Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The natural history of chronic hepatitis B virus (HBV) infection in children may lead to hepatic cirrhosis and hepatoma. Since the antiviral effect of recombinant interferon alpha (rIFN-alpha) in the treatment of chronic hepatitis in adults has been proven, a controlled study of therapy using rIFN-alpha in children chronic hepatitis due to HBV has been carried out. Twenty-four children (4-14 years old) HBsAg, HBeAg and HBV-DNA positive were randomly allocated to one of three groups: 1) n = 8, control; II) n = 8, who received 10 MU/m2 of rIFN-alpha (Boehringer Ingelheim)/m2 body surface, I.M., twice a week for six months and III) n = 8, treated with 7.5 MU/m2 under the same conditions. No basal differences between the three groups were observed. No intolerable toxicity was observed and all children completed the treatment period. At the end of the therapy, 5 patients in groups I (1 case), II (2 cases) and III (2 cases), had lost circulating HBV-DNA. With respect to HBeAg, 3 patients (one from each group) were negative by the sixth month, developing anti-HBe. Decreases in ALT levels among rIFN-alpha responder patients were observed, while no changes occurred in the rest. A significant decrease in the percentage of HBcAg positive hepatocytes was detected only among treated patients, when comparing the basal and final liver biopsies. In summary, rIFN-alpha therapy in children is well tolerated. In addition, these results suggest that rIFN-alpha has an antiviral effect.
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PMID:[A controlled study of treatment with recombinant interferon alpha of chronic hepatitis due to the B virus in childhood]. 203 70

Alpha-interferon has emerged as the most effective agent for the treatment of chronic hepatitis when active replication of virus B, C, or D is present. Exogenous administration of human alpha-interferon, now possible through modern large-scale production methods, is associated with suppression of virus in blood. Amelioration of liver disease occurs in 35% of patients with hepatitis B virus and in 50% with hepatitis C virus with interferon doses of 30 and 10 MU per week, respectively, for 16-26 weeks; after therapy, persistent normalization of serum alanine aminotransferase is observed in 35% and 27%, respectively. Similar results have now also been reported for chronic hepatitis D. Enhanced response rates (greater than 50%) may be obtained by prolonged intermittent interferon therapy. Combination of interferon with another 'antiviral' agent (vidarabine, acyclovir, prednisone) has not increased therapeutic efficacy. Alpha-interferon induces side effects such as fatigue, flu-like syndrome, myalgia, and changes in mood and granulocytes. Patients with decompensated cirrhosis are particularly prone to bacterial infection and disease exacerbation and should receive lower doses. Interferon, when applied skillfully, induces the highly beneficial transition of active viral replication into viral latency, thereby greatly reducing infectivity, symptoms, and activity of the liver disease. Prevention of death from liver failure or hepatocellular carcinoma is to be expected.
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PMID:Treatment of chronic viral hepatitis anno 1990. 212 46

Non-A, non-B (type C) hepatitis is a serious world problem which typically results in chronic hepatitis and may lead to cirrhosis and hepatocellular carcinoma. alpha-Interferon has recently been studied in a number of randomized controlled trials throughout the world. The results of those studies are reviewed here. ALT levels were normalized by 2-3 MU recombinant interferon alfa-2b, three times per week s.c. for 6 months (p less than 0.001 vs. control) in 36% of patients in five trials. Biopsy tests also demonstrated histological improvement in lobular and periportal inflammation. Unfortunately, relapse is a common problem in these studies, occurring in 49% of patients treated with 3 million units and 57% of those treated with 1 million units. Retreatment usually brings remission once again. In the future, long-term studies will further elucidate the natural history of the disease and documented guidelines for interferon dosage and duration of dosing in a wider range of patient subgroups will become available.
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PMID:Recombinant alpha-interferon treatment of non-A, and non-B (type C) hepatitis: review of studies and recommendations for treatment. 212 92

Among 30 consecutive patients diagnosed with primary biliary cirrhosis (PBC) in Taiwan, 27 were females and the median age of symptom onset was 54.5 years. Most had similar clinical manifestations to those reported in the Western countries, but ascites and oesophageal varices as commonly found at the late stages of cirrhosis of liver were noted in nine patients (30%) and 13 patients (43%) respectively. Only one patient was asymptomatic. Hyperbilirubinaemia was noted in 21 patients (70%) and hypoalbuminaemia in 8 patients (27%). All patients had elevated serum alkaline phosphatase and alanine aminotransferase and 28 (93%) had antimitochondrial antibodies. Ten out of 21 patients (48%) were positive in antinuclear antibodies, of which most were of speckled type. Sixteen out of 18 patients (89%) had elevated serum IgM levels. Interestingly, only one of 26 patients (3.8%) was positive for hepatitis B surface antigen, in contrast to its high prevalence (15%) in the Taiwan population. Special associated diseases, including systemic lupus erythematosus, scleroderma, malignant lymphoma and hepatocellular carcinoma, were each noted in one patient respectively. Eight patients had a history of gallstones before the diagnosis of PBC. The mean follow-up period was 23.6 +/- 19.8 months, and nine patients died during that period. In conclusion, the clinical manifestations of PBC in Taiwan are similar to those in Western countries, but most of our cases were at later stages.
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PMID:Primary biliary cirrhosis in Taiwan. 212 28

Radiation tolerance of the partially irradiated liver was studied in eight patients with primary hepatoma treated by a multimodal approach. Seven patients were treated by transarterial embolization therapy (TAE) with Lipiodol-MMC, and two patients were treated by operation, combined with radiotherapy. Six patients had liver cirrhosis and the other one had renal dysfunction. Respiration-gated irradiation was employed to reduce a treatment volume for seven patients. Radiation portals were carefully tailored using the embolized Lipiodol or a metal clip inserted into the tumor as references. Two or three portals were used for each patient. The treatment volume ranged from 64 to 1400 cm3. The target dose ranged from 50.4 Gy to 81.0 Gy, from 73.5 to 108.6 in TDF. Liver function tests (GOT, GPT, LDH, ALP, ChE and total Bilirubin) were examined for 30 weeks after initiation of irradiation. Three patients showed abnormal value in more than 5 tests. Of these three patients, the hepatic hilum was included in the treatment volume in two, and the tumor progressed during the observation period in two. Leukopenia and thrombopenia were observed, but these values were not below 2000 and 40000/mm3, respectively, although the thrombocyte count before irradiation was below 100000/mm3 in 7 patients. AFP titers decreased after the treatment in six out of seven patients with abnormally elevated pretreatment titer. The survival period after staring irradiation was 6.5 to 25 months. "The volume dose" did not correlate well with the degree of the liver function aggravation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Radiation tolerance of partially irradiated liver in a multidisciplinary treatment for hepatoma]. 216 20

In my opinion, independent, carefully conducted scientific studies indicate that an accurate, rapid, relatively sensitive, and inexpensive laboratory test substantially reduces the major long-term risk of blood transfusion in the United States; donor ALT has emerged as one of the most effective laboratory determinants for reducing the incidence of NANB PTH. Despite its nonspecificity and limited predictive value, ALT screening may prevent up to 30 percent of cases, one-half of which would progress to chronic liver disease and then possibly to cirrhosis and hepatocellular carcinoma. Blood donors appear to understand and accept the testing rationale as a reasonable precaution. Admittedly, ALT screening is not a perfect solution. It has not been validated by prospective studies and probably never will be. Determination of the proper cutoff value remains controversial. However, the risk of PTH progresses with increasing ALT levels, so that the real issue is not whether to test, but how best to configure the test to exclude the fewest false-positive donors while detecting the most true-positive donors. It is undesirable and expensive to discard safe units of blood, but the primary responsibility of blood collectors is to ensure an adequate supply of safe components. Some still consider the ALT assay technically too demanding for routine use. However, technical concerns regarding performance and interpretation are not insurmountable, and both quality control and proficiency testing are being addressed at the national level. The assay is capable of great precision, and a system employing a national standard and single cutoff has already been described and tested with excellent results. Circumstances have changed since donor screening with ALT was widely implemented in 1986. More thorough screening and testing have eliminated many high-risk donors. Public expectations have changed as well. While it is neither reasonable nor responsible to promise the public blood transfusions without risk, neither is it prudent to propose any major change in management of the blood supply without compelling evidence that such a change will not impair transfusion safety. It is hard to defend discontinuing the ALT screen at this time, especially when the costs of retaining it are minimal and the benefits clearly greater than those of screening for HTLV-I and for Treponema pallidum (in the United States) or HIV-2 (in West Germany). A first-generation assay specific for antibody to hepatitis C will probably be available within a year.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Controversies in transfusion medicine. Alanine aminotransferase screening of blood donors: pro. 234 35

We examined the clinical usefulness of serum tripeptide aminopeptidase (EC 3.4.11.4) activity in diagnosing liver diseases. We found that increased tripeptide aminopeptidase activity accompanied an elevation in alanine aminotransferase activity (ALT) in the sera of patients with non-cancerous liver diseases and that these enzyme activities were correlated (r = 0.826-0.972). In contrast, an increase in tripeptide aminopeptidase activity did not coincide with an elevation in ALT activity in the sera of patients with cancerous liver diseases. We also observed a correlation in acute hepatitis and in patients following transcatheter arterial embolization of hepatoma throughout their subsequent clinical courses. The difference in serum enzyme activities for cancerous and non-cancerous liver diseases seems to result from changes in enzyme activities in cancerous liver tissues. We found that the ratio of tripeptide aminopeptidase to ALT activity in hepatoma tissues (1.9) was 4 times higher than that in normal liver tissues (0.5).
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PMID:Clinical usefulness of serum tripeptide aminopeptidase activity in diagnosing liver diseases. 243 31

Seventy HBsAg-positive patients, including 24 with primary hepatocellular carcinoma, 34 with chronic active hepatitis, 12 with chronic persistent hepatitis and 30 asymptomatic healthy hepatitis B virus carriers were tested for anti-HBc IgM using the Corzyme-M test. Anti-HBc IgM was detected in 50% of the primary hepatocellular carcinoma patients, 26.5% of the chronic active hepatitis patients, 25% of the chronic persistent hepatitis patients, but in none of the healthy hepatitis B virus carriers. There was no correlation between the presence of anti-HBc IgM and HBeAg, hepatitis B virus DNA, ALT or alpha-fetoprotein levels in either the chronic active hepatitis or chronic persistent hepatitis patients. However, a significantly higher positive rate of anti-HBc IgM was noted in the HBeAg-positive or HBV DNA-positive primary hepatocellular carcinoma patients than in those with negative markers of viral replication, but no correlation was noted between the presence of anti-HBc IgM and serum ALT or alpha-fetoprotein levels in these primary hepatocellular carcinoma patients. Also, no differences in positivity for HBeAg, HBV DNA or levels of serum ALT were noted when patients with high titers of anti-HBc IgM were compared to those with low titers. Thus, anti-HBc IgM cannot distinguish between HBsAg-positive patients with chronic active hepatitis, chronic persistent hepatitis or primary hepatocellular carcinoma, does not correlate with serum ALT or alpha-fetoprotein levels and is only associated with markers for viral replication in primary hepatocellular carcinoma patients. Based on this, anti-HBc IgM appears to have a limited usefulness for diagnosis of either chronic hepatitis B or primary hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is anti-HBc IgM a useful clinical test in patients with HBsAg-positive chronic hepatitis or primary hepatocellular carcinoma? 245 29

Sera from 714 mentally retarded carriers of hepatitis B surface antigen were screened for alpha fetoprotein (AFP) by monoclonal radioimmunoassay. Serum AFP levels were less than 20 mcg/L in 708 (99.2%) carriers. One 29-year-old carrier with normal liver function had serum AFP level of 1500 mcg/L, which increased to 12,500 mcg/L after 72 days. She died of multifocal hepatocellular carcinoma (HCC) with cirrhosis. Five other carriers with serum AFP levels between 20 and 165 mcg/L are alive without clinical HCC. No correlation was found between serum AFP level and race, age, sex, Down's syndrome, serum alanine aminotransferase level, and hepatitis B e antigen positivity. Single cross-sectional serum AFP screening by itself is not sufficient for early diagnosis of HCC.
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PMID:Serum alpha fetoprotein in 714 mentally retarded carriers of hepatitis B surface antigen. 245 44

Ten patients with hepatocellular carcinoma, three of whom had pulmonary metastasis, were treated with adoptive immunotherapy using autologous lymphokine-activated killer cells plus recombinant interleukin 2. Patients received 15 micrograms per day of recombinant interleukin 2 consecutively (for 14 to 64 days), from Day 7 prior to the first leukapheresis, and received 10(9) to 10(10) lymphokine-activated killer cells once or twice per week intravenously; the lymphokine-activated killer cells had been generated from mononuclear cells obtained through leukapheresis. Preadministration of recombinant interleukin 2 prior to the first leukapheresis resulted in a remarkable increase of lymphokine-activated killer activity in seven of nine cases in whom lymphokine-activated killer activity had been poorly inducible even at high concentrations of recombinant interleukin 2. At the end of the treatment, liver tumor regression (34 and 63%, respectively, of two-dimensional size) was observed in two of two patients with a solitary tumor; no increase of liver tumor size was observed in seven patients with massive or multiple tumors, and no changes in the size or number of pulmonary metastatic tumors in any patients were observed. More than a 35% decrease in serum alpha-fetoprotein level was noted in four of nine alpha-fetoprotein-positive patients. However, Child's grades, performance status and lymphokine-activated killer activity on entry into the study could not be used as parameters to predict therapy responsiveness. Neither serious side effects nor significant changes of serum bilirubin, ALT and creatinine were noted. Thus, this treatment seems to be well tolerated even in advanced hepatocellular carcinoma with poor liver function reserve, and tumor regression could be expected in small-burden hepatocellular carcinoma. The assessment of the therapeutic effects and application in hepatocellular carcinoma awaits the development of this trial.
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PMID:Adoptive immunotherapy with lymphokine-activated killer cells plus recombinant interleukin 2 in patients with unresectable hepatocellular carcinoma. 247 81


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