Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.
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PMID:Pruritus as a presenting symptom of chronic hepatitis C. 979 Apr 51

The N-linked sugar chain structures of human hepatic, intestinal, and placental alkaline phosphatases (ALPs) were studied comparatively by chromatography on various lectin columns in combination with digestion by several kinds of exoglycosidases. The sugar chain structures were organ specific. On the basis of these organ-specific structures, we investigated serum ALP using a Neu5Ac(alpha)2-->6Gal(beta)1-->4 GlcNAc-specific Trichosanthes japonica agglutinin-I (TJA-I)-Sepharose column to clarify whether the level of TJA-I-binding serum ALP activity can be used as an indicator to discriminate one form of chronic liver disease from another. Levels of TJA-I-binding ALP in serum were higher in cases of liver cirrhosis and hepatocellular carcinoma than in chronic hepatitis (P < 0.01). The levels of TJA-I-binding ALP in serum did not change significantly after transcatheter arterial embolization, and the amounts of TJA-I-binding ALP activity in noncancerous cirrhotic liver tissues were higher than those in cancerous liver tissues derived from hepatocellular carcinoma patients, indicating that the TJA-I-binding ALP is mainly derived from cirrhotic liver tissues rather than cancerous liver tissues. These results indicate that analysis of the levels of TJA-I-binding ALP in serum is clinically useful for differentiating liver cirrhosis from chronic hepatitis and that altered sugar chain expression in ALP occurs mainly in liver cirrhosis.
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PMID:Elevated serum levels of Trichosanthes japonica agglutinin-I binding alkaline phosphatase in relation to high-risk groups for hepatocellular carcinomas. 982 41

Interferon (IFN) is the only drug that has been approved by the FDA for therapy of chronic hepatitis C. However, optimal dose and duration of therapy are still controversial. This study compares the effectiveness of treatment of chronic hepatitis C patients with 3 vs. 5 million units (MU) of recombinant alpha-interferon 2-b three times per week. We also evaluated the relapse rate with a shorter 12 week-course of therapy in those patients who had normalization of aminotransferases by week 12. Seventy-five patients were randomized to receive either 3 vs. 5 MU of IFN; seventy-two completed the study. A complete response was seen in 11/35 (31%) of those treated with 5 MU vs. 13/37 (35%) in the 3 MU dose (p = 0.74). Patients were followed after IFN was withdrawn and only 2 had persistently normal aminotransferases. Analysis of multiple variables was done to predict response to IFN and only elevations of GGT, ferritin and alkaline phosphatase were found to be predictors of a poor response. Therefore, we recommend initial therapy with 3 MU of IFN for a longer period than 12 weeks in patients who show a response.
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PMID:Chronic hepatitis C: treatment comparison between 3 and 5 million units of interferon alpha-2b. 988 67

A number of pitfalls can be encountered in the interpretation of common blood liver function tests. These tests can be normal in patients with chronic hepatitis or cirrhosis. The normal range for aminotransferase levels is slightly higher in males, nonwhites and obese persons. Severe alcoholic hepatitis is sometimes confused with cholecystitis or cholangitis. Conversely, patients who present soon after passing common bile duct stones can be misdiagnosed with acute hepatitis because aminotransferase levels often rise immediately, but alkaline phosphatase and gamma-glutamyltransferase levels do not become elevated for several days. Asymptomatic patients with isolated, mild elevation of either the unconjugated bilirubin or the gamma-glutamyltransferase value usually do not have liver disease and generally do not require extensive evaluation. Overall hepatic function can be assessed by applying the values for albumin, bilirubin and prothrombin time in the modified Child-Turcotte grading system.
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PMID:Special considerations in interpreting liver function tests. 1022 7

The main an etiological agents of chronic hepatitis are viral infections. The viral infection course and outcome depend mostly on the immunological response. Infected hepatocytes are damaged by appropriately viral antigen-specific cytolytic T lymphocytes. Those sensitised T cells react only with those hepatocytes which express viral antigen and antigen HLA on membrane surface. The aim of this study was to evaluate the expression of selected histocompatibility antigens HLA in liver biopsy specimens of patients with chronic viral hepatitis. Seventeen patients with chronic persistent hepatitis (inflammatory activity 1-4 points according to Scheuer scale modified by Gabriel) and 27 patients with chronic active hepatitis (5-10 points) were studied. In these groups of patients the intensity of HLA-I (A, B, C), HLA-II (DR) expression in liver biopsy specimens, alanine aminotransferase activity, markers of HBV and HCV in serum were examined. The monoclonal mouse anti-human antibodies and streptavidin-biotin with alkaline phosphatase method for estimation of HLA-I, HLA-II was used. Results were statistically analysed using Mann-Whitney's U test and Spearman's rank correlation test. Generally, the expression of HLA-I and HLA-II on hepatocyte membrane was shown. Significant differences in expression of HLA-II among studied groups were observed, moreover the highest degree of HLA-II intensity in the group of patients with greater inflammation activity was significantly more frequently observed. The expression of HLA-I, HLA-II was regardless of the viral a etiology and serological markers of HBV replication. The degree of studied parameters expression was positively correlated with biochemical activity of inflammation.
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PMID:[The HLA-I and HLA-II expression evaluation in liver biopsy specimens of patients with chronic viral hepatitis]. 1080 May 78

This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.
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PMID:The value of liver function tests in hepatocellular carcinoma. 1087 29

To assess epidemiological and clinical significance of drug hepatotoxicity in the setting of liver diseases consultation, ten thousand and three hundred forty two prospectively designed clinical records from patient cared for in our Liver Unit in the period 1988-1998 were incorporated into the study; 58 out of 10,342 (prevalence = 5.6%) fulfilled at least the first three of the following causality requirements: 1.--Liver injury associated in time to drug exposition; 2.--Negative evaluation of more common other etiologies; (alcohol, viruses, immunologic, metabolic, etc) 3.--Favourable response to drug withdrawal (ALT < 50% of baseline in 8 to 30 days in acute hepatitis type, and alkaline phosphatase and/or total bilirubin < 50% of baseline up to 6 months, in acute cholestasis) 4.--Inadverted or rarely prescribed positive challenge. Acute hepatitis type of injury were considered when serum ALT rise 8 times or more above normal superior level with alkaline phosphatase (APh) below 3 times; "pure" cholestasis when APh rise 3 times or more above normal with ALT below 8 times; mixed acute injury or cholestatic hepatitis when both ALT and APh were elevated above 8 and 3 times respectively, and indeterminate type when both enzymes were below the referred levels. Chronic injury were considered when six or more month of evolution and compatible liver histology happens. Clinical severity were expressed as mild (absence of major clinical complications, serum bilirubin < 5 mg/dl and prothrombin concentration > 75%), moderate (presence of clinical complications, bilirubin > 5 mg/dl and prothrombin concentration between 50-75%), and severe (major clinical complications with bilirubin > 5 mg/dl and prothrombin concentration < 50%). Female/male ratio was 1.4:1, with age average 39 years (R = 15-77) and major concentration of cases above 40. More than 50% of cases received 2 or more drugs. Jaundice was present in 60.4%, and systemic manifestations of hypersensibility (fever, adenomegalies, rush, mononucleosis like syndrome, eosinophilia) in 29.3%. Acute injury represented 91.4% of the cases: 41.4% acute hepatitis, 15.5% "pure" cholestasis, 24.1% cholestatic hepatitis, and 10.3% indeterminate type. Four patients (4.5% of acute injury cases) were presented as severe acute liver failure, leading to liver transplant in one of them, drug association (INH-rifampicin and carbamazepine-phenobarbital) and inadverted challenge (sulphonamides and pemoline) were associated to clinical severity. Chronic injury were found in five patient (8.6%), four of them associated to chronic hepatitis and the other one to a ductopenic syndrome. Six drugs represented 53.4% of our cases; oral contraceptives (7 cases), INH alone or combined with rifampicin (6 cases), sulfonamides and clorpropamida (5 cases each), carbamazepine and amiodarone (4 cases each). Normalization of liver enzymes after drug suppression took 2 to 8 weeks in acute hepatitis type (X = 4 weeks), 4 to 20 in "pure" cholestasis (X = 12 weeks) and 8 to 24 weeks in cholestatic hepatitis or mixed type (X = 16 weeks). Two cases of chronic hepatitis normalize the histological activity index in 20 and 18 month respectively, one case remains as chronic hepatitis at 10 month and the other one progress to cirrhosis; the ductopenic syndrome normalize histology in 19 months receiving urso-deoxicolic acid, 10 mg/k/day.
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PMID:[Clinic-epidemiological significance of drug hepatotoxicity in liver disease consultation]. 1092 31

Bile duct lesions are observed in the livers of chronic hepatitis C patients, but are inconstant and rarely associated with other features of chronic cholestasis and progressive bile duct injury or loss. We aimed to identify the clinical and biochemical characteristics of patients with chronic hepatitis C from our patient database presenting with prominent cholestatic features to determine if there is a correlation between histological evidence of bile duct injury and clinical or biochemical features observed in these patients. We retrospectively reviewed a hepatitis C database including 620 patients to identify those who presented with either alkaline phosphatase (AP) > or = 400 units/liter (normal 30-126 units/liter) or AP > or = 250 units/liter with pruritus. All patients were negative for anti-mitochondrial antibody (AMA). Appropriate exclusion criteria were used to exclude patients with other confounding factors. Histological features were compared with age- and sex-matched controls selected randomly from our hepatitis C database. Thirty-two patients were identified as meeting the above criteria. Twenty-four were excluded for the presence of other confounding factors and two for lack of liver biopsy. There were two men and four women. The mean age was 47 +/- 9 years. Four of the six presented with pruritus, which was severe in three. Liver biopsy showed evidence of moderate to severe fibrosis in all but one patient. Evidence of bile duct injury was seen in all patients and tended to be more severe than in controls. Bile ductular proliferation and mild ductopenia were the most commonly observed findings. A subset of patients with chronic hepatitis C may present with prominent cholestatic features. The majority of these patients present with pruritus and have histological evidence of bile duct injury, which may be progressive.
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PMID:Cholestatic presentation of chronic hepatitis C: a clinical and histological study with a review of the literature. 1168 May 77

The pathogenesis of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is poorly understood, but the cellular immune response is likely to have a major role. Daclizumab, an interleukin-2 receptor (IL-2R) antibody that blunts T-cell activation, leading to a decreased risk for cellular rejection, is used frequently in transplant recipients. The aim of this study is to evaluate the effect of daclizumab therapy on the incidence and severity of recurrent HCV. Forty-one liver transplant recipients (21 patients, HCV positive; 20 patients, HCV negative) at high risk for neurological or renal complications of calcineurin inhibitors were administered daclizumab, mycophenolate mofetil (MMF), and steroids in the early post-LT period, followed by tacrolimus and a steroid taper. All patients were followed up prospectively for graft function and disease recurrence with protocol liver biopsies day 7, month 4, and yearly. Compared with patients without HCV, patients with HCV administered daclizumab had greater 4-month serum alkaline phosphatase, total bilirubin, and alanine aminotransferase (ALT) levels. These biochemical differences resolved by 12 months, except for persistent elevation of ALT levels. Compared with a well-matched HCV control population, patients with HCV administered daclizumab were more likely to have an earlier onset of hepatitis, jaundice, and greater histological activity. Recurrent hepatitis progressed more rapidly in the daclizumab group; 45% developed advanced disease within 1 year. HCV viral load in the daclizumab group was significantly greater at both 4 months and 1 year. Results of this study suggest that the use of adjuvant IL-2R antibodies in combination with MMF in the early peritransplantation period may be associated with early recurrence of hepatitis C and more rapid histological progression of disease.
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PMID:Anti-interleukin-2 receptor therapy in combination with mycophenolate mofetil is associated with more severe hepatitis C recurrence after liver transplantation. 1175 8

We examined 170 patients with acute viral hepatitis B (AVH-B) and 10 patients with chronic hepatitis B (CH-B) exacerbation. 85% of them were under 40 years old. During the 12-hour night period we measured urine excretion of nitrites (NO2-) and nitrates (NO3-). It was significantly high in AVH-B but in CH-B exacerbation it did not differ from the controls. ACTH and hydrocortisone blood levels were significantly high in AVH-B and in CH-B exacerbation. Though hydrocortisonemia and nitrituria/nitraturia during AVH-B were both high, the correlation between them was negative due to nitric oxide (NO) synthesis suppression by hydrocortisone. A negative correlation between nitrituria/nitraturia and ALAT, ASAT, bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase is an indirect evidence for a protective role of NO against viral hepatitis B.
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PMID:[Changes in synthesis of nitric oxide, blood levels of ACTH and cortisol in viral hepatitis B]. 1181 Nov 11


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