Successful clinical and virological outcomes of liver transplantation for HDV/HBV-related disease after long-term discontinuation of hepatitis B immunoglobulins.

BACKGROUND: Indefinite, long-term administration of hepatitis B immunoglobulins (HBIg), together with a third generation nucleos(t)ide analog (NA), is the currently recommended prophylactic strategy to prevent viral recurrence after liver transplantation (LT) for Hepatitis Delta virus (HDV)/Hepatitis B virus (HBV)-related disease. METHODS: We retrospectively analyzed the safety and long-term clinical and virological outcomes of a consecutive cohort of 16 patients (10 males, median age 64.5, range 41-75) transplanted for HDV/HBV-related cirrhosis at our Institution, who discontinued HBIg after a median of 24.5 months (range 15-116) after transplant. All patients continued prophylaxis with same NA used before LT. Recurrence of HDV/HBV infection was defined as reappearance of serum HDV-RNA with detectable serum HBsAg and/or HBV-DNA. RESULTS: The median follow-up after LT was 138 months (range 73-316) and 110 months (range 52-200) after HBIg withdrawal. All patients were HBsAg-positive, HBV-DNA negative, and anti-HDV positive at the time of LT and without coinfections with HCV or HIV. Patients were followed with biochemical and virological tests every 3-6 months after HBIg withdrawal. No recurrences of HDV/HBV infection or disease were observed during monoprophylaxis with NA. In addition, eight patients (50%) spontaneously developed anti-HBs titers above 10 IU/L at a median of 74 months (range 58-140) following HBIG discontinuation. CONCLUSIONS: HBIg withdrawal after LT is a safe and efficacious strategy in patients transplanted for HDV/HBV disease and is frequently associated with the spontaneous development of serological immunity against HBV. These data call for a revision of current prophylactic recommendations in this setting.

Feasibility and cost effectiveness of ambulatory laparoscopic cholecystectomy. A retrospective cohort study.

Ambulatory surgery is an efficient, safe and widely performed procedure; this study would shows the advantages of the ambulatory laparoscopic cholecystectomy procedure from the point of view of patients and the Hospital/National Health System. Materials and Methods: Single-center retrospective cohort study including 288 patients who underwent laparoscopic-cholecystectomy at **** from January 2016 to July 2018. Ambulatory LC were compared to well-matched inpatient procedures performed in the same study period. The primary endpoints was the 30-day readmission rate. Secondary endpoints were the discharge rate in the ambulatory group, the post-operative complications rate and cost effectiveness. Results: 120/288 (41.7%) patients underwent ambulatory laparoscopic cholecystectomy. Thirty-two (26.7%) patients who underwent ambulatory laparoscopic cholecystectomy had major preoperative comorbidities and 35 (29.2%) had undergone prior abdominal surgery. The readmission rates for ambulatory patients and inpatients were 0.8% and 1.7% (p = 0.56), respectively; 104 (86.7%) ambulatory patients were discharged successfully on the same day. The two groups showed the same post-operative complication rate (p = 0.40). Ambulatory procedures resulted in related cost savings of more than 300% for the hospital and a remarkable financial benefit for the National Italian Healthcare System, accounting for savings exceeding € 27 000 per year. Conclusions: Ambulatory laparoscopic cholecystectomy is safe and cost effective. Since a third of ambulatory patients showed comorbidity or previous abdominal surgery, we believe that this procedure may be performed safely in a tertiary HPB centre, even in complex patients.

Serum Levels of Granulocyte-Macrophage-colony-stimulating Factor and Stem-cell Factor During Liver Regeneration after Partial Hepatectomy in Humans.

BACKGROUND: Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). AIM: To evaluate the serum changes of GM-CSF and SCF in patients undergoing surgical resection for liver tumor, in the regenerative phase after surgery in order to identify the possible relationship with the patient, tumor or surgical variables. METHODS: Thirty-two consecutive patients (50% male, median age 66), undergoing hepatic resection of liver neoplasm, were evaluated. The liver tumor was Hepatocellular Carcinoma (HCC) in 44% of cases. Other tumors were cholangiocarcinoma and metastasis. Serum levels of GM-CSF and SCF were assessed at baseline and 2 days, 7 days and 4 weeks after surgery. Personal and clinical patient data were also recorded. The statistical analysis was carried out using t-test for unpaired data or ANOVA (repeated measure) for continuous variables and Fisher test for discrete variables. RESULTS: GM-CSF levels remained constant after surgery and were compared to baseline values. SCF levels, on the other hand, increased during the time, after surgery. The evaluation of SCF levels (fold increase) according to surgical, patient and tumor variables evidenced some differences. At day 7 and week 4, SCF levels were statistically increased: i) in patients undergoing a large resection in comparison with others (p<0.05); ii) in patients non-cirrhotic in comparison with cirrhotic ones (p=0.02) and finally; iii) in patients with non-HCC tumor in comparison with HCC ones (p=0.02). CONCLUSION: During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.

Combined liver transplantation and sleeve gastrectomy for end-stage liver disease in a bariatric patient: First European case-report.

INTRODUCTION: Obesity is a contributor to the global burden of chronic diseases, including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH). NASH cirrhosis is becoming a leading indication for liver transplant (LT). Obese transplanted patients have higher morbidity and mortality rates. One strategy, to improve the outcomes in these patients, includes bariatric surgery at the time of LT. Herein we report the first European combined LT and sleeve gastrectomy (SG). CASE PRESENTATION: A 53 years old woman with Hepatocellular carcinoma and Hepatitis C virus related cirrhosis, was referred to our unit. She also presented with severe morbid obesity (BMI 40kg/m2) and insulin-dependent diabetes. Once listed for LT, she was assessed by the bariatric surgery team to undergo a combined LT/SG. At the time of transplantation the patient had a model for end-stage liver disease calculated score of 14 and a BMI of 38kg/m2. The LT was performed using a deceased donor. An experienced bariatric surgeon, following completion of the LT, performed the SG. Operation time was 8h and 50min. The patient had an uneventful recovery and is currently alive, 5 months after the combined procedure, with normal allograft function, significant weight loss (BMI=29kg/m2), and diabetes resolution. CONCLUSION: Despite the ideal approach to the management of the obese LT patients remains unknown, we strongly support the combined procedure during LT in selected patients, offering advantages in terms of allograft and patient survival, maintenance of weigh loss that will ultimately reduce obese related co-morbidities.

Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen-positive liver transplant recipients after longterm minimal immunosuppression.

Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis-free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD.

Different expression of VEGF and EGFL7 in human hepatocellular carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of several angiogenic factors expressed in cirrhosis and during progression to malignancy, that seem to play a major role in hepatocellular carcinoma development. Lately, another angiogenic factor, epidermal growth factor-like domain multiple 7 (EGFL7), has attracted interest due to its possible relationship with hepatocellular carcinoma metastasis. AIMS: To evaluate expression of VEGF and EGFL7 in human hepatocellular carcinoma, compared to corresponding cirrhotic surrounding tissue. METHODS: Tumoural and cirrhotic tissue was harvested from 12 consecutive patients undergoing surgical resection. VEGF and EGFL7 were assessed by immunofluorescence and quantitative reverse transcriptase-polymerase chain reaction, compared with normal controls. RESULTS: Both angiogenic factors were over-expressed in cirrhotic livers compared to normal controls. VEGF and EGFL7 expressions did not differ according to disease aetiology, nodule size or other clinical variables. While VEGF expression was constant, regardless of tumour differentiation stage and unchanged compared to surrounding cirrhotic tissue, EGFL7 expression increased in less differentiated hepatocellular carcinoma. CONCLUSIONS: The preferential expression of EGFL7 in less differentiated hepatocellular carcinoma compared to VEGF, suggests a possible important role of this angiogenic factor in a later oncogenic and infiltrative/metastatic phase.

The efficacy and safety of mammalian target of rapamycin inhibitors ab initio after liver transplantation without corticosteroids or induction therapy.

BACKGROUND: Mammalian target of rapamycin inhibitors have been used along with corticosteroids and/or induction therapy immediately after liver transplantation. Our aim was to assess the safety and tolerability of everolimus ab initio after liver transplantation without corticosteroids or induction, as well as efficacy in terms of liver function, rejection and graft loss. METHODS: A retrospective observational study of 50 adult patients (86% males, median age 54 years, range 25-68) who were liver transplanted between 2009 and 2013 and followed for 12 months. All recipients received everolimus plus low doses of calcineurin inhibitors (n=38) or mycophenolate (n=12) without corticosteroids and/or induction from the day of transplant. RESULTS: The overall patient and graft survival was 80%. Liver function was stable during one year follow-up. No rejections or graft loss were observed. Only five patients (10%) required therapy for onset dyslipidemia. CONCLUSION: Everolimus-based immunosuppression regimen without corticosteroids and/or induction immediately after liver transplantation seems to be safe and effective when administered with low doses of calcineurin-inhibitor or mycophenolate; although these findings require further investigation, these regimens could avoid adverse effects of standard immunosuppression regimens with higher doses.

Side-to-side caval anastomosis in a patient receiving a liver graft from a marginal donor with situs inversus totalis.

INTRODUCTION: The donor situs inversus totalis status was considered an absolute contraindication to liver transplantation due to the technical difficulties involved. Only in recent years has a very young deceased donor with situs inversus totalis been considered as a potential donor. PRESENTATION OF CASE: We herein report a single case of 57-year-old male patient with hepatocellular carcinoma who received a liver transplantation from a 73-year-old woman with situs inversus totalis. Liver was implanted using a 1992-Belghiti piggyback technique positioning the larger hemiliver in the left upper quadrant and the left in the liver fossa. We assisted a good graft reperfusion without surgical or anesthetic problems. His hospital stay was relatively uneventful and he was discharged from hospital on postoperative day 7. At 8 months of follow-up the patient is alive and in good clinical condition. DISCUSSION: The donor situs inversus totalis does not require any modification of transplant procedure if the donor-recipient size match permits a comfortable placement of the graft in a standard anatomical position. To the best of our knowledge, this is the first case of liver transplantation with a graft from a "marginal" donor with situs inversus totalis using a 1992-Belghiti piggyback technique. CONCLUSION: The donor situs inversus totalis status should not be considered a contraindication for LT and the piggyback technique should be considered the surgery of choice.

One-shot versus multidose perioperative antibiotic prophylaxis after kidney transplantation: a randomized, controlled clinical trial.

BACKGROUND: There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for renal transplant recipients. Some studies have reported that irrigation of the wound at the time of closure without systemic antibiotics may suffice to minimize the risk for surgical site infection (SSI), but many centers still use long-term, multidose regimens in which antibiotics are administered until removal of foreign bodies occur, such as the urethral catheter, drain and central line. METHODS: We designed a prospective, randomized, multicenter, controlled trial to compare a single dose versus a multidose regimen of systemic antibiotic prophylaxis in adult, nondiabetic, non-morbidly obese patients undergoing renal transplantation. The primary endpoint was the incidence of SSI; the assessment of other infection in the first postoperative month was the secondary endpoint. RESULTS: Two hundred five patients were enrolled and randomized to receive either a single (n = 103) or multidose antibiotic regimen (n = 102) for prophylaxis. The incidences of SSI and urinary tract infection were similar in both groups. CONCLUSION: As the dramatic increase in antibiotic resistance has mandated the implementation of global programs to optimize the use of antibiotic agents in humans, we believe that the single dose regimen is preferred, at least in nondiabetic, non-morbidly obese, adult renal transplant recipients.

Relationship between GH/IGF-1 axis, graft recovery, and early survival in patients undergoing liver transplantation.

BACKGROUND: High levels of IGF-1 have been reported in patients with initial poor function of the graft after liver transplantation (LT). Correlation with other clinical variables or early survival has not been extensively investigated. AIM: To evaluate the GH/IGF-1 profile as a function of liver recovery and patients' early survival after LT. METHODS: 30 transplanted patients (23 survivors and 7 nonsurvivors), were retrospectively enrolled in the study. GH and IGF-1 serum levels were assessed at baseline, graft reperfusion, and 1, 7, 15, 30 , 90, and 360 days after LT. Individual biochemical variables were also recorded. RESULTS: After grafting, IGF-1 in blood linearly correlated with cholesterol (r = 0.6, P = 0.001). IGF-1 levels from day 15 after surgery were statistically higher in survivors as compared to nonsurvivors. ROC curves analysis identified an IGF-1 cut-off >90 µg/L, from day 15 after surgery, as a good predictor of survival (sensitivity 86%, specificity 95%, and P < 0.001). CONCLUSIONS: After LT, GH levels correlate with the extent of cytolysis, while IGF-1 is an indicator of liver synthetic function recovery. IGF-1 levels >90 µg/L (day 15-30) seem to be an indicator of short-term survival.

Vitamin D3 modulates T lymphocyte responses in hepatitis C virus-infected liver transplant recipients.

BACKGROUND: Aim of the present study was to investigate whether 1,25(OH)(2)D(3) (Vitamin D3) modulates T lymphocyte functions in patients transplanted for hepatitis C virus-related cirrhosis. METHODS: Sixteen patients and ten healthy subjects were investigated. T lymphocytes were activated in vitro in the presence or absence of Vitamin D3 and then the proliferative response and IFN-γ and TNF-α production were assessed. RESULTS: Vitamin D3 potently reduced T-lymphocyte proliferation in a dose-related fashion. Similarly, FACS analysis and ELISA testing demonstrated that Vitamin D3 significantly decreased the response frequency and the response intensity of IFN-γ and TNF-α production in the whole CD3-positive T lymphocyte population as well as in "naive" CD4+ CD45RA+ and "memory" CD4+ CD45RO+ T lymphocyte subsets. The inhibitory effect of Vitamin D3 on T-cell proliferation and cytokine production was not different between patients and controls. No toxic effects were exerted by Vitamin D3 even at the higher concentration used (10nM). Finally, no statistically significant correlation was found between 25(OH)D serum levels and the proliferative response or cytokine production of T lymphocytes from transplanted patients. CONCLUSIONS: This study demonstrates that in patients transplanted for hepatitis C virus-related cirrhosis Vitamin D3 modulates T lymphocyte activation, and provides a rationale for the evaluation of this compound as an immunosuppressive agent in liver-transplanted patients.

Is it time to extend liver acceptance criteria for controlled donors after cardiac death?

BACKGROUND: Donation after cardiac death (DCD) has reemerged as potential way to increase donor liver availability. Earlier, programs with DCD liver transplantation used conservative donor criteria to allow safe results. Successful initial outcomes allowed extended DCD criteria to address transplant demand. METHODS: A total of 63 DCD liver grafts were used during the study period in carefully selected recipients. These were divided into two groups: "Standard" DCD within conservative criteria (n=33; age ≤60 years, body mass index <30 kg/m(2), donor warm ischemia time ≤30 min, and cold ischemia time ≤8 hr) and "Extended" DCD beyond these criteria (n=30). We compared donor and recipient characteristics and postoperative outcomes, including patient and graft survival. RESULTS: Both groups had satisfactory initial function; liver graft function at 1, 7, and 30 days after liver transplantation were similar. Median follow-up period was 25 and 18.5 months for Standard and Extended criteria DCD grafts, respectively, with 1-year patient and graft survival of 88% and 82% for the Standard group vs. 90% and 90% for the Extended. Overall, 8 of 63 (13%) patients developed biliary complications; however, the incidence was not different between the Standard and Extended groups. Seven early deaths occurred, four and three in the Standard and Extended groups, respectively. CONCLUSIONS: Recipients of DCDs beyond conventional acceptance criteria have equivalent early outcomes to standard DCD grafts. With careful selection of donors and recipients, these grafts can be safely used to expand the donor pool.

Long-term, maintenance MMF monotherapy improves the fibrosis progression in liver transplant recipients with recurrent hepatitis C.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

Preoperative localisation and surgical management of insulinoma: single centre experience.

BACKGROUND: The majority of insulinomas are benign, small and intrapancreatic. Preoperative localisation is important to plan the surgical management. METHODS: We retrospectively analysed our data on the preoperative imaging, type of surgery and histopathological features of the operated patients with an insulinoma from January 1993 to March 2010. Univariate and multivariate analyses were performed to detect the predictive factors for survival following surgery. RESULTS: Forty patients were operated on for insulinoma, of which 33 were benign and 7 were malignant. The sensitivity of preoperative computed tomogram scan, magnetic resonance imaging and endoscopic ultrasound, for localising the lesions was 62, 82 and 94%, respectively. Enucleation was performed in 21 (52.5%) patients, and remaining had pancreatic resection. Hepatic resection was performed in 2 and liver transplantation in 1 patient. Morbidity and perioperative mortality was 17 (42.5%) and 1 (2.7%), respectively. The overall 5- and 10-year survival was 89 and 86.5%, respectively. The presence of metastases was found to be an independent predictor of poor survival on multivariate analysis. CONCLUSION: Preoperative computed tomogram/magnetic resonance imaging and endoscopic ultrasound are sensitive in localizing the majority of insulinomas. Surgery offers a good long-term survival, even in patients with malignant insulinoma.

Safety of complete and sustained prophylaxis withdrawal in patients liver-transplanted for HBV-related cirrhosis at low risk of HBV recurrence.

BACKGROUND & AIMS: HBV reactivation after liver transplantation may be related to persistence of covalently closed circular (ccc) DNA. We investigated the safety of HBV prophylaxis withdrawal in selected HBV transplanted patients. METHODS: Thirty patients transplanted 64-195months earlier (23 males, median age 56yrs), HBsAg-positive, HBeAg, and HBV-DNA negative at transplant (43% HCV/HDV co-infected), with undetectable intrahepatic total and ccc-DNA were enrolled. All patients underwent HBIg withdrawal and continued lamivudine with monthly HBsAg and HBV-DNA monitoring and sequential liver biopsies. Those with confirmed intrahepatic total and ccc-DNA undetectability 24weeks after stopping HBIg, also underwent lamivudine withdrawal and were followed-up without prophylaxis. RESULTS: Twenty-five patients did not exhibit signs of HBV recurrence after prophylaxis withdrawal (median follow-up 28.7months, range 22-42). Five patients became HBsAg-positive: one early after HBIg withdrawal, the other four after HBIG and lamivudine withdrawal. None of these patients experienced clinically relevant events. In the first patient, HBIg were reinstituted with prompt HBsAg negativization. Of the other four, one remained HBsAg-positive with detectable HBV-DNA and mild ALT elevation and was successfully treated with tenofovir. In the remaining three, HBsAg positivity was transient and followed by anti-HBs seroconversion, thus no antiviral treatment was needed. CONCLUSIONS: Patients with undetectable HBV viremia at transplant and no evidence of intrahepatic total and cccDNA may safely undergo cautious weaning of prophylaxis, showing low rate of HBV recurrence after a 2 year follow-up. Undetectability of intrahepatic ccc-DNA may help to identify patients at low-risk of recurrence, yet studies with longer follow-up are needed.

Detection of pancreatic adenocarcinoma using circulating fragments of fibrinogen.

BACKGROUND: There is an urgent need for biomarkers to detect pancreatic cancer in the early, potentially curable, stages. METHODS: We have used SELDI profiling to analyze serum from 75 patients with pancreatic cancer and 61 patients with nonmalignant pancreaticobiliary diseases. RESULTS: A peak in the SELDI spectra corresponding to a 53 residue fragment of the α-chain of fibrinogen is remarkably elevated in approximately 50% of the cancer patients. In addition, fibrinogen degradation products were measured using the DR-70 assay. The areas under the receiver operating characteristic curves for the SELDI-detected fibrinogen fragment, DR-70 and CA19-9 were 0.65, 0.75 and 0.86, respectively. Class prediction models using combinations of these markers did not increase the area under the receiver operating characteristic curve compared with CA19-9. The novel fibrinogen fragment was not elevated to the same extent in other malignancies but was elevated in some patients with benign pancreatic disease. CONCLUSION: Both the SELDI-detected fragment of fibrinogen and DR-70 are significantly elevated in the serum of pancreatic cancer patients. However, they do not seem to improve pancreatic cancer detection over CA19-9 alone.

One-year vaccination against hepatitis B virus with a MPL-vaccine in liver transplant patients for HBV-related cirrhosis.

Conflicting results have been reported on vaccination against hepatitis B virus (HBV) as a prophylaxis against viral recurrence after liver transplantation. We investigated the efficacy of 1-year, monthly vaccination using an adjuvant 3-deacylated monophosphoryl-lipid-A (MPL) recombinant S vaccine initially administered together with hepatitis B immunoglobulins (HBIg) in 18 patients transplanted for HBV-related cirrhosis. All received 12 vaccine doses (HBsAg, 20 mcg plus MPL, 50 mcg): the initial six doses (phase I) were administered within 7days after intravenous HBIg (2000IU), while the last 6 (phase II) following HBIg withdrawal. All patients received lamivudine during the study. Anti-HBs titers were determined before each dose and then for 1year after vaccination. After phase I anti-HBs titers were greater than 100IU/l in all patients and in three (16.6%) were greater than 500IU/l. After phase II 10 patients (55.5%) achieved anti-HBs titers greater than 100IU/l and five (27.7%) greater than 500IU/l. One year after vaccination eight patients (44.4%) maintained anti-HBs titers greater than 100IU/l, with a median titer of 234IU/l (102-1205), and 2 (11.1%) greater than 500IU/l. One-year extended monthly vaccination with a MPL-adjuvant recombinant vaccine induces a sustained protective anti-HBs response in approximately half of transplant recipients.

Benign disease and unexpected histological findings after pancreaticoduodenectomy: the role of endoscopic ultrasound fine needle aspiration.

INTRODUCTION: We assessed the incidence and outcome of pancreaticoduodenectomy for patients with a pre-operative benign diagnosis and in patients who had an unexpected diagnosis of benign disease following resection. We have also compared how the introduction of endoscopic ultrasound fine needle aspiration (EUS-FNA) has altered our pre-operative assessment. PATIENTS AND METHODS: Between January 1997 and April 2006, 499 patients underwent pancreaticoduodenectomy at the Queen Elizabeth Hospital. Data were collected prospectively. A further 85 patients between 2006 and 2008 had a different diagnostic approach (after imaging these patients have been also studied by EUS-FNA). RESULTS: Overall, 78 (15.6%) patients had no malignant disease on final histology. Out of 459 patients who underwent pancreaticoduodenectomy for presumed malignancy, 49 (10.6%) had benign disease (sensitivity, 97%; positive predictive value, 89%). In a further 40 patients with a pre-operative benign diagnosis, we found 11 cases (27%) of malignancy (sensitivity, 37%; negative predictive value, 72%). Following the introduction of EUS-FNA, the sensitivity and specificity of the diagnostic work were 92% and 75%, respectively (positive predictive value, 93%; negative predictive value, 63%). The median follow-up was 35 months (range, 1-116 months). CONCLUSIONS: Prior to the introduction of EUS-FNA, a significant number of patients, in whom pancreaticoduodenectomy is carried out for suspected benign disease, turn out to have an underlying malignancy. The use of EUS-FNA has improved the specificity of diagnostic work-up.

Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis.

BACKGROUND: Life-long prophylaxis against HBV recurrence is recommended in patients transplanted for HBV-related disease. The risk of HBV reactivation is due to persistence of covalently closed circular (ccc) DNA in hepatocytes. Whether cccDNA persists in livers of long-term transplant survivors who received conventional prophylaxis is unknown. AIM: To investigate the presence of intrahepatic total and cccDNA in transplanted patients with no evidence of biochemical markers of HBV recurrence. METHODS: Intrahepatic total and cccDNA were assessed using sensitive nested and real-time PCR from 44 HBsAg-positive patients (75% male; mean age 55.2+/-8.9 years) who had undetectable serum HBV-DNA at transplant. The mean follow-up after transplant was 88.3 months (range, 18-159). RESULTS: One patient underwent HBV recurrence after transplant and was the only who tested positive for both intrahepatic total HBV-DNA and cccDNA. Of the 43 patients negative for all serological markers of HBV infection, only 2 tested positive for intrahepatic total HBV-DNA, but none for cccDNA. CONCLUSIONS: Most patients with undetectable HBV-DNA at transplant, who received conventional HBV prophylaxis, have no evidence of intrahepatic total HBV-DNA and cccDNA. cccDNA should be considered a new additional diagnostic tool, also to identify patients at low risk of HBV recurrence after liver transplantation.