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N Rayes

Publications and source records attributed to N Rayes.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antiviral combination therapy for lamivudine-resistant hepatitis B reinfection after liver transplantation.

Development of resistance is a major issue in antiviral treatment of hepatitis B reinfection after liver transplantation. Antiviral combination therapy is discussed for therapy or prevention of this breakthrough of viral replication. Eight patients were enrolled into this retrospective analysis after liver transplantation for chronic hepatitis B infection. All had reinfection of the graft and breakthrough of HBV during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy with lamivudine and interferon-alpha 2a (group I, n = 4) or lamivudine and famciclovir (group II, n = 4) was initiated. Combination therapy was started 61 months (group I) and 25 months (group II) after liver transplantation. It markedly reduced the viral replication rate in all patients despite lamivudine resistance. In group I three of four patients and in group II two of four patients became HBV-DNA negative. Two long-term responders were observed in group I, and none in group II. No patient became HBsAg negative or lost HbeAg. Pretreatment elevated ALT and AST levels were significantly reduced. No severe complications, and especially no rejection episodes, occurred. Lamivudine in combination with other antiviral agents, especially interferon-alpha, might be a therapeutic option for hepatitis B reinfection after liver transplantation. Suppression of virus replication to the point of undetectable values is possible even in patients with lamivudine-resistant virus mutations.

2-Aminopurine↗
PubMed2000

Lamivudine as first- and second-line treatment of hepatitis B infection after liver transplantation.

Lamivudine and famciclovir have expanded therapeutical options for HBV infection after liver transplantation. First studies confirm good antiviral effects of both, but at present the major problem seems to be a rapid resistance formation in immunosuppressed patients. Thirty-four adult patients with HBV recurrence despite passive immunoprophylaxis and seven with de novo infection after orthotopic liver transplantation (OLT) were treated with 100-150 mg lamivudine daily. Patients were either treated directly after infection (n = 14) or after breakthrough of viral replication during an initial famciclovir therapy (n = 27). All patients except two responded to treatment with a reduction of serum HBV-DNA of over 50%. Thirty-one patients (76%) turned HBV-DNA-negative during lamivudine therapy. Viral breakthrough was observed in 14 of these patients after 4-13 months of treatment. A total of 17 patients (40%) remained HBV-DNA-negative for more than 12 months. Only nine patients eliminated HBsAg, of which four had and an HDV coinfection. None of the HBeAg-positive patients converted to anti-HBe. Most patients showed a prompt and significant reduction of aspartate aminotransferase (ALAT) levels. No severe complications occurred. Therefore, a safe and effective therapy of HBV infection after transplantation is possible with lamivudine. Viral replication is suppressed even in patients who revealed breakthrough during famciclovir therapy. Resistance formation as a major drawback occurred in one third of the patients within the first year of treatment.

2-Aminopurine↗
PubMed2000

[Therapy of recurrent hepatitis B infection after liver transplantation. A retrospective analysis of 200 liver transplantations based on hepatitis B associated liver diseases].

BACKGROUND: Before introduction of passive immunoprophylaxis and new antiviral nucleoside analogues the course of hepatitis B recurrence after liver transplantation could hardly be influenced. The result was a inferior graft survival. In the present retrospective analysis of the efficacy of hepatitis B therapy after liver transplantation was analysed retrospectively. PATIENTS AND METHODS: Between 1988 and 1998 in total 179 patients were transplanted due to hepatitis B related liver failure at our centre. All patients received passive immunoprophylaxis with hepatitis B immunoglobulin. In case of reinfection after 1993 an antiviral therapy with famciclovir 1500 mg daily was initiated (n = 26), since 1996 lamivudine (100-150 mg daily) was used (n = 12). In case of viral breakthrough under famciclovir treatment or prophylaxis therapy was switched to lamivudine (n = 22). In case of ineffectiveness of lamivudine an antiviral combination therapy with lamivudine and interferon (n = 4) or lamivudine and famciclovir (n = 4) was initiated. Before availability of antiviral agents or in case of viral breakthrough in total 12 patients were retransplanted due to acute or chronic reinfection. RESULTS: With passive immunoprophylaxis reinfection rate was 33%, 43% and 44% after 1, 3 and 5 years respectively. Without antiviral treatment 52% of patients died within the first year after reinfection. Antiviral therapy with lamivudine or famciclovir improved the one year survival after reinfection to 79%. Suppression of viral replication was more effective with lamivudine. Under lamivudine 26 patients (76%) became HBV-DNA negative, 9 patients HBsAg negative (26%). In contrast no patient became HBsAg negative during famciclovir therapy. Lamivudine was effective also after famciclovir breakthrough in 94% of patients. In case of lamivudine resistant reinfection viral replication could be suppressed with an antiviral combination therapy up to negative HBV-DNA in the hybridization assay. Severe side effects were not observed during any of the antiviral therapies. The graft survival after retransplantation for hepatitis B reinfection was 42% and 25% after one and 3 years. CONCLUSION: Whereas it is generally accepted, that passive immunoprophylaxis lowers the reinfection rate it could be shown in the present study, that antiviral treatment lowers mortality of hepatitis B reinfection. The major problem of lamivudine and famciclovir is viral resistance formation. In this case an antiviral combination therapy might be useful, whereas retransplantation for hepatitis B reinfection should be considered carefully due to inferior graft survival rates.

2-Aminopurine↗
PubMed2000

Prognostic factors in patients with differentiated thyroid carcinoma.

OBJECTIVE: To study the prognostic factors in patients with differentiated thyroid carcinoma. DESIGN: Retrospective analysis. SETTING: University hospital, Germany. PATIENTS: 139 consecutive patients who underwent surgery for follicular (n = 42) and papillary thyroid carcinoma (n = 97). MAIN OUTCOME MEASURES: Survival rate, type of operation (systematic lymphadenectomy or no lymphadenectomy). RESULTS: Median observation time was 72 months (range 1-203). The 5 and 10 year survival rates in patients with papillary carcinoma were 92% and 89% respectively, and in those with follicular carcinoma 88% and 80%, respectively. Prognostic factors for papillary carcinoma were distant metastases, age, and extrathyroidal growth, and for follicular carcinoma they were distant metastases, extrathyroidal extension, and multifocal growth. The Union International contre le Cancer and European Organisation for Research and Treatment of Cancer scores and the age, grade, extent and size score were all highly significant. The extent of lymphadenectomy, primary or secondary thyroidectomy, and partial or total thyroidectomy did not influence survival. CONCLUSION: Staging and score systems may be helpful in calculating prognosis in differentiated thyroid carcinoma, but the benefit of systematic lymphadenectomy remains controversial.

Adenocarcinoma, Follicular↗
PubMed1999

[Motherhood and fatherhood after liver transplantation].

BACKGROUND AND OBJECTIVE: Liver transplantation for terminal liver failure enables patients to look forward to many years of good quality life. As a result, more and more of the often still relatively young transplant recipients inquire about the possible risks to a child procreated after transplantation. PATIENTS AND METHODS: During 9.5 years (between September 1988 and April 1998) 1000 liver transplantations were performed on 911 patients (374 females, 537 males) at our hospital. The potential for parenthood existed for 163 women (aged between 16 an 46 years) and 520 men. 14 children were born of 14 women, six pregnancies ended in spontaneous abortion or miscarriage and three other women are now pregnant. Seven men reported paternity of eight children after transplantation. All data were collected prospectively. RESULTS: Six of the 14 births (42.9%) proceeded normally, but up to three complications developed in the other eight (57.1%). Six women (35.7%) developed hypertension during the pregnancy. There was no case of transplant dysfunction or toxaemia of pregnancy. Half the births were by caesarean section. Premature births occurred in two women (14.3%); four children were underweight (< 2500 g) at birth (28.6%). The seven men, at a mean age of 44 (7-75) months after transplantation, fathered eight children, at present aged between 11 months and 6 years, all of whom have developed normally. The 13 children of the post-transplantation mothers are also without malformation or abnormal development. One child's development is retarded due to a fetal alcohol syndrome resulting from the mother's post-transplantation alcohol abuse during pregnancy. All the patients are well at present and live with their children. CONCLUSIONS: Both men and women can procreate at a relatively low risk to the off-spring. But for this to happen, an informed decision for parenthood must be made by the prospective parent together with her/his partner and the doctor in charge, she/he must be in good physical condition with stable transplant function, and there must be frequent interdisciplinary monitoring during any post-transplantation pregnancy.

Abortion, Spontaneous↗
PubMed1999

Influenza vaccination in liver transplant recipients.

BACKGROUND: The immunogenicity of the trivalent inactivated influenza split virus vaccine (Infusplit SSW 97/98) containing A/Bayern/07/95 (H1N1)-like (A/Johannesburg/82/96 [NIB-39]), A/Wuhan/359/95 (H3N2)-like (A/Nanchang/933/95 [Resvir-0]), and B/Beijing/184/93-like (B/Harbin/7/94) hemagglutinin antigens was tested in liver transplant recipients (TXL-R). SUBJECTS AND METHODS: Serum antibody titers were determined 21+/-2 days after a single vaccination in 62 adult TXL-R and 59 adult volunteers. RESULTS: Protective postimmunization antibody titers for the three antigens were similar in TXL-R (protection rates 92%, 92%, and 95%) and the comparison group (97%, 100%, and 100%). Adverse reactions were mild and less frequent in TXL-R. A significant decrease of CD8+CD38+ lymphocytes after vaccination was found in TXL-R. No association between antibody response and age, gender, time interval since transplantation, anti-hepatitis B surface antigen immunoprophylaxis, or immunosuppressive medication was detected. CONCLUSION: Our results show that the vaccine is safe and effective and should be recommended to TXL-R.

ADP-ribosyl Cyclase↗
PubMed1999

Long-term results of famciclovir for recurrent or de novo hepatitis B virus infection after liver transplantation.

Since the introduction of famciclovir in the treatment of hepatitis B virus (HBV) infection after liver transplantation, promising results have been published. In this study, the long-term efficacy and safety of famciclovir were assessed. Twenty-four patients with recurrent hepatitis B and 6 patients with de novo infection after liver transplantation were enrolled in an open prospective trial. Patients received oral famciclovir, 500 mg three times daily. Serum HBV-DNA, viral serology, and liver enzymes were measured sequentially; liver histology was taken before and during treatment in 12 patients. In the reinfected patients, 17 patients initially responded well to treatment, with a mean decrease of HBV-DNA of 82%, 5 patients became HBV-DNA negative. The drug was effective for 1-51 months (mean 16 months), then viral replication increased again in 13 out of 17 patients. One patient did not respond to treatment. Six out of 24 patients already had severe cirrhosis at the time of enrollment and died shortly afterwards, due to the HBV infection. The 6 patients with de novo infection all had a decline of HBV-DNA for 2-42 months (mean 14 months); 1 patient converted to HBV-DNA negative. Five out of 6 patients experienced a viral breakthrough later on. No severe side-effects were observed. Therefore, famciclovir is effective in certain HBV-infected patients after orthotopic liver transplantation (OLT), but in the long term, most of the patients relapse.

2-Aminopurine↗
PubMed1999

Preemptive therapy in CMV-antigen positive patients after liver transplantation--a prospective trial.

OBJECTIVE: Preemptive therapy with intravenous ganciclovir and CMV-hyperimmunoglobulin in asymptomatic CMV pp65-antigen positive patients was compared with treatment of only symptomatic CMV-disease after liver transplantation in an open prospective study. PATIENTS AND METHODS: 48 out of 200 liver transplant recipients became positive during six weeks follow-up after transplantation. 17 out of these 48 patients who were already symptomatic at the time of positive antigen testing were successfully treated with ganciclovir and CMV-hyperimmunoglobulin. 31 asymptomatic antigen-positive patients were randomised to receive preemptive therapy or to receive therapy only at onset of clinical symptoms. RESULTS: Only two out of 15 patients in this latter group without preemptive therapy developed CMV-syndrome and were successfully treated with intravenous ganciclovir. 13 patients did not experience any clinical symptoms or disease and were therefore spared unneccessary toxicity and costs. The overall incidence of CMV-infection and -disease in the whole study population of 200 liver transplant recipients was 25% and 10%. As expected, CMV-negative patients who received an organ from a seropositive donor were at a higher risk of CMV-infection and -disease, but did not show more severe infections clinically. Patients with IL-2 receptor antibody induction therapy seemed to have a higher risk for CMV-infection and -disease.

Adult↗
PubMed1998

Prompt treatment of initial acute rejection episodes may improve long-term graft outcome.

Acute rejection episodes have been cited as a major immunological risk factor for the development of chronic rejection. To examine the influence of a single rejection event on ultimate graft outcome, acutely rejection rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time Early structural changes (days 3 and 4) were completely reversible, while signs of chronic rejection did become obvious during the long-term follow up. More advanced deteriorated grafts (days 5 and 7) were irreversibly damaged and the rats died shortly after retransplantation. Those results indicate the critical impact of acute rejection episodes on chronic graft rejection. Immediate and aggressive treatment of acute rejection episodes may remove this event as a risk factor for late deteriorating changes.

Acute Disease↗
PubMed1998

Recurrence-free survival after liver transplantation for small hepatocellular carcinoma.

Recurrence-free survival (RFS) in patients with small hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) was analyzed. From 1988 until 1996, 725 OLTs were performed in 669 patients. In 52 adults, HCC was confirmed histologically. OLT was limited to patients with small (< 5 cm) HCC with a maximum number of three nodules. Actuarial survival for these 52 patients at 1 and 5 years is 88% and 71%. RFS was defined as time until death without recurrence time until follow up with a diagnosis of recurrence, or, in patients without recurrence, time of last follow up. Overall, the 5-year RFS was 60%. Five-year RFS was less for bilobar compared to unilobar tumors (36% vs 70%), less for stage IVa tumors (UICC) compared to stage I-III tumors (17% vs 71%), and less for multiple compared to solitary tumors (54% vs 67%). In conclusion, potential cure may be achieved in more than 50% of all transplanted patients.

Actuarial Analysis↗
PubMed1998

Pregnancies following liver transplantation--how safe are they? A report of 19 cases under cyclosporine A and tacrolimus.

The number of pregnancies following liver transplantation is increasing due to better patient and graft survival and quality of life. Out of 156 women of a reproductive age, there were 19 pregnancies in 16 women, 12 on CsA and seven on tacrolimus, which occurred between 7/92 and 1/97. The median age of the women was 27.9 yr, median time after transplantation 33 months. There were four spontaneous and two induced abortions in the first trimenon. Ten women delivered ten healthy babies; three newborns had problems (alcoholic embryopathy due to recurrent alcohol abuse of his mother, pneumonia, weight < 2000 g). In eight women mostly mild complications were observed, such as hypertension (n = 5), nonspecific elevation of liver enzymes (n = 2), infection (n = 3) and premature labor (n = 1). Mean gestational age was 39 wk and mean birth weight 2900 g. One case of prematurity and three cases of growth retardation occurred. Cesarean sections were performed in 7 patients (54%) for maternal hypertension (n = 2), presumed fetal hypoxia (n = 4) and breech position (n = 1). All children are normally developed, the oldest being 5 yr old. Although experience with tacrolimus is limited, pregnancies following liver transplantation carry an acceptable risk if carefully monitored by an experienced team of transplant surgeons and obstetricians.

Adult↗
PubMed1997

De novo malignancies after liver transplantation using tacrolimus-based protocols or cyclosporine-based quadruple immunosuppression with an interleukin-2 receptor antibody or antithymocyte globulin.

BACKGROUND: Although conventional immunosuppression after liver transplantation consists of cyclosporine A (CsA), steroids, and azathioprine, recently introduced protocols entail CsA-based quadruple induction protocols or tacrolimus-based combinations. These protocols aim to reduce the rejection rate and the considerable morbidity related to the side effects of additional immunosuppressive treatment, but have not yet been analyzed regarding their long term de novo neoplastic risk. METHODS: From September 1988 to May 1994, 500 liver transplantations were performed in 458 patients. The median follow-up was 50 months (range, 0.3-97 months) for all patients. Conventional triple therapy was implemented in 25 patients, CsA-based quadruple induction therapy using an antilymphocyte globulin preparation (ATG) in 190 patients, an interleukin-2 receptor antibody (BT563) in 141 patients, and tacrolimus-based dual or triple immunosuppression in 102 patients. The different protocols were evaluated in four randomized and two nonrandomized prospective trials. RESULTS: De novo neoplasias were detected in 33 patients (7.2%) and were comprised of lymphomas (n = 7), skin malignancies (n = 8 lesions in 7 patients), intraepithelial neoplasias of the cervix uteri (n = 7), breast carcinoma (n = 3), lung carcinoma (n = 3), and other malignancies (n = 6). The incidence of de novo neoplasias did not differ in the different trial arms. Only a positive T-crossmatch and a low CD4+/CD8+ ratio in patients receiving CsA-based immunosuppression demonstrated a significant correlation with the development of a de novo tumor in a multivariant logistic regression analysis. CONCLUSIONS: The development of de novo neoplastic diseases after liver transplantation with the use of CsA-based quadruple induction protocols or tacrolimus-based regimens for immunosuppresion was assessed over the long term. Recently introduced immunosuppressive protocols did not alter the posttransplant de novo tumor rate. Patients with a low CD4+/CD8+ ratio during CsA-based therapy or a positive T-crossmatch were identified to be at an increased risk for the development of a de novo malignancy.

Antibodies, Monoclonal↗
PubMed1995

[Cause of death after liver transplantation: an analysis of 41 cases in 382 patients].

UNLABELLED: The aim of this study was to analyse the causes of death after liver transplantation in order to find and to avoid preventable fatal complications if possible. METHODS: Between September 1988 and September 1993 415 orthotopic liver transplantations in 382 patients were performed at the Rudolf Virchow University Hospital in Berlin. During the same interval 41 (10.7%) of these patients died. Their clinical records were reviewed. RESULTS: The main cause of death was infection (29.3%), followed by recurrent malignancy (21.9%). Less patients died because of hepatitis B-reinfection (14.6%), chronic rejection (7.3%), hemorrhage (7.3%), cardiac failure (7.3%), trauma (4.8%), hypoxia (4.8%) and recurrence of alcoholic liver disease (4.8%). There was a wide spectrum of opportunistic infectious agents with CMV and Pneumocystis carinii being the most important pathogenic organisms. Only one isolated bacterial infection as principle cause of death was found. In all fatal infections the lung was the primary site of infection, 7 patients additionally developed sepsis. Altogether 75 patients (19.6%) with hepatitis B-cirrhosis were transplanted. Six of them (8%) developed a fatal hepatitis B-reinfection. Malignancy was the indication for OLT in 41 patients (10.7%). Six of these patients (14.6%) died because of recurrent tumor. Regarding the whole series, most deaths occurred four to twelve months (58.5%) and only five (12.2%) during the first month after OLT. CONCLUSION: Recurrence of primary disease is an important factor regarding total mortality. Therefore it is necessary to practise a careful selection of liver transplant recipients. In the future more attention needs to be drawn towards prevention, identification and management of opportunistic infections.

Adult↗