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Background: Migrants represent a key target population for viral hepatitis micro-elimination programs and are important targets for specific prevention, screening and treatment programs., Aims: To raise awareness on viral hepatitis among migrants and key stakeholders, assess the prevalence of HBV and HCV among migrants, and determine an optimal and scalable viral hepatitis screening and treatment protocol., Material and Methods: Unselected, consecutive migrants reaching the costs of Italy were screened for HBV, HCV, HDV and HIV markers. Anagraphic and anamnestic information were used to identify viral hepatitis endemic hotspots in the countries of birth or transit. Personal data, including migration route, test results and treatment, were collected and stored in a dedicated database RESULTS: 362 patients were recruited in 2019; median age was 28 years, 71% were male. Most of the patients were African (54%) or Asian (40%). 49% positive for at least one HBV marker: 2.2% HBsAg (asymptomatic carriers with low viremia); 10.6% anti-HBs; 28.5% anti-HBs and anti-HBc, 1.7% anti-HCV, 0.6% anti-HIV, with low or undetectable viral load. Libya was the nexus shared by most of the positive, reactive cases. HCV and HIV markers were only found in migrants already resident in Italy for more than 6-12 months., Conclusion: Low to moderate prevalence of hepatitis B markers were observed in African and Asian first arrival migrants. Migrants positive for HCV and HIV likely acquired the infection after arrival in Italy, suggesting migrants are at risk of contracting viral infections once in Italy, highlighting the importance of ensuring access to prevention for migrant communities., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Backgound: A significant proportion of hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive patients with non-Hodgkin lymphoma (NHL) undergoing rituximab-based chemotherapy (R-CT) may suffer hepatitis B virus (HBV) reactivation., Aims: We wanted to assess efficacy and safety of lamivudine (LMV) prophylaxis to prevent this complication., Methods: Eighty-five consecutive HBsAg negative/anti-HBc positive NHL patients (71 years, 100% serum HBV DNA undetectable, 74% anti-HBs positive) received LMV coadministered with R-CT and for 18 months after the end of R-CT. Serum ALT, HBsAg, anti-HBs and HBV DNA were assessed every 4 months during and after end of LMV., Results: During 39 (2-108) months of study period, including 21 months of LMV and 27 additional months after LMV discontinuation, one patient (2%) had HBV reactivation, 31 months after stopping LMV and during administration of new immunosuppressive regimens, without LMV prophylaxis, owing to incomplete oncological response. A 50% decline of anti-HBs titers occurred in 22/63 (35%) patients, including 12 who became anti-HBs seronegative. Five (6%) patients had ALT increase during R-CT but none required R-CT discontinuation. Seventeen (20%) patients died, all for tumour progression., Conclusion: LMV prophylaxis is safe and effective in preventing HBV reactivation in HBsAg negative/anti-HBc positive NHL patients receiving R-CT., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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.

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.

Progression of hepatitis B in patients with lamivudine-resistant strains is slowed down by adefovir dipivoxil (ADV). Whether the time point of ADV administration (genotypic vs. phenotypic resistance) influences the outcome of therapy is unknown. We compared the outcome of ADV therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients with genotypic and phenotypic resistance to lamivudine. Ten milligrams of ADV was administered daily for 2 years to 46 HBeAg-negative patients at the time of phenotypic resistance (group A, >6 log(10) copies/mL of hepatitis B virus [HBV] DNA and high alanine aminotransferase [ALT] levels) and 28 patients at the time of genotypic resistance (group B, 3-6 log(10) copies/mL of HBV-DNA and normal ALT). HBV DNA was assessed every 2 months using Versant 3.0 assay, and lamivudine resistance was confirmed via INNO-LiPA assay in all patients. By month 3, HBV DNA tested negative in all patients from group B compared with only 20 (46%) in group A (P < .0001). The 2-year rates of virological response were 100% in the former patients and 78% in the latter ones (P < .0001). ALT levels remained persistently normal in all group B patients, whereas in group A patients they normalized at rates of 50% at month 6 (P < .0001), 72% at month 12 (P < .01), and 93% at month 24. None of the patients developed ADV resistance or ADV-related side effects. In conclusion, to optimize antiviral treatment in HBeAg-negative patients selecting resistant strains to lamivudine, ADV should be added to lamivudine as soon as genotypic resistance is detected.

Background: In renal allograft recipients, most cases of liver dysfunction are caused by hepatitis B virus and hepatitis C virus (HCV). The natural history of hepatitis C and B was studied in 286 renal allograft recipients who received a kidney allograft between 1972 and 1989 when tests for anti-HCV became available., Methods: In all patients, hepatitis B (HB) surface (s) antigen (Ag) was tested before and anti-HCV (by enzyme-linked immunosorbent assay II) after transplantation., Results: At enrollment in 1989 (5.5+/-4 years after transplantation), 209 patients were anti-HCV positive (C+), 42 patients were HBsAg-positive (B+), and 35 patients were both B+ and C+ (C+B+). One hundred four patients were receiving azathioprine (AZA) and 182 were on cyclosporine A (CsA). Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients. Liver biopsy showed chronic hepatitis in 73 patients, cirrhosis in 20 patients, and fibrosing cholestatic hepatitis in 2 patients. In 34 patients, liver biopsy was repeated, and progression of fibrosis was observed in 24 patients. The 12-year patient survival rate was similar in B+, C+, and B+C+ patients (67%, 78%, and 71%, respectively; P=not significant). Liver-related death was the first cause of death in B+ and B+C+ infected patients (58% and 72%, respectively), whereas cardiovascular disease was the leading cause of death in C+ patients (40%). Multivariate analysis showed that older age (>40 years) (relative risk [RR], 2.8), B+ status (RR, 2.36), and C+ status (RR, 1.65) were independently associated with a worse patient survival., Conclusions: In the long term, B+ patients had a higher risk of death related to liver disease than C+ patients, and co-infection did not worsen patient survival.

Recurrence of hepatitis B impairs the outcome of liver transplantation (OLT). In serum hepatitis B virus (HBV)-DNA-positive recipients, prophylaxis using lamivudine and immunoglobulins (HBIg) reduces the risk of recurrence, but it is undefined whether this regimen also protects candidates with YMDD mutants. Seventeen OLT viraemic candidates received pre-emptive lamivudine followed by post-OLT prophylaxis with lamivudine and HBIg. Both sera and liver biopsies were prospectively collected and high-sensitive polymerase chain reaction (PCR) assay was applied for HBV-DNA detection. Finally, the presence of YMDD mutants was explored in all PCR-positive samples. All patients remained hepatitis B recurrence-free after a mean follow up of 32 months. By PCR, serum HBV-DNA was detectable in 64.3% of cases at OLT-baseline, in 64.7% under combined prophylaxis and in 58.8% in patients (70.5% of the total) with a minimum follow up of 24 months. At OLT-baseline, YMDD mutants were found in 44.4% of patients. After OLT, mutants were present in 50% of patients but only in 16.6% of cases in the long period. Although 41% of the native livers and 42.8% of the analysed grafts harboured HBV-DNA, YMDD mutants were detected in 57% of the native positive livers. YMDD mutants were largely detected both at OLT-baseline and post-OLT, but their presence decreased over time. Regardless of the presence of YMDD mutants, no hepatitis B recurrence was observed in our OLT recipients using pre-emptive lamivudine followed by continuous prophylaxis with lamivudine and HBIg.

Hepatitis C virus (HCV) infection is frequent among patients receiving long-term dialysis in developed and developing countries. It is difficult to assess the natural history of HCV in the dialysis population; however, recent studies have demonstrated that positive anti-HCV status is a significant and independent risk factor for mortality among dialysis patients. Recent meta-analyses have shown that interferon (IFN) initial monotherapy is effective in the treatment of chronic hepatitis C among dialysis patients, but tolerance to IFN mono-therapy was rather poor. Large, multicenter and prospective trials based on pegylated IFN for the treatment of chronic hepatitis C are planned. The frequency of HBV infection in patients undergoing maintenance dialysis in the industrialized world is low but not negligible; persistent HBsAg seropositivity is much higher in less-developed countries. Recent surveys have shown that detectable HBsAg/ HBV DNA status in serum is an independent and significant predictive factor for hepatocellular dysfunction in dialysis patients. No significant difference in morbidity and mortality between dialysis patients according to hepatitis B surface antigen status has been consistently shown. Preliminary reports suggest that lamivudine appears to be safe and effective in patients receiving long-term dialysis.

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.

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.

Controlling the spread of HBV infection in dialysis units has been one of the major advances in the treatment of patients with ESRD. The frequency of HBsAg carriers on maintenance dialysis is low in developed countries. However, prevalence and incidence rates of HBV infection among dialysis patients in less developed countries remain very high. Patients on maintenance dialysis and chronic HBsAg carriage are typically anicteric and rarely develop symptoms of hepatitis. The relationship between HBsAg and aminotransferase activity in dialysis population is stronger than has so far been recognized. HBsAg positivity is significantly associated with hepatocellular damage in dialysis patients. Aminotransferase activity in dialysis population is usually depressed; this hampers the recognition of HBV-related liver disease among dialysis patients by biochemical tests. The HBV viral load in HBsAg positive patients is low and stable over time; the low mortality attributable to liver disease in dialysis patients could be related to this finding. Numerous assays for detecting HBV DNA in serum of dialysis patients are available; they should not be used for purposes of routine screening within dialysis units. Continued implementation of the long-recommended infection control procedures against HBV within dialysis units is strongly suggested.

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.

: 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.: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients.: 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.: 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.: 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. [ABSTRACT FROM AUTHOR]

Nine patients with lamivudine-resistant chronic hepatitis B infection who had been treated with adefovir 10 mg/day and had had a suboptimal response but did not have genotypic resistance to adefovir were treated with high-dose adefovir (20 mg/day). The response to the increased dose of adefovir was compared with the response in 15 patients with a suboptimal response who did not receive an increase in the dose of adefovir. The increase in the dose of adefovir did not lead to a significant reduction in hepatitis B DNA when compared with patients maintained on the standard dose. These data suggest that increasing the dose of adefovir in patients with a suboptimal response does not lead to an improved response. [ABSTRACT FROM AUTHOR]