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)

The health care burden caused by hepatitis C is projected to increase significantly in the next 20 years, on the basis of modeling estimates of cirrhosis, hepatic decompensation, and HCC likely to be seen in this population in the future. The number of cases of HCV-induced liver decompensation and mortality in the United States is projected to be approximately 4 times higher by the year 2018 than is currently seen, because of the aging of those presently infected. HCV also poses a significant quality-of-life decrement in the majority of individuals with chronic infection. Quality-of-life assessment in these patients has shown substantial reductions in both somatic and physical functioning compared with the general population, regardless of disease severity. The impact of chronic HCV on quality-of-life issues has been equated to that of non-insulin-dependent diabetes. Thus, HCV imparts a considerable toll on individual level of functioning and on overall health care resources. Hepatitis C evolves into a chronic infection in approximately 85% of individuals exposed to the virus, and progression to cirrhosis occurs in 20% to 30% of patients, with a disease duration up to 20 years. Hepatic decompensation will occur in approximately 20% and HCC in about 10% of those with HCV-related cirrhosis within 5 years of the determination of cirrhosis. End-stage liver disease caused by HCV is now the most common indication for liver transplantation in this country. Patients in whom liver decompensation develops should be considered for liver transplant evaluation, with referral to appropriate centers if these complications arise. Individuals with decompensated disease should not be treated with any of the current regimens available for HCV eradication, because these agents can accelerate hepatic dysfunction and will not mitigate the clinical outcome after the onset of decompensation. Available treatment options for HCV are rapidly changing, with INF as the standard and combination therapy with INF plus ribavirin rising to prominence as the optimal option. The need for abstinence from alcohol cannot be underestimated, given its documented synergistic effects on hepatotoxicity when combined with chronic HCV. Patients must be counseled in this regard and provided with the rationale for this recommendation. The benefits of therapy from a medical resource standpoint have recently been defined through analyses of cost-effectiveness. Bennett et al. used a mathematical model to estimate the cost-effectiveness of INF in the treatment of mild chronic HCV (no bridging fibrosis or cirrhosis). Therapy was found to be cost-saving for patients aged 20 to 35 years and was found to increase life expectancy by 3 and 1.5 years, respectively, at the spectrums of this age range. Kim et al. found the cost-effectiveness of a 12-month course of INF to compare favorably to other accepted medical interventions in the United States in patients younger than 60 years. Similar data for combination therapy has not yet been reported but would be expected to be comparable. Interferon monotherapy for 12 months is the current standard treatment recommendation for individuals with chronic HCV and elevated ALT levels. The explosive expansion of information now available to, and frequently quoted by, HCV patients seeking treatment will increasingly make this option less acceptable to a great many of this group. Combination therapy has emerged as the most efficacious option to date, both as initial treatment and for patients who relapse after standard INF. Unless data appear to the contrary, combination therapy should be considered first-line treatment in these groups. A suggested treatment algorithm for chronic HCV is outlined in Figure 2. Patients intolerant to ribavirin should be considered for continuation of INF to complete a 12-month course, dependent upon the assessment of HCV PCR status at week 12 of therapy. (ABSTRACT TRUNCATED)
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PMID:Advances in the treatment of hepatitis C. 1063 46

The number of deaths due to HCC is increasing in Japan. Males in particular have seen a marked increase in the past 20 years, and HCV infection accounts for this increase. In patients treated with IFN and followed up for more than 12 months, HCV clearance was achieved in 29.8% and sustained normalization of ALT levels was achieved in 41.4% following IFN therapy. The incidence of HCC following IFN treatment is dependent on the effect of IFN on ALT levels. The incidence of HCC was low in patients with sustained normalization of ALT levels following IFN therapy, regardless of whether or not HCV had been eradicated. In the future, in addition to the development of therapies to eradicate HCV, treatments to lower ALT levels will also be important.
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PMID:Relationship between infection with hepatitis C virus and hepatocellular carcinoma in Japan. 1072 64

To study the short- and long-term outcomes of acute hepatitis C, three groups of patients were enrolled. Of 26 patients with acute hepatitis C, 18 (69%) maintained HCV viraemia and 8 had cleared virus naturally at 12 months after the onset. Normalization of ALT was seen in all 8 patients with acute resolving hepatitis, but in only 1 (5%) of the 18 patients with chronic HCV infection (P< 0.001). Changes in liver histology were analysed in 43 patients with acute hepatitis C who underwent repeated liver biopsy. The mean score of the fibrotic stage was 0.9 within 1 year of the onset, and it increased gradually up to 3.5 at 30 years from the onset (0.1 grade/year). The fibrotic stage increased more rapidly in patients aged more than 50 years. In 115 patients, the mean duration between blood transfusion and the diagnosis of HCC increased significantly (P< 0.001) in accordance with increasing age at blood transfusion; 35 +/- 5.3 years in patients aged less than 30 years, 30 +/- 4.9 years in those aged between 30 and 40 years, and 25 +/- 6.8 years in those aged more than 40 years. In conclusion, approximately 70% of patients with acute hepatitis C develop chronic hepatitis. Once patients develop chronic hepatitic fibrosis of the liver, it progresses over several decades, faster in older patients.
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PMID:Natural history of acute hepatitis C. 1092 90

During long-term follow-up of patients chronically infected with the hepatitis C virus (HCV) and treated with interferon (IFN), we identified some who had persistent normalization of serum alanine aminotransferase (ALT) but remained positive for HCV RNA. The aims of this study were to clarify the characteristics of these patients and to examine their clinical outcome after treatment. Nine hundred and ninety-eight patients treated with IFN were followed-up biochemically and virologically, and by liver ultrasound, for 13-95 months. A short-term biochemical sustained response, where ALT remained within the normal range for 6 months after the completion of IFN therapy, was found in 296 patients; in 240 of these patients serum HCV RNA remained undetectable during long-term follow-up. The rate of HCV RNA persistence was 7.09 times greater in short-term biochemical sustained responders with a high viral load than in those with a low viral load (P=0.0001, odds ratio [OR]=7.09), and 3. 70-fold lower in those treated with a large dose of IFN than in those treated with a small dose (P=0.02, OR=0.27). Thirty-three (59%) of 56 patients without HCV eradication showed continuous ALT normalization for 26-80 months after cessation of IFN therapy. Short-term biochemical sustained responders who were older (P=0.009, OR=10.43) and who were male (P=0.03, OR=6.98) had a significantly greater probability of maintaining a normal ALT level, even when serum HCV RNA was positive. When the incidence of HCC was investigated during long-term follow-up in patients without HCV eradication, it was found to be significantly lower in patients with persistently normal ALT levels than in those with abnormal ALT levels (P=0.03). Hence, when HCV is not eradicated as a result of IFN therapy, it may induce a long-term carrier state of HCV infection with normal ALT levels in older or male patients, in whom the cumulative incidence of HCC is markedly decreased.
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PMID:Clinical characteristics of patients with chronic hepatitis C showing biochemical remission, without hepatitis C virus eradication, as a result of interferon therapy. The Osaka Liver Disease Study Group. 1097 22

US-guided puncture is the simplest and most popular method in the RFA treatment for HCC. However, depending on the location of tumors, it is often difficult to detect them by US. We report here the utility of CT-guided RFA for the treatment of HCC. We performed CT-guided RFA for 27 nodules in 21 patients with HCC from July 1999 to June, 2001. We used the LeVeen Needle Electrode made by Boston Company and the Cool-tip type electrode made by Radionics Company. We judged the effects of the treatment by dynamic CT within 7 days after RFA. We were able to accomplish the treatment for all patients with the exception of one case who developed severe pain during RFA. We experienced transient increases of AST/ALT in a few cases, subcutaneous emphysema in one case, pleural effusion and ascites in two cases, but conservative treatments were effective for all cases. US-guided puncture was especially useful for the treatment of the tumors localized below the diaphragm that were hardly detectable by US.
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PMID:[Usefulness of CT-guided RFA for hepatocellular carcinoma]. 1170 86

The majority of patients with primary or metastatic liver tumors are not candidates for resection because of the size, location, or multifocality of their tumors, or because of inadequate hepatic function related to cirrhosis. Radiofrequency ablation (RFA) is an evolving technique for treating patients with unresectable primary or metastatic liver cancers. After obtaining the approval of our institutional review board for this study, 12 patients with HCC and 6 patients with metastatic liver tumors were treated using the LeVeen RF ablation system at the Department of Surgery of Osaka National Hospital between March 2000 and February 2002. Informed consent was obtained from all patients. Ultrasound-guided RFA was done during open surgery. In 12 patients, RFA was performed during laparotomy, while in 6 patients it was done transdiaphragmatically during thoracotomy. All treated tumors showed complete necrosis on imaging after the completion of RFA. After a median follow-up period of 288 days, the tumor had recurred in 5 out of 18 patients, and the median overall survival rate was 362 days. No deaths or major complications occurred in these 18 patients. Liver function tests (ALT, AST, GGT) that were elevated after RFA returned to baseline in most patients by day 7. In 5 patients who underwent RFA at laparotomy, bile leakage and liver abscess developed. There were no cases of bile duct injury or liver abscess in the patients receiving transdiaphragmatic RFA. In conclusion, transdiaphragmatic RFA during thoracotomy is a safe, well-tolerated, effective treatment for unresectable hepatic malignancies.
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PMID:[Transdiaphragmatic radiofrequency ablation of malignant liver tumors]. 1248 43

Ninety individuals (76 males and 14 females) were classified into four groups. G1 (Control) included 20 healthy individuals. G2 (Chronic hepatitis) included 20 patients, G3 (Liver cirrhosis group) included 30 patients, and G4 (HCC) included 20 patients with HCC. All groups were subjected to clinical examination, abdominal ultrasonography, complete blood picture, HCV antibodies, HBs Ag, and function tests (total and direct bilirubin, total plasma proteins and albumin, prothrombin time and concentration, and liver enzymes AST, ALT and ALP). Patients of G3 & 4 were classified according to Child-Pugh classification into A. B and C. Upper endoscopic examination was done for 36/50 patients with chronic hepatitis or HCC. Circulating VEGF levels were determined by ELISA. There was a statistically high significant levels of circulating VEGF in G1, 2 & 3 than in the controls. A statistically significant higher level of circulating VEGF in G4 than in G3 & G4, and a statistically negative significant between VEGF levels and platelet count in G2. No significant correlation between VEGF and the grade of esophageal varices in G3 & G4. and no significant correlation between VEGF and upper GIT bleeding or spider naevi (vascular skin changes) in G2. A statistically significant was in correlation between VEGF and degree of hepatic dysfunction.
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PMID:Vascular endothelial growth factor level in chronic liver diseases. 1251 23

The incidence of newly acquired hepatitis C infection has diminished in the United States. This decline is largely because of a decrease in cases among IDUs for reasons that are unclear and, to a lesser extent, to testing of blood donors for HCV. The virus is transmitted by blood, and such transmission now occurs primarily through injection drug use, sex with an infected partner or multiple partners, and occupational exposure. Most infections become chronic, and therefore the prevalence of HCV infections is high, with about 3 million Americans estimated, to be chronically infected. HCV is a leading cause of cirrhosis, a common cause of HCC and the leading cause of liter transplantation in the United States. The disease spectrum associated with HCV infection varies greatly. Various studies have suggested that 3% to 10% of chronically infected patients will develop cirrhosis over a 20-year period, and these patients are at risk for HCC. Persons who are older at the time of infection, patients with continuous exposure to alcohol, and those coinfected with HIV or HBV demonstrate accelerated progression to more advanced liver disease. Conversely, individuals infected at a younger age have little or no disease progression over several decades. The diagnosis of chronic hepatitis C infection often is suggested by abnormalities in ALT levels and is established by EIA followed by confirmatory determination of HCV RNA. Several sensitive and specific assays are automated partly for the purposes of detecting HCV RNA and quantifying the viral level. Although there is little correlation between viral level and disease manifestations, these assays have proven useful in identifying those patients who are more likely to benefit from treatment and, particularly, in demonstrating successful response to treatment as defined by an SVR. Liver biopsy is useful in defining baseline abnormalities of liver disease and in enabling patients and healthcare providers to reach a decision regarding antiviral therapy. Noninvasive tests do not provide the information that can be obtained through liver biopsy. Information on the genotype of the virus is important to guide treatment decisions. Genotype 1, most commonly found in the United States, is less amenable to treatment than genotypes 2 or 3. Therefore, clinical trials of antiviral therapies require genotyping information for appropriate stratification of subjects. Recent therapeutic trials in defined, selected populations have shown clearly that combinations of interferons and ribavirin are more effective than monotherapy. Moreover, trials using pegylated interferons have yielded improved SVR rates with similar toxicity profiles. Results continue to show, however, that the SVR rate is less common in patients with genotype 1 infections, higher HCV RNA levels, or more advanced stages of fibrosis. Genotype 1 infections require therapy for 48 weeks, whereas shorter treatment is feasible in genotype 2 and 3 infections. In genotype 1, the lack of an early virologic response (< 2 log decrease in HCV RNA) is associated with failure to achieve an SVR. The SVR is lower in patients with advanced liver disease than in patients without cirrhosis. Ongoing trials are exploring the usefulness of combination therapy in various populations. Preliminary experience in IDUs, individuals coinfected with HIV, children, and other special groups suggests similar responses are achievable in these populations. Patients with acute hepatitis C may be treated, but specific recommendations for antiviral treatment must await further evaluation of the rate of spontaneous clearance of the virus and determination of the optimal time to initiate treatment. Preventive measures beyond blood-banking practices include prompt identification of infected individuals, awareness of the potential for perinatal transmission, implementation of safe injection practices, linkage of drug users to drug treatment programs. and implementation of community-based education and support programs to modify risk behavior. Some of these measures have been implemented successfully in the control of HIV infections, and it stands to reason that they would be valuable for reducing HCV transmission. Future advances in the diagnosis and management of hepatitis C require continued vigilance concerning the transmission of this infection, extending treatment to populations not evaluated previously in treatment trials, and the introduction of more effective therapies.
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PMID:Appendix: The National Institutes of Health Consensus Development Conference Management of Hepatitis C 2002. 1269 70

OLT in HIV infected patients still remains a challenging option requiring a careful monitoring of patients for HCV reinfection, drug interactions and antiretroviral toxicity. Severe adverse events due to HAART have been already reported for post exposure prophylaxis in HIV infected patients. Here we report a case of liver graft toxicity related to HAART in a HIV-HCV co-infected patient (46 yrs-male) with associated a small HCC transplanted with a marginal liver graft. The patient had pre-OLT plasma HIV 1-RNA levels undetectable and CD4+ T-cell count of > 200 cells/microL for 6 months. At day 2 a severe graft dysfunction was observed (AST 1570 U/L, ALT 2180 U/L, BIL tot 8.3 mg/dL, BIL Dir 6.6 mg/dL and PT 35%--INR 2.5). Doppler scan showed hepatic artery always patient. Later the postoperative in-hospital course was complicated by tense ascites and severe cholestasis. Serum bilirubin reached 42 mg/dL in day 12. Hypertransaminasemia ended at day 15 while cholestasis ended after 46 days. Tacrolimus was reintroduced at day 7. A liver biopsy 10 after OLT showed severe intrahepatic cholestasis, centrolobular necrosis and macrovesicular steatosis (30%). The patient was discharged 48 days after OLT with good liver function. After seven months HIV-RNA is still undetectable and HAART has not been restarted. We believe that the early complications we observed may be attributed to a sudden increase in plasma concentration of antiretroviral drugs secondary to drug redistribution from peripheral tissues and hepatic clearance deficiency after OLT. Although a pre-OLT withdrawal of HAART seems unjustified a delayed re-introduction of HAART or the use of less hepatotoxic drugs may be advisable.
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PMID:[Acute liver toxicity of antiretroviral therapy (HAART) after liver transplantation in a patient with HIV-HCV coinfection and associated hepatocarcinoma (HCC)]. 1290 79

Our aim was to investigate whether different human leukocyte antigen (HLA) genes might be associated with hepatitis C virus (HCV) infection. DNA obtained from 141 Spanish patients with HCV infection (48 with alanine aminotransferase levels in the range considered to be normal, 47 with liver cirrhosis, and 46 with hepatocellular carcinomas [HCCs]) and from 116 control subjects were typed for HLA-B, HLA-DRB1, and HLA-DQB1 alleles, as well as for major histocompatibility complex class I chain-related gene A (MICA) transmembrane polymorphism. The frequency of HLA-DR11 was increased in HCV carriers, compared with patients with end-stage liver disease (ESLD) (corrected P value [Pc],.0002) and, especially, with patients who had HCC (Pc=.003). The frequency of the HLA-B18 allele was increased in patients with HCC, and the allele was absent in HCV carriers (Pc=.003). The MICA-A4 allele was overrepresented in patients with HCC, compared with HCV carriers (Pc=.0002). The DR3/MICA-A4/B18 haplotype was associated with HCC (Pc=.01). In conclusion, HLA-DR11 seems to be protective against the development of severe forms of infection, and the DR3/MICA-A4/B18 haplotype may be an important factor in the progression to the most severe HCV-infection status.
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PMID:Extended human leukocyte antigen haplotype EH18.1 influences progression to hepatocellular carcinoma in patients with hepatitis C virus infection. 1499 97


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