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)

Immunity to allogeneic MHC Ags is weak in rodent livers, raising questions as to the mechanisms that might control responses in this organ. Infection with an adenovirus vector reveals that T cell-mediated immunity to nonself-Ags in the liver is self-limiting. Virus-induced liver injury decreases and coincides with disappearance of virus-specific CTL, concomitant to an increase of apoptotic T cells early after infection. But whereas death in CD4 cells is independent of Fas, perforin, and TNF-alpha, that of CD8 cells requires Fas and not perforin or TNF-alpha pathways. Fas ligand is expressed on liver-infiltrating cells, pointing to death by fratricide that causes almost complete disappearance of virus-specific CTL 4 wk after infection. CTL elimination is virus dose dependent, and high doses induced high alanine aminotransferase values, elevated expression of Fas ligand on CD8 cells, and increased CD8 cell migration into the infected liver.
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PMID:Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver. 1120 53

An 11-year-old Thai boy who had received multiple blood transfusions from 12 different donors for treatment of Dengue shock syndrome presented with symptoms of acute hepatitis 5 weeks thereafter. He was found positive for antibodies to hepatitis C virus (HCV) and HCV-RNA was detected by reverse transcription PCR (RT-PCR). When his alanine aminotransferase (ALT) level peaked at 1,879 U/l in the 8th week, interferon therapy (3 million units, thrice weekly for 6 months ) was initiated. After initially decreasing to tenfold the normal level, the ALT dropped to fivefold the normal level at 6 months. HCV RNA is still detectable in his serum 6 months later. Using RT-PCR and subsequent restriction fragment length polymorphism (RFLP) analysis we identified one of the donors as harboring HCV genotype 3a, identical to that found in the patient. Moreover, polymorphism analysis on the hypervariable region employing five distinct restriction endonucleases suggested this donor as the source of infection. We hence recommend thorough screening of all blood donors as the only means of prevention presently feasible.
Infection
PMID:Acute posttransfusion hepatitis C: identification of a common hepatitis C virus strain in donor and recipient using polymorphism analysis. 1126 58

A 69-year-old male was hospitalized in January 1999 because of visceral leishmaniasis. He had also suffered from anti-hepatitis C virus (HCV)-positive chronic hepatitis for years. All serum hepatitis B virus (HBV) antigens and antibodies were negative except for anti-HBc. The patient was treated with amphotericin B cholesteryl sulfate (2 mg/kg twice a day for 7 days, iv). Fever disappeared on the 3rd day of treatment, the clinical condition improved rapidly and the patient recovered. In May 1999 the patient developed icteric HBsAg-negative acute hepatitis (aspartate aminotransferase 722 U/l; alanine aminotransferase 988 U/l). Anti-HBc IgM was positive and HBV-DNA was detected in serum by PCR. Anti-HAV IgM was negative. A serum sample obtained on presentation and stored at -80 degrees C was retrospectively tested and found positive for HBV-DNA. In July 1999, complete remission of acute hepatitis and seroconversion to anti-HBs was observed. We suppose that a moderate depression of the immune system, probably associated with leishmaniasis, may have enhanced HBV replication in the patient who had an HBsAg-negative 'silent' HBV infection. Restoration of the immune system after successful antiprotozoan therapy might have induced cell-mediated necrosis of the HBV-infected hepatocytes and seroconversion to anti-HBs.
Infection
PMID:Clinical expression of 'silent' hepatitis B virus infection in a patient with visceral leishmaniasis. 1144 Mar 89

The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but surprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral factors that influence disease progression will help provide an evidence based approach were realistic expectations regarding patient prognosis can be ascertained.
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PMID:The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (review). 1178 30

Infection with hepatitis C virus (HCV) generally progresses to chronic disease, although a minority of patients appear to clear viremia spontaneously. In this investigation, serum samples were analyzed for virological parameters, serum alanine aminotransferase (ALT) levels, and neutralizing antibody response against pseudotyped vesicular stomatitis virus (VSV) generated using chimeric envelope glycoprotein 1 (E1) or 2 (E2) of HCV. Testing of sequential serum samples that were collected beginning at the onset of acute-phase disease demonstrated intermittent viremia, elevated ALT levels, and detectable neutralization activity against VSV in 9 of 10 patients. Serum neutralization activity did not exhibit a correlation with the genotype of the infecting HCV or with virus load. On the other hand, patients with chronic HCV infection consistently had detectable amounts of virus present but no significant variation in ALT levels, and serum samples from a majority (>90%) of patients failed to show detectable neutralization activity.
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PMID:Neutralization of pseudotyped vesicular stomatitis virus expressing hepatitis C virus envelope glycoprotein 1 or 2 by serum from patients. 1193 Mar 27

Infection with the hepatitis B virus has switched over the last 20 years from the classical HBeAg positive serologic pattern to a HBeAg negative form that is linked, in the Mediterranean basin, with the epidemiologic replacement of the causative wild-type of virus B with mutant variants, whereby mutations in the core-promoter and in the pre-core region prevent the secretion of HBeAg. The wild-type pattern of infection (characterized by relatively high steady level ALT, high HBV-DNA levels and clinically overt liver disease) responds relatively well to Interferon: 3 to 5 mega units daily or 10 mega units every other day for 16 weeks induce anti-HBe seroconversion, normalize the ALT and possibly also eliminate the HBsAg in some 40% of the adults with a minimal (7%) risk of relapse. However, the mutant type infection (anti-HBe positive / HBe Ag negative) is less responsive to Interferon; this has led to the search for novel nucleoside analogues which has currently culminated in the advent of Lamivudine. This competitor of cytidine is 80% bioavailable and devoid of side-effects at the oral dose of 100 mg daily; tolerance continues for therapies up to 3 years. Lamivudine therapy shares with Interferon a rapid decline of ALT accompanied by improvement of histology; at variance with Interferon there is a delayed accumulating seronconversion to anti-HBe and the switch to anti-HBs is rare. Over the long term its activity is abolished by the emergence of specific viral mutations (YMDD mutants) that rekindle the disease. The indications to Lamivudine therapy in HBeAg negative chronic hepatitis B are currently under investigation. Lamivudine is highly efficacious in preventing HBV reinfection in liver transplants.
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PMID:Treatment of chronic hepatitis B. 1194 41

We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed histologically. Infections with hepatitis B and C viruses were ruled out by assaying serum virus markers. No tumor was detected in liver by ultrasonography and computed tomography during observation period. None of the patients studied were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast, only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic liver cirrhosis approached its rates in HCC. However, the time course for the elevation of serum PIVKA-II levels was different each other in alcoholic liver cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until therapy. In contrast, its elevation was transient and its levels returned to baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis occurred, we studied the effect of vitamin K on production of PIVKA-II and AFP by hepatocytes. Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no effect on AFP production. In contrast, PIVKA-II production was inhibited by addition of vitamin K in a dose dependent manner. Moreover, elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by administration of vitamin K (Kaytwo) to these patients. Taken together, these results suggest that vitamin K may have a role in the mechanism of PIVKA-II elevation in sera of these patients. Then, we measured serum concentrations of vitamin K(PK, MK-4, MK-7) in these patients. There was no correlation observed between vitamin K and PIVKA-II in these patients. This result suggests that elevation of serum PIVKA-II in these patients may not be due to vitamin K deficiency. One question not answered here is how serum PIVKA-II levels in these patients are suppressed by treatment with vitamin K (Kaytwo). More detailed analysis of the mechanism of elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis is needed.
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PMID:[Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic liver cirrhosis]. 1198 59

One hundred twenty-six mother-infant couples were studied and 105 exposed babies were monitored for at least 12 months to define the risk of mother-to-infant HCV transmission. Infection occurred in 5 out of 76 infants (6.6%) born to 69 viraemic mothers and in none of 29 born to 26 non-viraemic mothers. Only one child was HCV RNA positive one month after birth, while the remaining children became positive at the 3rd to 4th month. HCV genotypes of the babies matched those of their mothers. No difference was found between women who transmitted the virus and those who did not with regard to age, history of drug abuse, HIV infection, ALT abnormal values, HCV genotype, type of delivery, and breast-feeding. Four out of 5 infected infants were born to mothers with IgM anti-HCV (P = 0.04). The mean viral titre in transmitting women (10(7.2)) was higher than in non-transmitting (10(6.5)), and the proportion of mothers with viral load > or = 10(7) was statistically higher in transmitting than non-transmitting women (P = 0.03). These data show that HCV perinatal infection is a rare event and suggest that IgM positivity and high viral load (> or = 10(7)) in the mother are independent variables correlated with HCV transmission (O.R. = 14.5; 95% CI: 1.3-160.7 and O.R. = 16.3; 95% CI: 1.5-179.9, respectively).
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PMID:Mother-to-infant transmission of hepatitis C virus: rate of infection and assessment of viral load and IgM anti-HCV as risk factors. 1199 74

Infection with hepatitis C virus (HCV) is a matter of great concern because of its potentially grave consequences. Instead of relying on the conventional anti-HCV antibody test to detect HCV infection after needlestick incidents, we used the polymerase chain reaction (PCR) to achieve earlier detection, to manage a patient more effectively, and to exclude possible infection more quickly. Fourteen incidents were studied in which the source patients were positive for both the anti-HCV antibody and HCV RNA, and the exposed subjects were negative for anti-HCV antibody at the time of the incidents. In one of the exposed subjects, a nurse, the result of the PCR test for HCV RNA was positive at 2 wk after the needlestick incident; the nurse's viral load was very low (800 copies/ml) and she responded well to immediate medical treatment. She never developed acute hepatitis C; her serum anti-HCV antibody level and alanine aminotransferase (ALT) activity did not become elevated, and results of her PCR test for HCV RNA were negative following treatment. In the other 13 needlestick incidents, the results of PCR tests of the exposed subjects were negative for HCV RNA throughout the study and possible infections were quickly ruled out.
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PMID:Use of polymerase chain reaction for early detection and management of hepatitis C virus infection after needlestick injury. 1201 94

Infection with Hepatitis B virus (HBV) genotype C predominates in Japan. We analyzed the efficacy of interferon (IFN) alpha or beta in the treatment of chronic hepatitis B patients with HBV genotype C and the clinical predictors for therapeutic response. Forty-three genotype C-infected, chronic hepatitis B e antigen (HBeAg)-positive patients (32 men and 11 women with a mean age of 35.6+/-10.1 years) who had been treated with IFN therapy were retrospectively studied. The patients were classified into two treatment groups. Short-term therapy group was administered a 5-6 MU dose three times weekly for 4 weeks, and the long-term therapy group for 24 weeks. At the end of the follow-up period, 4 (15%) of 27 short-term therapy group patients and 6 (38%) of 16 long-term therapy group patients had normalized serum ALT levels and seroconversion of HBeAg to anti-HBe (p=0.137). Multivariate analysis for parameters most important for the efficacy of IFN therapy was performed using Cox proportional hazard models in order to investigate the association between baseline characteristics of patients and the response to IFN treatment. As a result, the p-values of IFN treatment group and sex were <0.05, and both factors can be recognized as independent significant factors (relative risk, 2.93 and 2.53; p=0.027 and 0.040, respectively). Furthermore, the cumulative rates of seroconversion of HBeAg to anti-HBe analyzed by the Kaplan-Meier method was significantly higher in the female group (p=0.015) and in the long-term IFN therapy group (p=0.0046). In summary, long-term IFN therapy may be more effective than short-term IFN therapy for patients with chronic HBV genotype C infection.
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PMID:Efficacy of long-term interferon therapy in chronic hepatitis B patients with HBV genotype C. 1211 59


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