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)

Treatment of chronic hepatitis C virus (HCV) infection in naive patients with interferon alpha alone or in combination with ribavirin is reviewed. Two placebo-controlled randomised studies including 150 patients have shown that ribavirin as single therapy at standard dosage (15 mg/kg bodyweight in two divided doses daily) only reduces ALT levels transiently during therapy, whereas HCV RNA levels are not substantially reduced. Interferon alpha (IFN) alone at standard dosage (3 MU t.i.w.) given for 12 months results in sustained virological response (SR) rates of some 15-25% depending on the genotype and baseline HCV RNA levels. Ribavirin in combination with alpha interferon, in standard doses for 6-12 months significantly improves the sustained biochemical and virological response rates 2-3 times compared with IFN alone for 12 months. In the future, combination therapy will become standard therapy for most naive patients, at least those with unfavourable viral parameters such as a high baseline viral load (>2-3 million gE/ml serum) and genotype 1a+1b. In patients with favourable baseline viral characteristics (genotypes 2 and 3, irrespective of viral load) 6 months of combination therapy is likely to be sufficient, whereas those with unfavourable viral baseline characteristics will need longer combination treatment. Both genotype and baseline viral load need to be assessed to optimise the choice of therapy. Many questions must still be answered, such as the optimal dose of ribavirin and IFN in combination regimens, and the optimal treatment length. Furthermore, should induction treatment be used in combination regimens? What regimen should be used for patients with more advanced disease such as those with cirrhosis and decompensation?
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PMID:Treatment of naive patients with chronic hepatitis C. 1062 81

In the great majority of patients, hepatitis C virus (HCV) infection is not self-limiting. Approximately 70% to 85% of patients exposed to HCV will go on to develop chronic hepatitis. Among those who undergo treatment with interferon alpha, only 15% to 20% can be expected to respond to a 12- to 18-month course of therapy. With the addition of ribavirin to interferon monotherapy, the likelihood of sustained response (defined as normal alanine aminotransferase levels and negative HCV RNA persisting 6 months after the end of therapy) increases to approximately 40%. The fact remains, however, that there is still a substantial proportion of patients who will fail to respond to treatment. Without viral eradication, cirrhosis and hepatocellular carcinoma persist as long-term risks. Several options are available for the treatment of patients who fail to respond to interferon monotherapy. These include interferon dose escalation, whether by administering higher doses or administering them more frequently; changing to a different form of interferon; retreatment with a combination of interferon and ribavirin; adjunctive therapies, of which the best studied is phlebotomy to decrease hepatic iron stores; use of long-term, low-dose "maintenance"-type therapy; and watchful waiting with frequent follow-up. In the absence of long-term, large-scale clinical trials to support these modalities, physicians must exercise their best clinical judgment and individualize treatment to suit the patient's condition, needs, and preferences.
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PMID:Available options for treatment of interferon nonresponders. 1065 61

The aim of this study was to evaluate the most appropriate therapeutic protocol for patients with chronic hepatitis C not responding to a previous course of recombinant interferon alpha-2b (rIFN). Sixty patients were randomly assigned to two groups of 30 subjects each: group A was treated with double dose of the same type of rIFN (6 MU t.i.w.) plus ribavirin for 6 months; group B was treated with the same rIFN dose and duration as group A, but without ribavirin. An end of treatment complete response (ETCR) was defined as alanine transaminase (ALT) normalization with undetectable serum HCV-RNA at the end of the treatment, while an end of treatment biochemical response (ETBR) as ALT normalization with still detectable viraemia. The two groups were homogeneous. The patients with ETCR or ETBR were than followed-up for at least 1 year. A sustained biochemical response (SBR) was defined as the persistence of normal ALT with still detectable viraemia after a 12-month follow-up, and a sustained complete response (SCR) as the persistence of normal ALT with undetectable viraemia. Side-effects were only observed in patients treated with rIFN plus ribavirin: four cases (13%) discontinued the therapy owing to haemolytic anaemia. Combination therapy induced an ETCR in 11 patients (37%) and an ETBR in six (20%), while a SCR was observed in two subjects (7%) and a SBR in four (13%). The use of a double dose of rIFN alone obtained an ETCR in four cases (13%) and an ETBR in five (17%), with a SCR in two (7%) and a SBR in three (10%). Hence, both combination therapy and single treatment with higher rIFN doses were unable to show statistically significant long-term benefits in patients with chronic hepatitis C resistant to a previous course of rIFN treatment.
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PMID:Interferon plus ribavirin in chronic hepatitis C non-responders to recombinant alpha-interferon. 1071 46

Resistance formation is a major problem in antiviral treatment of hepatitis B recurrence after liver transplantation. One possible therapeutic approach is an antiviral combination therapy with synergistic drugs. Four patients who were transplanted for chronic hepatitis B were analyzed retrospectively. All patients had reinfection of the graft and breakthrough of hepatitis B virus (HBV) during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy of lamivudine and interferon alpha 2a (3 times 3 million units weekly) was initiated. Addition of interferon markedly reduced viral replication rate in all patients. Three patients became HBV-DNA negative despite lamivudine resistance, but only two had a sustained response. No patient seroconverted to anti-HBe or lost HBsAg, but all patients showed a normalization of alanine aminotransferase and aspartate aminotransferase levels. No severe complications, and especially no rejection episodes occurred. Therefore lamivudine combined with interferon might be used for the therapy of hepatitis B reinfection after liver transplantation.
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PMID:Additional interferon alpha for lamivudine resistant hepatitis B infection after liver transplantation: a preliminary report. 1083 94

We report the case of a 64-year old woman with hepatitis C virus infection, mixed cryoglobulinemia type II (IgG + IgM kappa) and cryoglobulinemic glomerulonephritis. The patient was treated with the standard dose of recombinant interferon alpha-2b (3 million units 3 times a week) for one year, resulting in complete clinical remission and undetectable levels of serum hepatitis C virus RNA. AST and ALT normalized and proteinuria decreased from 2.78 to 0.98 g/day. However, a relapse occurred when therapy was stopped. Additional therapy with interferon-alpha (5 million units 3 times a week for 9 months) resulted again in quick and prolonged remission. The clinical course of our patient showed sustained clinical and virologic response after high-dose interferon-alpha treatment confirming the usefulness of interferon alpha in treatment of patients with cryoglobulinemic glomerulonephritis. Our observation is in agreement with others, suggesting that recommended standard dosage and duration of initial treatment with interferon alpha should be re-evaluated. Although our patient had sustained virologic and clinical response after interferon alpha monotherapy, recent studies clearly support combination therapy of interferon alpha and ribavirin for treatment of chronic HCV infections.
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PMID:Complete remission of cryoglobulinemic glomerulonephritis (HCV-positive) after high dose interferon therapy. 1094 19

Currently, the best option for patients with hepatitis delta is interferon alpha therapy for at least one year. To evaluate the effect of the combination lamivudine-high-dose interferon alpha therapy, we first treated eight patients with chronic hepatitis delta infection with lamivudine for at least 24 weeks; then lamivudine was combined with a high dose of interferon alpha followed by a regular dose (9 MU tiw). Follow-up was 12 weeks. Virological, biochemical and histological features were evaluated for response to therapy. At baseline, all patients were HBsAg positive in serum and HDV RNA-(PCR)positive in plasma; HBV DNA was undetectable with the Digene Hybrid Capture assay (limit of detection 1.5 x 10(6) geq ml-(1)) in all cases. Transaminases were elevated in all patients; median ALT 68 (range 48-143) IU l(1). Seven of eight patients completed the course; one patient with a pre-existing sickle cell trait was withdrawn from the trial due to the development of a nephrotic syndrome. The HBsAg-concentration in serum decreased in two out of seven patients (29%). However, there was no significant decrease in the HBsAg-concentration in serum during treatment (median 3654 PEU l(-1) (range 548-7,684) to 5300 PEU l(-1) (range 168-19,639)). The drop of HDV RNA in plasma from baseline during treatment was not significant. Decrease of HDV RNA was observed in three out of seven patients (43%) (median 10(5) geq ml(-1); range 10(3)-10(6) to median 10(3) geq ml(-1); range 10(2)-10(7)). Serum ALT did not change as reflected by a median of 68 IU l(-1) (range 48-143) at start of therapy to 63 IU l(-1) (range 20-171) at the end of therapy. At the end of treatment transaminases had normalised in one patient and decreased in three other patients (improvement in 57%). However, three of these four patients showed a rebound after withdrawal of therapy. The Histology Activity Index (HAI) indicated a drop from a median score of 7 (range 5-9) at baseline to 5 (range 3-8) at the end of treatment, but an increase in fibrosis from a median grade of 2 (range 1-3) at baseline to 3 (range 1-4) at the end of treatment was observed. In conclusion, this study does not yield support for the combination of an HBV suppressor and 16 weeks of high-dose interferon for therapy aimed at eradicating the hepatitis delta virus.
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PMID:Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus. 1111 54

Immunosuppressive therapy increases levels of hepatitis C virus (HCV) RNA, and when combined with interferon, corticosteroids have been reported to variably improve or have no effect on sustained response rates. We conducted a randomized double-blind placebo-controlled trial in 39 patients with biopsy-proven chronic HCV infection and elevated alanine aminotransferase levels. Patients received either 6 weeks of a tapering dose of prednisone (60 ng, 40 mg, and 20 mg in 2-week intervals) or an identical placebo. All patients then received recombinant interferon alpha-2b, 3 million units three times a week for 24 weeks. Patients were then followed for a further 24 weeks. At the end of the study there was no significant difference in the sustained biochemical response rates between the two groups (4/20 vs. 3/19, p value was not significant). Prednisone-treated patients had a significant increase in HCV RNA from baseline during steroid treatment (400 +/- 60% increase vs. -280 +/- 140% decrease; p = 0.005). Two prednisone-treated patients were withdrawn from the study secondary to serious complications related to therapy. Prednisone priming before interferon alpha therapy in patients with chronic HCV infection does not improve the sustained response rate. This therapy was associated with an increase in viral burden and significant morbidity.
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PMID:Prednisone withdrawal followed by interferon alpha for treatment of chronic hepatitis C infection: results of a randomized controlled trial. 1120 48

New treatment options for chronic hepatitis C (HCV) infection are examined. Studies show the efficacy of interferon alfa-2b in normalization of serum alanine aminotransferase and histological improvement in necroinflammatory liver disease. However, 70 to 80 percent experiencing normalization usually relapse within 1 year after treatment. Ten to 20 percent will have a sustained response lasting at least 3 years. Ideas for improving treatment response include longer initial treatment regimens, increasing dosages of interferon alpha, or adding another agent to interferon alpha. Based on encouraging study results, the interferon/ribavirin combination has been approved by the Food and Drug Administration (FDA) in HCV patients relapsing following interferon alpha monotherapy. So far the FDA has approved interferon alfa-2b, interferon alfa-2a, alfacon-1, and interferon alfa-2b/ribavirin as treatments for HCV; ribavirin alone is not effective against HCV infection. Other drugs are being tested with interferon alpha but have not generated enough substantive data. Thymosin, an immune modulator that enhances the body's production of interferon and interleukin rather than attacking HCV directly, is also being investigated. Oral dosing of interferon is in clinical trials for hepatitis B, and the results may be applicable to HCV. Alternative therapies are gaining wider interest such as using milk thistle for liver regeneration or using licorice root for quelling liver inflammation. As for transmission risk, there is little evidence supporting sexual activity as a major risk factor, however, some risk is reported with anal intercourse, sex during the menstrual cycles, and years of cohabitation with an infected partner.
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PMID:Can science meet the challenges of the HCV pandemic: new treatment options for chronic hepatitis C. 1136 38

Fifty-five patients with chronic viral hepatitis B were randomly divided into two groups. Thirty patients were treated with Phyllanthus amarus compound (PA Co) for three months in the treatment group, another 25 patients were treated with domestic recombinant human interferon alpha-1b (IFN-alpha 1b) for three months as controls. The total effective rate in the treatment group was 83.3%, showing no significant difference from the control (p>0.05). The normalization rates of ALT, A/G and SB in the treatment group were 73.3%, 80.0% and 78.2% respectively, which were significantly higher than that in the control (p<0.05). The negative conversion rates of HBeAg and HBV-DNA in the treatment group were 42.3% and 47.8%, showing no significant difference from the control (p>0.005). It is indicated that PA Co has remarkable effect for chronic viral hepatitis B in recovery of liver function and inhibition of the replication of HBV.
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PMID:A comparative study of Phyllanthus amarus compound and interferon in the treatment of chronic viral hepatitis B. 1148 76

Polymyositis is a rare complication of interferon alpha treatment as a result of immune-modulating role of the drug itself. In this case, interferon alpha induced polymyositis and cardiomyopathy is diagnosed in a 33-yr-old male patient with history of chronic hepatitis B. To treat hepatitis B, interferon alpha was administered until the proximal muscle weakness developed. Thereafter, sixteen cycles of immunoglobulin treatment (400 mg/kg) along with corticosteroids were instituted and led to an improvement in subjective symptoms with decreases in level of CPK and LDH. However, dilated cardiomyopathy has not improved in spite of the cessation of interferon treatment. Unlike the persistently elevated serum HBV DNA level, the serum ALT and AST levels have gradually decreased. Our case shows that clinical symptoms of polymyositis improved with steroid and immunoglobulin treatment without deterioration of the hepatitis B. To our knowledge, this is the first case of polymyositis associated with dilated cardiomyopathy after the administration of interferon in a patient with hepatitis B.
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PMID:A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B. 1185 Jun 6


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