Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation.

INTRODUCTION: Accumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection. METHODS: Serum levels of IL-34 were determined in 20 healthy subjects and 45 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 30 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. RESULTS: The concentrations of IL-34 were higher in the rejection group vs nonrejection group during the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-34 serum levels than the controls at all times after liver transplantation. CONCLUSIONS: Our preliminary results could be related to the recent finding that IL-34 may play an immune-suppressive role in liver transplantation. In our case, although we must be cautious with serum data, increased IL-34 would help to control alloresponse during rejection and protect from graft lost.

De Novo Donor-Specific Anti-Human Leukocyte Antigen Antibody Detection in Long-Term Adult Liver Transplantation.

INTRODUCTION: Information about the consequences of de novo donor-specific anti-human leukocyte antigen (DSA) antibody development in the long term after adult liver transplantation (LT) is scarce. We conducted a cross-sectional study in LT patients with a follow-up of at least 6 years. METHODS: A total of 28 adult LT patients were included, with a median follow-up of 77 months (range, 63 to 96) and without preformed anti- human leukocyte antigen (HLA) antibodies prior to LT. The anti-HLA identification was performed with LABScreen Single Antigen, whereas the ability to fix the complement was demonstrated with C1q test (One Lambda). In both assays, a value >3.500 mean fluorescence intensity (MFI) was considered positive. The anti-HLA antibody specificities were compared with donor HLA antigens to confirm them as DSA. Hepatic fibrosis was assessed by transient elastography. RESULTS: In 5 patients (17.8%), de novo DSA were detected, all them against DQ locus. In all of these cases (100%) the complement fixation was confirmed by C1q binding. The grade of hepatic fibrosis in de novo DSA patients was significantly higher compared with No-DSA patients (13.2 ± 9.2 KPa vs 7.3 ± 3.7 KPa; P = .02). It is noteworthy that in both groups of patients the levels of liver function tests (LFT) at the time of the study were normal or near the normal range with no difference between patients with or without de novo DSA. CONCLUSIONS: Our preliminary results are consistent with those previously demonstrated in pediatric LT, where de novo DSA production and humoral response could contribute to the liver fibrosis observed in the long term after LT in pediatric patients with normal or near-normal LFT.

Hepatitis B virus quasispecies evolution after liver transplantation in patients under long-term lamivudine prophylaxis with or without hepatitis B immune globulin.

AIMS: To investigate an optimal long-term prophylactic strategy for prevention of hepatitis B virus (HBV) recurrence after liver transplantation, we conducted a randomized study of 29 transplant recipients receiving a short course of hepatitis B immune globulin (HBIg) + lamivudine (LAM), followed by randomization to long-term prophylaxis with LAM with or without HBIg. METHODS: The efficacy and safety, and impact on survival and HBV recurrence of these 2 prophylactic regimens were compared over a mean period of 10 years. In patients with viral recurrence, the HBV quasispecies in the surface/polymerase region were studied by ultra-deep pyrosequencing (UDPS). RESULTS: The 10-year survival rate was 76% and was not affected by the type of prophylaxis. Four patients had hepatitis B surface antigen (HBsAg) recurrence within the first 48 months after orthotopic liver transplantation (OLT). HBsAg-positive and -negative patients showed similar mean survival times, with no differences between the 2 regimens. Low HBV DNA levels were transiently detected in 32% of HBsAg-negative patients. UDPS showed major changes after OLT in the HBV quasispecies of patients with viral recurrence, which may be explained by a "bottleneck" effect of OLT together with prophylactic therapy. CONCLUSION: Long-term survival after OLT in end-stage chronic hepatitis B patients was good with both prophylactic strategies. However, low, transient HBV DNA levels were detected even in the absence of HBsAg, showing the importance of continuing HBV prophylaxis.

Galectin-1 in stable liver transplant recipients.

INTRODUCTION: The achievement of a state of tolerance and minimization of the immunosuppressive load form part of the "Holy Grail" in solid organ transplantation. Galectin-1 recently has been described to be involved in the maintenance of a tolerant environment, but there is no evidence of its role in human liver transplantation. The aim of our study was to measure the serum levels of galectin-1 in stable liver transplant recipients. METHODS: Serum levels of galectin-1 were determined in 30 stable liver transplant recipients who had been free of rejection episodes for at least 8 years. Fifteen patients with an acute rejection episode and 34 healthy subjects were used as the control group. RESULTS: The concentrations of galectin-1 were significantly higher in stable liver transplant recipients compared with healthy subjects and with the acute rejection group. CONCLUSIONS: These preliminary results indicate that galectin-1 is upregulated in stable liver transplant recipients. Thus, our results extend the recent findings that galectin-1 may play an immune-suppressive role in liver transplantation. It remains to be established whether it might help to induce tolerance in liver transplantation.

Serum levels of interleukin-9 during acute rejection in liver transplantation.

INTRODUCTION: Interleukin-9 (IL-9) has been cast as a player in autoimmunity, but its role in liver transplantation remains to be clarified. The aim of our study was to investigate the time course of IL-9 serum levels during hepatic allograft rejection. METHODS: IL-9 serum levels were determined in 34 healthy subjects and 50 hepatic transplant recipients. The patients were divided into two groups: group I was composed of 15 patients with acute rejection episodes, and group II, 35 patients free of this problem. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. RESULTS: The concentrations of IL-9 were similar in the rejection and nonrejection groups over the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-9 serum levels than the controls at all times after liver transplantation. CONCLUSIONS: These preliminary results suggest a lack of participation of IL-9 in human liver allograft rejection.

Interleukin-9 in stable liver transplant recipients.

INTRODUCTION: Interleukin-9 (IL-9) has recently been described to be involved in the maintenance of a tolerant environment, but there is no evidence of its role in human liver transplantation. The aim of our study was to measure the serum levels of IL-9 in stable liver transplant recipients and examine their influence on immunosuppressant load. METHODS: Serum IL-9 levels were determined in 34 healthy subjects and 30 stable liver transplant recipients who were free of rejection episodes for at least 8 years. The results were analyzed according to the blood levels of calcineurin inhibitors (CNIs) at the time of the study: 13 patients showed high concentrations of either cyclosporine or tacrolimus (high CNI: cyclosporine > 80 ng/mL or tacrolimus > 5 ng/mL) and another 17 patients showed low CNI levels. RESULTS: The concentrations of IL-9 were significantly higher among liver transplant recipients compared with healthy subjects. In addition, patients with low CNI blood levels showed higher serum levels of IL-9, an effect that was greater with tacrolimus, albeit not significantly. CONCLUSIONS: These preliminary results indicated that increased serum IL-9 concentrations accompanied a lower immunosuppressive load. It remains to be established whether this relates to induction of tolerance in liver transplantation.

Liver transplantation with donors older than 75 years.

INTRODUCTION: Orthotopic liver transplantation has shown successful results over the last years. For this reason there are increased numbers of patients on waiting lists. To expand the pool of liver donors, elderly donors have been used as a strategy. OBJECTIVE: We report our experience comparing donors of ≥ 75 years with younger ages for their characteristics, clinical outcomes, and survivals. METHODS: From January 2001 to December 2009, we performed 174 consecutive liver transplantation from cadaveric donors in 166 patients. During this period, we used 24 liver grafts from donors ≥ 75 years. We analyzed their outcomes retrospectively, describing donors and recipient characteristics and their clinical evolution. RESULTS: The mean follow-up time among the entire study population was 42 ± 39 months. We observed an overall survival of 68.3% with similar incidences in both groups: 83% in the younger versus 78% in the older group at 1 year, and 69% versus 63%, at 5 years respectively. Both groups showed similar lengths of intensive care unit stay, cold and warm ischemia times, and intraoperative transfusion requirements. The older group had a total operative time than was longer and fewer hypotensive episodes than the younger group. There were no significant differences in the rates of rejection and retransplantation between the groups. The use of older donor livers was associated with a significantly higher rate of poor initial graft function (P = .027), an increased number of reinterventions (P = .013) in the older donor group, as well as more frequent vascular and biliar complications, without reaching significance. CONCLUSION: Our data suggested that donor age alone did not engendered a survival disadvantage for graft or recipient. However, careful donor selection is needed to avoid additional risk factors that can increase the morbidity or mortality of the procedure.

Effect of immunosuppressant blood levels on serum concentration of interleukin-17 and -23 in stable liver transplant recipients.

INTRODUCTION: T(H)17 cells have been recently described to be involved in inflammatory and immune-mediated diseases, but there is no evidence of their role in human liver transplantation. Interleukin (IL)-23 is considered an inducer cytokine, whereas IL-17 is the main cytokine released by T(H)17 cells. The aim of our study was to measure the serum levels of IL-17 and IL-23 in stable liver transplant recipients and examine the influence of immunosuppressant concentrations. MATERIALS AND METHODS: Serum levels of IL-23 and IL-17 were determined in 38 healthy subjects and 35 stable hepatic transplant recipients who were free of rejection episodes for at least 8 years. The results were analyzed according to the simultaneous blood levels of cyclosporine (n = 20) or tacrolimus (n = 15). RESULTS: No significant differences were observed in the serum levels of IL-17 and IL-23 between healthy subjects and transplanted patients. In addition, patients with low blood levels of tacrolimus (<6 ng/mL), but not cyclosporine, showed significantly lower serum levels of the 2 cytokines. CONCLUSION: These preliminary results suggested a lack of activation of the T(H)17 pathway, which was more pronounced among the patient subgroup treated with tacrolimus.

Traumatic neuroma of extrahepatic bile ducts after orthotopic liver transplantation.

Traumatic neuromas (TN) of the biliary tree causing strictures have only occasionally been described after liver transplantation. Herein, we have reported 15 cases of TN that were detected between 1 and 17 months after transplantation (median: 4 months) during surgery for obstructive jaundice (12 cases), after alterations of liver function tests (two cases), or incidentally discovered after retransplantation (n = 1) we resected the lesion and the biliary anastomosis. Pathological examination and immunostaining for S-100 protein were performed to study the nerve fascicles. After a median follow-up time of 64 months (range = 0-127), 10 patients are alive without any complication related to the previous biliary TN. We propose the following classification: type I: TN originating from and located in the main biliary tract wall, and type II: TN arising from the surrounding tissues next to the main biliary tract. We conclude that TN are not uncommon after liver transplantation and that they are sometimes symptomatic, causing a biliary stricture that requires surgical treatment. We propose a classification to help patient selection for surgery. In our opinion, resection of the TN is the operation of choice, together with resection of the involved biliary tract in type I TN.

Value of soluble CD30 in liver transplantation.

INTRODUCTION: CD30 is a membrane glycoprotein that belongs to the tumor necrosis factor superfamily. It is expressed on activated T cells. After activation of CD30(+) T cells, a soluble form of CD30 (sCD30) released into the bloodstream, can be measured in the serum. The aim of our study was to investigate the time course of serum levels of sCD30 during hepatic allograft rejection. MATERIALS AND METHODS: Serum levels of sCD30 were determined in 30 healthy subjects and 50 hepatic transplant recipients. These patients were divided into two groups: group I, 35 patients without rejection; and group II, 15 patients with acute rejection. Samples were collected on day 1 and 7 after transplantation and on the day of liver biopsy. RESULTS: The concentrations of sCD30 were similar in the rejection (40.4 +/- 16.5 U/mL) and nonrejection groups (43.0 +/- 18.2 U/mL) on postoperative day 1. We observed a significant increase in sCD30 levels in the rejection group on postoperative day 7 (76.3 +/- 61.8 U/mL vs 46.8 +/- 20.5 U/mL; P = .01). The difference increased when a diagnosis of acute rejection had been established: namely 133.0 +/- 113.5 U/mL versus 40.1 +/- 22.0 U/mL; (P = .001). These levels were also significantly higher during the entire postoperative period in all the patients, with or without rejection, than those observed in healthy controls (26.6 +/- 5.3 U/mL; P = .005). CONCLUSIONS: The release of circulating sCD30 is a prominent feature coinciding with the first episode of hepatic allograft rejection. So, monitoring of sCD30 levels may be useful for the early diagnosis of an acute rejection episode.

Papel del sobrecrecimiento bacteriano intestinal y de la motilidad intestinal en la traslocación bacteriana en un modelo experimental de cirrosis / Role of intestinal bacterial overgrowth and intestinal motility in bacterial translocation in experimental cirrhosis

Introducción: el sobrecrecimiento bacteriano intestinal (SBI) está relacionado con la motilidad del intestino delgado y diferentes trabajos con modelos experimentales han sugerido su relación con el desarrollo de traslocación bacteriana (TB). Tanto el sobrecrecimientobacteriano intestinal como la traslocación bacteriana soneventos frecuentes en la cirrosis hepática. Objetivos: los objetivos de este estudio han sido analizar lapoblación cecal de bacterias aerobias y el tránsito intestinal en un modelo de ratas cirróticas y su relación con la TB. Material y métodos: el estudio se ha realizado en un modelo experimental de cirrosis inducida por tetracloruro de carbono por vía oral en ratas Sprague-Dawley. Se llevaron a cabo cultivos microbiológicosconvencionales a partir de ganglios linfáticos mesentéricos (GLM), sangre portal y periférica, hígado, bazo, y muestras cecales de todos los animales. Además se determinó el tiempo de tránsito intestinal en 10 ratas cirróticas y en 10 controles. Resultados: la prevalencia de la traslocación bacteriana en los animales cirróticos fue de un 56%. La población de gérmenes aerobios en el ciego en las ratas cirróticas fue significativamentemayor (p < 0,01) que en las ratas controles. Las ratas cirróticas con TB presentaron un población bacteriana intestinal más elevada que las ratas sin TB (p < 0,05). La prevalencia de SBI en los animales cirróticos fue de un 67% frente a un 0% en los animales control (p < 0,01); también el SBI fue más frecuente en las ratas cirróticas con TB que en las cirróticas sin TB (93 vs. 33%) (p <0,01). De las bacterias que traslocaron un 95,6% presentaban sobrecrecimiento en ciego. El tránsito intestinal fue más lento en las ratas cirróticas (60,5 ± 12,7 vs. 81,2 ± 5,7 cm) que en los animales controles (p < 0,01). Conclusiones: estos resultados sugieren que el sobrecrecimiento bacteriano es frecuente en ratas cirróticas y predispone al desarrollo de traslocación bacteriana intestinal. Además, este sobrecrecimientoprobablemente está favorecido por la existencia deuna dismotilidad intestinal, frecuente en este modelo de cirrosis experimental

Background: intestinal bacterial overgrowth (IBO) is related to small bowel motility and has been involved in the pathogenesis of bacterial translocation (BT) in experimental models, and both overgrowing gut flora and translocating bacteria to mesenteric lymph nodes are common features in cirrhosis. Objectives: the aims of this study were to analyze cecal aerobic bacteria and intestinal transit in cirrhotic rats, and their relationship with BT, evaluating the role of intestinal bacterial overgrowth and small bowel dismotility in the development of BT in experimental cirrhosis. Material and methods: we included twenty-seven male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis without ascites and ten controls. Cultures of mesenteric lymph nodes (MLN), peripheral and portal blood, liver, spleen and cecal samples were carried out. Small intestinal transit was determined in ten cirrhotic rats and in ten control rats. Results: the prevalence of bacterial translocation was 56%. Total cecal aerobic bacteria count was significantly higher in cirrhotic rats than in control rats (p < 0.001). Cirrhotic rats with translocated bacteria had higher total aerobic intestinal counts than culture-negative MLN bacteria (p < 0.05). The prevalence of total intestinal bacterial overgrowth in cirrhotic animals was 67%, and 0% in control animals (p < 0.001). According to BT, total IBO was more frequent in cirrhotic rats with BT versus those without BT (93 vs. 33%) (p < 0.001). Of the translocating bacteria, 95.6% were found to be overgrown in the cecum. The mallintestinal transit was slower in cirrhotic rats (60.5 ± 12.7 cm vs. 81.2 ± 5.7 cm) than in control animals (p < 0.001). Conclusions: these results suggest that the increase of intestinal aerobic bacteria in experimental cirrhosis is associated with translocation. In addition, IBO is frequent in cirrhotic rats, and is supposed to play an important role in the development of BT. Impaired motility of the small intestine is a common feature in cirrhosis and may be implicated in the pathogenesis of IBO

Role of intestinal bacterial overgrowth and intestinal motility in bacterial translocation in experimental cirrhosis.

BACKGROUND: Intestinal bacterial overgrowth (IBO) is related to small bowel motility and has been involved in the pathogenesis of bacterial translocation (BT) in experimental models, and both overgrowing gut flora and translocating bacteria to mesenteric lymph nodes are common features in cirrhosis. OBJECTIVES: The aims of this study were to analyze cecal aerobic bacteria and intestinal transit in cirrhotic rats, and their relationship with BT, evaluating the role of intestinal bacterial overgrowth and small bowel dismotility in the development of BT in experimental cirrhosis. MATERIAL AND METHODS: We included twenty-seven male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis without ascites and ten controls. Cultures of mesenteric lymph nodes (MLN), peripheral and portal blood, liver, spleen and cecal samples were carried out. Small intestinal transit was determined in ten cirrhotic rats and in ten control rats. RESULTS: The prevalence of bacterial translocation was 56%. Total cecal aerobic bacteria count was significantly higher in cirrhotic rats than in control rats (p < 0.001). Cirrhotic rats with translocated bacteria had higher total aerobic intestinal counts than culture-negative MLN bacteria (p < 0.05). The prevalence of total intestinal bacterial overgrowth in cirrhotic animals was 67%, and 0% in control animals (p < 0.001). According to BT, total IBO was more frequent in cirrhotic rats with BT versus those without BT (93 vs. 33%) (p < 0.001). Of the translocating bacteria, 95.6% were found to be overgrown in the cecum. The small-intestinal transit was slower in cirrhotic rats (60.5 +/- 12.7 cm vs. 81.2 +/- 5.7 cm) than in control animals (p < 0.001). CONCLUSIONS: These results suggest that the increase of intestinal aerobic bacteria in experimental cirrhosis is associated with translocation. In addition, IBO is frequent in cirrhotic rats, and is supposed to play an important role in the development of BT. Impaired motility of the small intestine is a common feature in cirrhosis and may be implicated in the pathogenesis of IBO.

[Triple immunosuppressive therapy in the treatment of severe ulcerative colitis]. / Triple terapia inmunosupresora en el tratamiento de la colitis ulcerosa grave.

INTRODUCTION: Severe episodes of steroid-refractory ulcerative colitis (UC) were considered an indication for surgery until the introduction of new immunosuppressive agents such as cyclosporine. OBJECTIVES: 1) To confirm the efficacy of intravenous cyclosporine in inducing remission in severe episodes of steroid-refractory UC; 2) To analyze the efficacy of triple immunosuppressive therapy with cyclosporine, azathioprine and prednisone in the maintenance of remission induced by intravenous cyclosporine. PATIENTS AND METHOD: Fourteen patients diagnosed with a severe episode of steroid-refractory UC were treated with intravenous cyclosporine at a dose of 4 mg/kg/day. In all patients, after response was induced, this regimen was substituted by oral cyclosporine plus azathioprine at a dose of 2-2.5 mg/kg/day and decreasing doses of corticoids. Neoral cyclosporine was progressively reduced until discontinuation within 3 months, coinciding with a simultaneous decrease of oral steroids. RESULTS: All patients showed response to intravenous cyclosporine with a significant reduction in the Truelove index calculated before and after treatment. After remission was induced, all patients followed triple immunosuppressive therapy for 3 months. In the follow-up for a mean of 24 months (range: 14-34) only two patients required admission for a new episode of UC and colectomy was finally indicated in only one. None of the 14 patients treated with cyclosporine showed severe adverse effects attributable to the drug. CONCLUSIONS: Intravenous cyclosporine is a safe and effective alternative in the treatment of severe episodes of steroid-refractory UC. Early initiation of oral administration associated with azathioprine is useful in maintaining response, reducing subsequent relapses and the need for colectomy during the follow-up of these patients.

Involvement of the Fas system in liver allograft rejection.

OBJECTIVE: Recent studies suggest that apoptosis is an important mechanism of cell death in the rejection of liver allografts and that this process is mediated via Fas. The aim of this study was to analyze the expression of the Fas system during the liver allograft rejection and its evolution after treatment. METHODS: We evaluated 14 patients with liver allograft rejection before and after treatment. Fas immunostaining was performed by the labeled streptavidin-biotin peroxidase method using a 200-fold dilution of a monoclonal antibody. Assessment of apoptosis was determined by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) technique on deparaffined liver samples. Serum levels of soluble Fas antigen (sFas) were detected by an enzyme immunoassay procedure. Twelve liver transplant patients without allograft rejection were analyzed as a control group. RESULTS: The number of hepatocytes expressing Fas antigen, the percentage of apoptotic hepatocytes, and the sFas levels were higher in patients with liver allograft rejection than in controls (27.9+/-23.1% vs 1.4+/-1.2%, p < 0.001; 2.2+/-0.9% vs 1.0+/-0.1%, p = 0.02; 24.2+/-39.6 vs 2.8+/-4.0 IU/ml, p = 0.03, respectively). There was a correlation between the levels of sFas, AST (r = 0.86, p < 0.001), ALT (r = 0.78, p = 0.02), and gamma-globulin levels (r = 0.86, p < 0.001). After the rejection treatment we found a significant decrease in the Fas antigen expression (18.6+/-13.3%, p < 0.05), TUNEL index (0.2+/-0.4, p < 0.05), and levels of sFas (9.9+/-30.25 IU/ml, p = 0.005). CONCLUSIONS: 1) The demonstration of hepatocytes with Fas antigen expression and the labeling of the nuclei by the TUNEL assay suggest that apoptosis mediated by the Fas system plays a role in the pathogenesis of liver allograft rejection. 2) The Fas expression and the sFas levels decreased in patients with treatment response.

Apoptosis mediated by the Fas system in the fulminant hepatitis by hepatitis B virus.

The pathogenesis of the fulminant hepatitis B is poorly understood and both viral factors and the hosts immune response play a role. Previous studies in liver tissues of patients with chronic hepatitis B showed overexpression of Fas antigen and this was correlated with the activity of the hepatitis. The present study was done to determine the role of Fas in fulminant hepatitis B and the virological characteristics of hepatitis B infection. We studied three patients with fulminant hepatitis B. HBV-DNA was detected by dot-blot hybridization and polymerase chain reaction. The S and C gene were sequenced. Levels of serum soluble Fas antigen were detected by enzymoimmunoassays procedure. Apoptosis was determined by the TUNEL technique. Fas antigen expression was evaluated by a immunoperoxidase method. Ten healthy subjects acted as controls. The three patients showed a high expression of Fas antigen particularly among infiltrating lymphocytes; in these areas we also found many cells with in situ DNA nick labelling signals in the nuclei of most viable hepatocytes. Serum levels of soluble Fas antigen were higher in patients with fulminant hepatitis B than in controls. No specific genome mutations of hepatitis B virus were found. These data suggest that the Fas system involved in the liver injury of patients with fulminant hepatitis B.

Liver transplantation in a case of steatohepatitis and subacute hepatic failure after biliopancreatic diversion for morbid obesity.

BACKGROUND: Biliopancreatic diversion (BPD) was designed to avoid the serious complications of jejunoileal bypass (steatohepatitis and hepatic failure). Although this is today considered a safe and effective procedure, a few reports of patients who developed steatohepatitis and subsequently died in hepatic failure exist. METHODS: We report a morbidity obese patient who developed subacute hepatitis resulting in hepatic failure 1 year after BPD. RESULTS: Because of irreversible liver failure the decision to perform a liver transplantation was made. The patient underwent emergency liver transplant and lengthening of the common limb. The course of liver transplantation and the patient's recovery were uneventful. CONCLUSION: Severe liver disease may rarely follow BPD. Liver transplantation and lengthening of the common bowel may be performed to treat these patients.

Dendroaspis natriuretic peptide in hepatic cirrhosis.

OBJECTIVES: Dendroaspis natriuretic peptide (DNP) is a novel peptide that is structurally similar to atrial, brain, and C-type natriuretic peptides. Many natriuretic peptides are increased in hepatic cirrhosis, but the role of DNP in cirrhosis is unknown at present. The aim of the study was to investigate plasma levels of dendroaspis natriuretic-like immunoreactivity in cirrhosis. METHODS: We measured plasma concentrations of DNP by radioimmunoassay methods in 12 cirrhotic patients without ascites and 44 cirrhotic patients with ascites, and compared these values with 20 age-matched healthy subjects. Renal function, plasma cGMP concentration, plasma renin activity, and plasma endothelin concentration were measured in each patient. RESULTS: Patients without ascites had circulating levels of DNP similar to those of healthy subjects. By contrast, patients with ascites had increased circulating DNP levels compared to both patients without ascites and healthy subjects. In addition, circulating levels of DNP increased in relation to the severity of cirrhosis. Significant positive correlations were also found between DNP levels, endothelin concentrations, and plasma renin activity. CONCLUSIONS: The results of this study indicate that plasma DNP is increased in cirrhotic patients with ascites.

Involvement of the fas system in hepatitis C virus recurrence after liver transplantation.

To date, there have been no reports of the involvement of the Fas system in recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT). In 25 patients who underwent OLT for HCV-related liver cirrhosis, we evaluated the expression of the Fas antigen (FasAg) on hepatocytes, apoptic hepatocytes, and serum levels of soluble Fas (sFas). The level of HCV viremia and HCV genotype were determined by polymerase chain reaction. Serum sFas levels were determined by an enzyme immunoassay procedure. DNA fragmentation was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) technique on deparaffinized liver samples. FasAg expression was evaluated by an immunoperoxidase method. Sixteen patients had evidence of recurrent HCV disease. The number of hepatocytes expressing FasAg and the percentage of apoptotic hepatocytes was greater among patients who developed recurrent hepatitis than among those who did not (P <.01 and P <.0001, respectively). There was a correlation between hepatic expression of FasAg, intensity of lobular inflammation (P =.007), and TUNEL index (P <.001). The levels of sFas were greater among the patients with recurrent HCV hepatitis than those without recurrent hepatitis (P <.04). We conclude that (1) Fas expression is up-regulated in recurrent HCV after OLT and is related to the grading of liver disease; likewise, levels of sFas were greater in the patients with recurrent HCV hepatitis; and (2) the demonstration of hepatocytes with FasAg expression and the labeling of the nuclei by TUNEL assay suggest that hepatic apoptosis mediated by the Fas system may have a role in the pathogenesis of recurrent HCV hepatitis after OLT.