The role of HBIG in real life for patients undergoing liver transplantation due to HDV-related cirrhosis.

Recommended post-liver transplant (LT) prophylaxis in patients with hepatitis delta includes a nucleos(t)ide analogue (NA) and anti-hepatitis B immunoglobulin (HBIG) indefinitely. We analysed the use of HBIG in real-life clinical practice and its impact on HBV/HDV recurrence in 174 HDV-related LT patients from 10 Spanish liver transplant centres (1988-2018). Median post-LT follow-up was 7.8 (2.3-15.1) years and patient survival at 5 years was 90%. Most patients (97%) received HBIG in the immediate post-LT, but only 42% were on HBIG at the last control. Among those discontinuing HBIG, the median time on treatment was 18 (7-52) months. Post-LT HBsAg+ was detected in 16 (9%) patients and HBV-DNA in 12 (7%). Despite HBsAg positivity, HDV recurrence was reported only in three patients (1.7%), all of whom were not receiving NA and had discontinued HBIG. Our data suggest that a finite HBIG prophylaxis in HDV-LT is feasible, especially if high-barrier NAs are used.

Sinusoidal obstruction syndrome as a manifestation of acute antibody-mediated rejection after liver transplantation.

Antibody-mediated rejection (AMR) after liver transplantation is uncommon but, when present, manifests as graft dysfunction. We report the case of a 54-year-old woman who developed portal hypertension with pleural effusion and ascites secondary to sinusoidal obstruction syndrome (SOS) due to acute AMR following an ABO-matched liver transplantation for autoimmune cirrhosis and hepatocellular carcinoma. Initial immunosuppression comprised basiliximab, decreasing prednisone, tacrolimus, and mycophenolate mofetil. After 1 month, she presented with the massive pleural effusion, slight ascites, and normal liver tests. After excluding common causes of pleural effusion, we performed a liver biopsy that showed atypical rejection with the involvement of large centrilobular veins partially occluded by marked endotheliitis and lax fibrosis suggestive of SOS. Direct immunofluorescence study of C4d showed diffuse endothelial sinusoidal staining, and de novo donor-specific anti-human leukocyte antigen antibodies were detected in his blood. Thus, we diagnosed AMR focused on centrilobular veins and initiated treatment with defibrotide, steroid pulses, and diuretics. However, this was ineffective, and the pleural effusion only resolved when plasmapheresis and intravenous immunoglobulin were started. This case shows that AMR can cause SOS with portal hypertension and present with a pleural effusion, and as such, it should be suspected after excluding other more common causes of effusion.

Adoption of a novel smart mobile-health application technology to track chronic immunosuppression adherence in solid organ transplantation: Results of a prospective, observational, multicentre, pilot study.

BACKGROUND: Low adherence to chronic immunosuppression is associated with suboptimal transplantation outcomes. Mobile-health technology is a promising tool to monitor medication adherence, but data on patient engagement to these tools are lacking. METHODS: Prospective, observational, multicenter, 2-phase trial in kidney and liver transplant recipients, investigating the degree of engagement to TrackYourMed® (TYM), a novel m-Health technology with a QR code-scan app to track immunosuppression adherence and its association with drug monitoring. RESULTS: Out of 204 consecutive transplant patients, 90 patients were eligible to participate. 61 (68%) used TYM regularly, 21 (23%) never or barely used it, 5 (5.5%) were irregular users, and 3 (3.3%) were lost to follow-up. 6-month total correct intakes (CIN) ranged between 69%-76%, 12%-19% intakes were out-of-time (OUT), and 9%-12% were missed (MIS). Notably, a rate of intakes out of the scheduled time higher than 20% in the 6 days prior to blood immunosuppressant trough levels was associated with a higher intra-patient variability (17 IQR 13-21% vs. 29 IQR 23%-36%, p = .001), and with a higher dose-adjustment (p < .001). At 1 year, 53(59%) patients were still active users of TYM. CONCLUSIONS: Implementing m-Health technologies promoting immunosuppression adherence may be useful for a relevant number of transplant patients and help transplant physicians identifying erratic immunosuppression adherence.

Significant decrease in the prevalence of hepatitis C infection after the introduction of direct acting antivirals.

BACKGROUND AND AIM: Accurate information on the epidemiology of hepatitis C and B infection is mandatory to establish a national/regional plan. We aim to update the prevalence of hepatitis C and B infection in Catalonia using point-of-care tests to analyze the risk factors related and to implement a linkage-to-care circuit. METHODS: This is a community-based study. A random list of adult individuals was retrieved from censuses of primary care centers. Point-of-care tests for anti-hepatitis C virus (HCV) and HBV surface antigen (HBsAg) and a questionnaire for risk factor assessment were performed. Positive results were validated and a circuit for linkage-to-care was established. RESULTS: A total of 3328 individuals were included. The anti-HCV and HBsAg overall prevalence were lower than expected [1.02%, 95% confidence interval (CI) 0.65-1.39; and 0.52%, 95% CI 0.26-0.77, respectively]. Anti-HCV positive subjects were mostly (88%) autochthonous. The prevalence increased with age; only 12% were under age 40. The associated risk factors were drug use, blood transfusion, relative with HCV, and diabetes. Notably, the prevalence of active infection was only 0.49% (95% CI 0.23-0.74), 40% less than previously reported, reflecting the impact of direct acting antiviral therapy. Differently, HBsAg positive subjects were mostly foreign migrants (53%) with no other risk factors. Despite the implementation of a linkage-to-care circuit, one third of HBsAg positive subjects were lost. CONCLUSIONS: The prevalence of HCV infection was lower than previously reported, showing a strong impact of direct acting antiviral therapy in the last years. Because of hepatitis B universal vaccination, HBV infection in Catalonia is mainly associated with migrant population. Linkage-to-care in patients with hepatitis B was challenging and warrants additional efforts.

Short- and long-term outcomes of arterial reconstruction on recipient splenic artery in adult liver transplantation. Single-center prospective study 25 years after first description.

Several techniques have been proposed for liver transplantation with inadequate hepatic artery (HA) anastomosis. We aimed to analyze outcomes of arterial reconstruction with the splenic artery (SA). This was a prospective study of our experience with recipients who underwent arterial anastomosis on the SA compared with patients who underwent standard HA. We included 54 patients in the SA group and 1405 in the HA group. Patients in SA group were more frequently retransplantation (31% vs. 8%; P = 0.001), required more transfusion (11 ± 12 vs. 6 ± 9.9 PRC; P = 0.001), had longer surgeries (424 ± 95 vs. 394 ± 102 min; P = 0.03), and longer hospital stays (28 ± 29 vs. 20 ± 18 days; P = 0.002). There were no differences in vascular and biliary complications (15% and 7%; P = 0.18; and 32% and 23%; P = 0.32), primary dysfunction (11% and 9%; P = 0.74), reoperation (12% and 10%; P = 0.61), postoperative mortality (13% and 7%; P = 0.12) and 5 years survival (66% vs. 63%; P = 0.71). Following primary transplantation, there were no differences. The outcomes of arterial reconstruction using the recipients' SA in adult liver transplantation are comparable to those for standard HA reconstruction after a first transplant.

The efficacy of direct anti-HCV drugs improves early post-liver transplant survival and induces significant changes in waiting list composition.

BACKGROUND & AIMS: The efficacy of direct-acting antivirals (DAAs) has dramatically changed the prognosis of patients with chronic hepatitis C. We aimed to evaluate the impact of DAA therapy on the composition of the liver transplant (LT) waiting list and the early post-transplant survival. METHODS: We evaluated all patients admitted to the waiting list for a primary LT between 1st January 2008 and 31st of December 2016 in Catalonia, Spain. Time span was divided into two periods according to the availability of different antiviral therapies: 2008-2013 (interferon-based therapies) and 2014-2016 (DAA). Changes in the indications of LT and the aetiology of liver disease, as well as post-LT patient survival, were evaluated according to the year of inclusion and transplantation, respectively. RESULTS: We included 1,483 patients. Admissions in the waiting list for hepatitis C virus (HCV)-related liver disease decreased significantly, from 47% in 2008-2013 to 35% in 2014-2016 (p <0.001), particularly because of a reduction in patients with decompensated cirrhosis. In contrast, NASH-related inclusions increased from 4% to 7% (p = 0.003). Three-year post-LT patient survival increased significantly in the second period in the whole cohort (82% vs. 91%, p = 0.002), because of better survival in anti-HCV positive patients (76% vs. 91%, p = 0.001), but not in anti-HCV negative patients (88% vs. 91% p = 0.359). Anti-HCV positive serology, the time period of 2008-2013 and higher donor age were independently associated with post-LT mortality in the whole cohort; while time period and donor age were independently associated with post-LT mortality in anti-HCV positive recipients. CONCLUSIONS: The high efficacy of DAAs is associated with significant changes in the composition of the LT waiting list and, more importantly, results in improved post-transplant survival. LAY SUMMARY: The efficacy of the new direct-acting antivirals is associated with a significant improvement in survival of patients undergoing liver transplantation because of hepatitis C virus-related liver disease. In addition, it has decreased the number of patients with hepatitis C that need a liver transplant.

Treatment of hepatitis C virus infection in patients with cirrhosis and predictive value of model for end-stage liver disease: Analysis of data from the Hepa-C registry.

Direct-acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus infection, including those with compensated cirrhosis. However, fewer data are available in patients with more advanced liver disease. Our retrospective, noninterventional, national, multicenter study in patients from the Spanish Hepa-C registry investigated the effectiveness and safety of interferon-free DAA regimens in patients with advanced liver disease, including those with decompensated cirrhosis, in routine practice (all currently approved regimens were registered). Patients transplanted during treatment or within 12 weeks of completing treatment were excluded. Among 843 patients with cirrhosis (Child-Turcotte-Pugh [CTP] class A, n = 564; CTP class B/C, n = 175), 90% achieved sustained virologic response 12 weeks after treatment (SVR12). Significant differences in SVR12 and relapse rates were observed between CTP class A and CTP class B/C patients (94% versus 78%, and 4% versus 14%, respectively; both P < 0.001). Serious adverse events (SAEs) were more common in CTP class B/C versus CTP class A patients (50% versus 12%, respectively; P < 0.001). Incident decompensation was the most common serious adverse event (7% overall). Death rate during the study period was 16/843 (2%), significantly higher among CTP class B/C versus CTP class A patients (6.4% versus 0.9%; P < 0.001). Baseline Model for End-Stage Liver Disease (MELD) score alone (cut-off 18) was the best predictor of survival. CONCLUSION: Patients with decompensated cirrhosis receiving DAAs present lower response rates and experience more SAEs. In this setting, a MELD score ≥18 may help clinicians to identify those patients with a higher risk of complications and to individualize treatment decisions. (Hepatology 2017;65:1810-1822).

Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C.

BACKGROUND & AIMS: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. METHODS: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. RESULTS: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004). CONCLUSIONS: Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy. LAY SUMMARY: Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

BACKGROUND AND AIMS: Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. METHODS: This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. RESULTS: Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. CONCLUSIONS: In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.

Technical options for outflow reconstruction in domino liver transplantation: A single European center experience.

Venous outflow is critical to the success of liver transplantation (LT). In domino liver transplantation (DLT), the venous cuffs should be shared between the donor and the recipient, and the length can be compromised. The aim of this study was to describe and compare the technical options for outflow reconstruction used at our institution. This was a retrospective analysis of 39 consecutive DLT recipients between January 1997 and May 2013. Twenty-seven men and 12 women (mean age, 61.8 ± 4.3 years) underwent LT and consented to receive a liver from a donor with familial amyloid polyneuropathy (FAP). The main indications were hepatocellular carcinoma and hepatitis C virus cirrhosis. All recipients underwent transplantation by a piggyback technique. Liver procurement in the FAP donors was performed with the classic technique in 22 patients and with the piggyback technique in the last 17. In these latter cases, for vascular outflow reconstruction, a cadaveric venous graft was interposed between the hepatic vein (HV) stump of the FAP liver and the recipient HV in 11 cases (28%). Since 2011, we have employed arterial grafts to be interposed between the vessels stumps: a tailored arterial graft in 5 patients and an aortic graft in 1 case. There was no postoperative mortality. Arterial and portal complications presented in 2 (5.1) and 4 patients (10.3), respectively. Postoperative outflow complications (post-LT subacute Budd-Chiari syndrome) occurred in 4 patients, and all of them had received a venous interposed graft for reconstruction. The incidence of outflow complications tended to be higher among patients with venous grafts than those with arterial graft interposition. Overall patient survival at 1, 3, 5, and 10 years was 97%, 79%, respectively. Arterial grafts constitute a feasible and safe option for vascular outflow reconstruction in DLT because they are associated with a relatively low incidence of complications. The recently proposed Bellvitge arterial graft technique should be added to the current range of available surgical modalities.

Outcomes of liver transplant with donors over 70 years of age.

UNLABELLED: Organ shortage has forced transplant teams to progressively expand the acceptance of marginal donors. METHODS: We performed a comparative analysis of the post-transplant evolution depending on donor age (group I: less than 70 years old (n=474) vs. group II: 70 or more years old [n=105]) over a 10 year period (2002-2011). RESULTS: Donors over 70 years old were similar to donors less than 70 years old in terms of ICU stay, gender, weight, laboratory results, and use of vasoactive drugs. However, the younger donor group presented with cardiac arrest more often (GI: 14 vs. GII: 3%, P=.005). There were no differences in initial poor function (GI: 6% vs. GII: 7,7%; P=.71), ICU stay (GI: 2.7±2 vs. GII: 3.3±3.8, P=.46), hospital stay (GI: 13.5±10 vs. GII: 15.5±11, P=.1), or hospital mortality (GI: 5.3 vs. GII: 5.8%, P=.66) between receptors of more or less than 70 year old grafts. After a median follow up of 32 months, no differences were found in the incidence of biliary tract complications (GI: 17 vs. GII: 20%, P=.4) or vascular complications (GI: 11 vs. GII: 9%, P=.69). The actuarial 5 year survival was similar for both study groups (GI: 70 vs. GII: 76%, P=.54). CONCLUSIONS: In our experience, the use of grafts from donors older than 70 years, when other risk factors are avoided (cold ischemia, steatosis, sodium levels), does not worsen the results of liver transplantation on the short or long term.

[Early detection, prevention and management of renal failure in liver transplantation]. / Detección precoz, prevención y manejo de la insuficiencia renal en el trasplante hepático.

Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function.

Improvement of quality of care provided to outpatients with hepatic cirrhosis after an educational intervention.

OBJECTIVE: A set of indicators has been reported to measure the quality of care for cirrhotic patients, and previously published studies report variable adherence rates to these indicators. This study aimed to assess the quality of care provided to cirrhotic outpatients before and after an educational intervention by determining its impact on adherence to quality indicators. METHODS: We conducted a quasi-experimental, cross-sectional study including 324 cirrhotic patients seen in 2017 and 2019 at a tertiary teaching hospital in Spain. Quality indicators were assessed in five domains: documentation of cirrhosis etiology, disease severity assessment, hepatocellular carcinoma (HCC) screening, variceal bleeding prophylaxis, and vaccination. After identifying areas for improvement, an educational intervention was implemented. A second evaluation was performed after the intervention to assess changes in adherence rates. RESULTS: Before the intervention, adherence rates were excellent (>90%) for indicators related to variceal bleeding prophylaxis and documentation of cirrhosis etiology, acceptable (60-80%) for HCC screening and disease severity assessment, and poor (<50%) for vaccinations. After the educational intervention, there was a statistically significant improvement in adherence rates for eight indicators related to HCC screening (70-90%), disease severity assessment (90%), variceal bleeding prophylaxis (>90%), and vaccinations (60-90%). CONCLUSION: Our study demonstrates a significant improvement in the quality of care provided to cirrhotic outpatients after an educational intervention. The findings highlight the importance of targeted educational interventions to enhance adherence to quality indicators in the management of cirrhosis.

Prophylaxis versus preemptive therapy for cytomegalovirus disease in high-risk liver transplant recipients.

Cytomegalovirus (CMV) infection is an opportunistic infection frequently found after solid organ transplantation, and it contributes significantly to mortality and morbidity. CMV-seronegative recipients of grafts from CMV-seropositive donors have the highest risk of CMV disease. The most appropriate strategy for preventing CMV disease in this population is a matter of active debate. In this study, we compared prophylaxis and preemptive therapy for the prevention of CMV disease in donor-seropositive/recipient-seronegative (D+ /R-) liver recipients. To this end, we selected a retrospective cohort of liver recipients (1992-2009) for analysis. D+ /R- patients were identified from the liver transplant program database. Eighty of 878 consecutive liver recipients (9%) were D+ /R-. Six of these patients died within 30 days of transplantation and were excluded. Thirty-five of the remaining D+ /R- patients (47%) received prophylaxis, and 39 patients (53%) followed a preemptive strategy based on CMV antigenemia surveillance. Fifty-four (73%) were men, the median age was 49 years (range = 15-68 years), and the mean follow-up was 68 months (range = 8-214 months). The baseline characteristics and the initial immunosuppressive regimens were similar for the 2 groups. Ganciclovir or valganciclovir was the antiviral drug used initially in both strategy groups. CMV disease occurred more frequently among D+ /R- liver recipients receiving preemptive therapy (33.3% versus 8.6% for the prophylaxis group, P = 0.01), whereas late-onset CMV disease was found only in patients receiving prophylaxis (5.7% versus 0% for the preemptive therapy group, P = 0.22). No significant differences in acute allograft rejection, other opportunistic infections, or case fatality rates were observed. According to our data, prophylaxis was more effective than preemptive therapy in preventing CMV disease in high-risk liver transplant recipients.

[Biliary complications after liver transplant]. / Complicaciones biliares tras el trasplante hepático.

There have been biliary complications since the beginning of liver transplants, and is a topic of great interest due to its high incidence, as well as their influence on morbidity and mortality. The biliary fistula is currently uncommon and its management is straightforward. Anastomotic stenosis continues to have an incidence of 10-15%. Although the current treatment of choice is endoscopic retrograde cholangiopancreatography (ERCP), surgical treatment (hepatico-jejunostomy) continues to have an important role. Non-anastomotic stenosis has an incidence of 5-10%, and is associated with ischaemic or immunological factors, and usually involves a re-transplant. Choledocholithiasis has an incidence of 5-10%, with the treatment of choice being ERCP. However the treatment of biliary complications should be individualised. We must take into account, liver function, the general health status of the patient, and the availability and experience of the team in the different therapeutic options.

Is Liver Retransplantation Justified in the Current Era? / ¿Está justificado el retrasplante hepático en la era actual?

INTRODUCTION: Liver retransplantation (LRT) is a controversial indication. Our aim was to evaluate the rate of LRT at our institution, and to analyze its indications and short- and long-term results. METHODS: We conducted a retrospective study of a prospectively collected database, including 1645 LT from 1984 to 2018. Results have been analyzed depending on type of LRT (early vs late), study period and indications. RESULTS: We performed 150 LRT in 140 patients. The LRT rate was 9%. Of these, 45 LRT were early (30%), and the other 70% were late LRT. The main indications were: ischemic cholangitis (27%), arterial thrombosis (19%), primary non-function (15%), and HCV recurrence (15%). Mean surgery duration (395 vs. 270 min; P = .001), cold ischemia time (435 vs. 390 min; P = .005) and transfused units required (8 vs. 5 RBC; P = .034) were higher in cases of late LRT. Postoperative mortality (10 vs. 20%; P = .01) was better in cases of late LRT. One- and 5-year actuarial survival rates were 71% and 58%, respectively, which were significantly better during the last decade (80% and 64%). Five-year actuarial survival for ischemic cholangitis is better than other indications, such as recurrence of HCV (78 vs. 51%; P = .02). CONCLUSIONS: Liver retransplantation is complex and associated with high morbidity and mortality. However, indications and long-term results have improved during recent years. Therefore, LRT is justified.

Secondary bacterial peritonitis in cirrhosis: a retrospective study of clinical and analytical characteristics, diagnosis and management.

BACKGROUND & AIMS: Secondary bacterial peritonitis in cirrhotic patients is an uncommon entity that has been little reported. Our aim is to analyse the frequency, clinical characteristics, treatment and prognosis of patients with secondary peritonitis in comparison to those of patients with spontaneous bacterial peritonitis (SBP). METHODS: Retrospective analysis of 24 cirrhotic patients with secondary peritonitis compared with 106 SBP episodes. RESULTS: Secondary peritonitis represented 4.5% of all peritonitis in cirrhotic patients. Patients with secondary peritonitis showed a significantly more severe local inflammatory response than patients with SBP. Considering diagnosis of secondary peritonitis, the sensitivity of Runyon's criteria was 66.6% and specificity 89.7%, Runyon's criteria and/or polymicrobial ascitic fluid culture were present in 95.6%, and abdominal computed tomography was diagnostic in 85% of patients in whom diagnosis was confirmed by surgery or autopsy. Mortality during hospitalization was higher in patients with secondary peritonitis than in those with SBP (16/24, 66.6% vs. 28/106, 26.4%) (p<0.001). There was a trend to lower mortality in secondary peritonitis patients who underwent surgery (7/13, 53.8%) than in those who received medical treatment only (9/11, 81.8%) (p=0.21). Considering surgically treated patients, the time between diagnostic paracentesis and surgery was shorter in survivors than in non-survivors (3.2+/-2.4 vs. 7.2+/-6.1 days, p=0.31). CONCLUSIONS: Secondary peritonitis is an infrequent complication in cirrhotic patients but mortality is high. A low threshold of suspicion on the basis of Runyon's criteria and microbiological data, together with an aggressive approach that includes prompt abdominal computed tomography and early surgical evaluation, could improve prognosis in these patients.

Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation.

Recent reports of the transmission of systemic transthyretin (TTR) amyloidosis after domino liver transplantation (DLT) using grafts from patients with familial amyloid polyneuropathy (FAP) have raised concerns about the procedure. The aim of this study was to evaluate the transmission incidence of systemic TTR amyloidosis after DLT with a complete clinical, neurological, and pathological assessment. At our institution, DLT has been performed 31 times with livers from patients with FAP. Seventeen of the 19 patients still alive in 2008 agreed to enter the study. This cross-sectional study of this cohort of patients included clinical assessments, rectal biopsy, and electroneuromyography (as well as sural nerve biopsy when it was indicated). The mean follow-up at the time of the study was 62.6 ± 2.9 months. Clinically, 3 patients complained of weak dysesthesia. When a focused study was performed, 8 patients reported some kind of neurological and/or gastrointestinal disturbance. Six of the rectal biopsy samples showed amyloid deposits (TTR-positive). Electromyography (EMG) showed signs of mild sensorimotor neuropathy in 3 cases and moderate to severe sensorimotor neuropathy in 1 case. Only 2 of the 4 patients with EMG signs of polyneuropathy showed amyloid deposits in their rectal biopsy samples. Sural nerve biopsy revealed amyloid deposits (TTR-positive) in all 4 patients with EMG signs of polyneuropathy. Two patients with normal EMG findings had TTR-positive amyloid deposits in their sural nerve biopsy samples. In conclusion, de novo systemic amyloidosis after DLT may be more frequent and appear earlier than was initially thought. In our opinion, however, the graft shortage still justifies DLT in selected patients, despite the risk of de novo systemic amyloidosis. Sural nerve biopsy with EMG and clinical correlation is mandatory for confirming the disease. Indeed, other causes of neuropathy should be excluded.