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)

To assess the features of multicentric occurrence in hepatocellular carcinoma, we analyzed 10 of 72 patients (14%) who had undergone hepatic resection for hepatocellular carcinoma from May 1989 to October 1992 both clinically and pathologically. The multicentric occurrence of hepatocellular carcinoma was defined among the simultaneously detected small tumors as (a) at least one tumor consisting of extremely well-differentiated (grade I) hepatocellular carcinoma growing in a replacing pattern or (b) one of a group of hepatocellular carcinomas growing in an area of adenomatous hyperplasia. Of the 10 patients, the tumors in 9 were diagnosed as synchronous multicentric hepatocellular carcinomas, whereas the tumor in 1 was considered metachronous. All patients had cirrhosis; one of them had hepatitis B virus infection and nine patients had HCV infection. The inflammatory findings in the parenchyma were determined on the basis of serum enzyme values (AST, 89 +/- 27 IU/L; ALT, 96 +/- 43 IU/L). One or two tumors in 9 of 10 patients had thin trabecular or trabecular patterns showing replacing growth. In addition, one of the two tumors in two of nine patients was observed growing in areas of adenomatous hyperplasia. Recurrences were found in 4 of 10 patients. The 3-yr disease-free survival rate was 23%. Multiple recurrences were recognized in the two patients, and in the patients who underwent repeat surgery, grade I tumors were also found. Even though these tumors were small and well-differentiated, the recurrence rate was high. Therefore to detect the recurrence of metachronous multicentric hepatocellular carcinoma at an earlier stage, careful follow-up after surgery should be carried out.
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PMID:Possible multicentric occurrence of hepatocellular carcinoma: a clinicopathological study. 813 62

We examined the efficacy of decreasing high doses (beginning at 18 MU/day) of interferon-alpha 2a vs. that of daily low doses (3 MU) in the treatment of chronic hepatitis delta virus infection. Patients treated with 18 MU had a somewhat higher frequency of normalization of serum ALT levels than patients treated with low doses (31% and 12%, respectively, on an intention-to-treat basis). A decrease in the percentage of hepatitis D virus RNA positivity was observed in both groups at the end of treatment. Thus, whereas in baseline samples 10 (62%) of the patients in each group were positive for hepatitis D virus RNA in serum on slot-blot hybridization, these numbers decreased to 5 (31%) and 4 (25%) patients in groups 1 and 2, respectively, at the end of therapy. However, hepatitis D virus RNA, detected by means of nested polymerase chain reaction, remained in all but two (one in each group) patients who completed the treatment. Finally, during posttreatment follow-up, hepatitis D virus RNA levels returned to baseline values, and only one patient remained negative for this marker. The beneficial effect of interferon-alpha was only transient. Only two patients (one from each treatment group) had persistently normal serum ALT levels after 18 mo of follow-up. Finally, the presence of serum hepatitis D virus RNA at the end of therapy, detected with nested polymerase chain reaction, might be a good marker for the prediction of viral replication relapse.
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PMID:Treatment of chronic hepatitis D virus infection with low and high doses of interferon-alpha 2a: utility of polymerase chain reaction in monitoring antiviral response. 818 63

To evaluate the clinical significance of sequence variations in the hypervariable region of hepatitis C virus during the course of chronic infection, we performed pairwise comparison of the predominant nucleotide sequences. Hepatitis C virus RNA was extracted from two plasma samples obtained from 12 chronically infected Japanese patients over approximately 1 yr. Complementary DNA containing the hypervariable region was amplified by means of reverse transcription-polymerase chain reaction and was directly sequenced for determination of predominant sequences. In all 12 individuals, the predominant sequence of the hypervariable region at the second time point differed from that at the first time point, and significant sequence variation was observed during this short period. A high proportion of these nucleotide substitutions (90%) resulted in changes of predicted amino acid sequences, indirect evidence of in vivo positive selection for these variants. There appeared to be an important difference in the rate of nucleotide sequence variation of the hypervariable region between four patients with flare-ups of their ALT levels (1.54 to 2.24 x 10(-1)/genome site/yr) and eight patients with quiescent courses (0.13 to 1.21 x 10(-1)/genome site/yr). These results demonstrate that rapid sequence variations of the hypervariable region of predominant virus population take place during the natural course of chronic hepatitis C virus infection. These sequence variations seem to occur as an adaptive response of hepatitis C virus to evade host immunity and may play a major role in the establishment of persistent infection and in the occasional flare-up of hepatitis.
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PMID:Rapid sequence variation of the hypervariable region of hepatitis C virus during the course of chronic infection. 824 52

A 47-year-old man with acute hepatitis B virus (HBV) infection who had been receiving immunosuppressants after renal transplantation developed progressive liver failure. During the clinical course (approximately 7 months), anti-HBc IgM antibody and HBV-DNA polymerase levels remained high, but the serum alanine aminotransferase (ALT) level was consistently less than 150 K.U. Histopathologic examination of the liver showed submassive hepatic necrosis without significant inflammation accompanied by marked fibrosis. Most hepatocytes showed strong nuclear expression of HBc antigen by immunohistochemical staining and electron microscopy revealed numerous intranuclear core-like particles. Hepatitis B virus infection in immunosuppressed individuals occasionally insidiously progresses, resulting in liver failure. The clinical course of such patients thus merits close scrutiny.
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PMID:Fatal acute hepatitis B virus infection while receiving immunosuppressants after renal transplantation. 828 32

In an analysis of the clinical and laboratory variables that can influence the response to interferon alfa-2b treatment, 48 patients with chronic hepatitis C virus infection received interferon 5 million units (MU) subcutaneously three times weekly for eight weeks followed by 3 MU three times weekly for seven months. Response related factors on univariate analysis were found to be age > 40 years, non-parenteral source of infection, pretreatment positive antinuclear antibodies (ANA), cirrhosis, and high serum iron, ferritin, gamma glutamyl transferase, and IgM. An independent predictive value (multivariate analysis) was also found for cirrhosis, ANA, serum iron, and ferritin. A baseline aspartate aminotransferase/alanine aminotransferase ratio of 0.5 and a striking increase during interferon treatment were associated with a complete response.
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PMID:Response related factors in recombinant interferon alfa-2b treatment of chronic hepatitis C. 831 82

The aim of this study was to investigate the presence of hepatitis B virus occult infection in asymptomatic subjects with persistent anti-HBc reactivity but no other hepatitis B virus serological markers, including HBsAg, anti-HBs, IgM anti-HBc and HBV-DNA. For this purpose we used both polymerase chain reaction assays in sera and immunohistochemistry for HBsAg and HBcAg in liver biopsy specimens. Twenty-four cases were studied: 15 were drug abusers or homosexuals (eight with normal alanine aminotransferase levels) and nine were heterosexuals with raised alanine aminotransferase levels (> 45 U/l) but with no history of blood transfusion or ethanol intake (< 80 g daily). In all but five cases, liver biopsy was performed in subjects with persistent elevated alanine aminotransferase levels. In 10 out of 24 cases (41.66%) hepatitis B virus infection was demonstrated by polymerase chain reaction or immunohistochemistry, and when results from both procedures were available (n = 11) hepatitis B virus infection was detected in 63.63% of the subjects. The only clinical feature associated with HBV infection was the presence of persistent elevated alanine aminotransferase levels (p < 0.05). In conclusion, persistent isolated anti-HBc reactivity may be a relatively common serologic pattern for hepatitis B virus occult infection, at least in patients with chronic liver disease.
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PMID:Hepatitis B virus occult infection in subjects with persistent isolated anti-HBc reactivity. 831 57

A lethal Pichinde (An 4763 strain) virus infection was produced in 3-week-old random-bred Golden Syrian (LVG/Lak strain) hamsters inoculated intraperitoneally with virus, causing mortality in 6-9 days. High virus titers (> or = 10(7.5) cell culture infectious doses/g) were present in visceral organs, serum, brain and salivary glands near the time of death. Intraperitoneal treatments with ribavirin (10 and 32 mg/kg) and ribamidine (32, 100, and 320 mg/kg) for 10 days starting 24 h after virus challenge significantly decreased mortality and reduced virus titers by 100- to > 10,000-fold in liver, spleen, brain, and serum. Serum alanine aminotransferase (an indicator of liver damage) was also reduced in animals treated with the two compounds (ribavirin at 32 mg/kg; ribamidine at 100 and 320 mg/kg). Intraperitoneal selenazofurin (1-100 mg/kg per day for 10 days) and ampligen (0.5 and 5 mg/kg every other day for 5 injections) treatments provided neither protection from the lethal infection nor increased mean survival times. In fact, selenazofurin was overtly toxic, causing death of uninfected hamsters at 32 and 100 mg/kg. The random-bred LVG/Lak hamster appears to be a viable and cost-effective model for evaluating new therapies for arenavirus infections.
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PMID:Treatment of lethal Pichinde virus infections in weanling LVG/Lak hamsters with ribavirin, ribamidine, selenazofurin, and ampligen. 838 33

We describe a method for quantifying hepatitis C virus RNA in serum. This competitive assay combines reverse transcription and polymerase chain reaction and is based on coamplification of the target RNA with known amounts of synthetic mutated RNA. We tested serum samples from 104 hepatitis C virus carriers (9 asymptomatic blood donors and 95 patients with type C chronic liver disease) to determine the relationship between the replicative level of hepatitis C virus and various stages of the carrier states. The amount of circulating hepatitis C virus RNA ranged from 10(4) to 10(9.5) genomes/ml serum. The titer of hepatitis C virus RNA (logarithmic transformed copy numbers of RNA per milliliter of serum) was lower in asymptomatic blood donors (5.4 +/- 2.0) and in patients with chronic persistent hepatitis (7.3 +/- 1.1) than in patients with chronic active hepatitis (7.9 +/- 0.8), cirrhosis (7.8 +/- 0.7) or hepatocellular carcinoma (7.9 +/- 0.7). The titer of hepatitis C virus RNA was significantly lower in carriers younger than 40 yr old and correlated positively with the logarithmic transformed serum ALT level. Logistic regression showed that age and titer of hepatitis C virus RNA correlated independently with the stages of liver disease. These results showed that the replicative level of hepatitis C virus is higher in advanced liver disease and that elevation of viral replication may play an important role in liver injury and progression of liver disease. This competitive assay is useful in evaluating the state of viral replication in hepatitis C virus infection.
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PMID:Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease. 838 92

After undergoing withdrawal treatment for alcoholism as an in-patient for one year a 49-year-old woman was started on disulfiram, 250 mg daily, her liver function tests being normal. Except for vitamin B1 she received no further medication. Jaundice developed 13 days after onset of treatment and acute liver failure was diagnosed on the 18th day after a total disulfiram dose of 4.5 g (Quick value < 10%; bilirubin 460 mumol/l; GPT 5099 U/l; GOT 4142 U/l), as well as early renal failure (creatinine 300 mumol/l). An acute viral infection, autoimmune hepatitis and a metabolic liver disease were excluded by biochemical, serological and molecular biology tests. All toxicological tests were negative. The patient died 25 days after the onset of disulfiram treatment in hepatic coma due to a fulminant hepatitis with hepatorenal syndrome. Both a liver biopsy and the autopsy showed the signs of an acute hepatic dystrophy without cirrhosis. The temporal relationship between the disulfiram intake and onset of the illness, the exclusion of other causes of the fulminant hepatitis and the liver histology, which was compatible with a chemical-toxic hepatitis, indicate that this was a case of disulfiram-induced hepatitis. The hepatotoxicity of disulfiram is a very rare idiosyncratic reaction which is often fatal. Disulfiram administration must be discontinued at once if there is a rise in liver enzyme activity or jaundice occurs.
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PMID:[Fulminant hepatitis caused by disulfiram]. 840 76

The epidemological and clinical features of hepatitis C virus infection have been evaluated in a cohort of 227 intravenous drug users enrolled at a drug dependence treatment center in the Veneto area in 1992-1993 and followed periodically. Hepatitis C virus infection was detected using second-generation anti-HCV ELISA in 171 (75%) subjects at enrollment. Anti-HCV seropositivity correlated with: a) the duration of drug abuse: 91% of intravenous drug users injecting for more than 8 years were seropositive as compared to 40% of those with a history of abuse lasting 4 years or less, p < 0.001; b) sharing of injection equipment: 85% anti-HCV positive intravenous drug users had shared at some time as compared to 64% seronegative subjects, p < 0.001; c) seropositivity for immunodeficiency virus infection: 25% anti-HCV positive intravenous drug users were coinfected as compared to 3.5% anti-HCV negative, p < 0.001; d) markers of ongoing (two cases) or previous hepatitis B virus infection were detected in 62% of anti-HCV positive but in 21% of anti-HCV negative cases, p < 0.01. Two initially anti-HCV negative intravenous drug users seroconverted during follow up giving an incidence rate of hepatitis C virus infection of 6.2 per 100 person-years. During the survey abnormal alanine aminotransferase levels were detected in 75% anti-HCV positive but in 24% anti-HCV negative cases (p < 0.001), with significantly higher levels in the former. These findings suggest that the circulation of hepatitis C virus among intravenous drug users has been decreasing in recent years, although new infections still occur.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects. 854 44


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