Kinetics of hepatitis B virus load and haemodialysis: a prospective study.

The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been an important goal in the management of patients on regular dialysis but infected patients continue to enter the dialysis system. It is evident that HBV viraemia in hepatitis B surface antigen (HBsAg)-positive patients on dialysis is low but it remains unclear whether haemodialysis per se can contribute to viral load reduction in such patients. HBV DNA was determined in 40 HBsAg-positive patients on maintenance haemodialysis immediately before and at the end of a 4-h haemodialysis session. The same measurements were repeated 48 and 72 h later. Twenty (50%) of 40 HBsAg-positive patients had detectable HBV DNA in serum. Detectable HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in the majority of patients after haemodialysis, although the difference was not significant (29 390 +/- 48 820 vs 23 862.8 +/- 4 350 copies/mL, NS). There was a strong relationship between mean HBV DNA levels before dialysis and absolute reduction of HBV DNA during haemodialysis sessions (r = 0.75, P = 0.0001). No difference occurred in the magnitude of change in HBV DNA titre when comparing cellulosic to synthetic membranes. Haemodialysis per se leads to a reduction in HBV load in HBsAg-chronic carriers on maintenance dialysis. This phenomenon could explain the low viral loads in these patients. Prospective studies are in progress to identify the mechanisms responsible for reduction in HBV load during haemodialysis.

Gamma glutamyltranspeptidase activity and viral hepatitis in dialysis population.

BACKGROUND: Numerous investigations have reported that viral hepatitis is associated with significant hepatocellular damage, as expressed by raised aminotransferases in serum, in dialysis population. However, scarce information exists on the activity of gamma glutamyltranspeptidase (GGTP) in dialysis patients with infection by hepatotropic viruses. OBJECTIVES: We measured serum GGTP values in a large cohort (n=757) of patients receiving long-term dialysis; healthy controls were also included. The relationship between GGTP values and a series of demographic, clinical, and biochemical parameters was analyzed. METHODS: Serum GGTP levels were tested by spectrophotometry. A subset (n=333) of dialysis patients was tested by molecular technology (branched-chain DNA (bDNA) assay) to evaluate the relationship between serum GGTP and HCV viremia. A subgroup (n=78) of dialysis patients was analyzed by an ultrasound scan of gallbladder and biliary tract to assess the presence of gallstone disease. Multivariate analyses were made using regression models; serum GGTP values were included as a dependent variable. The usefulness of serum GGTP levels in detecting HBsAg and anti-HCV positivity was evaluated using receiver operating characteristics (ROC) curve analysis. RESULTS: Univariate analysis showed that serum GGTP levels were significantly higher in HBsAg positive and/or anti-HCV positive patients than in HBsAg negative/anti-HCV negative patients on dialysis; 85.1+/-184.1 versus 25.86+/-23.9 IU/l (P=0.0001). The frequency of raised GGTP levels was 22.2% (41/184) among dialysis patients with chronic viral hepatitis. Multivariate analysis showed a significant and independent association between serum GGTP values and positive HBsAg (P=0.005) and anti-HCV antibody (P=0.0001) status. Mean GGTP values were significantly higher in study patients than controls, 32.32+/-60.02 versus 23.5+/-16.92 IU/L (P=0.01); however, no significant difference with regard to GGTP between study and healthy cohorts persisted after correction for age, gender, race, and viral markers. No relationship between gallstone disease and serum GGTP was found (NS). An independent and significant association (P=0.0291) between raised GGTP levels and detectable HCV RNA in serum was noted among patients tested by biology molecular techniques. ROC technology demonstrated that GGTP was equally useful for detecting HBV (P=0.0004) and HCV (P=0.0005) among dialysis patients. CONCLUSIONS: We found an independent and significant association between serum GGTP values and HBsAg and/or anti-HCV antibody in dialysis population. Twenty-two percent of dialysis patients with chronic viral hepatitis had elevated GGTP. No difference in GGTP between HBsAg- negative/anti-HCV- negative dialysis patients and healthy individuals was found. Routine testing for serum GGTP levels to assess liver disease induced by hepatotropic viruses or other agents in dialysis population is suggested.

Occult hepatitis B virus infection in dialysis patients: a multicentre survey.

BACKGROUND: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. AIM: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. METHODS: We screened a large cohort (n = 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n = 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. RESULTS: Occult hepatitis B virus infection was absent (zero of 213 = 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P = 0.0001]. No dialysis patients seropositive for anti-hepatitis B core antibody in serum (zero of 123 = 0%) had detectable hepatitis B virus-DNA by polymerase chain reaction technology. No significant association between abnormal biochemical liver tests and serum anti-hepatitis B core antibody was noted in our population. Nominal logistic regression analysis demonstrated an independent and significant relationship between anti-HCV antibody and anti-hepatitis B virus core antibody in serum (Wald chi-square 16.06, P = 0.0001). The rate of seropositive patients for anti-hepatitis B virus core antibody was higher among study patients than controls with normal renal function [36.9% (216 of 585) vs. 21.4% (59 of 275), P = 0.0001]; this difference partially persisted after correction for demographic parameters, and viral markers. CONCLUSION: In conclusion, occult hepatitis B virus was absent in our study group. Anti-hepatitis B core antibody was significantly related to presence of anti-HCV antibody supporting shared modes of transmission. Clinical studies based on molecular biology techniques provided with higher sensitivity are planned.

Influence of hepatitis B virus virema upon serum aminotransferase activity in dialysis population.

BACKGROUND: The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been one of the major advances in the management of patients with end-stage renal disease (ESRD). However, clinical and biochemical expression of HBV in dialysis patients have not been adequately addressed. Elevated values of serum aminotransferase activity are a sensitive measure of hepatocellular injury, but the role of HBV infection in the development of liver disease among dialysis patients has not been adequately analysed. Also, the clinical impact related to the virological characteristics of HBV in dialysis has not been evaluated. METHODS: Demographic, biochemical and virological data from 727 patients undergoing chronic dialysis in seven dialysis units in northern Italy were collected in order to assess the biochemical consequences related to the presence of HBV infection in this population. We have measured by RT-PCR technology the titers of HBV viremia in HBsAg positive patients receiving dialysis. RESULTS: Univariate analysis showed that AST and ALT values were significantly higher in HBsAg positive/HBV DNA positive than HBsAg negative patients on dialysis; AST, 22.86+/-31.34 vs. 14.19+/-9.7 IU/L (P=0.00001); and ALT, 25.07+/-41.59 vs. 13.9+/-41.59 IU/L (P=0.00001). In the subgroup of HBsAg positive patients, the frequency of detectable HBeAg in serum was 14.9% (7/47). The median value of HBV DNA in patients with detectable HBV DNA in serum was 2.160 x 10(3) copies/mL (range, 2.5 x 10(2)-4 x 10(6) copies/mL). HBsAg positive/HCV positive patients had higher aminotransferase activity than other subgroups (P=0.0001). Multivariate analysis showed a significant and independent association between detectable HBsAg/HBV DNA in serum and AST (P=0.00001) and ALT (P=0.0001) activity AST and ALT levels were lower in dialysis than healthy individuals--this finding persisted in age- and gender-matched comparisons. CONCLUSIONS: The HBV viral load in HBsAg positive patients receiving maintenance dialysis is not high. HBsAg positivity with detectable HBV DNA in serum is a strong and independent predictor of raised aminotransferase activity among dialysis patients. HBsAg positive patients had greater aminotransferase activity than HBsAg negative individuals even if both the groups had mean aminotransferase levels within the normal range considered for healthy population. Clinical trials aimed at identifying the best cut-off value to enhance the diagnostic yield of AST/ALT for detecting HBV in dialysis population are under way.

[Natural history of hepatitis B virus infection in dialysis patients: prospective study by quantitative analysis of HBV viremia]. / Storia naturale dell'infezione da virus dell'epatite B in dialisi: studio prospettico mediante analisi quantitativa della viremia HBV.

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.

[Hepatopathy and hepatitis B virus infection in dialysis patients: cross-sectional study]. / Epatopatia e infezione da virus dell'epatite B nei pazienti in dialisi: studio trasversale.

BACKGROUND: Control of spread of HBV infection in dialysis units in developed countries has been one of the major advances in managing end-stage renal disease (ESRD). Patients with chronic HBV, however, continue to enter the population pool of dialysis patients and transplant candidates. The clinical significance related to the presence of HBsAg in serum of dialysis patients has not been completely understood. AIM AND METHODS: We collected demographic, biochemical and virological data from a large (n=464) population of patients on maintenance dialysis. This was done to assess the influence of virological and host factors on hepatocellular damage, as shown by serum aminotransferase activity. RESULTS: The frequency of HBsAg positivity in our dialysis population was 8.2 % (38/464); the rate of HBsAg positive patients showing HBe antigen was 20.6% (7/34). Twenty-two (84.6%) of 26 HBsAg positive patients showed detectable HBV DNA in serum by Amplicor HBV MonitorTM Test. HBsAg positive patients had serum aminotransferase activity significantly higher than HBsAg negative individuals; GOT (AST) 25.1+/-29.9 vs. 16+/-21.5 UI/L (p=0.001), and GPT (ALT) 31.3+/-52.5 vs. 17.7+/-21.9 UIL (p=0.034). In the subset of HBsAg positive dialysis patients, those in the replicative phase HBeAg positive) had aminotransferase activity higher than HBeAg negative individuals, AST, 42.3+/-43.6 vs. 22.4+/-27.3 UI/L (p=0.097) and ALT, 49.41+/-54.7 vs. 29.17+/-55.76 UI/L (NS) respectively. We did a multivariate analysis by standard least square model on the entire patient group and we found independent and significant association between detectable HBsAg in serum and AST (p=0.0089)and ALT (p=0.0159) values. There was an independent and significant relationship between age and ALT (p=0.01). CONCLUSIONS: In our study group, HBsAg positive patients on dialysis had serum aminotransferase activity significantly higher than that measured in HBsAg negative individuals. However, mean transaminase levels in HBsAg positive patients on dialysis were below the upper limit of normal for the reference range of healthy controls. HBsAg positive dialysis patients with active viral replication showed the greatest liver damage. Studies are in progress to understand further HBV-related liver disease in dialysis population.

IgA nephropathy: remission during pregnancy and relapse in the puerperium.

A 39-year-old woman, with proteinuria and microhematuria, at about the 8th week of pregnancy showed a reduction in proteinuria. After the 16th week, proteinuria disappeared. In the 40th week, the patient spontaneously delivered a 1.990-kg still-born female. Six days later, blood pressure increased (to 150/100 mm Hg), and laboratory examinations showed that proteinuria was 2.7 g/24 h. Given that urinalysis confirmed the presence of proteinuria, 6 weeks later, a renal biopsy was performed. The final diagnosis was IgA nephropathy. It is possible that the presence of the fetus may have led to changes in the maternal immunological system which may have attenuated the immunopathogenic mechanisms responsible for IgA nephropathy.