrhosis and fibrosis, when found, could not be solely attributed to TPN.
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PMID:Chronic liver disease in children on long-term parenteral nutrition. 874 28

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and to analyze their relationship with liver damage markers. One group of male Wistar rats was bile duct ligated and another group was sham operated, both groups were sacrificed 28 days after BDL. Plasma and liver cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10 (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA. Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method. Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen were quantified in liver. Two histopathological staining techniques were performed. BDL-induced cirrhosis was corroborated by the elevated liver damage markers and histopathological analysis. Chronic BDL significantly increased (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic IFN-gamma amount. NO was increased in both tissues, but such change was only significant in plasma. Biliary cirrhosis produces interesting changes in plasma and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats has not been previously described in both tissues for such cytokines and NO. Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.
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PMID:Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat. 1661 7

It is well known that IAP elevation, even at the level of 10mmHg used for laparoscopic surgery leads to an increase in portal pressure and decrease in portal blood flow. Since hepatic hemodynamics are already disturbed in cirrhotics, we decided to investigate the possible role of chronically elevated intra-abdominal pressure thus simulating ascites under tension-in liver perfusion and function in cirrhotic portal hypertensive rats. Four groups of 10 rats each were studied, including two control and two CCl(4)(-) induced cirrhotic groups. These were subdivided into normal and increased IAP. Elevation and maintenance of increased IAP to 20mmHg for 7 consecutive days was achieved by means of an intraperitonially placed balloon filled with water. Liver microcirculation was assessed by means of laser-Doppler technique, while venous blood samples were obtained for determination of the biochemical parameters of liver function. Cirrhotic rats showed a significant decrease in liver microcirculation in relation to controls (15.7+/-2.5 versus 23.2+/-2.2, p=0.001). Elevation of IAP led to a significant decrease (p=0.001) of liver microcirculation in both groups, i.e. from 15.7+/-2.5 to 12.7+/-1.7 units of flow in cirrhotics and from 23.2+/-2.2 to 15.9+/-2.6 units of flow in control rats. Alkaline phosphatase, alanine aminotransferase and bilirubin concentrations were found increased in cirrhotics in comparison to controls (p=0.05). IAP elevation resulted in a further impairment of liver function, but the differences, were not statistically significant. In conclusion, chronically elevated IAP in cirrhotic rats is associated with a significant impairment of the already decreased hepatic blood flow due to liver cirrhosis. Thus, the possible consequences of decreased liver perfusion must be taken under consideration in any case of severe cirrhosis presented with ascites under tension.
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PMID:Hepatic microcirculation after continuous 7-day elevated intra-abdominal pressure in cirrhotic rats. 1689 Jan 71

Cirrhosis is a very common disease and its treatment is limited due to lack of effective drugs. Some studies indicate that this disease is associated with oxidative stress. Therefore, we decided to study the effect of trolox, an effective antioxidant, on experimental cirrhosis. Cirrhosis was induced by CCl4 administration (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks) to Wistar male rats. Trolox was administered daily (50 mg/kg, orally). Fibrosis was assessed histologically and by measuring liver hydroxyproline content. Glutathione, lipid peroxidation and glycogen were measured in liver; serum markers of liver damage were also quantified. Transforming growth factor-beta (TGF-beta) was determined by Western blot and quantified densitometrically. Alkaline phosphatase, gamma-glutamyl transpeptidase and alanine aminotransferase increased in the group receiving CCl4; trolox completely or partially prevented these alterations. Glycogen was almost depleted by CCl4 but was partially preserved by trolox. Lipid peroxidation increased while glutathione decreased by CCl4 administration; trolox corrected both effects. Histology showed thick bands of collagen, necrosis and distortion of the hepatic parenchyma in the CCl4 group, such effects were prevented by trolox. Hydroxyproline content increased 5-fold by CCl4, while the group receiving both CCl4 and trolox showed no significant difference compared to the control group. CCl4 increased 3-fold TGF-beta, while trolox completely prevented this increase. We found that trolox effectively prevented cirrhosis induced with CCl4 in the rat. Our results suggest that the beneficial effects of trolox may be associated to its antioxidant properties and to its ability to reduce the profibrogenic cytokine TGF-beta expression.
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PMID:Trolox down-regulates transforming growth factor-beta and prevents experimental cirrhosis. 1881 77

Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.
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PMID:The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid improves the biliary cirrhosis in the rat. 1909 29

Steroid responsive biliary strictures in patients fulfilling criteria for primary sclerosing cholangitis (PSC) have been reported. The clinical course and response to therapy in patients with PSC with elevated immunoglobulin G4 (IgG4) levels has not been investigated previously. Patients with PSC were screened for IgG4-related biliary disease during 2006 to 2008 and data were collected prospectively. A total of 33 out of 285 (12%) patients with PSC (18 males) had elevated IgG4 (>140mg/dL) with a median age of 46 years (interquartile range 29-60); 24 could be evaluated. All patients had both intrahepatic and extrahepatic biliary strictures. Pancreatic disorders were found in 4 (17%), and 11 of 24 (46%) presented with jaundice; 8 of 24 (33%) received biliary stenting for a median time of 4 months (0-6). Liver cirrhosis was diagnosed in 12 of the 24 (50%). Overall, 18 patients were treated with corticosteroids and 6 patients managed conservatively. Nine of 10 patients with elevated bilirubin had improvement. Alkaline phosphatase decreased significantly at 2 months and at last follow-up. IgG4 levels at baseline were 242 (216-357) mg/dL and decreased to 109 (80-236) at 2 months (P < 0.05) and 174 (115-269) at last follow-up (P < 0.05). A total of 39% had adverse effects of steroids, mostly hyperglycemia. Relapses occurred in 7 of the 14 (50%), but biliary stents could be removed in all. Elevated IgG4 levels were observed in 12% of typical patients with PSC. Prevalence of cirrhosis was high, suggesting a severe liver disease course. Most patients had a good biochemical response to steroids, but adverse effects were common. Future work should be directed at finding therapy that is more effective, better tolerated, and of more lasting benefit.
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PMID:Primary sclerosing cholangitis associated with elevated immunoglobulin G4: clinical characteristics and response to therapy. 2022 74


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