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Biomedical subjects

P Colombatto

Publications and source records attributed to P Colombatto.

31 records · Page 2Linked to original sources
PubMed1997

Intrahepatic expression of c-fos, c-myb and c-myc oncogenes: correlation with virus-induced chronic liver disease and response to interferon.

BACKGROUND & AIMS: Oncogenes were activated in experimental models of hepatocyte regeneration. We studied the intrahepatic expression of c-fos, c-myb and c-myc protooncogenes in 117 patients with chronic liver disease: 12 with hepatitis B, 15 HBsAg carriers, 73 with hepatitis C and 17 with non-viral liver damage. METHODS: Oncoproteins were detected by indirect immunofluorescence using high affinity and monoclonal antibodies. Grade and stage of liver damage were measured by numerical score. RESULTS: Nuclear c-fos and/or c-myb were found in 7 (58.3%) hepatitis B patients, in 38 (52%) hepatitis C patients, in 1 (6.6%) HBsAg carrier (p < 0.004) and in none of the non-viral disease patients (p < 0.0001). In no case was c-myc detected. Oncoproteins were correlated with the histological activity index (p < 0.0001) and its components: lobular degeneration and periportal necrosis (p < 0.0001), fibrosis (p < 0.005) and portal inflammation (p < 0.03). Thirty-one chronic hepatitis C patients were treated with alpha-IFN: 9 out of 14 oncoprotein-positive patients (64%) were non-responders, 5 (36%) relapsed and none was a sustained responder. Conversely 9 out of 17 (53%) oncoprotein-negative patients, including 3 patients with histologically active cirrhosis, showed long-term response (p < 0.005). CONCLUSIONS: Intrahepatic c-fos and c-myb were detected in chronic viral hepatitis patients, but not in non-viral liver diseases. Their expression correlated with the grade and stage of liver disease and with poor response to alpha-IFN.

Adult↗
PubMed1996

Quantitative analysis of IgM anti-HBc in chronic hepatitis B patients using a new "gray-zone" for the evaluation of "borderline" values.

BACKGROUND/METHODS: In order to define the clinical significance of borderline levels of IgM anti-HBc in chronic hepatitis B patients, we followed up 89 untreated hepatitis B patients (19 HBeAg pos and 70 anti-HBe pos) for 1 year, with monthly monitoring of IgM anti-HBc using a highly sensitive quantitative microparticle enzyme immunoassay (IMx CORE-M, Abbott). As a control group we used 304 healthy subjects: 150 HBsAg negative and anti-HBc/anti-HBs positive, and 154 without markers of HBV infection. The statistical analysis performed by Receiver Operating Characteristic curve indicated the 100% sensitivity cut-off at 0.081 IMx index and 100% specificity cut-off at 0.358 IMx index. RESULTS: We could define the range of a chronic hepatitis B "gray-zone" between 0.100 [80.6% specificity (95% CI, 76.2%-85%), 96.6% sensitivity (95% CI, 92.8%-100%)] and 0.200 [95.7% specificity (95% CI, 93.4%-98%) and 78.7% sensitivity (95% CI, 70.2%-87.2%)] of the IgM anti-HBc-IMx index. In fact, none of the chronic hepatitis B patients had IgM anti-HBc-IMx values persistently below 0.100 during the follow-up, whereas 57.3% had values persistently higher than 0.200. In 38.2%, IgM anti-HBc values occasionally fell within the "gray-zone" limits. In the remaining four patients (4.4%), the results overlapped the "gray-zone" values. CONCLUSIONS: These results suggest that the use of a chronic hepatitis B "gray-zone" for values of quantitative IgM anti-HBc assays helps to distinguish "true healthy carriers" from asymptomatic chronic anti-HBe positive hepatitis B patients who have been shown to have temporary remissions of liver disease and frequently undetectable serum HBV-DNA.

Adolescent↗
PubMed1996

Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase: a specific liver disease? [corrected].

We tested the sera of 67 consecutive patients for hepatitis G virus (HGV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). These patients (42 males and 25 females, median age 35 years, range 13-64 years) had liver disease of unknown aetiology and were without markers of hepatitis (A-E) viruses or signs of genetically determined, autoimmune, alcoholic or drug-induced liver disease. The controls in this study were 110 patients (50 females and 60 males, median age 45 years, range 9-65 years) with chronic hepatitis B virus (HBV) infection (19 patients) or hepatitis C virus (HCV) infection (91 patients). Ten of 67 (14.9%) patients with cryptogenic disease were positive for HGV RNA by at least three separate tests; HGV RNA was also detected in one of 19 (5.3%) hepatitis B surface antigen (HBsAg) carriers and in nine of 91 (16.6%) patients with antibody to HCV. These data suggest that HGV occurs as frequently in HCV-infected patients as in those with cryptogenic disease. Elevated serum gamma glutamyl transpeptidase (gamma-GT) (higher than twice the normal value) and alkaline phosphatase levels were found in eight of 10 (80%) HGV RNA positive patients and in six of 57 (10.5%) HGV RNA negative patients (P < 0.0001). Five (50%) HGV RNA positive patients had non-specific inflammatory bile duct lesions. A statistically significant difference was observed between HGV RNA positive and negative patients with chronic HBV or HCV infections (P < 0.029). Therefore, the spectrum of liver disease associated with HGV is wide, but a characteristic lesion of the bile duct leading to elevation of cholestatic enzymes might be specific for this virus.

Adolescent↗
PubMed1996

Hepatitis C virus infection in Italian patients with oral lichen planus: a prospective case-control study.

To assess the aetiology of liver disease associated with lichen planus, we prospectively studied 70 consecutive newly diagnosed patients with oral lichen planus (OLP) living in northwest Italy (Piemonte) and 70 controls matched for age and sex with other oral keratoses coming from the same district. Twenty-two patients with OLP (31.4%) and 9 controls (12.9%) were found to be affected by chronic liver disease (CLD) (P = 0.014). In sixteen of the 22 OLP patients with CLD the liver disease was hepatitis C virus (HCV)-related, whereas 2 of the 9 controls had a HCV-related CLD (P = 0.016). In another OLP case, liver damage was related to a combination of HCV and alcohol abuse. The prevalence of HCV antibodies in the whole OLP group (27.1%) was significantly higher than in controls (4.3%) (P = 0.014), whereas no difference was found between the OLP and control groups regarding hepatitis B virus markers and other common causes of CLD. HCV infection was more frequently found in patients with erosive OLP (58.8%) than in patients with non-erosive OLP (13.2%) (P = 0.004). Serum HCV-RNA was detected by polymerase chain reaction (RT-PCR) in the majority (93.7%) of OLP patients who had HCV antibodies. Excluding OLP and control patients with HCV markers, there was no difference between the two groups regarding frequency of CLD. Our data show that HCV is probably the main pathogenic factor in liver disease of Italian patients with OLP, and suggests that HCV could be involved in the pathogenesis of OLP.

Adolescent↗
PubMed1996

Variations in the hypervariable region 1 of the envelope region E2 of hepatitis C virus RNA appear associated with virus persistence independently of liver disease.

The high genetic variability of the 5' end of the envelope protein-coding region E2 (HVR1 E2) of Hepatitis C Virus (HCV) RNA has been suggested by many authors to play an important role in both virus persistence and outcome of liver disease. We studied the relations between HVR1 E2 variability and HCV genotypes, HCV-RNA levels and liver disease in 8 chronic HCV carriers (5 males and 3 females, median age 41 years, followed-up for a mean period of 3 years). Four were healthy HCV carriers with persistently normal ALT levels and normal liver histology and 4 patients with chronic liver disease. In each patient, the HVR1 E2 variability of 2 serum HCV-RNA isolates obtained at least 12 months apart were evaluated by direct sequencing. Nucleotide and amino acid homologies ranged between 97.6%-57.1% and 92.8%-25% in healthy carriers and 95.2%-55.9% and 89.3%-32.1% in patients, respectively. We did not observe any correlation between HVR1 E2 heterogeneity and HCV genotypes, viraemia levels, presence and extent of liver necroinflammation. Our findings suggest that HVR1 E2 heterogeneity has no direct implications in hepatitis, pathogenesis but it could play a major role in virus persistence.

Adult↗
PubMed1995

Treatment of chronic anti-HBe-positive hepatitis B with interferon-alpha.

We studied the prevalence of long-term responders to interferon-alpha (IFN-alpha) treatment (undetectable levels of serum IgM anti-HBc, HBV-DNA and normal ALT values for 3 years) in 53 anti-HBe-positive chronic hepatitis B patients. Forty-two of them were treated with (6-18 MU) alpha-2a-recombinant-IFN t.w. for 4-6 months, and the remaining 11 with 10 MU of lymphoblastoid-IFN thrice weekly for 6 months. At the end of treatment, HBV-DNA levels were undetectable and ALT values within the normal range in 34 of 53 patients (60%); IgM anti-HBc levels decreased in all the 34 patients, falling below 10 PEI U in 2/34 (6%). Response to treatment was maintained throughout the follow-up (mean 3 years, range 2-7 years) in five patients (9.4%). The remaining 29 patients experienced HBV reactivation within median follow-up of 6 months (range 1-22 months; 90% of cases within 12 months). Overall 4/9 long-term responders (44.4%) cleared serum HBsAg. In conclusion, chronic anti-HBe-positive hepatitis B has a lower IFN treatment response rate than the HBeAg-positive form; however, among long-term responders, the incidence of serum HBsAg clearance is comparable in the two forms. Because of the high rate of relapses, stringent monitoring criteria (HBV-DNA, IgM anti-HBc and ALT monthly tested for at least 12 months) are mandatory.

Adolescent↗
PubMed1995

Hepatocellular carcinoma and infections with multiple hepatitis viruses.

Hepatitis B virus (HBV) plays a major role in liver carcinogenesis. HBV-DNA integration into cellular DNA provides some molecular basis for understanding the mechanisms of neoplastic transformation of the liver cell. Persistence of HBV-DNA episomic forms, necro-inflammation in the liver, and cirrhosis appear to be additional promoting factors. We studied the possible association between hepatocellular carcinoma (HCC) and the defective hepatitis D virus (HDV), a virus that requires the helper function of HBV. Patients infected with HDV and HBV develop HCC about 10 years earlier than those infected with HBV alone. Persistence of active HDV disease and low levels of "wild-type" HBV (i.e., secreting the hepatitis B surface antigen [HBsAg]) are associated with progressive liver disease and HCC. Therefore, HBV replication, in spite of being inhibited by HDV, appears to play a major role sustaining HDV pathogenicity. Detection of antibody to the hepatitis C virus (HCV) in many HCC patients raises the important question whether HCV has oncogenic potential. Clinico-epidemiological data show that the most severe forms of liver disease in patients with multifactorial liver damage occur in those infected with HCV. The prevalence of HBV markers in patients with cirrhosis, HCC, and HCV infection is higher than in individuals with comparable age and other diseases. HBV-DNA integration occurring early during HBV infection can persist in those with and without detectable HBsAg in their serum. Therefore, one can speculate that in patients with integrated HBV-DNA and concurrent HCV infection, cirrhosis and HCC may develop more easily than in patients without HBV-DNA integration. HCV hampering the immune system also might play a role in the genesis of HCC. The evidence that multiple hepatitis viruses are more frequently associated with HCC than infections of one virus alone has important practical consequences. It warrants the identification of high risk patients so that they can be monitored frequently for early diagnosis and treatment.

Adolescent↗
PubMed1994

Hepatitis C virus infection and liver disease: peculiar epidemiological and clinicopathological features.

Hepatitis C virus (HCV) infection is associated with a wide spectrum of liver disease ranging from asymptomatic carriage to severe forms of chronic hepatitis. HCV is not invariably pathogenic and genetic heterogeneity of HCV could be a major cause of such a variability. In clinical practice this means that presence and replication of the virus do not invariably imply a virus-induced liver damage. IgM antibodies that are the best diagnostic tools for the other forms of viral hepatitis are not sensitive and specific enough for hepatitis C, therefore we have to look for alternatives. Detection of anti-HCV does not help to distinguish past from present infections and only anti-HCV seroconversion in previously negative patients can indicate a recent HCV infection. However, the significant association between serum anti-C100-3 and HCV-RNA suggests that anti-HCV can be considered an indirect marker of HCV infectivity. In anti-HCV-negative infections and early acute hepatitis cases HCV-RNA detection will represent a valid diagnostic alternative. In patients undergoing antiviral therapy monitoring anti-HCV by immunoblotting assays and HCV-RNA by quantitative assays represent a valid tool to predict response that invariably has occurred in patients who had undetectable serum HCV-RNA and/or decreasing anti-HCV titres. Assays that detect multiple anti-HCV antibodies all together appear unsuitable for monitoring because they miss the disappearance of single antibodies. Anti-C22 appears the most frequent and earliest to be detected and usually it has the highest titre. Anti-C100 titres decrease earlier than anti-C33 and anti-C22 in patients with chronic HCV hepatitis who respond to antiviral therapy. The natural course of HCV infection appears to be characterized by three consecutive phases: disease, asymptomatic carrier and recovery. If transition from the first to the last occurs very slowly or the disease phase persists for years it may warrant in susceptible hosts severe forms of liver disease.

Hepacivirus↗
PubMed1993

Problems in diagnosing viral hepatitis.

The most reliable method of making a specific aetiological diagnosis of chronic viral hepatitis would be to identify virus specific cytotoxic T lymphocytes responsible for the killing of virus infected hepatocytes in each patient's liver. Unfortunately, this can not be proposed for routine diagnosis and surrogate tests are required. The detection of virus markers, and even of the virus itself, does not imply that liver damage is caused by virus infection. Indirect markers of the host's antiviral immunoresponse have to be used to confirm more specifically the diagnosis of viral hepatitis. IgM antibodies against viral antigens implicated in the elimination of the virus seem to be suitable alternative candidates. Significant changes in the serum values of viraemia and aminotransferases occur within a few days, while a significant variation in liver histology takes much longer. Only the kinetics of the highly variable parameters can be used for an appropriate study of the relationship between viraemia, antiviral immunoresponse, and liver cell necrosis. Quantitative and dynamic analyses of hepatitis virus markers seem the most suitable and reliable methods of monitoring the patients eligible for antiviral treatment and identifying the most appropriate time to start this.

Antibodies, Viral↗
PubMed1993

Is high AgNOR quantity in hepatocytes associated with increased risk of hepatocellular carcinoma in chronic liver disease?

AIMS: To evaluate whether high numbers of silver staining nucleolar organiser regions (AgNORs) in hepatocytes are associated with increased risk of hepatocellular carcinoma in chronic liver disease. METHODS: The quantitative distribution of AgNORs was studied in the liver biopsy specimens of 33 patients with chronic liver disease, 11 of whom developed hepatocellular carcinoma. The interval between liver biopsy and diagnosis of hepatocellular carcinoma was 26 months (range one to 61 months); the mean follow up of patients without hepatocellular carcinoma was 45 months (range 24-59 months). Quantitative evaluation of AgNORs was carried out on silver stained routine sections by morphometric analysis, using a computer assisted image analysis system. RESULTS: High interphase AgNOR values (> 3 microns2) were found in hepatocytes of nine out of the 11 (82%) patients in whom neoplastic transformation occurred. Of the remaining 22 patients, only seven (31%) had AgNOR values higher than > 3 microns2 (chi 2 4.83; p = 0.036). CONCLUSIONS: These results indicate that high numbers of interphase AgNORs are associated with increased risk of hepatocellular carcinoma in patients with chronic liver disease.

Adult↗
PubMedDate not supplied

Hepatitis C virus infection and liver disease.

Hepatitis C Virus (HCV) is a RNA virus that lacks the retroviral properties of surviving in infected hosts by integration into cellular DNA, nevertheless it is capable to cause chronic infection and disease in a considerable number of infected individuals (30-70% of cases). This results in a worldwide prevalence of chronic HCV carriers similar to those of hepatitis B virus carriers. We review and discuss here some of the peculiar aspects of chronic HCV infection and associated disease.

Hepatitis C↗