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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)., (© 2017 by the American Association for the Study of Liver Diseases.)

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., (© 2015 American Association for the Study of Liver Diseases.)

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., (Copyright © 2012 American Association for the Study of Liver Diseases.)

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., (Copyright © 2010 American Association for the Study of Liver Diseases.)

The purpose of this study was to evaluate the influence of a steroid-free immunosuppression on hepatitis C virus (HCV) recurrence. A total of 198 liver transplantation (LT) patients were randomized to receive immunosuppression with basiliximab and cyclosporine, either with prednisone (steroid [St] group) or without prednisone (no steroids [NoSt] group). The group of 89 HCV-infected patients was followed up with protocol biopsies for 2 years after LT. This group of HCV patients are the patients evaluated in the present study. The rejection rate was 19% (St: 21% versus NoSt: 17%; P = 0.67). Patients in the St group had a slightly higher rate of bacterial infections (59% versus 38%; P = 0.05). Almost all patients had histological HCV-recurrence (St: 39/40 (97%) versus NoSt: 40/41 (97%); P = 1). The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months, 1 year, and 2 years were, 23%, 49%, and 49% in the NoSt group, compared to 33%, 55%, and 69% in the St group, respectively (P = 0.04 at 2 years). The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months, 1 year, and 2 years were 0%, 8%, and 22% in the NoSt group, compared to 8%, 19%, and 31% in the St group, respectively. Immunosuppression without steroids in HCV patients is safe, reduces bacterial infections and metabolic complications, and improves histological short-term evolution of HCV recurrence.

We studied the use of reagent strips for diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. A reagent strip for leukocyte esterase designed for the testing of urine with a colorimetric 5-grade scale (0 to 4) was used to evaluate ascitic fluid in 228 nonselected paracentesis performed in 128 cirrhotic patients. We diagnosed 52 SBP and 5 secondary bacterial peritonitis by means of polymorphonuclear cell count and classical criteria. When we considered positive a reagent strip result of 3 or 4, sensitivity was 89% (51 of 57), specificity was 99% (170 of 171), and positive predictive value was 98%. When we considered positive a reagent strip result of 2 or more, sensitivity was 96% (55 of 57), specificity was 89% (152 of 171), and negative predictive value was 99%. In conclusion, the use of reagent strips is a rapid, easy to use, and inexpensive tool for diagnosis of ascitic fluid infection. A positive result should be an indication for empirical antibiotic therapy, and a negative result may be useful as a screening test to exclude SBP.

The best system for organ allocation is still a controversial issue. The aim of this study was to study the accuracy of four different scores to predict mortality on the waiting list and, thus, their usefulness to determine organ allocation. We retrospectively compared two groups of patients, those who died on waiting list (group D) and those who successfully underwent transplantation (group T) during the same time period. Four scores, at the time of entering the waiting list and just before liver transplantation or death, were evaluated. The evaluated scores were as follows: (1) the Child-Pugh classification; (2) the Model for End-Stage Liver Disease (MELD) score; (3) the Freeman scale; and (4) the Guardiola et al index. The mortality rate on waiting list was 15.9%. All studied scores, except Freeman scale, were higher in group D at the time of entrance on waiting list (MELD, 17.4 +/- 8 v 12.3 +/- 6, P = .02; Child, 9.9 +/- 2 v 7.7 +/- 2, P = .002; Freeman, 9.7 +/- 4 v 7.3 +/- 3.9, P = .09; Guardiola, 2.6 +/- 0.9 v 1.7 +/- 0.7, P = .001). C-statistics of all scores were similar and in all cases lower than 0.8 (MELD, 0.75; Child, 0.78; Freeman, 0.65; Guardiola, 0.79). None of the studied scores have an excellent accuracy to predict prognosis of patients on waiting list, mainly in case of populations with high proportion of hepatocellular carcinoma. Although the MELD score is rapidly available, standardized, and objective, it does not reflect the severity of patients with cancer or metabolic disorders.

Biliary complications after orthotopic liver transplantation (OLT) may occur because of preservation injury (PI). In this study, we examine findings on routine reperfusion biopsy specimens in relation to the occurrence of biliary complications and graft outcome. From 1997 to 2000, a total of 193 OLTs were performed in our center. Postreperfusion biopsy specimens were analyzed and histological lesions were graded. For analysis, grafts were grouped into 2 categories: the presence or absence of PI (severe to moderate lesions versus mild or no lesions). Histological evidence of PI was present in 17% of the biopsy specimens. The incidence of grafts with PI and ischemia time longer than 12 hours was 38% compared with 14% in PI and short ischemia time (P =.02). Biliary complications were also more frequent in the PI group (28% v 14%; P =.03). Study of risk factors by means of logistic regression analysis confirmed that the PI group had a greater risk for biliary complications (relative risk, 2.8; 95% confidence interval, 1 to 7.4; P =.03). Moreover, moderate macrovesicular steatosis was found in 6% of the grafts, resulting in a 40% graft loss rate. We found that an increased presence of neutrophilic infiltrates in the postreperfusion biopsy specimen, indicating PI, was related to an increased incidence of biliary complications. Moreover, moderate macrovesicular steatosis was associated with increased graft loss. Therefore, postreperfusion biopsies are useful in anticipating post-OLT complications.

Cumulative recurrence after surgical resection for hepatocellular carcinoma (HCC) is very high. Several retrospective analyses have shown that liver transplantation was more effective than resection for patients with HCC at early tumor stages. Consequently, in January 1990, we decided to prospectively indicate orthotopic liver transplantation (OLT) as the first surgical treatment for small, localized HCC in cirrhotic patients without nodal involvement independently of the degree of liver function. The aim of this prospective cohort study was to analyze prognosis, recurrence rate, and survival after liver transplantation in patients in whom the main indication was HCC with cirrhosis. Thirty-eight patients in whom the main indication for liver transplantation was HCC and hepatic cirrhosis were compared with 136 transplantations because of cirrhosis without tumor, performed in our unit from January 1990 to December 1995. HCC arising in noncirrhotic livers and those incidently discovered after OLT were excluded from the study. Chemoembolization using doxorubicin, lipiodol, and Gelfoam was performed before OLT in 31 patients with good liver function. There were no differences in gender, but HCC patients were older (57 +/- 7 vs. 50 +/- 10 years [P < .001]). Liver function was better in HCC (Child-Pugh score: 6.9 +/- 2 vs. 8.6 +/- 1.8; P < .001), and hepatitis C virus antibody was positive in 31 (82%) vs. 51 (37%) (P < .007). Seven tumors had bilobar involvement (18%). Capsule was present in 22 (58%). The mean size of the tumor was 3.4 +/- 2 cm. Seventeen tumors (45%) were larger than 3 cm, and 4 (11%) were larger than 5 cm. The average number of nodules was 2 +/- 1. The tumor-node-metastasis stage of the tumors was pT1 in 6 patients (16%), 11 were pT2 (29%), 12 were pT3 (31%), and 9 were pT4 (24%). Seven patients were retransplanted in the HCC group (18%) and 19 (14%) in the nontumor group (not significant). Tumor recurrence was detected in three patients (8%). One, 3-, and 5-year survival rates were 82% vs. 79%, 75% vs. 71%, and 63% vs. 68%, respectively, for patients with and without HCC, and no differences were found between the two groups (P = .84). Survival was significantly reduced in patients with a macroscopic vascular invasion and tumors greater than 5 cm in diameter. Recurrence and mortality after liver transplantation in cirrhotic patients with carefully selected HCC are similar to the results in cirrhotic patients without tumor.

Eleven episodes of spontaneous bacterial empyema were identified in eight cirrhotic patients with ascites. Criteria for spontaneous bacterial empyema included positive pleural fluid culture or polymorphonuclear cell concentration greater than 500 cells/mm3, evidence of pleural effusion before an infectious episode and transudate characteristics during infection. In five cases, spontaneous bacterial empyema was culture-negative and was associated with spontaneous bacterial peritonitis. Ascitic fluid was culture-negative in two of these cases and culture-positive in three. Blood cultures were negative in all five of these cases. In six cases spontaneous bacterial empyema was culture-positive (Escherichia coli in four, Klebsiella pneumoniae in one and Clostridium perfringens in one). Four of these patients had the same organism in ascites; one had culture-negative spontaneous bacterial peritonitis and one had no infection of ascites. Blood cultures were positive in four of these patients; three died. Death was more frequent in patients with positive cultures than in those with negative ones (p less than 0.05). Patients with hydrothorax are prone to spontaneous bacterial empyema. This infection probably occurs through hematogenous seeding, but transfer of infected ascites from the abdominal cavity through the diaphragm cannot be excluded. Patients with spontaneous bacterial empyema may be asymptomatic or may be seen with fever, chills and dyspnea. Spontaneous bacterial empyema must be differentiated from parapneumonic empyemas. The presence of pleural effusion before the infectious episode, fluid characteristics and the organisms isolated are the clues for differential diagnosis. Treatment includes antibiotics; chest tube insertion probably is not necessary.