[A new approach to the evaluation of hypertensive disease].
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Biomedical subjects
Publications and source records attributed to G Lunghi.
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BACKGROUND: Prevalence and pathogenicity of hepatitis G virus infection in long-term renal transplant recipients, are not fully known. AIM: To evaluate long-term impact of HGV infection on liver disease of renal transplanted patients. PATIENTS AND METHODS: A total of 155 hepatitis B surface antigen negative kidney transplant recipients, followed for a mean of 11 years after renal transplantation, were studied. Of these 48 (31%) patients had persistently elevated serum aminotransferase values. Frozen serum samples were tested for HGV-RNA and HCV-RNA by nested reverse transcribed polymerase chain reaction, and for anti-hepatitis G virus and anti-hepatitis C virus by enzyme-linked immunosorbent assay Hepatitis C virus-RNA was typed by a line probe assay and quantified by a branched DNA signal amplification assay RESULTS: Hepatitis G virus-RNA was detected in 37 (24%) patients and anti-hepatitis G virus in another 26 (17%). Seventy (45%) patients had serum anti-hepatitis C virus and 63 of these (90%) had serum hepatitis C virus-RNA. Hepatitis G virus-RNA positive and negative patients were similar in terms of age, sex, duration of dialysis, rate of transfusion, chronic liver disease, rate of hepatitis C virus infection and immunosuppressive therapy. Fifteen (41%) hepatitis G virus-RNA seropositive patients were hepatitis C virus co-infected. Hepatitis C virus-RNA levels were significantly lower in the 15 hepatitis C virus/hepatitis G virus co-infected patients than in the 48 patients with hepatitis C virus infection only (2.2 vs 10.8 MEq/ml, p = 0.02). Only 3 hepatitis G virus carriers had persistently elevated alanine aminotransferase compared to 29 hepatitis C virus carriers (14% vs 60%, p < 0.001), 10 patients co-infected with both hepatitis G virus and hepatitis C virus, and in 6 patients with neither infection (67% vs 8%, p < 0.001). CONCLUSIONS: Hepatitis G virus infection is common among kidney transplant patients, it carries a low risk of chronic liver disease even in long-term follow-up. Low levels of hepatitis C virus-RNA found in hepatitis G virus carriers suggest an interaction between these two viruses in immunosuppressed patients.
Patients with end-stage renal disease (ESRD) appear to be at high risk for GBV-C/HGV infection. This information has been obtained with virological techniques (RT-PCR) but few serological data exist. A prototype enzyme immunoassay has now been developed to detect antibodies against the putative envelope protein (E2) located on the surface of the GBV-C/HGV virion particle. We studied the prevalence of GBV-C/HGV infection, as detected by RT-PCR and anti-E2 GBV-C/HGV antibody, in a cohort of chronic dialysis patients (n=157) and renal transplant (RT) recipients (n=77); as a control group, 136 healthy blood donors were tested. The total prevalence of GBV-C/HGV in ESRD was 23% (54/234). The frequency of GBV-C/HGV viremia was 7.7% (18/234) in ESRD and 4.4% (3/68) among healthy blood donors; the prevalence of anti-E2 GBV-C/HGV was 15% (36/234) and 8.8% (12/136) in ESRD and controls, respectively. No relationship was seen between anti-E2 GBV-C/HGV antibody (or GBV-C/HGV viremia) and age, sex, time on renal replacement therapy, anti-HCV, HBsAg and transfusion requirement. No statistical association was observed between GBV-C/HGV and AST/ALT activity. Two of 54 GBV-C/HGV positive patients (3.7%) had raised ALT but were negative for HBV/HCV. In the majority of patients (35/36, 97%) the presence of anti-E2 GBV-C/HGV antibody was linked with the loss of GBV-C/HGV viremia from serum. In conclusion, GBV-C/HGV infection, as detected by RT-PCR and anti-E2 antibody, was common in ESRD, and the rate of infection was higher than in controls. No association was seen between GBV-C/HGV and various demographic or clinical factors. A small group of GBV-G/HGV positive patients tested negative for HBV/HCV and had raised ALT. In many patients exposed to GBV-C/HGV infection the virus was cleared. The clinical significance of GBV-C/HGV in ESRD remains controversial. Prospective studies with additional serological assays are in progress.
TT virus is a novel hepatitis-associated DNA virus that has been provisionally designated as transfusion-transmitted virus (TTV). Infection by TTV has been frequently demonstrated in humans. Few reports, however, have been published on the epidemiology of TTV infection in patients with ESRD. The prevalence of TTV in patients undergoing maintenance dialysis varies widely and various demographic, virologic or clinical features can explain these differences; in some series, the prevalence of TTV in HD was significantly higher than in control groups. Blood transfusion requirement and nosocomial transmission of TTV within dialysis units seem to be important in the diffusion of TTV in the HD setting; however, other routes of TTV acquisition may play a role. The clinical significance related to the presence of TTV in HD population remains unclear; it is possible that TTV may aggravate liver disease caused by hepatitis C virus (HCV) infection. The natural history of TTV in dialysis is an area of avide research, since TTV has a propensity for establishing long-term infection in HD patients. The possibility that TTV causes pathological changes outside the liver cannot be ruled out. Further studies are in progress to understand the natural history and the epidemiology of TTV infection in patients with ESRD.
BACKGROUND: The natural history of hepatitis B virus (HBV) infection in patients undergoing maintenance dialysis is still unclear. The aim of this study was to measure the HBV viral load (HBV DNA) in a cohort (n=20) of HBsAg positive chronic dialysis patients over a 12-month observation period. METHODS; HBV DNA was measured by the Amplicor HBV MonitorTM Test Kit, an in vitro test that utilizes Polymerase Chain Reaction (PCR) nucleic acid amplification and DNA hybridisation for the quantitative measurement of hepatitis B viral DNA in human serum. Amplicor HBV MonitorTM Test Kit amplifies a sequence in the pre-Core/Core region of the HBV genome with biotinylated and non-biotinylated oligonucleotide primers. RESULTS: There was no significant difference between the median HBV load at the start and the end of the study, 1.85 x 104 HBV copies/ml (percentile 16.84; 6.35 x 102 - 3.5 x 106 HBV copies/ ml) and 8.5 x 103 HBV copies/ml (percentile 16.84; 5.5 x 102 - 6.38 x 105 HBV copies/ml), respectively. These serum HBV DNA levels were lower than those measured by the same test in patients with chronic hepatitis B and normal renal function (Hepatology 2000; 32: 116-23). In the group of HBsAg positive carriers on dialysis, we identified three patterns of HBV viremia over time: 1) patients (n=6) with persistent HBV DNA, 2) those (n=2) with undetectable HBV DNA and 3) those (n=12) with intermittent HBV DNA. Patients with persistent HBV DNA (median, 3.3 x 104 HBV copies/ml; percentile 16.84; 3.5 x 103 - 2.3 x 106 HBV copies/ml) had higher viral HBV load than those with intermittent HBV viremia (median, 1.2 x 103 HBV copies/ml; percentile 16.84; 3.5 x 102 - 2.3 x 104 HBV copies/ml) (p=0.0001). Patients with persistent HBV DNA had higher frequency of serum hepatitis B e antigen (HBeAg) positivity than those showing intermittent and negative HBV DNA, 50% (3/6) vs. 0% (p=0.04). The frequency of serum IgM antibody against hepatitis B core antigen (IgM anti-HBc) was higher in patients with persistent HBV DNA than those having intermittent or negative HBV DNA, 100% (6/6) vs. 33% (4/12), p=0.03. We detected no difference in aminotransferase activity between patients with persistent HBV DNA and those showing intermittent or negative HBV DNA. In the group with persistent HBV DNA, the mean difference between maximum and minimum values of HBV DNA observed in each individual patient was 6.13+/-1.25 decimal logarithm (Log10) and in patients with intermittent HBV DNA 3.87+/-1.49 Log10 (p=0.006). In the entire group, the fluctuations in HBV DNA values over time between and within individuals were not significant. CONCLUSIONS: The viremic HBV load was low and relatively stable over a 12-month follow-up period; three patterns of HBV viremia over time were observed; 30% of the viremic patients had persistent HBV viremia, and those patients had larger viral load and higher frequency of HBeAg and anti-HBc IgM than did patients with intermittent or negative HBV DNA. Prospective studies with longer observation periods are in progress to fully understand the natural history of HBV in these immunosuppressed patients.
Dialysis patients remain at risk for acquiring hepatitis C virus (HCV) infection. The issue of the natural history of HCV infection among patients undergoing long-term dialysis is surrounded by great controversy. An accurate assessment of the clinical outcomes of HCV in end-stage renal disease (ESRD) is hampered by numerous items, namely the primary features of the disease: its onset is rarely recognized and its course is prolonged exceedingly. Viral, host, and/or environmental factors may influence the outcome of chronic HCV infection but their precise role in promoting disease progression are yet to be defined in dialysis patients. It is well known that HCV-related liver disease usually runs an asymptomatic course and the liver-related mortality in the dialysis population is very low. In addition, it has been suggested that the HD procedure may exert a protective effect on the course of HCV and several mechanisms have been advocated to this purpose. However, the rate of persistence of HCV after acute hepatitis C is probably extremely high among dialysis patients. Recently a strong and independent relationship between HCV status and survival in the dialysis population has been observed. The frequency of liver cancer in dialysis patients appears higher than that seen in the general population. These findings have been obtained by several prospective studies with adequate size and long follow-ups. The natural history of HCV in patients on long-term dialysis will be better defined as more data are generated from ongoing studies. Dialysis patients desperately need effective and safe antiviral agents for the treatment of HCV-related liver disease.
Dialysis patients remain at risk of acquiring hepatitis B virus (HBV) infection. The issue of the natural history of HBV among patients undergoing long-term dialysis remains unclear. Assessing the natural history of hepatitis B in patients on maintenance dialysis is problematic because of the unique characteristics of this population: serum aminotransferase activity is lower in dialysis patients compared with patients without renal disease; also, chronic hepatitis B has an insidious and prolonged natural history, and the competing mortality from complications of end-stage renal disease may obscure the long-term consequences of hepatitis B. HBV-related liver disease frequently runs an asymptomatic course in dialysis patients and the liver-related mortality in this population is very low; thus, the prognosis for chronic HBV infection in dialysis patients has been reported as benign. However, the frequency of liver cancer in dialysis patients appears higher than that observed in the general population, this has been related to a greater exposure to HBV/HCV. Cirrhosis is not a frequent comorbid condition in the dialysis population of industrialised countries, but the death rate for dialysis patients with cirrhosis is 35% higher than for those without it. In addition, it has been observed that liver disease remains a significant cause of mortality among HbsAg-positive carriers on dialysis in developing countries. The low viral load measured in dialysis patients with persistent HBsAg carriage could be accounted for by the relatively benign course of HBV-related liver disease in this population. Prospective clinical trials are under way to better define the virological features of HBV in the dialysis population.
Liver disease has emerged as an important cause of morbidity and mortality after renal transplantation (RT). Hepatitis C virus (HCV) is the leading cause of liver disease after RT. The impact of HCV infection on patient and graft survival is currently a major concern. Retrospective studies with appropriate follow-up have mainly demonstrated that HCV positive patients have greater mortality compared to HCV negative recipients after RT. Novel investigations by large databases (United States Renal Data Systems (USRDS)) have shown that recipients of donor HCV-positive kidneys are at an independently increased risk of mortality, adjusted hazard ratio 2.12 (95% confidence interval (95% CI), 1.72-2.87, p<0.001); there was no evidence that any subgroup was less affected. With appropriate informed consent, the use of a renal graft from an HCV positive donor could be offered to an HCV infected recipient. Many renal transplant candidates have satisfactory virological responses to antiviral therapy; the persistence of HCV clearance over a prolonged follow-up after RT has been recently noted. Further prospective studies are needed to define better the course of HCV infection among renal allograft recipients.
Hepatitis C virus (HCV) infection remains frequent among patients on maintenance dialysis. It has been claimed that infrequent and slight abnormalities in serum aminotransferase activity could occur in dialysis patients with HCV. We describe a 61-year-old male patient on maintenance dialysis who acquired HCV by a nosocomial route. The natural history of HCV in this patient over 8 yrs featured frequent and high increases in serum aminotransferase and gamma-glutamyl transpeptidase (gamma-GT) levels. In December 2001, serum GOT and GPT were, respectively, 965 and 1294 UI/L; gamma-GT activity was 241 UI/L. HCV genotype was 2a/2c; median HCV RNA values in serum were 2.3 x 10⁵ UI/mL (range, 1.14 x 10⁴ to 4.6 x 10⁵ UI/mL). Total bilirubin, serum albumin, and colinesterase levels remained normal over the entire follow-up. Liver biopsy was not performed and interferon (IFN) therapy was not given. Currently, biochemical liver tests (GOT/GPT/gamma-GT) are in the upper range of normal values and the patient remains viremic. Efficacy and tolerability of initial monotherapy with IFN for chronic hepatitis C among dialysis patients are briefly discussed. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in the dialysis population.
OBJECTIVE: To evaluate the relationship between hepatitis C virus antibodies (HCV-Ab) and viremia and to compare the prevalence of HCV-Ab and HCV viremia in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Cross-sectional study. SETTING: Dialysis unit of a nephrology division in a public university hospital. PATIENTS: All dialysis patients who came for routine clinic visits during the study period. None denied informed consent. Forty-eight patients on HD and 79 on CAPD were examined. INTERVENTION: Blood samples were tested by second-generation enzyme-linked immunosorbent assay (ELISA II) and recombinant immunoblot assay (RIBA II) to look for HCV-Ab and by the polymerase chain reaction (PCR) to look for HCV viremia. RESULTS: ELISA II was positive in 52% of HD patients and in 14% of CAPD patients. RIBA II was positive in 48% of HD patients and in 11% of CAPD patients. HCV viremia was positive by PCR in 41.6% of HD patients and in 12% of CAPD patients. Two of these PCR-positive patients did not show HCV-Ab by ELISA II and RIBA II. The sensitivity and specificity of ELISA II were 93% and 92%, the sensitivity and specificity of RIBA II were 86% and 94%. CONCLUSIONS: Our data confirm a higher prevalence of HCV viremia in HD than in CAPD patients. The absence of Ab against virus C in 2 patients positive with PCR might be due to recent HCV infection or to weak virus replication or to a poor immune response.