Biomedical subjects

Kinan Rifai

Publications and source records attributed to Kinan Rifai.

14 recordsLinked to original sources

PubMed2006

Leptin and insulin response to long-term total parenteral nutrition depends on body fat mass.

BACKGROUND & AIMS: Circulating leptin and insulin concentrations are physiologically representing energy homeostasis. However, the artificial situation of long-term total parenteral nutrition (TPN) and its effects on serum leptin and insulin is not fully understood. METHODS: We studied 42 gastroenterological patients who received TPN for 19+/-11 days. Serum leptin and insulin levels as well as body composition assessed by bioelectrical impedance analysis were evaluated on days 0, 7 and 14. Insulin sensitivity was estimated by calculating the QUICKI. RESULTS: Before the start of TPN, leptin correlated positively with female gender (P<0.03), BMI (P<0.02), fat mass (P<0.02), insulin levels (P<0.001) and QUICKI (P<0.001). Within the first week of TPN, an increase of leptin levels was found only in patients with a body fat mass of >30% (P<0.02). As these were predominantly women, their leptin levels increased likewise (P<0.003). In regression analysis, fat mass (P<0.001), female gender (P<0.04), insulin levels (P<0.03), and i.v. glucose supply rates (P<0.05) were independently associated to leptin levels. CONCLUSIONS: TPN-especially glucose-induces a neurohumoral response as shown here for leptin and insulin that is mainly depending on the fat mass. Better understanding of this regulatory mechanism during artificial nutrition could offer a new approach to improve its therapeutic effects.

Adipose Tissue↗

PubMed2006

Removal selectivity of Prometheus: a new extracorporeal liver support device.

AIM: To evaluate whether treatment with the Prometheus reg system significantly affects cytokines, coagulation factors and other plasma proteins. METHODS: We studied nine patients with acute-on-chronic liver failure and accompanying renal failure. Prometheus reg therapy was performed on 2 consecutive days for up to 6 h in all patients. Several biochemical parameters and blood counts were assessed at regular time points during Prometheus reg treatment. RESULTS: We observed a significant decrease of both protein-bound (e.g. bile acids) and water-soluble (e.g. ammonia) substances after Prometheus reg therapy. Even though leukocytes increased during treatment (P<0.01), we found no significant changes of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha plasma levels (all P>0.5). Further, antithrombin 3, factor II and factor V plasma levels did not decrease during Prometheus reg therapy (all P>0.5), and the INR remained unchanged (P=0.4). Plasma levels of total protein, albumin, and fibrinogen were also not altered during Prometheus reg treatment (all P>0.5). Finally, platelet count did not change significantly during therapy (P=0.6). CONCLUSION: Despite significant removal of protein-bound and water-soluble substances, Prometheus reg therapy did not affect the level of cytokines, coagulation factors or other plasma proteins. Thus, the filters and adsorbers used in the system are highly effective and specific for water-soluble substances and toxins bound to the albumin fraction.

Blood Coagulation Factors↗

PubMed2006

A new side effect of immunosuppression: high incidence of hearing impairment after liver transplantation.

Little is known about hearing impairment in patients after organ transplantation. We conducted a single-center study to evaluate hearing impairment in patients after orthotopic liver transplantation (OLT). A questionnaire was sent to 695 adult patients after OLT to assess characteristics and course of auditory impairment. Risk factors such as ototoxic drugs were taken into consideration. Clinical follow-up, including immunosuppressive therapy, was analyzed in detail. The questionnaire was completed by 521 patients (75%). Hearing impairment was reported by 184 patients (35%). A total of 43 patients (8%) suffered from hearing abnormalities prior to OLT. The remaining 141 patients (27%) developed hearing impairment after transplantation. Main problems were hearing loss (52%), tinnitus (38%), and otalgia (30%). There was no association of post-OLT hearing disorders with age or known risk factors. In 43% of patients, onset of hearing impairment was within 2 yr post-OLT. Hearing loss was positively associated with tacrolimus immunosuppression in univariate (P < 0.05) and multivariate analysis (P < 0.02). Patients using a hearing aid received tacrolimus more frequently than cyclosporine (P < 0.05). In conclusion, subjective hearing impairment is frequent in patients after OLT and contributes to post-OLT morbidity. Calcineurin inhibitor-related neurotoxicity appears as a possible mechanism. Further prospective investigations with objective hearing tests are necessary to confirm these results and to evaluate the role of immunosuppression.

Adult↗

PubMed2006

Outcome and quality of life in patients with polycystic liver disease after liver or combined liver-kidney transplantation.

In advanced stages of polycystic liver disease, often associated with polycystic kidney disease, a curative therapy is liver or combined liver-kidney transplantation. However, little is known about long-term outcome and quality of life. Between 1990 and 2003, 36 patients (32 female, 4 male) with polycystic liver or combined liver-kidney disease underwent liver (n = 21) or liver-kidney (n = 15) transplantation at our center. Main indications for liver transplantation were cachexia, muscle atrophy, loss of weight, recurrent cyst infections, portal hypertension, and ascites. Apart from clinical parameters, 2 anonymous questionnaires (standard short form 36 and self-designed) addressing quality of life and social status were evaluated. Five patients (14 %) died due to sepsis or myocardial infarction with pneumonia, all within 61 days after transplantation. The follow-up time of the remaining 31 patients ranged from 5 to 156 months, with a mean of 62 months. Of the 23 (74%) answered the questionnaires, 91% of patients felt "much better" or "better," only 9% felt "worse" than before, and 52% of patients participated in sports regularly. Fatigue, physical fitness, loss of appetite, and vomiting improved significantly after transplantation. Physical attractiveness and interest in sex increased as well. Professional occupation did not change for 71% of patients. Family situation before and after transplantation changed in 1 case only. Finally, 78% of patients said they would opt for transplantation again, while 17% were undecided; 1 patient would not repeat transplantation. In conclusion, patients with advanced polycystic liver or polycystic liver-kidney disease have an excellent survival rate and an improved quality of life after liver or combined liver-kidney transplantation.

Adult↗

PubMed2006

Treatment of severe refractory pruritus with fractionated plasma separation and adsorption (Prometheus).

OBJECTIVE: Severe pruritus is a serious complication of cholestatic liver disease. Prometheus is a recently introduced extracorporeal liver support system with direct toxin adsorption of the patient's albumin fraction (FPSA; fractionated plasma separation and adsorption). Here we report on the effect of Prometheus therapy in patients with intractable cholestatic pruritus. MATERIAL AND METHODS: Seven patients with different liver diseases and severe pruritus refractory to all medical treatment efforts for more than 4 weeks were treated with Prometheus (3-5 times, 18+/-3 h total). Pruritus intensity was assessed using the visual analogue scale (VAS; from 0 = no pruritus to 10 = unbearable pruritus), and VAS, serum bile acids and total bilirubin were evaluated directly before and after Prometheus treatment, as well as 4 weeks later. RESULTS: After Prometheus therapy, VAS values had dropped significantly from 9+/-1 to 3+/-3 (p<0.001). Likewise, serum bile acids decreased (from 248+/-192 to 101+/-85 micromol/l; p<0.03). All patients, with the exception of one with no initial bile acid elevation, reported a pronounced improvement in pruritus with Prometheus therapy, although in two anicteric patients the amelioration lasted only a few days. In the other four patients a distinct benefit was still observed 4 weeks after the treatment. CONCLUSIONS: Prometheus therapy significantly improved refractory pruritus in all patients with elevated bile acid levels, but in some patients the clinical benefit was of short duration. The clinical findings suggest that we have to better characterize those patients who might derive a long-lasting benefit from this invasive and expensive treatment.

Adsorption↗

PubMed2006

Hepatitis B virus immunization with an adjuvant containing vaccine after liver transplantation for hepatitis B-related disease: failure of humoral and cellular immune response.

Long-term hepatitis B reinfection prophylaxis after liver transplantation with hepatitis B immunoglobulin (HBIG) and nucleoside analogues is expensive and inconvenient. Studies evaluating humoral immune responses to hepatitis B virus (HBV) vaccines showed conflicting results. Best results were achieved under continuous HBIG administration with an adjuvant-containing HBsAg vaccine. In the present study, 8 patients who had been HBsAg positive and HBV DNA negative prior to liver transplantation were immunized with HBsAg-vaccine containing the adjuvant 3-deacylated monophosphoryl-lipid-A. Vaccination was started after discontinuation of HBIG. Six vaccinations were administered at weeks 0, 2, 4, 12, 16 and 24. Humoral (anti-HBs titres) and cellular (enzyme-linked immunospot assay and fluorescence-activated cell sorting analysis) immune responses were studied. Only one of eight patients responded with a humoral immune response (maximum anti-HBs titre 561 U/l). In this patient, decrease of anti-HBs titre before vaccination was significantly slower than in the other seven patients and anti-HBs did not become negative before first vaccination. A T-cell response to HBsAg could not be detected in any of the patients. The responder was the only patient who showed a T-cell response to HBcAg. In conclusion, the adjuvant-containing vaccine did not induce a humoral or a detectable cellular immune response in most patients. Patient-related preconditions and concomitant HBIG administration should be further investigated as possible predictors for response.

Adjuvants, Immunologic↗

PubMed2006

Review article: clinical experience with Prometheus.

Prometheus is a new extracorporeal liver support device which facilitates the combined removal of both albumin-bound and water-soluble toxins based upon the method of fractionated plasma separation and adsorption (FPSA). The pilot trial included 11 patients with acute-on-chronic liver failure and concomitant renal failure. Prometheus therapy was found to be safe except for a reversible decrease of blood pressure. In three patients, clotting of the secondary system occurred. Prometheus treatment significantly improved blood levels of protein-bound (conjugated bilirubin, bile acids, ammonia) and water-soluble (creatinine, urea) substances. Thus, Prometheus might be a new therapeutic option in patients with severe hepatorenal syndrome. Furthermore, there is some preliminary experience with Prometheus in the treatment of refractory cholestatic pruritus and in successful bridging to liver transplantation. In order to compare extraction capacities of Prometheus and the molecular adsorbent recirculating system (MARS), five patients were crossover-treated with both systems. Prometheus resulted in significantly higher reduction ratios of bilirubin, ammonia and urea. Another study closely monitored whether the device causes an unselective removal. Neither important cytokines nor coagulation factors were found to be removed. In conclusion, Prometheus seems to be a new therapeutic option in artificial liver support. A significant improvement of the biochemical milieu was already observed after two treatments. The potential to remove protein-bound and water-soluble substances has been shown without signs of a significant unselective removal.

Blood Chemical Analysis↗

PubMed2005

The Prometheus device for extracorporeal support of combined liver and renal failure.

BACKGROUND/AIMS: Prometheus is a newly developed extracorporeal liver support system that combines removal of albumin-bound substances (adsorption on resin adsorbers) and water-soluble substances (diffusion during high-flux hemodialysis). Therefore, it is a promising treatment option for patients with hepatorenal syndrome (HRS). METHODS: We studied 10 patients with HRS in a prospective clinical study. All patients underwent 2 consecutive Prometheus treatments. A variety of clinical and biochemical parameters were assessed. RESULTS: Prometheus treatment was uncomplicated and safe. A statistically significant improvement of serum creatinine and urea concentrations as well as blood pH was observed after Prometheus treatment. Furthermore, liver detoxification was supported by a significant decrease of serum levels of conjugated bilirubin, bile acids and ammonia. CONCLUSIONS: Prometheus is a safe treatment for patients with HRS. Both, albumin-bound and water-soluble substances were effectively removed. Controlled studies will evaluate the effect of this new treatment option on survival in patients with HRS.

Blood Chemical Analysis↗

PubMed2004

Donor age influences 10-year liver graft histology independently of hepatitis C virus infection.

BACKGROUND/AIMS: Factors influencing the long-term histological outcome of liver graft are not known. We conducted a prospective study based on a 10-year liver biopsy in order to identify the main factors influencing long-term graft histology. METHODS: 270 of 423 patients who still had their first functional graft 10 years after liver transplantation accepted to undergo routine liver biopsy. All slides were blindly reviewed by two pathologists. RESULTS: Main histological findings were fibrosis in 143 patients (54%) and ductopenia in 76 patients (29%). Ductopenia was independently related to higher donor age (32+/-12 vs 28+/-13 years; P<0.02). Severity of fibrosis was influenced by hepatitis C virus (HCV) infection (P<0.001), hepatitis B virus (HBV) recurrence (P=0.001) and higher donor age (P=0.03). Eighty biopsies (30%) showed minimal-change lesions which were associated with the absence of HCV infection (24/80 vs 99/185; P<0.001) or of HBV infection (1/80 vs 15/185; P=0.03) and lower donor age (25+/-11 vs 31+/-13 years; P<0.001). CONCLUSIONS: Post-transplant infection by HCV or HBV are main factors influencing the histological course of liver graft. Donor age was also a strong factor in HCV infected patients as well as in HCV-negative patients. This variable should be taken into account, particularly for candidate recipients with long life expectancy.

Adult↗

PubMed2004

Long-term outcome of liver transplantation for autoimmune hepatitis.

BACKGROUND: Liver transplantation is the final therapeutic option for about 10% of patients with autoimmune hepatitis (AIH) who do not respond to medical therapy. The aim of this study was to evaluate the long-term outcome in serologically defined subgroups of AIH after transplantation. METHODS: Pre- and post-transplantation data of 28 patients with AIH transplanted between 1987 and 1999 were retrospectively analyzed and compared with 24 patients, who underwent liver transplantation because of Wilson's disease and glycogen storage disease type 1. RESULTS: Serological analyses identified patients with AIH type 1 (n = 13), type 2 (n = 5), and type 3 (n = 10). The 5-yr patient survival rate after liver transplantation was 78.2%, which was not significantly different from the control group. Six AIH patients and four control patients required re-transplantation because of initial non-function, chronic rejection or AIH recurrence. Patients transplanted for AIH (88%) had more episodes of acute rejection when compared with patients transplanted for genetic liver diseases (50%). Clinical and histological features of chronic rejection were present in four patients, which did not differ significantly from the controls. Recurrence of AIH was diagnosed in nine patients (32%) based upon the presence of autoantibodies, increased gamma-globulins, steroid dependency, and histological evidence of chronic hepatitis. These combined features were not found in any of the controls. CONCLUSIONS: Our data do not suggest that AIH subtypes influence prognosis after liver transplantation. Despite a high frequency of acute cellular rejection episodes and disease recurrence, transplantation for AIH has a 5-yr survival rate, which does not differ from that observed in patients transplanted for genetic liver diseases.

Adolescent↗

PubMed2003

[New devices in liver replacement therapy].

Despite the possibilities of liver transplantation, liver failure is still associated with a high mortality rate. Liver replacement therapies have been developed to bridge the acute decompensation of liver function. A variety of artificial and bioartificial devices as well as hepatocyte transplantation are already tested in clinical settings. To date, few controlled data are available, especially with regard to patient survival. Therefore, liver replacement therapy should only be used in clinical studies at specialized centers.

Animals↗

PubMed2003

Prometheus--a new extracorporeal system for the treatment of liver failure.

BACKGROUND/AIMS: Extracorporeal detoxification systems for supportive therapy of liver failure have recently gained much interest. We herein report results from the first clinical application of Prometheus, a new liver support system in which albumin-bound substances are directly removed from blood by special adsorber. In a simultaneous step, high-flux hemodialysis is performed. We assessed safety, adsorber efficiency and clinical efficacy of the Prometheus system. METHODS: Eleven patients with acute-on-chronic liver failure and accompanying renal failure were treated with Prometheus on 2 consecutive days for >4 h. RESULTS: Prometheus treatment significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no significant changes in hemoglobin and platelet levels, whereas leucocytes increased without signs of systemic infection. No treatment-related complications except a blood pressure drop in two patients with systemic infection were noted. In one patient (Child-Pugh score: 15) Prometheus treatment could not be completed due to onset of uncontrolled bleeding 16 h after dialysis. CONCLUSIONS: Prometheus is a safe supportive therapy for patients with liver failure. A significant improvement of the biochemical milieu was observed already after two treatments. Prospective controlled studies with the Prometheus system are necessary to evaluate hard clinical end-points.

Adult↗

PubMed2003

All liver recipients benefit from the protocol 10-year liver biopsies.

The value of late protocol biopsies after liver transplantation remains to be evaluated to highlight the therapeutic policies. The study population was composed of patients who survived with the initial graft and with an available 10-year protocol biopsy (n = 143). The long-term histologic outcome of the graft, particularly the rate of ductopenia in cases with chronic rejection (CR), and Metavir scoring of fibrosis in cases with viral chronic hepatitis (VCH), were assessed. Fibrosis progression (FP) rates were compared over 3 periods (0-5, 5-10, and 0-10 years). At 10 years, histologic abnormalities present in 80% of the patients were not identifiable from liver function tests (LFTs), which were strictly normal in 52% of the patients. Histologic CR occurred in 24% at 10 years, with a mean rate of ductopenia higher at 10 years than at 5 years (49% vs. 34%, P <.001). In cases of VCH, fibrosis worsened, with a median FP rate of 0.20 fibrosis units/year. During the first 5 years, FP was as follows; hepatitis B virus infection was greater than recurrent hepatitis C virus (HCV) infection, which was greater than acquired HCV infection (P =.029). In patients with HCV, FP was higher during the second 5-year period than during the first one (P =.042). In conclusion, given the high prevalence of histologic abnormalities and the lack of sensitivity and specificity of LFTs, late protocol biopsies clearly are justified to adjust treatments, not only in HCV-infected patients in whom FP was fast and not linear, but also in the whole population of recipients.

Adolescent↗

PubMed2002

Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis.

BACKGROUND: The management of acute pancreatitis (AP) frequently includes parenteral nutrition, but conditionally essential amino acids such as glutamine are not included in conventional total parenteral nutrition (TPN). AIM: This study was conducted to determine whether the inclusion of glutamine has a beneficial effect in patients with AP receiving TPN. METHODS: In a randomized, controlled study 28 patients with AP received either a standard TPN with 1.5 g/kg body weight protein or an isonitrogen, isocaloric TPN which contains 0.3 g/kg L -alanine- L -glutamine. Patients were assessed for nutritional and inflammatory parameters, infectious complications, length of TPN, length of hospital stay (LOS) and cost of TPN. RESULTS: There were no side-effects related to glutamine substitution observed. Glutamine was associated with a significant increase of cholinesterase, albumin and lymphocyte count in AP as well a decrease of C-reactive protein compared to standard TPN at day 14. There was a reduced length of TPN (10 [6-16] vs 16 [10-18] days, P<0.05) and a trend of reduced LOS (21 [14-32] vs 25 [19-40] days) in AP patients receiving glutamine. The overall cost per patient for TPN did not differ (gln+: 929+/-586 vs gln-: 981+/-507 euro/patient). CONCLUSION: Our results suggest that glutamine substitution is beneficial and does not increase the overall cost of parenteral feeding in patients with acute pancreatitis.

Acute Disease↗