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A 34-year-old man from Sao Tome and Principe, Africa, with a history of tuberculosis and alcohol ingestion greater than 100 g/day presented with progressively worsening dyspnoea, right upper quadrant pain and progressively increasing abdominal volume. Physical examination revealed distended jugular veins, tender hepatomegaly, moderate ascites and oedema of lower limbs. MRI revealed collection of pericardial fluid compressing the right ventricle and a thickened pericardium, consistent with an effusive-constrictive pericarditis. Cultures and biopsies were undertaken. Antituberculosis drugs and prednisolone were initiated and drainage of the pericardial collection and pericardiectomy were performed. He recovered with complete remission of signs and symptoms.

Background/aims: The role of genotype and viremia were retrospectively evaluated on sustained virological response (SVR) rates in routine clinical practice., Methodology: From 1907 patients with chronic hepatitis C proposed for treatment, we analysed 1380 (1124 naive and 256 treatment-experienced) with complete follow-up. Genotype and HCV RNA quantification were assayed by commercial tests. Viremia was considered high if >800,000IU/mL, and low if <400,000IU/mL. Liver fibrosis was staged in 614 patients., Results: Genotype 1 was the most frequent (60%), followed by 3 (25%), 4 (9%) and 2 (2%); 3.2% had other or unclassified genotype. Genotype 1 was more prevalent in central Portugal and genotype 4 in the south. Viremia was =800,000IU/mL in 54.6% and <400,000IU/mL in 34.6% of the patients, particularly in genotype 2 (p<0.03) and 4 (p<0.001). Genotype non-1 had a significantly lower viral load (p=0.004). Mild or moderate fibrosis was present in 71.7% and bridging fibrosis or cirrhosis in 28.3%, with no differences among genotypes. Treatment was discontinued in 19.8%. SVR was achieved in 55.3% of naive and 36.3% of re-treated patients., Conclusions: Standard treatment of chronic hepatitis C in real-life achieves similar results obtained in clinical trials, despite differences of demographic and viral parameters.

Background: The effect of a sustained virological response (SVR) to interferon (IFN) on clinical outcomes of hepatitis C virus (HCV)-related cirrhosis is controversial., Aims: Evaluate the effect of SVR to IFN on the incidence of hepatocellular carcinoma (HCC) and mortality in patients with compensated HCV-induced cirrhosis., Methods: A cohort of 130 consecutive patients (92 men, mean age 51.7 years) with histologically proven cirrhosis who received one or more courses of IFN monotherapy or combination therapy with ribavirin were analyzed. SVR was defined as undetectable serum HCV RNA by real-time polymerase chain reaction (PCR) 24 weeks after IFN discontinuation. HCC was assessed by alfa-fetoprotein and ultrasound every 6 months. Predictors of clinical outcomes, defined as HCC, orthotopic liver transplantation (OLT) and mortality, were assessed by Cox regression analysis., Results: The mean follow-up was 6.4 ± 4.0 years (range 1-18). HCC developed in 21 patients: one with SVR versus 20 with non-SVR (P = 0.017). Logistic regression analysis showed that non-SVR (odds ratio [OR] = 27.0; confidence interval [CI], 1.6-452.1), male (OR = 11.6; CI, 1.8-75.4), and greater number of treatments (OR = 4.7; CI, 1.4-16.0) increased the probability of HCC development. Multivariate analysis found that SVR was associated with lower risk of HCC (HR 0.09; CI, 0.01-0.77), OLT (HR 0.04; CI, 0.003-0.63) and any event (HR 0.11; CI, 0.02-0.46) as compared to non-SVR., Conclusions: In compensated HCV-related cirrhosis, SVR markedly reduces the risk of HCC and improves survival. Clearance of the virus should be intensively attempted in these patients.

Reactivation of infection with hepatitis B virus (HBV) is a potentially serious complication of immunosuppression, which can be identified and efficiently prevented. There have been an increasing number of cases of HBV reactivation in patients receiving immunosuppression in the context of rheumatic diseases such as rheumatoid arthritis or systemic lupus erythematosus. The recommendations in this area should be individualized taking into account two aspects: immunosuppressive regimens used (high or low risk of reactivation) and the different stages of HBV infection: chronic hepatitis B, inactive HBV carrier, occult hepatitis B infection defined by HB surface antigen (HBsAg) negative and antibody anti-HB core (anti-HBc) positive. In patients with rheumatic diseases that will start high-risk immunosuppressive drugs, we propose a universal screening with serological tests for hepatitis B (HBsAg, anti-HBs and anti-HBc). Patients with chronic hepatitis B (HBsAg positive, HBV DNA ≥ 2000 IU/ml, elevated ALT) should initiate antiviral therapy. Inactive HBV carriers (HBsAg positive, HBV DNA <2000 IU / ml, normal aminotransferases) exposed to high risk immunosuppressive therapy should undergo prophylaxis of HBV reactivation. Prophylaxis should be started 2 to 4 weeks before the beginning of immunosuppressive therapy and maintained for at least 6 to 12 months after its suspension. It is recommended to use entecavir or tenofovir as first line antiviral agents. In inactive HBsAg carriers under low-risk immunosuppressive therapy and patients with HBsAg negative/anti-HBc positive (HBV infection in the past), the strategy should be monitoring of viral reactivation with aminotransferases and HBV DNA determination in every 6 months.

Chronic Liver Disease is a progressive, most of the time asymptomatic, and potentially fatal disease. In this paper, a semi-automatic procedure to stage this disease is proposed based on ultrasound liver images, clinical and laboratorial data. In the core of the algorithm two classifiers are used: a k nearest neighbor and a Support Vector Machine, with different kernels. The classifiers were trained with the proposed multi-modal feature set and the results obtained were compared with the laboratorial and clinical feature set. The results showed that using ultrasound based features, in association with laboratorial and clinical features, improve the classification accuracy. The support vector machine, polynomial kernel, outperformed the others classifiers in every class studied. For the Normal class we achieved 100% accuracy, for the chronic hepatitis with cirrhosis 73.08%, for compensated cirrhosis 59.26% and for decompensated cirrhosis 91.67%.

The association between hepatitis C and B-cell non-Hodgkin lymphoma (NHL) has been suggested by several studies. We report the case of a 70 year-old patient with the diagnosis of chronic hepatitis C and splenic lymphoma with villous lymphocytes, who had undergone splenectomy and chemotherapy with fludarabine, with transient effectiveness. He was sent to our Hepatology Clinic for the treatment of hepatitis C, and Pegylated Interferon and Ribavirin were started. He had virological and hematological response (63% of villous lymphocytes in the peripheral blood at the beginning of therapy and 0% at the end). With the suspension of antiviral therapy, recurrence of HCV infection and reappearance of atypical lymphocytes (24%) were observed, and Pegylated Interferon was restarted, with good response. The relationship between viral and hematologic response (remission and relapse) supports the hypothesis that hepatitis C virus has an active role in the pathogenesis of splenic lymphoma with villous lymphocytes.

Objective: The risk of recurrence has limited the acceptability of conservative therapies of gallbladder stones. The aim of the present study was to determine the long-term rate of stone recurrence and its risk factors after successful extracorporeal shock-wave lithotripsy (ESWL)., Material and Methods: The study comprised a prospective ultrasound follow-up at yearly intervals or whenever biliary pain was reported. A total of 192 consecutive patients (primary single stones, n=159; primary 2 or 3 stones, n=33) were followed for up to 11.2 years after becoming stone-free and after termination of adjuvant treatment with ursodeoxycholic acid (UDCA)., Results: Eighty-four patients developed recurrent stones after a median of 2.6 years (maximum?=?8.8 years). The 108 patients without recurrence were followed for a median of 6.7 years (maximum=11.2 years). By actuarial analysis, the cumulative recurrence rates for these 192 stone-free patients were 27%+/-3%, 41%+/-4% and 54%+/-4% (observed +/-SE) at 3, 5 and 10 years, respectively. Cox's regression analysis was used to identify the presence of slight calcification in the primary stone(s) as a protective feature against recurrence (p=0.03)., Conclusions: 1) The risk of recurrence continues to increase over time, and although it rises less steeply after 5 years, it does not reach a plateau until at least 10 years. 2) Having had slightly calcified stone(s) seems to be associated with a reduced risk of recurrence and might signal a "burnt out" lithogenic process. 3) The long-term results are unsatisfactory and ESWL of gallbladder stones should be offered only in special cases.

Background/aims: The natural history of chronic hepatitis C virus (HCV) infection still has some details to be established, namely in what concerns progression to hepatic cirrhosis (HC). The study aims to define predictive factors for progression to HC in patients with HCV chronic infection., Methodology: A cross-sectional study was performed on 129 patients consecutively submitted to liver biopsy. Thirty-six percent (n=46) had HC at histological evaluation., Results: Patients with HC did not show statistically significant differences on gender, viruses genotypes, alcohol consumption or proportion of positivity to markers of previous hepatitis B virus (HBV) infection - anti-HBc/anti-HBs+. Patients with HC seem to have had their infection sporadically (50%) or post-transfusion (35%) -p=0.052, and iv drugs addiction was related to non-HC patients (39%) -p=0.006. Age at infection, time of infection and positivity for anti-HBc/anti-HBs were factors independently related to HC (multivariate analysis). Patients older than 40 years by the time of infection [OR=4.5 (95% CI=1.9-10.8], those with less than 5 years of time of infection [OR=4.2 (95% CI=1.6-10.8)], and patients with previous HBV infection [OR=2.51 (1.00-6.69)] are at higher risk for HC., Conclusions: We argue that older patients, with a shorter time interval between HCV infection and diagnosis, and namely those with markers for previous HBV infection represent patients with higher risk for progression to hepatic cirrhosis.

With more patients reaching end-stage renal disease, the demand for living kidney donation is increasing rapidly. Many potential donors are now in older age groups. The effects of increasing BP with age and the measurement criteria for hypertension in this group are not well defined. A total of 238 potential donors between 18 and 72 yr of age were prospectively studied, with a comparison of "clinic" BP values measured in the outpatient clinic with an oscillometric recorder (Dinamap; Critikon), ambulatory BP monitoring (ABPM) findings, and standardized BP values determined by nurses using American Heart Association criteria. Renal function was evaluated on the basis of iothalamate clearance (GFR) and urinary protein and microalbumin excretion. Ninety-six percent of subjects were Caucasian. All subjects exhibited normal GFR and urinary protein excretion. Three age groups were defined (group I, /= 50 yr, n = 65). BP increased with age, as determined with all methods. Subjects >/= 50 yr of age exhibited the highest clinic readings (145 +/- 2/83 +/- 1 mmHg, compared with 129 +/- 2/76 +/- 1 mmHg for group I, P < 0.01). Awake ABPM and nurse-determined BP measurements were lower than clinic readings, including those for group III (131 +/- 2/80 +/- 1 mmHg, compared with 145 +/- 2/83 +/- 1 mmHg in the clinic, P < 0.001). With the use of systolic BP values of >140 mmHg and/or diastolic BP values of >90 mmHg, 36.7% of subjects were initially considered hypertensive; this proportion decreased to 11% overall with awake ABPM findings (>135/85 mmHg). Measurement variability (SD in ABPM) and the effects of misclassification were greatest for donors >/= 50 yr of age. Multivariate regression indicated that GFR of both donors and recipients decreased with age, but regression identified no independent effect of BP. Recipient outcomes for up to 2 yr were equally good for donor kidneys considered normotensive or hypertensive on the basis of clinic BP measurements. These data indicate that higher arterial BP with age can lead to misclassification of many older living kidney donors. Sixty-two subjects with excellent kidney function were misclassified as hypertensive with clinic oscillometric measurements alone. Detailed evaluations of ABPM findings, GFR, and urinary protein levels are warranted for Caucasian subjects with high clinic BP readings who are otherwise suitable potential donors.

With the established benefits of living-donor kidney transplantation, our primary emphasis at Mayo Clinic, Rochester has been to develop protocols that allow living donation to occur even in the presence of relatively unusual or generally contraindicated situations. This approach has significantly increased the number of patients receiving kidney transplants in the past few years. Our protocols for extended criteria donors and recipients along with the exclusive use of laparoscopic donor nephrectomy have been major contributors to the increase in volume. ABO-incompatible and positive-crossmatch living-donor kidney transplant protocols also have increased the availability of transplants for our patients. Protocol biopsies have aided in the diagnosis of subclinical rejection, polyoma virus and chronic allograft nephropathy. Innovative immunosuppressive protocols such as calcineurin inhibitor-free immunosuppression have decreased rejection and improved both short and long-term renal allograft survival.

Background: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients., Methods: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated., Results: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients., Conclusions: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.

Background: Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete., Methods: In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy., Results: We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness., Conclusions: We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.

Sirolimus in combination with cyclosporine reduces the incidence of acute rejection in renal transplant recipients when administered in double- or triple-therapy immunosuppressive regimens. Sirolimus administered as primary therapy has a beneficial effect on renal function, and the frequency of rejection episodes is similar to that of primary immunosuppression with cyclosporine. A strategy that may result in a more benign immunologic course with a substantially beneficial effect on renal function is to administer sirolimus and a calcineurin inhibitor early after transplantation, thereby promoting immunologic adaptation, and then to withdraw the calcineurin inhibitor at some point after transplantation to prevent nephrotoxicity. This article examines the results of this approach in recent studies that evaluated the effect of cyclosporine withdrawal on renal function, acute rejection, and safety in patients treated with sirolimus. Two open-label randomized trials of cyclosporine withdrawal were conducted in the United States, Canada, Europe, and Australia. In one of the studies, graft survival, patient survival, and the incidence of acute rejection at 6 months posttransplantation were not statistically significantly different between the patients receiving cyclosporine and the group that had undergone cyclosporine withdrawal. Furthermore, significantly better renal function was observed in the patients who underwent cyclosporine withdrawal compared with patients who continued to receive full-dose cyclosporine. These studies indicate that cyclosporine withdrawal has a beneficial effect on renal function without a significant increase in the incidence of acute rejection episodes.

We studied early renal function in 241 consecutive patients who received cadaveric renal transplants at two different transplantation centers (group 1, n = 90; group 2, n = 151). Univariate and multivariate analyses of data from group 1 showed a significant correlation between seven donor variables and early renal function after cadaveric renal transplantation. A scoring system was developed from these seven donor variables (cause of death, 0-6 points; history of hypertension, 0-6; final creatinine clearance before procurement, 0-6; age, 0-6; history of diabetes mellitus, 0-3; cold ischemia time, 0-3; and severity of renal artery plaque, 0-3). Data from group 2 were used to validate the donor scoring system and stratify cadaver kidneys on the basis of score: grade A, 0-5 points; grade B, 6-10; grade C, 11-15; and grade D, 16-32. A significant decline in early renal function was observed with increasing donor score and grade of cadaver kidney. In conclusion, a donor scoring system based on information available at the time of procurement can be used to estimate early graft function after cadaveric renal transplantation and may assist in the allocation of marginal organs.

This article reviews the pharmacologic treatment of anxiety disorders in children and adolescents. These disorders are quite common and can be considered a "silent epidemic" because they are more often reported by the children and adolescents than by their parents. Tricyclic antidepressants (TCAs), benzodiazepines, buspirone, and selective serotonin reuptake inhibitors (SSRIs) have been used to treat anxiety disorders in children and adolescents with varying degrees of success. Considering safety and efficacy, the SSRIs appear to be the first-line treatment for anxiety disorders in youth, but more studies are needed to confirm preliminary results. Tricyclic antidepressants and benzodiazepines may be considered when the child has not responded to SSRIs or when adverse effects have exceeded benefits. Although nonpharmacologic approaches for the treatment of anxiety in children and adolescents are beyond the scope of this article, their importance is to be underscored and they should be considered as part of the treatment plan. Over the next decade, research data will be generated regarding the treatment of anxiety disorders in youth. Ongoing research studies include the use of fluoxetine (B. Birmaher, personal communication, 1999) and fluvoxamine (J. Walkup, personal communication, 1999) for the treatment of generalized anxiety disorder, separation anxiety disorder, or social phobia; and buspirone for generalized anxiety disorder in children. Despite these efforts, there is a need for more studies to examine the safety and efficacy of different pharmacologic treatments, as well as longitudinal studies to monitor for long-term tolerability and side effects. Pharmacokinetic studies for children and adolescents will provide information on the metabolism and absorption of these medications and delineate the developmental differences between children and adolescents when compared to adults. Finally, and perhaps most importantly, studies that compare medication, psychosocial treatments, and their combination are needed.

Diabetic nephropathy is the leading cause of kidney failure in the United States. Poor glycemic control, hypertension, and smoking have been implicated as risk factors for the development and progression of diabetic nephropathy in patients with type 1 diabetes mellitus. Improved medical therapy including angiotensin-converting enzyme inhibitors and tight glycemic control with use of intensive insulin therapy have been shown to reduce the progression of diabetic nephropathy substantially based on albumin excretion rates. Despite these improvements in medical management, many patients still experience progression from early diabetic nephropathy to end-stage renal disease. Successful pancreas transplantation leads to normal glycemic control in patients with type 1 diabetes, but historically it has generally been limited to patients with both kidney failure and diabetes. In this review of the current treatment of diabetic nephropathy, we examine the potential role of preemptive pancreas transplantation in patients with diabetic nephropathy.

Our objective was to evaluate the histopathological features of chronic hepatitis C of 64 liver biopsies and to correlate this with the route of transmission of hepatitis C virus, the genotype of HCV, and the patient's age. Moderate chronic hepatitis was the most frequently observed (62.5%). Cirrhosis was observed in 14 patients (21.9%) and was more frequently found among patients over 40 years of age (34.3% vs. 6.9%, P = 0.025). The mean histopathological activity index (HAI) was significantly higher in the sporadic (10+/-3.1) than the posttransfusional (7.5+/-3.7) and the intravenous drug use (IVDU) groups (6.3+/-2.8) (P<0.02). Moreover the sporadic group showed more fibrosis (P<0.04) than the posttransfusional group. No liver cirrhosis was found in the IVDU group. The overall prevalence of HCV variants was: 54.7% type 1b, 4.6% type 1a, 37.5% type 2c, 1.6% type 2b, 1.6% type 2. The genotype distribution showed no relation to the HAI, hepatitis activity (grade), and fibrosis (stage) of the liver disease. In conclusion, the sporadic route of transmission of HCV was related to a more severe chronic hepatic disease, a finding that could influence future antiviral therapies. The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our data suggests that the ultimate consequence of HCV chronic infection depends on patient age rather than on HCV genotype.

We determined the prevalence of hepatitis B markers and the compliance to hepatitis B vaccination in a University Hospital of Santa Maria, Lisbon. The program was begun in 1989 for all hospital personnel and students of the medical school. The screening included 2,360 health care workers and 1,153 students; 57% (2,360/4,103) of hospital personnel and 41% (1,153/2,779) of medical students appeared for vaccination. The prevalence of hepatitis B markers was 16.8% (397/2,360) for hospital personnel and 5.5% (64/1,153) for students, the chronic carrier appearing in 0.95% (22/2,360) of hospital personnel and 0.3% (4/1.153) of students. The departments with the highest prevalence were the Biochemical Laboratory (64%, 7/11), Surgery (42%, 13/31), Pulmonary (39%, 9/23), Emergency (29%, 7/24), Hematology Laboratory (29%, 7/24), and Orthopedics (29%, 10/35). The prevalence was higher in students in the last 3 years of medical school than those in the first 3 years (12.2% [22/181] vs. 7.2% [8/110], p = NS). Adverse effects to vaccination occurred in 14.5%, with local pain the most frequent in 8.6%. The serologic efficacy was 95% (1,044/ 1,097). A nonresponse was observed in male workers, 13% (26/200) compared with 5% (45/897) for females (p < 0.05). Older employees also showed higher nonresponse: The average age of workers with anti-HBs of 0 IU/l was 52.3 years and those with anti-HBs of more than 100 IU/l was 38.4 years (p < 0.02). Hepatitis B vaccination is safe and effective. Our study shows the need for a more aggressive approach to the vaccination of health care workers because a significant percentage of them are not protected.

In a blinded fashion, 165 serum samples from patients with biopsy-characterized acute and chronic renal diseases (ACRDs), 34 serum samples from patients with congenital renal diseases (CRDs), and 100 serum samples from healthy adults were assayed for immunoglobulin G (IgG), IgM, and IgA antibodies to Hantaan and Puumala viruses by enzyme immunoassay (EIA). Twenty-six percent (44 of 165) of ACRDs, 3% (1 of 34) of CRDs, and none (0 of 100) of the healthy serum samples were positive for hantavirus-specific antibodies (P < 0.001, Fisher's exact test). Thirty of 44 positive serum samples (68%) were from three groups: ie, acute tubulointerstitial nephritis (AIN), 20% (9 of 44); necrotizing glomerulonephritis (NG), 27% (12 of 44); and IgA nephropathy, 20% (9 of 44). The remaining 14 positive samples were from patients with a varied group of renal conditions. IgA antibody levels alone were elevated in 37%, IgG alone in 33%, IgM alone in 17%, and all three isotypes in 13% of the AIN-, NG-, and IgA-positive samples. These data indicate that three renal diseases account for approximately 68% of the hantavirus-positive sera tested and that serological evaluations should include all three isotypes of antibodies.

Hepatitis B virus infection is one of the world's major health problems and health care workers are especially at risk, leading to the need for a high priority vaccination program. Such a program was begun in 1989 in S. Maria Hospital and included all hospital personnel and students of the Faculty of Medicine. The screening included 2360 health care workers and 1153 students. Fifty-five percent of hospital health care workers and 41% of the students participated in the vaccination program. The overall prevalence of hepatitis B markers was 16.8%, for hospital personnel, the chronic carrier being 0.95%, and for the students, 5.5% and 0.3% respectively. The highest prevalence was observed in the Biochemical Laboratory--64% (7/11), Surgery--42% (13/31), Pneumology--39% (9/23), Emergency Department--29% (7/24), Hematology Laboratory--29% (7/24) and Orthopedics--29% (10/35). The prevalence was also higher in students in the last three years of Medical School compared to those in the first three years, 12.2% vs 7.2%, p = NS. Local pain has been the most frequent complaint in 8.6% of vaccinees. The control with the quantification of anti-HBs in the 7th month has shown a serological efficacy of about 95%. A non-response was observed in male workers, 13% compared to 5% for females, p < 0.05. Older employees also showed higher non-response: the average age of workers with anti-HBs of 0 U/L was 52.3 years, and those with anti-HBs of more than 100 U/L was 38.4 years, p < 0.02. Hepatitis B vaccine is a safe and effective preventative measure that has been widely used for years. Our study shows the need for a more aggressive approach to the vaccination of health care workers because a significant percentage of them in our country are not protected.

Three multicenter studies have shown that the addition of mycophenolate mofetil (MMF) to an immunosuppressive regime consisting of cyclosporin A (CSA) and prednisone (PRED) decreases the incidence of acute rejection episodes when compared with azathioprine (AZA) or placebo (1-3). In those patients receiving 3 g/d of MMF, the highest dose used in the studies, there was a trend towards an increased incidence of cytomegaloviral sepsis (CMV). We postulated therefore that MMF may represent an independent risk factor for the development of CMV infection in patients receiving renal allografts and MMF at our institution. Having altered the triple drug regime from CSA, AZA (2-2.5 mg/kg/d) and PRED to CSA, MMF (2 g/d) and PRED in July 1995, we elected to study all patients undergoing kidney transplantation for the 33-month period January 1994-September 1996, by undertaking a case control analysis to determine independent risk factors for the development of CMV infection, as defined by CMV viremia or tissue-invasive CMV. Three CMV disease-free control patients were matched to each case, these patients having been randomly selected from the entire pool of patients in the observation period. There were 31 CMV case patients and 102 control patients. Univariate analysis indicated that gender, a concomitant pancreas transplant, acute rejection and CMV seropositivity in the donor were risk factors. However, multivariate analysis indicated that only acute rejection and donor CMV seropositivity were independently linked (p < 0.05) to CMV disease in this sample. Specifically, the odds ratio (OR) for CMV disease between MMF and AZA was 1.0 (95% confidence interval (CI): 0.46-2.18). Therefore, in this case control study we find no evidence that MMF at a dose of 2 g/d is an independent risk factor for primary CMV viremia or tissue invasion in renal allograft recipients.

A 49-year-old man with progressive obstructive jaundice secondary to primary sclerosing cholangitis developed acute, anuric renal failure requiring prolonged hemodialysis. Renal biopsy showed evidence of tubular epithelial toxicity, pigmented casts, interstitial fibrosis, and ischemic glomerular changes. After orthotopic liver transplantation (OLT), there was an immediate return of urine output. The introduction of tacrolimus (FK506) was delayed for 3 weeks after transplantation, during which time a gradual improvement in renal function occurred. Renal function remained stable 1 year later at a level of moderate impairment with good hepatic function.

In this article, we describe two pregnancies in the same patient after pancreatic-renal transplantation. Severe, labile hypertension necessitated delivery at 35 weeks during the patient's first pregnancy and at 30 weeks (associated with renal graft obstruction) during her second pregnancy. Women with insulin-dependent diabetes mellitus who undergo pancreatic-renal transplantation can have a successful pregnancy if adequate multidisciplinary, specialized medical care is rendered.

Background: IgA Nephropathy (IgA N) is one of the most common glomerulopathies and may lead to renal failure in 10-20% of cases. After renal transplantation, IgA N has a strong tendency to recur in the graft. Initially considered a benign condition, graft losses from recurrent IgA N have been reported over the last 20 yr, casting doubt on the initial premise. Since large single-center studies of the fate of renal allografts in IgA N are rare and the Mayo Clinic transplant experience for IgA N is extensive (dating back to 1970), a review of these issues appeared worthwhile., Methods: A retrospective study was done of all renal transplant patients who had had biopsy-proven IgA N as underlying disorder. We extracted data on the underlying disease, history leading to renal transplantation, factors affecting transplant outcome, and on the course after transplantation with special attention to rejection activity and recurrence of the primary disease. Standard statistical methods were employed., Results: 53 renal allografts were transplanted to 51 biopsy-proven IgA N patients: 12 were cadaveric (CAD) grafts, 3 HLA-mismatched living related donor (LRD) kidneys, 29 one haplotype-matched LRD and 9 HLA-identical LRD organs. Five-year actuarial graft survival was 100% in HLA-identical LRD, 88% in one haplotype-matched LRD, and 74% in CAD grafts. All three HLA-mismatched LRD kidneys were functioning up to 1.6 yr (longest follow-up). Only one patient died after acute rejection of the CAD graft. There were 3 early graft losses from acute rejection and 4 late losses. IgA N recurred in 26% of allograft and led to significant loss of graft function in 10 of the 14 patients (71%) over a long period of observation. Three of four late graft losses were in patients with recurrent IgA N. Recurrence was not related to the type of graft, i.e. CAD vs. LRD, nor to the extent of HLA-matching in LRD transplantation., Conclusion: Renal transplantation in patients with IgA N has excellent patient and graft survival. There is a high rate of recurrence of the primary glomerulopathy in the renal allograft, and this event is by no means inconsequential. Loss of renal function and even graft loss occur over prolonged periods of time. There is no disadvantage getting a well matched LRD in regard to incidence of recurrent IgA N. Thus, we encourage LRD transplantation in IgA N.

We describe several atypical serological profiles of hepatitis B virus infection (HBV), which can arise difficulties in diagnostic and classification of the infection stage. Its knowledge is important in establishing a more accurate strategy of the screening of blood donors and candidates for vaccination. On the other hand, vaccination may be useful in interpretation of the serological profile. We also discuss the role of HBV mutants in this context.

Posttransplantation lymphoproliferative disorder (PTLD) is an uncommon but often fatal complication of solid organ transplantation that occurs in approximately 3% of patients. To determine the relative importance and relationship of potential risk factors for PTLD before transplantation (i.e., Epstein-Barr virus [EBV] serostatus of the recipient and the cytomegalovirus [CMV] sero-status of the recipient and the potential donor) and the principal risk factor after transplantation (immunosuppression with antilymphocyte antibody), we analyzed the findings for the first 381 consecutive adult nonrenal transplant recipients seen at Mayo Clinic. In the absence of the other risk factors, the incidence rate of PTLD for EBV-seronegative recipients was 24 times higher (95% confidence interval [CI]: 6.2, 89) than that for EBV-seropositive recipients. The additional risk factors of therapy with OKT3 for rejection and CMV seromismatch (i.e., a negative recipient and a positive donor) each further amplified this risk four- to sixfold. Together, all three risk factors acted synergistically to increase the incidence rate of fatal and/or CNS PTLD by a factor of 654 (CI: 368, 1,162) compared with the low incidence rate (.458 cases per 100 person years) when none of these risk factors were present. Pretransplantation determination of recipient EBV and CMV serostatus can identify a subgroup of patients whose risk for severe PTLD may preclude transplantation.

Objectives: to evaluate the accuracy of endoscopic ultrasonography (EUS) in the pre-operative T and N staging of gastric cancer., Patients and Methods: 41 consecutive patients with gastric cancer (35 carcinomas and 6 lymphomas) underwent EUS using an Olympus GF-UM20, with 360 degrees sector scan and interchangeable frequency (7.5-12 MHz). They were classified as T1-T4 and N0-N2, according to the TNM system. These results were then compared with the surgical and pathological staging (SP), by the weighted K statistic (Kw)., Results: In 2 patients EUS staging was not possible due to cardiac stenosis and in other 4 patients, information about SP staging was not available. In the remaining 35 patients the EUS/SP agreement was good (Kw = 0.80) for stage T and moderate (Kw = 0.49) for stage N. Non-agreement was mostly due to EUS understaging, both T and N., Conclusions: 1) EUS is the most accurate procedure for pre-operative local staging of gastric cancer, and 2) EUS should preferably be performed by endoscopists with sonographic experience and a particular interest in the method.

The infectious complications following pancreatic transplantation in 34 consecutive recipients were analyzed during a mean follow-up of 39 months. Twenty-seven recipients (79%) developed a mean of 2.1 serious infectious complications. Three of the six deaths (overall mortality, 18%) were infection related. Thirty-three percent of severe infectious episodes were caused by bacteria (72% by gram-positive cocci) and 26% by fungi (87% by Candida species); severe cytomegalovirus (CMV) infection accounted for 33% of infectious complications. CMV disease and organ involvement occurred most frequently in the donor-seropositive/recipient-seronegative group (36%), followed by the donor-seronegative/recipient-seropositive group (25%). In four patients (12%) Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disease (PTLD) developed, directly resulting in two deaths. PTLD developed in two of the three EBV-seronegative and two of the 31 EBV-seropositive recipients. Infections due to herpes simplex and zoster viruses and Pneumocystis carinii (2, 3, and 1, respectively) developed in 6 patients. The use of OKT3 for rejection therapy was associated with symptomatic CMV disease and EBV-related PTLD. In summary, severe infectious complications are the main cause of morbidity and death among patients who undergo pancreas transplantation. Aggressive antimicrobial prophylactic regimens are required to decrease the effects of such complications.

Background: The relative importance and interrelationship of risk factors for posttransplantation lymphoproliferative disorder are poorly understood., Methods: The prospective pretransplantation serologic testing for Epstein-Barr virus of all nonrenal solid organ transplant recipients at our institution made it possible to assess the relative risk for posttransplantation lymphoproliferative disorder in seropositive and seronegative recipients., Results: Fourteen cases of lymphoproliferative disorder were identified in the first 389 consecutive transplant recipients (288 liver, 44 heart, 20 lung, 37 kidney-pancreas) undergoing transplantation from 1985 to 1992 (mean follow-up 33 months). The incidence rates of lymphoproliferative disorder (per 100 person-years) during the first 2 years after transplantation (a period in which all cases occurred) were 1.4 for liver, 2.0 for heart, 6.2 for lung, and 5.2 for kidney-pancreas transplant recipients and were significantly different between liver and lung (p = 0.005) and liver and kidney-pancreas (p = 0.002) groups. Of 367 seropositive patients, lymphoproliferative disorder developed in only three. The incidence rate ratios between seronegative and seropositive recipients were as follows: 76 ([95% confidence interval; 46, 144], p = 0.0000) for any form of lymphoproliferative disorder and 145 ([60, 347], p = 0.0000) for fatal or brain forms. The incidence rate of lymphoproliferative disorder was significantly higher for seronegative recipients who required antilymphocyte antibody therapy for rejection than for those who received none., Conclusions: The high intrinsic risk for lymphoproliferative disorder in the Epstein-Barr virus seronegative patient, which is amplified by higher levels of immunosuppression, may, in some instances, preclude transplantation.

We retrospectively reviewed all (n = 369) percutaneous renal allograft biopsies performed at our institution between 1987 and 1992, comparing 14-gauge Franklin-Silverman (internal diameter = 2.0 mm, n = 169) and 18-gauge automated (internal diameter = 1.2 mm, n = 200) core biopsy needles. Visualization method, specimen adequacy, and complications were grouped by needle type. Five or more glomeruli were present in 88.9% of specimens obtained with Franklin-Silverman needles and in 82.7% with automated needles. A histologic diagnosis was obtained in 94.1% and 95.5% of Franklin-Silverman and automated biopsies, respectively. A complication was detected in 27 Franklin-Silverman biopsies (16.0%) and in 21 automated biopsies (10.5%) (not significant [NS], P > 0.05). Some procedures had more than one complication. Excluding asymptomatic gross hematuria, incidental hematomas, and incidental arteriovenous fistulas detected by routine ultrasonography, clinically significant complication rates were 6.5% for Franklin-Silverman biopsies and 2.5% for automated biopsies (NS). No allograft losses or patient deaths occurred as a result of allograft biopsy. Subgroup analysis of all biopsies performed with ultrasound marking alone (Franklin-Silverman, n = 119; automated, n = 148) revealed no significant (NS) difference in complication rates (15.1% vs. 10.8%). Additional subgroup analyses of palpation, ultrasound marking, and real-time ultrasonographic visualization techniques within each needle type also revealed no significant difference in the complication rate. Biopsy within 30 days of transplantation and no antihypertensive therapy were the only factors univariately associated (P < 0.05) with an increased complication rate. Multivariate analysis found biopsy within 30 days of transplantation (P = 0.007) was associated with the overall presence of one or more complications of any type. Type of needle (Franklin-Silverman vs. automated) achieved borderline significance (P = 0.047) when time to biopsy was statistically adjusted for; the Franklin-Silverman needle had a higher complication rate.

Objective: To determine whether pancreas transplantation alters lipid and lipoprotein concentrations and whether peripheral hyperinsulinemia is always associated with altered lipid levels., Design: We assessed the lipid profiles of seven pancreas-kidney recipients with insulin-dependent diabetes mellitus, seven kidney recipients without diabetes who received the same immunosuppressive agents, and eight normal subjects., Material and Methods: In the three study groups, fasting and postprandial plasma glucose, insulin, C-peptide, cholesterol, triglyceride, free fatty acid, and apolipoprotein A-I, A-II, C-II, and C-III concentrations were determined., Results: Fasting and postprandial glucose concentrations did not differ between the two transplant groups; however, peripheral insulin concentrations were twice as high (P < 0.05) in the pancreas-kidney recipients as in the kidney recipients both before (102 +/- 15 versus 53 +/- 6 pmol/L) and after (123 +/- 22 versus 61 +/- 6 nmol/L per 6 hours) ingestion of a meal. Preprandial and postprandial insulin levels in both transplant groups also were greater (P < 0.05) than those in normal subjects (35 +/- 6 pmol/L and 40 +/- 7 nmol/L per 6 hours, respectively). Despite significant differences in insulin concentrations, no differences were noted in total cholesterol, high-density or low-density lipoprotein cholesterol, plasma free fatty acids, or apolipoprotein A-I, A-II, C-II, and C-III concentrations among the study groups. Plasma triglyceride concentrations in the two transplant groups were similar (114 +/- 20 versus 142 +/- 18 mg/dL) and were slightly more than those in the normal subjects (80 +/- 7 mg/dL)., Conclusion: Despite peripheral hyperinsulinemia, pancreas transplantation can result in normal or near-normal lipid and lipoprotein concentrations. Thus, systemic delivery of insulin does not invariably produce an atherogenic lipid profile.

We prospectively assessed the value of anti-neurtrophil cytoplasmic autoantibodies (ANCA) and nuclear or perinuclear anti-neutrophil autoantibodies measured by indirect immunofluorescence microscopy and antimyeloperoxidase autoantibodies measured by a solid-phase assay in the diagnosis of idiopathic (pauci-immune) necrotizing-crescentic glomerulonephritis (NCGN) and renal vasculitis at our institution. A diagnosis was established on the basis of clinical and renal biopsy findings, and follow-up continued for at least 6 months. ANCA were measured at the conclusion of the study. Of the 111 study patients, 28 had NCGN and renal vasculitis. The immunofluorescence assay had 50% sensitivity and 79% specificity. The combination of the enzyme-linked immunosorbent assay for antimyeloperoxidase autoantibodies and the immunofluorescence assay for cytoplasmic ANCA had 78% sensitivity and 84% specificity. A firm diagnosis was established before the determination of ANCA in 26 of the 28 patients with NCGN and renal vasculitis. The antimyeloperoxidase autoantibody values would have suggested the diagnosis in the other two patients. Of these 28 patients, 5 had negative ANCA results. High antimyeloperoxidase autoantibody values were detected in patients with NCGN and renal vasculitis, whereas lower values were less specific and were detected mainly in patients with anti-glomerular basement membrane antibody disease and lupus glomerulonephritis.

The prevalence of chronic hepatitis and its different aetiologies was studied in all patients above 10 years of age seen in the specialised outpatient clinic of our hospital over a 3 year period. Defining chronic hepatitis as a persistent elevation of the transaminases, 988 patients (62% of all the patients observed) were classified as follows: viral aetiology in 82%, metabolic in 2%, biliary in 2%, alcoholic in 11%, autoimmune in 1.5% and idiopathic in 2%. Among the viral group, hepatitis B virus infection was predominant (65%), followed by hepatitis C virus (26%) and delta hepatitis (8%). While the hepatitis C and delta patients presented high transaminases, in the HBsAg carriers this occurred in 94% and 20% of the HBeAg and anti-HBe-positive patients, respectively. Thirty per cent of the patients with chronic hepatitis B, 35% of those with chronic hepatitis C and 18% with delta hepatitis were selected for alpha interferon therapy. This demonstrated that in a significant proportion of patients with chronic viral hepatitis, therapy with interferon is not indicated. Corroborating other studies, with even stronger data, our study shows that viral aetiology is the most frequent type of chronic hepatitis.

In order to evaluate the interference of hepatitis delta virus (HDV) in hepatitis B viral particle (HBsAg, HBcAg) expression in the liver of chronic HDV patients, 39 and 81 liver biopsies of HBsAg carriers seropositive for anti-HDV and anti-HDV negative controls, respectively, were studied. HBcAg was positive in 16.7% of the HBeAg-positive patients with HDAg in the liver and in 91,4% of controls. In contrast, in HBeAg- and anti-HDV negative patients the intrahepatic expression of HBcAg was detected in 32.6%. In anti-HDV negative patients the HBcAg liver expression correlated significantly with the HBeAg in serum (p < 0.00001). The distribution of HBcAg was exclusively cytoplasmatic in 30% of HDV-infected patients but mixed nuclear and cytoplasmic in 38.3% of the controls. The nuclear expression of HBcAg was decreased in chronic HDV infection. HBsAg was positive in 70.3% of patients who were anti-HDV positive and in 82.3% of controls. The membranous expression of HBsAg was detected less frequently in HDV-infected patients (p < 0.05) than in controls, while associated with HBeAg in serum of HBV carriers without HDV superinfection (p < 0.00001). The prevalence and the HBsAg cytoplasmic expression was not different for the chronic HDV infection or controls. Our results show: 1) decreased intrahepatic expression of HBcAg and membranous HBsAg in HBV carriers superinfected with HDV, suggesting decreased HBV replication in the liver of these patients. 2) the changing of HBcAg and HBsAg expression in the liver of HDV-infected patients, suggest not so much a decrease but rather a modulation in HBV replication.

Nineteen patients with light-chain deposition disease (LCDD) were studied retrospectively. This report presents data on long-term patient and renal survival and the response to intermittent administration of melphalan and prednisone. Immunoelectrophoresis or immunofixation demonstrated a monoclonal protein in the serum of 78% and in the urine of 84% of the patients; 16% had no demonstrable monoclonal protein in serum or urine. The median age at presentation was 51 years (range, 37 to 77 years). Twelve (63%) of the patients had a monoclonal protein of undetermined significance without evidence of myeloma. The typical glomerular lesion was a diffuse mesangial nodular lesion that was positive for periodic acid-Schiff (PAS) stain with acute and chronic tubulointerstitial changes. Fifteen patients had kappa light-chain deposition and four had lambda light-chain deposition. Five-year actuarial patient survival and survival free of end-stage renal disease were 70% and 37%, respectively. Seventeen patients received melphalan and prednisone, and one patient received chlorambucil and prednisone. All of the patients had some impairment of renal function at presentation, and 58% had a serum creatinine concentration greater than 354 mumol/L (4.0 mg/dL). There was either stabilization or improvement in renal function after chemotherapy in five of eight patients who had a serum creatinine concentration less than 354 mumol/L (4.0 mg/dL) at the initiation of therapy. Of the 11 patients with a high serum creatinine concentration (greater than 354 mumol/dL [4.0 mg/dL]), 82% progressed to end-stage renal disease despite therapy. Follow-up urine protein studies demonstrated at least a 50% decrease in urine protein excretion in five of 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

An abbreviated screening magnetic resonance (MR) imaging examination was used to determine the prevalence of clinically occult avascular necrosis (AVN) of the hip in 100 asymptomatic renal transplantation patients treated with corticosteroids. All patients were more than 18 years old, had been treated with corticosteroids for at least 6 months, and had no symptoms of AVN before MR imaging. Of the 100 patients screened, six were found to have clinically occult AVN at MR imaging (rate: 6%, with a 95% confidence interval of 2.2%-12.6%). No significant differences were found regarding the total dose of corticosteroids and exposure time between patients with and patients without asymptomatic AVN. The authors conclude that there is a significant prevalence of asymptomatic, clinically occult AVN among renal transplantation patients treated with corticosteroids and that a potentially low-cost screening MR imaging examination can be used to detect such disease.

To assess the efficacy of therapy with alfa Interferon in chronic hepatitis C (NANB), 18 patients were enrolled in an open trial. Eleven were males and 7 females with a mean age of 43 years. Interferon alfa 2b was used in titrated doses for 9 months and the treatment was started with 5 m.U./Ti. During therapy, the patients were evaluated clinically and biochemically. A liver biopsy was done within 3 months after the completion of treatment. The serum alanine aminotransferase (ALT) level 1 became completely normal in 11 patients (61%) at 3 months of therapy and a partial response was seen in 3 (16%). At the 6 months the ALT sustained normal in 10 patients (55%) and a partial response was seen in 5 (27.7%). Four out of 7 patients (57%) who completed the therapy had complete response and 2 (28.5%) a partial response. From 5 patients who completed the follow-up, 3 (60%) had a relapse of ALT levels. A low level of ALT at the beginning of treatment had a predictive value of response to the therapy (P less than 0.05). The side effects of interferon therapy were usually mild. Fever, myalgias and headaches were seen in 72% of patients in the first two weeks of therapy. No haematological alterations were seen. We conclude that a 9 month course of interferon therapy is effective in controlling disease activity in many patients with chronic NANB hepatitis. However, the high relapse rate suggest that future studies should establish the optimal dose and duration of treatment to induce a complete resolution of the disease.

Background: Because a pancreas allograft is placed in the pelvis, pancreas transplantation abolishes the normal gradient between portal-vein and peripheral-vein insulin concentrations and causes systemic hyperinsulinemia. Whether pancreas transplantation restores carbohydrate metabolism to normal is not known., Methods: We studied seven patients with insulin-dependent diabetes mellitus after pancreas-kidney transplantation, seven nondiabetic patients after kidney transplantation (to control for immunosuppression), and eight normal subjects. Measurements were made after an overnight fast and after ingestion of a mixed meal., Results: Although plasma glucose concentrations did not differ in the two transplant groups, plasma insulin concentrations were significantly higher in the diabetic pancreas-kidney recipients than in the nondiabetic kidney recipients, both before the meal (mean +/- SE, 102 +/- 15 vs. 53 +/- 6 pmol per liter; P less than 0.05) and afterward (123 +/- 22 vs. 61 +/- 6 nmol per liter per six hours; P less than 0.05). Plasma C-peptide concentrations were the same in both groups, indicating that hyperinsulinemia was due to decreased insulin clearance rather than increased insulin secretion. Despite drainage of the venous effluent from the transplanted pancreas into the systemic circulation, the values for splanchnic clearance of ingested glucose, suppression of hepatic glucose release, incorporation of carbon dioxide into glucose, stimulation of glucose oxidation, glucose uptake, and forearm glucose clearance were all similar in the transplant groups and differed minimally from the values in the normal group. The similar rates of glucose uptake in the presence of higher systemic insulin concentrations indicated that the extrahepatic tissues of the diabetic pancreas-kidney recipients were insulin-resistant., Conclusions: Despite systemic delivery of insulin, pancreas-kidney transplantation in patients with diabetes results in carbohydrate metabolism similar to that in nondiabetic subjects receiving the same immunosuppressive agents after kidney transplantation.

A retrospective analysis of 135 drug addicts followed between 1986 to 1987, was done, in order to asses the seroprevalence of hepatitis B virus (HBV), hepatitis Delta virus (HDV), hepatitis C virus (HCV) and Human Immunodeficiency virus (HIV), as also their clinical and prognostic significance. A high prevalence of HBV, HDV and HCV infection was observed in this study: 81%, 64% and 83% respectively; in contrast just one case was positive for HIV. Among the drug addicts the frequency of multiple infections (HBV/HCV 51.6%; HBV/HDV/HCV 18.7%; HBV/HDV 2.2%; HCV/HIV 1.1%) was highest in comparison with isolated (HBV 5.5%; HCV 12.1%) or absent infection (73.6% vs 17.6% vs 8.8% respectively; p less than 0.001). Eleven of 12 (92%) patients with Delta hepatitis and HCV superinfection were seronegative for IgM anti-HD; in contrast the case without HCV superinfection was IgM anti-HD positive. In the former group the Alanine Amino-transferases (ALT) were significantly lower comparatively with those HBV positive patients superinfected by HCV (97 +/- 92 IU/L vs 249 +/- 125 IU/L; p = 0.001), and were not different from drug addicts with isolated HCV infection (62 +/- 49 IU/L). The results of this study indicate, a low prevalence of HIV infection in the Portuguese drug addicts and a high frequency of multiple HBV, HDV and HCV infection in the same period of study. Our observations suggest that HCV may have the capacity to inhibit the replication and pathogenic activity of hepatitis Delta virus.

A group of forty-nine HBV chronic carriers with histologically confirmed active liver disease and undetected serum HBV DNA by dot-blot hybridisation were re-investigated using the polymerase chain reaction (PCR) for amplification of serum DNA. The group comprised 16 persistently serum HBeAg-negative and thirty-three anti-HBe-positive patients. The use of PCR followed by Southern blot analysis has increased the sensitivity of HBV DNA detection to about 10-50 virions per ml of serum. Our results showed 14/16 (87.5%) of the HBeAg-positive group and 27/33 (81.8%) of the anti-HBe group to be positive for HBV DNA using PCR. Of the nine cases where HBV DNA was undetected four were positive for markers of hepatitis delta virus (HDV) infection. Demonstration of low level HBV replication associated with active liver disease in chronic HBV carriers where it was previously undetected meets a basic requirement for the proposed role of cytotoxic T lymphocyte-mediated immunopathogenesis in chronic hepatitis B and suggests a combined antiviral and immunotherapeutic approach to achieve eradication of the infection.