Staphylococcus Infection-Associated Glomerulonephritis in a Kidney Transplant Patient: Case Report.

BACKGROUND: Staphylococcus infection-associated glomerulonephritis is a rare cause of graft dysfunction in kidney transplant. Suspicion should be high in the setting of elevation of serum creatinine, active urinary sediment, with or without hypocomplementemia, and simultaneous Staphylococcus aureus infection. A kidney biopsy is usually diagnostic. CASE REPORT: A 56-year-old man, who received a kidney transplant in 1998, with basal serum creatinine of 1.2 mg/dL and normal urinary sediment, was admitted to our kidney transplantation unit with graft dysfunction and a urinary tract infection caused by S aureus with septicemia, treated with antibiotics, in the context of recently intensified immunosuppression for a primary immune thrombocytopenia diagnosed 3 weeks earlier. After antibiotic treatment, the patient persisted with graft dysfunction, edema, and hypertension, with a S aureus isolation in the urine culture, active urinary sediment, and low C3. A kidney biopsy was performed, showing diffuse proliferative endocapillary and mesangial glomerulonephritis, with IgA(++) and C3(++) mesangial and endocapillary deposits in immunofluorescence. The patient was treated symptomatically and maintained his regular immunosuppression. At the last follow-up, his serum creatinine value was stable at 2.5 mg/dL. CONCLUSIONS: The onset of a nephritic syndrome with a simultaneous S aureus infection should lead to suspicion of this uncommon entity, confirmed histologically. Despite its association with poor graft survival, our patient's graft survival remained stable.

Fibrogenesis in Kidney Transplant: Dysfunction Progress Biomarkers.

INTRODUCTION: Fibrogenesis markers, such as alpha-actin (AA), CD163 (macrophages), and E-cadherin, have been studied as chronic kidney allograft injury (CAI) predictors, a major cause of allograft failure. OBJECTIVE: Investigate the value of these markers in predicting CAI and initiation of dialysis. MATERIALS AND METHODS: Retrospective analysis of 26 kidney allograft biopsies (from 22 patients with CAI) during 2 years, evaluating intensity and percentage of marked cells on glomeruli and tubulointerstitial compartment. At the time of the biopsy, patients were 45.5 ± 15.8 years and 4.2 years after transplant, and they had a mean glomerular filtration rate (GFR) of 25.8 ± 9.9 mL/min. From an average of 8.5 glomeruli per biopsy, there was ≤25% sclerosis in 17 cases, 26% to 50% in 5, and >50% in 4. Interstitial fibrosis or tubular atrophy affected ≤25% of cortical area in 14 cases, 26% to 50% in 8, and >50% in 2. Twelve patients started dialysis 5.8 ± 4.7 years after transplant, with an average GFR 20.9 mL/min at the time of the biopsy. RESULTS: There was a higher intensity and percentage of CD163-marked cells in the tubulointerstitial compartment in advanced interstitial fibrosis. We found an association between intensity of AA in the tubulointerstitial compartment and initiation of dialysis (P = .003) and a negative correlation between intensity of E-cadherin loss and GFR (r = -0.56, P = .012). CONCLUSIONS: In our study, intensity of tubulointerstitial AA was shown to be a predictor of initiation of dialysis, and E-cadherin loss intensity was associated to CAI progression. However, prospective and larger studies are needed to evaluate the predictive value of these markers.

Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study.

INTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss.

Polyomavirus Nephropathy: Ten-Year Experience.

BACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL). METHODS: Retrospective analysis of 23 biopsies, from patients with CAD and histological evidence of BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30 mL/min in 16 patients at the time of the BKVN diagnosis. RESULTS: BKVN was histologically diagnosed in 23 recipients (19 men, 4 women). All patients were white, with age of 51.2 ± 12.1 years (6 patients, age >60 years), and 22 had a deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus infection in 2, and AR in 15. All patients were medicated with calcineurin inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an antimetabolite. One year after antimetabolite reduction/discontinuation and/or CNI reduction/switching and/or antiviral agents, graft function was decreased in 11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9 patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk factors for GL. The lower GFR at the time of the BKVN diagnosis was associated with an increased risk of initiation of dialysis. CONCLUSIONS: GL occurred in 39.1% of patients with BKVN and DGF; older age and lower GFR at the time of diagnosis were important risk factors. Early diagnosis of BKVN is essential to prevent GL.

What Can We Do When All Collapses? Fatal Outcome of Collapsing Glomerulopathy and Systemic Lupus Erythematosus With Diffuse Alveolar Hemorrhage: Case Report.

INTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury. Although commonly associated with human immunodeficiency virus (HIV) infection, it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT: We present the case of a 50-year-old man, with chronic kidney disease secondary to focal and segmental glomerulosclerosis, who received a cadaveric kidney transplant in 2007. There were no relevant intercurrences until May 2015, when he presented with nephrotic range proteinuria (± 4 g/d). A graft biopsy was performed and it did not show any significant pathological changes. In September, he developed a full nephrotic syndrome (proteinuria 19 g/d) and a graft biopsy was repeated. CG features were evident with a rich immunofluorescence. Antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies were positive; the remaining immunologic study was normal. Viral markers for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) were negative. The patient was treated with corticosteroid pulses and plasmapheresis (seven treatments). A rapid deterioration of kidney function was seen and he became dialysis dependent. He was discharged with a low-dose immunosuppressive treatment. In October, he was hospitalized with diffuse alveolar hemorrhage (DAH). The auto-immune study was repeated, revealing complement consumption and positive titers of ANA and Anti-dsDNA antibodies. Anti-neutrophil cytoplasmic antibodies (ANCAs) and antiglomerular basement membrane antibody (anti-GBM) were negative. Treatment with intravenous corticosteroids, plasmapheresis, and human immunoglobulin was ineffective and the outcome was fatal. CONCLUSION: This case report highlights the possible association of CG and SLE. To our knowledge, it is the first case of SLE presenting with CG and DAH, with the singularity of occurring in a kidney transplant recipient receiving immunosuppression.

Accumulation of Trace Metals by Mangrove Plants in Indian Sundarban Wetland: Prospects for Phytoremediation.

The work investigates on the potential of ten mangrove species for absorption, accumulation and partitioning of trace metal(loid)s in individual plant tissues (leaves, bark and root/pneumatophore) at two study sites of Indian Sundarban Wetland. The metal(loid) concentration in host sediments and their geochemical characteristics were also considered. Mangrove sediments showed unique potential in many- fold increase for most metal(loid)s than plant tissues due to their inherent physicochemical properties. The ranges of concentration of trace metal(loid)s for As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn in plant tissue were 0.006-0.31, 0.02-2.97, 0.10-4.80, 0.13-6.49, 4.46-48.30, 9.2-938.1, 0.02-0.13, 9.8-1726, 11-5.41, 0.04-7.64, 3.81-52.20 µg g (-1)respectively. The bio- concentration factor (BCF) showed its maximum value (15.5) in Excoecaria agallocha for Cd, suggesting that it can be considered as a high-efficient plant for heavy metal bioaccumulation. Among all metals, Cd and Zn were highly bioaccumulated in E. agallocha (2.97 and 52.2 µg g (-1) respectively. Our findings suggest that the species may be classified as efficient metal trap for Cd in aerial parts, as indicated by higher metal accumulation in the leaves combined with BCF and translocation factor (TF) values.

C4d deposits in acute "cell-mediated" rejection: a marker for renal prognosis?

BACKGROUND: Accumulation of C4d along peritubular capillaries (PTC) of renal allografts is normally attributed to antibody-mediated rejection. The prognostic implication of these deposits associated with "cell-mediated" rejection on graft survival remains uncertain. Our study aims to evaluate the impact of C4d deposits along PTC of patients with acute cell- mediated rejection on graft function and survival. METHODS: We retrospectively analyzed patients transplanted between 2005 and 2010 with histopathologic diagnosis of acute rejection (AR). Eleven patients with "pure" antibody-mediated rejection were excluded. The remaining 79 patients were divided into two groups according to type of AR by Banff 2003 criteria: type I (69.6%) versus type II (30.4%). In each group, comparisons were made between C4d-negative (-) and C4d-positive (+) biopsies. RESULTS: Fifty-five patients presented with type I AR: 35 (63.6%) C4d- and 20 (36.4%) C4d+. Twenty-four patients presented with type II AR: 13 (54.2%) C4d- and 11 (45.8%) C4d+. In the type I AR group, graft survival at the first and second years was similar in C4d- and C4d+ patients (94% and 91% versus 75% and 75%, respectively, log-rank P = .26). No differences were encountered in estimated glomerular filtration rate (eGFR) between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 14.7% of C4d- patients versus 25% in C4d+ patients (P = NS). In the type II AR group, graft survival at the first and second years was similar in C4d- and C4d+ patients (85% and 85% versus 72% and 61%, respectively, log-rank P = .50). No differences were encountered in eGFR between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 30.8% of C4d- patients versus 45.5% in C4d+ patients (P = NS). CONCLUSION: Our results suggest that detection of C4d staining in acute "cell-mediated" rejection does not imply a worse renal prognosis.

Short-term changes of metal availability in soil. Part I: comparing sludge-amended with metal-spiked soils.

Sewage sludge application to soils is regulated by its total metal content. However, the real risk of metals is determined by the fraction that is biologically available. The available fraction is highly related to the strength of metal binding by the matrix, which is a dynamic process. The evaluation of the fate of metals in time can contribute increased accuracy of ecological risk assessment. Aiming to evaluate short-term changes in metal availability when metals were applied to soil directly (metal-spiked) or by way of an organic matrix (sludge-amended), a laboratory experiment was performed using open microcosms filled with agricultural soil. A concentration gradient of industrial sludge (11, 15, 55, and 75 t/ha) that was contaminated predominantly with chromium, copper, nickel, and zinc, or soil freshly spiked with the same concentrations of these metals, were applied on top of the agricultural soil. After 0, 3, 6, and 12 weeks, total (HNO(3) 69 %) and 0.01 M CaCl(2)-extractable metal concentrations in soil and metal content in the percolates were measured. Results demonstrated that comparison between sludge-amended and metal-spiked soils may give important information about the role of sludge matrix on metal mobility and availability in soil. In sludge-amended soils, extractable-metal concentrations were independent of the sludge concentration and did not change over time. In metal-spiked soils, metal extractability decreased with time due to ageing and transport of metals to deeper layers. In general, the sludge matrix increased the adsorption of metals, thus decreasing their mobility in soils.

Toxicity to Eisenia andrei and Folsomia candida of a metal mixture applied to soil directly or via an organic matrix.

Regulatory limits for chemicals and ecological risk assessment are usually based on the effects of single compounds, not taking into account mixture effects. The ecotoxicity of metal-contaminated sludge may, however, not only be due to its metal content. Both the sludge matrix and the presence of other toxicants may mitigate or promote metal toxicity. To test this assumption, the toxicity of soils recently amended with an industrial sludge predominantly contaminated with chromium, copper, nickel, and zinc and soils freshly spiked with the same mixture of metals was evaluated through earthworm (Eisenia andrei) and collembolan (Folsomia candida) reproduction tests. The sludge was less toxic than the spiked metal mixture for E. andrei but more toxic for F. candida. Results obtained for the earthworms suggest a decrease in metal bioavailability promoted by the high organic matter content of the sludge. The higher toxicity of the sludge for F. candida was probably due to the additive toxic effect of other pollutants.

Renal transplantation with expanded criteria donors: the experience of one Portuguese center.

BACKGROUND: The shortage of kidneys available for transplantation has led to enlarged criteria donors (ECD): namely, donors older than 60 years or aged between 50 and 59 years with 2 of the following characteristics-hypertension, predonation serum creatinine level higher than 1.5 mg/dL or cerebrovascular disease as the cause of death. The aim of this study was to analyze renal transplants using ECD compared with standard criteria donors (SCD) concerning the incidences of delayed graft function (DGF), acute rejection episodes (ARE), and patient and graft survivals. MATERIALS AND METHODS: This retrospective study of 409 cadaveric renal transplants over the last 4 years identified ECD in contrast with SCD. RESULTS: Of the transplants, 24.4% used ECD. The baseline characteristics of recipients of ECD versus SCD kidneys were similar, except for age and cold ischemia time. Comparing ECD and SCD, we observed an higher incidence of DGF (35% vs 18%), occurrence of ARE (34.4% vs 16.6%), average serum creatinine levels at 6 (1.87 vs 1.4 mg/dL), and 12 months (1.88 vs 1.43 mg/dL) as well as lower graft survival at 1 (82% vs 91%) and 3 years (75% vs 84%) after transplantation. Recipient survival at 1 year was not different. Multivariate analysis identified recipient age, cold ischemia time, ARE, and DGF as risk factors for graft failure. CONCLUSIONS: Renal transplantation with grafts from ECD shows significantly worse outcomes with higher rates of DGF and ARE, worse graft function, and lower graft survival.

Cadaveric donor factor variations during a 12-year period: influence on kidney transplant outcomes.

UNLABELLED: Our purpose was to evaluate changes in cadaveric donor factors between 1993 and 2004 and their impact on the short- and long-term outcomes of renal transplants in a single center. PATIENTS AND METHODS: Cadaveric renal transplants performed in our unit between 1993 and 2004 were divided in two groups of identical length: A (n = 455; 1993-1998) and B (n = 465; 1999-2004). Major differences related to donor, graft, and recipient factors were analyzed between groups and correlated with main outcome parameters. Recipient age, gender, weight, etiology of end-stage renal disease, average length of dialysis, and cold ischemia were not different in the two periods. RESULTS: Grafts harvested in our hospital were more frequent in group A (92.3 vs 78.2%; P < .005). Traumatic causes of death were more frequent before 1999: 90.9 vs 70.9% (P < .001). Mean donor age was higher after 1999: 31.37 vs 35.94 years (P < .005). Female donors were more frequent in the second period: 20.5 vs 26.6% (P < .05). Mean donor weight was also higher: 52.36 vs 67.86 kg (P < .05). All of these differences were unfavourable characteristics regarding graft outcomes. Delayed graft function (A = 13%, B = 24.2%), acute rejection episodes (A = 41.2%, B = 28%), and chronic allograft dysfunction (A = 23.5%, B = 14.4%) were also significantly different between the two cohorts (P < .005). Graft function (serum creatinine at 1 and 2 years), patient and graft survivals, causes of graft loss, and of patient death were similar across time. CONCLUSION: The unfavorable tendency in the quality of cadaveric donors during the last 12 years had no negative impact on graft function and patient outcome.

Genetic basis of Alzheimer's dementia: role of mtDNA mutations.

Alzheimer's disease (AD) is the most common neurodegenerative disorder associated to dementia in late adulthood. Amyloid precursor protein, presenilin 1 and presenilin 2 genes have been identified as causative genes for familial AD, whereas apolipoprotein E epsilon4 allele has been associated to the risk for late onset AD. However, mutations on these genes do not explain the majority of cases. Mitochondrial respiratory chain (MRC) impairment has been detected in brain, muscle, fibroblasts and platelets of Alzheimer's patients, indicating a possible involvement of mitochondrial DNA (mtDNA) in the aetiology of the disease. Several reports have identified mtDNA mutations in Alzheimer's patients, suggesting the existence of related causal factors probably of mtDNA origin, thus pointing to the involvement of mtDNA in the risk contributing to dementia, but there is no consensual opinion in finding the cause for impairment. However, mtDNA mutations might modify age of onset, contributing to the neurodegenerative process, probably due to an impairment of MRC and/or translation mechanisms.

Calcineurin inhibitor-free immunosuppression in renal transplantation.

PURPOSE: To describe our initial results using a calcineurin inhibitor-free immunosuppression protocol in renal transplants. PATIENTS AND METHODS: Between October 2001 and June 2003, 56 recipients of a renal allografts were started on an immunosuppression protocol without calcineurin inhibitors, consisting of basiliximab, sirolimus, mycophenolate mofetil, and steroids. We analyzed patient and graft survival, acute rejection episodes, and renal function. RESULTS: The mean follow-up was 19.6 months. Actuarial patient survival at 1 and 2 years was 98.1% and 95.3%, respectively. Actuarial graft survival at 1 and 2 years was 92.9% and 87.6%, respectively. Acute rejection occurred in 27.8% of the patients, usually Banff 1 (73.3%). There was stable renal function with mean serum creatinine of 1.3, 1.4, 1.3, and 1.3 mg/dL at 1, 6, 12, and 24 months after transplant. CONCLUSIONS: The use of immunosuppression free of calcineurin inhibitors is effective and safe. Further follow-up is needed to evaluate the impact on long-term results.

Analysis of serpentinophytes from north-east of Portugal for trace metal accumulation--relevance to the management of mine environment.

In north-east of Portugal, the serpentinized area is about 8000 ha with a characteristic geology and flora. The serpentine plant community and respective soils were analyzed to examine the trace metal budget in different tissues of the plants exhibiting resistance to trace metals. One hundred and thirty five plant species belonging to 39 families and respective soils have been analyzed for total Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Substantial amounts of Ni, Cr, Co and Mn were detected in plant tissues which are listed below: NI: Alyssum serpyllifolium (38105); Bromus hordeaceus (1467); Linaria spartea (492); Plantago radicata (140); Lavandula stoechas (118) and Cistus salvifolius (114); CR: L. spartea (706.7); Ulmus procera (173.4); A. serpyllifolium (129.3); Cistus ladanifer (40.8); L. stoechas (29.5); P. radicata (27.81); Setariopsis verticillata (25.7); Plantago lanceolata (24); Digitalis purpurea (23.4); Logfia minima (23.1); Arenaria querioides (23); Hieracium peleteranum (22.7); Arenaria montana (14.5); CO: A. serpyllifolium (145.1); L. spartea (63.2); P. radicata (10.4); H. peleteranum (7.3); Lepidium heterophyllum (6.9); A. querioides (6.6); C. salvifolius (6.5); C. ladanifer (6.3); L. stoechas (6.1); Anthyllis lotoides (6.1); L. minima (6.1); Euphorbia falcata (5.7) and B. hordeaceus (5.6); MN: A. serpyllifolium (830); L. spartea (339); L. stoechas (187.1); L. minima (182.7); Castanea sativa (125); Spergula pentandra (124); P. radicata (119); Cytisus striatus (115.4); Quercus pyrenaica (110); Teucrium scorodonia (109.4); Fraxinus vulgaris (109); Anthyllis sampaiana (108); Quercus ilex (108). The significance of serpentine flora, need for conservation of these fragile and environmentally invaluable plant resources for possible use for in situ remediation of metalliferous substrates are presented in this paper.

Plant community tolerant to trace elements growing on the degraded soils of São Domingos mine in the south east of Portugal: environmental implications.

The selection of trace element tolerant species is a key factor to the success of remediation of degraded mine soils. Mining activities generate a large amount of waste rocks and tailings, which get deposited at the surface. The degraded soils, the waste rocks and tailings are often very unstable and will become sources of pollution. The direct effects will be the loss of cultivated land, forest or grazing land, and the overall loss of production. The indirect effects will include air and water pollution and siltation of rivers. These will eventually lead to the loss of biodiversity, amenity and economic wealth. Restoration of a vegetation cover can fulfil the objectives of stabilization, pollution control, visual improvement and removal of threats to human beings. Thus, remediation of mine spoils/tailings and biogeochemical prospecting would rely on the appropriate selection of plant species. Plant community responds differently on their ability to uptake or exclude a variety of metals. In this work, plant species were sampled from all populations established in an abandoned copper mine of São Domingos, SE Portugal. Plants belonging to 24 species, 16 genera and 13 families were collected from the degraded copper mine of São Domingos. Plant samples were analysed for total Ag, As, Cu, Ni, Pb, and Zn. The highest concentrations of metals in soils dry matter were 11217.5 mg Pb kg(-1), 1829 mg Cu kg(-1), 1291 mg As kg(-1), 713.7 mg Zn kg(-1), 84.6 mg Cr kg(-1), 54.3 mg Co kg(-1), 52.9 mg Ni kg(-1) and 16.6 mg Ag kg(-1). With respect to plants, the higher concentrations of Pb and As were recorded in the semi-aquatic species Juncus conglomeratus with 84.8 and 23.5 mg kg(-1) dry weight (DW), Juncus efusus with 22.4 and 8.5 mg kg(-1) DW, and Scirpus holoschoenus with 51.7 and 8.0 mg kg(-1) DW, respectively. Thymus mastichina also showed high content of As in the aboveground parts, 13.6 mg kg(-1) DW. Overall, the results indicate accumulation of various metals by different plant species, with some of these metals being partitioned to the shoots. Environmental implications of these observations are discussed.

One year of Lamivudine therapy for portuguese patients with chronic hepatitis B.

OBJECTIVE: To assess the efficacy of lamivudine treatment on hepatitis B e antigen (HBeAg) and/or hepatitis B surface antigen (HBsAg) seroconversion, on other virological and serological markers of response including hepatitis B virus (HBV) DNA and serum aminotransferases, and the safety of lamivudine treatment in hepatitis B patients. PATIENTS: This phase III open-label study evaluated the virological and biochemical response to lamivudine in 70 Portuguese patients with HBeAg positive chronic hepatitis B. Patients were treated with lamivudine 100mg once daily for 12 months. METHODS: Antiviral activity was assessed by measuring alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels at all protocol visits, and hepatitis B serology and HBV DNA were performed at baseline and at month 12 visits. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. RESULTS: The primary endpoint was virological response at month 12, defined as loss of detectable HBeAg from serum with a reduction of HBV DNA to undetectable levels, and this was observed in 19/69 (27.5%) of patients. Almost half of the patients were HBV DNA negative by this time. Mean ALT values decreased steadily during treatment and by 12 months 61% of patients had values within the normal range. HBeAg seroconversion (HBeAg negative, HBeAb positive) was achieved in 27.9% of patients by 12 months, although all patients remained HBsAg positive. CONCLUSION: Lamivudine was well tolerated and the incidence of adverse events was similar to those reported in previous studies. Lamivudine treatment resulted in virological and biochemical improvements in HBeAg positive chronic hepatitis B patients, with HBeAg seroconversion in one-third of patients.