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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-nine subjects (19 women and 60 men) with chronic viral hepatitis were studied to determine the role of hepatic iron and its biochemical correlates in determining response to interferon alpha therapy. Each subject was treated for 6 months with interferon alpha. A total of 45 (57%) subjects achieved either a full or partial response. No differences between responders and non-responders were evident for the type of hepatitis, age, initial alanine aminotransferase, serum iron, total iron binding capacity, %sat, or ferritin. In contrast, the hepatic iron content of non-responders was almost twice that of responders (1156 +/- 283 micrograms/g dry weight vs. 638 +/- 118; p < 0.05). Hepatic iron correlated with total iron binding capacity (r = 0.435) and ferritin (r = 0.585). This study showed that: 1) the hepatic iron content of responders is less than that of non-responders, 2) the relationships of hepatic iron with %sat and ferritin in patients with viral hepatitis are weak, and 3) hepatic iron content predicts a response to interferon therapy.
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PMID:Response to interferon alpha therapy is influenced by the iron content of the liver. 801 55

Hepatitis C virus (HCV) is able to replicate in peripheral blood mononuclear cells (PBMC) of HCV-infected patients. Few data are available on PBMC testing for HCV RNA in serum HCV RNA negative patients, positive for anti-HCV and with histological evidence of chronic hepatitis. Twenty such patients were studied; of these, 11 were tested during interferon alpha (IFN) treatment, at the time of serum HCV RNA clearance and ALT normalisation: only one was found to be positive for HCV sequences in PBMC. Within 3 months of IFN withdrawal all 11 patients relapsed with high ALT and recurrence of serum HCV RNA. Of nine serum HCV RNA negative patients with chronic hepatitis C who were not receiving IFN when tested (four untreated patients and five patients who had already completed IFN schedule), PBMC HCV RNA was detected in four. Evidence of active HCV replication (presence of the minus strand genome) in PBMC was also observed in two cases. Thus, five of the 20 patients without detectable serum HCV RNA turned out to be carriers of HCV sequences in PBMC. These data indicate that: 1. PBMC are an extrahepatic replication site of HCV; this is true also in the absence of serum HCV RNA; 2. the role of PBMC as a "viral reservoir" after IFN-induced serum HCV RNA clearance is questioned; 3. the absence of both serum and PBMC HCV RNA in patients under IFN is not predictive of sustained viral loss; 4. testing for PBMC viral sequences might enhance the chances of detecting HCV infection.
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PMID:Testing for hepatitis C virus sequences in peripheral blood mononuclear cells of patients with chronic hepatitis C in the absence of serum hepatitis C virus RNA. 779 39

A 28-year-old man with recurrent swelling of both upper eyelids was found to have increased values in several liver function tests (GOT 162 U/l, GPT 356 U/l, gamma-GT 643 U/l, bilirubin 3.0 mg/dl, alkaline phosphatase 925 U/l). Abdominal ultrasonography demonstrated lymph node enlargements up to 3 cm, dilated intra- and extrahepatic bile ducts, as well as a cyst of 3 cm size in the pancreatic tail. Endoscopic retrograde cholangiopancreatography and punch biopsy of the liver revealed sclerosing cholangitis. In addition to the eyelid swellings the patient also had protrusion of the left eyeball, blood eosinophilia (800/microliter) and marked increase in polyclonal IgG (6930 mg/dl) with lymphadenopathy suggesting the diagnosis of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD, lymphogranulomatosis X), confirmed by lymphocyte surface marker analysis. However, histological examination of a lymph node was more suggestive of a T-zone lymphoma. Treatment with ursodeoxycholic acid (250 mg three times daily) and prednisolone (initially 2 mg/kg daily) quickly led to normal biochemical values and regression of the eye changes. In addition, treatment with interferon alpha-2b (initially 3 mill. U daily for 10 days) was begun. The abnormalities in the bile ducts disappeared 6 months later. The patient has been in full remission for 25 months (prednisolone dosage reduced to 12.5/7.5 mg alternating daily and interferon alpha-2b 3 mill. U three times weekly). This response makes AILD with secondary involvement of the bile ducts the most likely diagnosis.
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PMID:[Angioimmunoblastic lymphadenopathy with dysproteinemia and sclerosing cholangitis]. 812 36

The efficacy of r-interferon alpha 2a (IFM) versus acyclovir (ACV) and vitamin therapy in the treatment of herpes zoster is reported. A total of 305 patients were randomly divided into 3 groups. One million units of IFN were administered i.n. once a day for 6 days in 223 cases, oral ACV 200 mg five times daily for 7 days in 34 cases, and vitamin B12, B1 and B2 therapy at conventional doses for 7-14 days in 48 cases. The results showed that both IFN and ACV could reduce pain in patients with herpes zoster and cut the total duration of symptoms, in comparison with vitamin therapy (P < 0.01). In the IFN group, 45 patients (20.2%) experienced side effects, including mild fever in 35 cases (15.7%) and a slightly depressed leukocyte count or increased serum ALT level (3 cases each). In the ACV group, one complained of discomfort in the gastroenteric tract, and another patient reported lumbodynia.
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PMID:Treatment of herpes zoster: recombinant alpha-2a-interferon versus acyclovir and vitamin therapy. Clinical Study Group on Interferon. 827 20

HCV is an RNA-virus which contains a positive-strand RNA genome. The RT-PCR method is used to detect the HCV-RNA in plasma. Quantification of HCV-RNA is difficult, but it can now be done by a competitive RT-PCR method developed recently. Genotypes of HCV can be classified into at least six basic groups, genotype I-IV can be distinguished by RT-PCR with type-specific primers. We report here that the prevalence of type-I, II, III, IV, and mixed type (II + IV) are 1.0%, 90.3%, 3.2%, 3.2%, and 2.2%, respectively. The DNA-probe method was recently developed and is less sensitive than the RT-PCR method, but simple and handy to detect HCV-RNA. Patients with chronic active hepatitis C received 3MU (9MU) of natural-interferon alpha (recombinant-interferon alpha 2a) daily for two weeks followed by three times a week for 22 weeks. Although the relationship between genotype of HCV and response to interferon-alpha therapy is unclear, the titer of HCV-RNA was significantly lower in long-term responders (ALT level remained within the normal range during the 12 weeks after the end of therapy) and short-term responders (ALT level rose again during the 12 weeks after the end of therapy) than that in nonresponders (ALT level was not normalized in spite of interferon-alpha therapy).
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PMID:[HCV]. 828

We studied the effects of two different types of interferon alpha (natural interferon from human leukocytes vs. recombinant interferon 2b) in 64 patients with chronic Non-A, Non-B hepatitis; other finalities were: definition of the optimal duration of therapy with interferon alpha (IFN alpha), entity of side effects, cost-benefit ratio. Patients were randomly assigned to one of three groups, according to duration of IFN alpha treatment: Group I was treated for 12 months, Group II for six months, Group III for 3 months. Each group consisted of two subgroups, divided on the basis of the type of IFN used: subgroup A was administered natural IFN alpha, and subgroup B received recombinant IFN alpha 2b. Each patients was given 3 million units of IFN alpha by intramuscular injection on alternate days. At the end of treatment, a decrease in serum ALT activity was achieved in 39 cases (65%). The response rate was higher in Group I (89%) than in Group II (54%) and Group III (55%). Natural and recombinant IFN alpha 2b induced similar effects in patients treated for twelve months (Group I); recombinant IFN was more effective than natural IFN alpha in patients treated for six and three months. We conclude that the 12-month treatment with 3 million units of intramuscular recombinant IFN alpha, administered on alternate days, might be the optimal therapy schedule. This proposal is also supported by the evaluation of the cost benefit ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapy of chronic non-A, non-B hepatitis with alpha interferon. A comparison between natural and recombinant alpha interferon. 830 72

Forty-seven patients with chronic hepatitis C were treated with recombinant interferon alpha-2a (rIFN alpha 2a) given subcutaneously in a standard dose of 3 MU thrice weekly for 12 months. Stored baseline sera and monthly samples during treatment were assayed for anti-interferon neutralizing antibodies using the antiviral neutralization bioassay against 5 IU of rIFN alpha 2a. During therapy, 15 of 47 patients (31.9%) developed detectable levels of neutralizing antibodies within 2-8 months after starting treatment. After 12 months of therapy, 26 of 32 antibody-negative patients (81.3%) showed normalization or marked reduction of ALT levels compared to 4 of 15 (26.6%) who developed anti-IFN neutralizing antibodies (p = 0.0009). Four patients demonstrated antiviral response during treatment even in the presence of low levels or late occurrence of neutralizing antibodies. Six of the seven patients who had disease reactivation after an initial response developed high titers of neutralizing antibodies. Our results suggest that reactivation of chronic hepatitis C before completion of therapy seems to be an obvious consequence of anti-IFN neutralizing antibody formation.
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PMID:Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection. 833 26

10 patients with chronic hepatitis C virus (HCV) infection who previously had responded temporarily to 9 months interferon alpha-2b treatment with normalization of ALT levels during treatment but later relapse were given a second 6-month treatment course. All patients were positive for anti-HCV by a second generation ELISA confirmed by second generation RIBA and positive for HCV RNA in serum before retreatment with interferon. Serum HCV RNA titers and ALT levels were monitored before, during and after treatment. ALT levels fell significantly from mean 1.95 mu kat/l before treatment to mean 0.96 and 0.85 mu kat/l after 4 and 24 weeks treatment, respectively (p < 0.005-p < 0.009). Six patients had normal ALT levels (< 0.07 mu kat/l) at treatment stop. 12 weeks post treatment cessation, however, the mean ALT level, 2.29 mu kat/l, was not significantly changed from the pretreatment level and all patients had raised ALT levels. The mean pretreatment HCV RNA titer in serum 10(5) (range 10(7)-10(3.5)) fell in all patients to mean 10(1.3) (range 10(3)-10(0)) already after 4 weeks treatment and became undetectable at treatment cessation in 5 patients, of whom 4 had normal ALT levels. ALT levels, however, were also normal in 2/5 patients who continued to have detectable HCV RNA titers at treatment cessation. After treatment was stopped HCV RNA titers rose again and 12 weeks post treatment the mean titer was 10(4.7) (range 10(3.5)-10(5.5)).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum HCV RNA levels in patients with chronic hepatitis C given a second course of interferon alpha-2b treatment after relapse following initial treatment. 838 32

Seven patients with decompensated posthepatitis B cirrhosis were treated with low doses of interferon alpha. The initial plasma level of HBV-DNA ranged from 3.0 to 189.3 pg/ml, and that of ALT from 37 to 156 IU/l. Liver biopsies demonstrated ongoing piecemeal necrosis. In sera of all but one patient, HBV-DNA became undetectable by hybridisation techniques within 10 to 28 weeks. Plasma HBeAg became negative in four and HBe-antibodies positive in three patients. Serum transaminase levels showed a marked initial rise 3 to 13 weeks after onset of therapy; they dropped to normal values later in all except one patient. Therapy was initiated at 1 MU (million units) three times a week for 2 weeks and was increased to 2.5 MU for 16 weeks. Later, this dosage was raised to 5 MU three times a week in some patients. Complications included variceal haemorrhage, aggravation of ascites or of encephalopathy, development of pneumonia, recurrence of spontaneous bacterial peritonitis or of gastric ulcer bleeding. One year after stopping the therapy, three patients are well and without any feature of liver decompensation. Three patients died before they could undergo a liver transplantation. In one patient treatment was interrupted because of marked exacerbation of liver cell necrosis. It thus seems possible to suppress HBeAg and HBV-DNA in patients with decompensated cirrhosis. This is important to prepare them for possible liver transplantation. Interferon should be initiated at low doses and the patients be very carefully monitored. Prophylactic therapy for bacterial peritonitis and for variceal haemorrhage is warranted.
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PMID:Treatment of decompensated viral hepatitis B-induced cirrhosis with low doses of interferon alpha. 845 21

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant recipients. To assess the efficacy and the safety of therapy with interferon alpha (IFN alpha) in such a population we conducted a prospective study where 16 kidney transplant recipients with chronic hepatitis C received recombinant IFN alpha 3 million units three times weekly scheduled for 24 consecutive weeks. All the patients had stable renal function for at least 1 year (mean serum creatinine 125.4 +/- 41 mumol/l). Fifteen patients had a positive HCV viraemia at the beginning of the study. In 15 patients serum alanine aminotransferase (ALT) levels decreased rapidly and normalized (48 +/- 44 vs 98.5 +/- 46 IU/l; P = 0.0044). ALT remained in the normal range as long as IFN alpha was continued. Serum levels of gamma glutamyl transpeptidase decreased from 129.75 +/- 111.2 to 88 +/- 85 IU/l; P = 0.012). After discontinuation of IFN alpha therapy seven responders relapsed within 1-9 weeks. HCV viraemia assessed 1 month after the end of IFN alpha therapy remained positive in all the patients who scored positive at the beginning, i.e. 15. Side effects of IFN alpha (fatigue, anorexia, weight loss) were frequent leading to four patients dropping out of the study. The haematological tolerance was moderate. The major concern was the increase in serum creatinine (162.5 +/- 57.6 vs 125.4 +/- 41 mumol/l; P < 0.05). In fact only six patients experienced renal failure occurring 45-168 days after the beginning of IFN alpha. Kidney transplant biopsies showed oedema, scarce scattered interstitial inflammatory cellular infiltration and moderate mesangial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preliminary results of treatment of chronic hepatitis C with recombinant interferon alpha in renal transplant patients. 852 7


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