Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Candida arteritis occurring in a liver transplant recipient.

We report the first case, to our knowledge, of Candida arteritis in a liver transplant recipient. The patient presented with hemorrhagic shock requiring emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida glabrata were growing in the arterial tissue, the patient received antifungal therapy for 5 months, but died because of chronic graft dysfunction. No evidence of fungal infection was found in the tissue on postmortem examination.

Preliminary results of treatment with pegylated interferon alpha 2A for chronic hepatitis C virus in kidney transplant candidates on hemodialysis.

INTRODUCTION: At present, there is little published information on the outcome of treatment with pegylated interferon (Peg-IF alpha 2a) in hepatitis C virus (HCV)-infected hemodialysis patients awaiting renal transplantation. The objective of this study was to assess the efficacy and tolerance of Peg-IF alpha 2a in this population. PATIENTS AND METHODS: Twelve noncirrhotic HCV-infected patients (10 men, 50 +/- 8 years of age, genotype 1b 84%), were prescribed Peg-IF alpha 2a, at 135 microg/wk for 48 weeks. Liver biopsy was performed in 11 of 12 cases. RESULTS: Six patients completed 48 weeks of treatment, with one end of treatment response (ETR), two sustained viral responses (SVRs), and three HCV relapses. Treatment was shorter in the six remaining patients: two cases 24 weeks (one due to medical reasons with relapse, one due to nonresponse), one patient chose to discontinue at 14 weeks (with relapse), one patient died of stroke at 10 weeks, and in two additional patients interferon was withdrawn at 18 weeks because of severe anemia (SVR) and at 26 weeks due to prolonged fever (relapse). Other secondary treatment-related events included anemia (requiring transfusion in two patients and major erythropoietin administration in six), and fever in four patients. CONCLUSIONS: Peg-IF had limited efficacy in this group, with ETR in 83%, SVR in only 25%, and recurrence in 50%. Tolerance was moderate, with 4/12 (33%) discontinuing treatment due to adverse events, personal decision, or death. Large randomized controlled studies are needed to determine the role of Peg-IF treatment in this population.

[Prognostic utility of scintigraphy with 99mTc-HMPAO labelled leukocytes in inflammatory bowel disease]. / Utilidad pronóstica de la gammagrafía con leucocitos marcados 99mTc-HMPAO en la enfermedad inflamatoria intestinal.

OBJECTIVE: The inflammatory bowel disease (EII) has a chronic evolution with a frequent relapses. There is no specific diagnosis method to detect the patients with a high risk to relapse. The aim of the work was to analyse the prognostic value of 99mTc-HMPAO leukocyte scintigraphy (LS) performed during an acute attack of EII. MATERIAL AND METHODS: 18 patients (mean age 32 +/- 10 years) admitted for an acute attack of EII has been prospectively studied (5 ulcerative colitis [UC] and 13 Cronh's disease [CD]), excluding patient with prior steroids or immunosuppressive therapy during the last year. LS were obtained in basal conditions and following 3 weeks of steroid treatment and the scintigraphic activity index (SAI) has been calculated. Colonoscopy has been done in all patients, and CDAI in CD and Truelove index in UC have been calculated. Patients were followed up for 1 year. In the evolution the therapy requirements as well as the good response to initial treatment have been evaluated. RESULTS: All patients with UC and 4 patients with CD showed a SAI decrease > 50 % and all had a good clinical evolution. Only 2 out of the 9 patients with CD showing a IAG decrease < 50 % and had a good clinical evolution, the 7 remaining required additional medical treatment (immunosuppressors or surgery). CONCLUSION: LS may be of prognostic value in the management of EII. A SAI decrease > 50 % at 3 weeks of steroid treatment indicates a good clinical evolution.

Clinical and virological effects during two years of ongoing adefovir dipivoxil in the treatment of lamivudine-resistant chronic hepatitis B infection.

OBJECTIVE: Our aim was to evaluate the efficacy and safety of adding adefovir to lamivudine therapy for hepatitis B virus (HBV)-infected patients resistant to Ramivudine. PATIENTS AND METHODS: Among 17 studied patients, 7 had chronic active HBV infection and 10 were posttransplant with HBV infection (9 with de novo HBV). They received lamivudine plus adefovir therapy for 2 years. We assessed reductions in serum HBV-DNA and alanine aminotransferase (ALT) levels, loss of HBeAg (in HBeAg+ cases), and HBsAg clearance. RESULTS: A virological response, as defined by HBV-DNA below the cut off by hybridization, was observed in 12 (70.6%) patients and loss of HBeAg in 4 (44.4%) of the 9 initially HBeAg-positive cases. A biochemical response, defined as a decreased serum ALT to the normal range, occurred in 4 (26.7%) patients. Median serum creatinine increased in 3 of 15 (20%) patients, excluding those on hemodialysis. There were two noteworthy cases of sustained HBsAg seroconversion with adefovir (11.8%): one patient with de novo HBV infection posttransplantation and positive hepatitis C virus-RNA serology, and one patient with decompensated HBV cirrhosis in whom viral replication ceased, making him eligible for transplantation. CONCLUSIONS: Currently, adefovir is an effective rescue therapy that broadens the existing range of options for patients with lamivudine-resistant chronic hepatitis B infection, particularly those with decompensated cirrhosis awaiting a liver graft, and those with recurrent posttransplantation HBV. The relatively small biochemical response seen in these patients may be attributable to the high prevalence of concomitant hepatitis C virus infection (41%).

[Gammagraphy with 111In-labelled leukocytes in an acute outbreak of inflammatory intestinal disease. Evaluation of the localization, extension and degree of activity]. / La gammagrafía con leucocitos marcados con 111In en el brote agudo de la enfermedad inflamatoria intestinal. Valoración de la localización, extensión y grado de actividad.

We have studied 59 patients suspected of presenting an acute bout of inflammatory bowel disease: 23 had Crohn's disease and 36 had ulcerative colitis. All them underwent scintigraphic examination using 111In labelled leukocytes during the first 72 hours after their admittance and in a period no longer than 30 days, they also underwent barium enema and/or endoscopic study. Scintigraphic examination was more sensitive (100%), specific (100%) and accurate (100%) than endoscopy (72%, 100% and 78%) and barium enema (69%, 80% and 71%) in Crohn's disease. In ulcerative colitis, although endoscopy (100%) was slightly more sensitive than scintigraphy (100% and 94% against 78% and 93%). Reliability of barium enema was always lower to that of scintigraphy. In both conditions, scintigraphic examination detected a higher number of affected segments than barium enema did (40/16 in Crohn's disease and 65/31 in ulcerative colitis). Correlation between the index of scintigraphic activity and Harvey's index of clinical and biologic activity was highly significant (p less than 0.001) in both diseases. We conclude that scintigraphic examination using 111In labelled leukocytes is a reliable examination method for evaluation of localization, extension, and degree of activity of inflammatory bowel disease and that it must be a part of the examination protocol.

[Comparison of endoscopy, radiology and scintigraphy with Tc-99m-exametazine labeled leukocytes and In-111 labeled human polyclonal immunoglobulin G in the diagnosis of inflammatory bowel disease]. / Comparación de la endoscopia, la radiología y la gammagrafía con leucocitos marcados con 99mTc-exametazina y con inmunoglobulina G policlonal humana marcada con 111In en el diagnóstico de la enfermedad inflamatoria intestinal.

BACKGROUND: The 99mTc-exametazine labelled leukocytes (99mTc-WBC) scintigraphy is an established method for the inflammatory bowel disease (IBD) diagnosis, but the labelled procedure is a large and laborious process. The 111In-labelled human polyclonal immunoglobulin G (111In-IgG) can be an alternative in the non invasive IBD diagnosis. PATIENTS AND METHODS: Thirty-four patients routinely referred for investigation of IBD were studied. The 99mTc-WBC and 111In-IgG were simultaneously injected and images were obtained at 30 min, 3 and 24 h post-injection. The diagnostic was established by histology of endoscopy and/or surgery samples. Images were blindly evaluated by two experienced observers who only knew of the clinical suspicion of IBD. IBD was confirmed in 27 patients (17 with Crohn's disease [CD] and 10 with ulcerative colitis [UC]). RESULTS: Sensitivity, specificity and accuracy were 88.5, 100 and 90.3% respectively for endoscopy, 73.7, 75 and 73.9% for radiology, 59.3, 85.7 and 64.7% for 111In-IgG scan and 96.3, 85.7 and 94.1% for 99mTc-WBC scan. In the diagnosis of CD involvement of small bowel, the 99mTc-WBC scan identified 9/11 patients with confirmed disease, whereas the 111In-IgG scan diagnosed only four of them. In the evaluation of colonic disease, the 99mTc-WBC scan correctly diagnosed 21/22 confirmed patients, being the 111In-IgG scan positive in 13 of them. As far as disease extension concerned, the 99mTc-WBC demonstrated a statistically significance rather number of disease segments than endoscopy, radiology and 111In-IgG scan. CONCLUSIONS: The 99mTc-WBC was an effective method in the diagnosis of suspected IBD patients, both in the evaluation of small bowel disease and colonic disease, with slightly best results for colonic disease, whereas the 111In-IgG scan seems to have no utility neither in diagnosis nor in extension evaluation of IBD.

[Analysis of 500 liver transplantations at Bellvitge Hospital, Spain]. / Análisis de 500 trasplantes hepáticos en el Hospital de Bellvitge.

BACKGROUND: We present the experience of the liver transplantation program at the Hospital of Bellvitge with 500 transplantations performed during 15 years, to describe changes in liver transplantation observed throughout the time and to analyze the long term results. PATIENTS AND METHOD: Five groups each one including 100 consecutive transplantations are studied. RESULTS: The main indications were hepatocellular carcinoma (23%), alcoholic cirrhosis (22.8%), and post-hepatitis C cirrhosis (18.8%). Sixty-five retransplantations were performed in 59 patients (13%), being the more frequent indications arterial thrombosis (13 patients) and primary nonfunction of graft (10 patients). In 10 patients a hepatorenal transplantation was performed. In group I, the most frequent donor cause of death was cranial traumatism (80%), while in group V it was the vascular pathology (52%). There were other significative differences between these groups of patients (I vs V): patients with stage 2 or 3 from UNOS status (45 vs 19%), blood use (29.6 [26] vs 4.6 [5.3] PRBC), ICU stay (13 [13] vs 7.4 [11] days), hospital stay (40 [52] vs 23.7 [17] days), rejection rate (46 vs 20%) and primary graft nonfunction (9 vs 3%). However, the infection rates (48 vs 54.5%) and biliary tract complications (26 vs 20%) have not shown statistically significant differences. Actuarial one and 5-year survival are 83 and 70% respectively. CONCLUSIONS: An important and progressive improvement of liver transplantation results has been observed. However, de novo tumours, hepatitis C virus recurrence and chronic rejection can limit long term results.

[Spontaneous rupture of the abdominal wall in cirrhotic patients with ascites]. / Rotura espontánea de la pared abdominal en enfermos cirróticos con ascitis.

The abdominal wall hernia is a common finding in cirrhotic patients. Spontaneous disruption of the abdominal wall through these herniae is an uncommon complication, is associated with a high mortality and should be considered a gastroenterologic emergency. It occurs through a skin ulceration over the hernia in the 70% of all cases. Intravascular expansion plus long antibiotic prophylaxis with anti-staphylococcal agents are the mainstays of medical therapy. The definitive treatment must be surgical. Each case must be evaluated individually to determine the optimal surgical management, not necessarily on an emergent basis. We report three new cases surviving this complication.

[Infectious gastroenteritis in relapses of inflammatory bowel disease. Therapeutic implications]. / Gastroenteritis infecciosa en los brotes de enfermedad inflamatoria intestinal. Implicaciones terapéuticas.

The incidence and clinical importance of infectious gastroenteritis was studied in 67 consecutive relapses of inflammatory bowel disease (IBD). A stool culture was done in every case before starting treatment. Stool culture was positive in 6 relapses (8.9%): Four were exacerbations of ulcerative colitis and two of Crohn's disease (8.8% in ulcerative colitis vs 9% in Crohn's disease; NS). The microorganisms isolated were Campylobacter jejuni in three cases, Salmonella enteritidis in two and Staphylococcus aureus in one case. There were not clinical differences between patients with positive and negative stool culture. Treated with antibiotics, stool cultures became negative in all of them but only in three the disease was controlled. The other three had to be treated with corticosteroids to achieve remission. We conclude that stool culture should be practised in all relapses of IBD and in case of positivity, antibiotic therapy should be started. With this approach the use of corticosteroids can be avoided in some patients.

[Chemoembolization in the treatment of hepatocarcinoma]. / La quimioembolización en el tratamiento del hepatocarcinoma.

Transcatheter arterial chemoembolization with lipiodol and adriamycin was performed in 46 patients with hepatocellular carcinoma (HCC). In 27, this procedure was followed by selective arterial embolization using gelatin sponge particles. Surgical resection was carried out in 5 cases and 13 patients were transplanted (OLT). The aim of the study was to analyze the survival and degree of tumor necrosis. In the nonsurgical group the overall survival was 67% after 24 months in the OKUDA I stage, 31% after 20 months in the OKUDA II stage and 25% after 6 months in the OKUDA III stage. For the patients who underwent surgery, survival was 38% after 20 months in 5 patients who were resected and 72% after 24 months in 13 patients who were transplanted. Transcatheter arterial chemoembolization improves survival in patients who are not operated on, and can be used as a complementary treatment for patients who undergo surgery. A full tumor necrosis was observed in well encapsulated tumors.

[Is surgery for portal hypertension a contraindication for liver transplantation?]. / Representa la cirugía de la hipertensión portal una contraindicación al trasplante hepático?

INTRODUCTION: Orthotopic liver transplantation (OLT) is the only curative treatment for hepatic cirrhosis and is the most effective in the control of portal hypertension. The aim of this study was to analyze whether greater morbi-mortality is observed in patients undergoing liver transplantation with previous surgery for portal hypertension with respect to patients not having undergone this surgery. MATERIALS AND METHODS: Different variables were analyzed in 2 groups of transplanted patients: one of 18 patients who had previously undergone surgery for portal hypertension and another group of 54 patients without this previous surgery. RESULTS: The following factors were studied: mean operative time and length of anahepatic phase, intraoperative consumption of concentrates of erythrocytes, fresh frozen plasma, units of platelets and cryoprecipitates, days of mechanical ventilation, stay in the ICU and total postoperative stay. No significant differences were observed (p < 0.05) in any of these factors or in survival. DISCUSSION: On analysis of the difficulty of surgical technique, postoperative evolution and survival and based on the variables described it may be concluded that previous surgery for portal hypertension does not only not contraindicate posterior liver transplantation, but rather may be useful in patients with an adequate hepative reserve presenting variceal hemorrhage since posterior transplantation does not present a worsened prognosis.

[Resection as elective treatment of hilar cholangiocarcinoma (Klatskin tumor)]. / La resección como tratamiento de elección del colangiocarcinoma hiliar (tumor de Klatskin).

A retrospective analysis of our experience in the treatment of hiliary cholangiocarcinoma or Klatskin tumor was performed with the aim of evaluating the morbi-mortality and prognosis of its treatment to thereby determine the usefulness of the different therapeutic options. From 1989 to 1997, 51 patients diagnosed with hiliary cholangiocarcinoma were treated in our hospital. Surgery was indicated in 16 with curative aims (group I) while palliative treatment with percutaneous biliary drainage was indicated in 35 (group II). Biliary resection was carried out in 8 patients being associated with hepatic resection in 4 (group IA) and in 8 patients undergoing liver transplantation (group IB). Clinico-epidemiologic data and hospital stay were similar in all the groups. The frequency of complications was similar in groups I and II although the frequency of cholangitis (49%) in group II was noticeable. The percentage of readmissions was also greater in group II (12 vs 46%, respectively; p = 0.03) with prosthesis obstruction being the most frequent cause. Accumulated survival at 1, 2, and 3 years in group I was 84, 64 and 48% with a median survival of 33 months, while in group II the median survival was of 6 months with no patient surviving more than 2 years (p = 0.0001). When groups IA and IB were compared, greater frequency of complications in groups IA (100 vs 37%; p = 0.002), similar frequency of readmissions (87 vs 75%; p = NS), median survival greater in group IB (12.5 months vs 48 months) and significantly higher actuarial survival in group IB (48% in 2 years vs 83% to 2 years; p = 0.02) was observed. In conclusion, surgery is the treatment of choice in hiliary cholangiocarcinoma whenever possible, given the greater survival without a significant increase in morbimortality. Likewise, we consider that liver transplantation is a useful option in the treatment of patients with cholangiocarcinoma type IV of Bismuth.

Risk factors, clinical characteristics, and outcomes of invasive fungal infections in solid organ transplant recipients.

BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity and mortality among solid organ transplant (SOT) recipients. We sought to assess risk factors, clinical characteristics, and current outcomes of IFI in SOT recipients. METHODS: We reviewed all episodes of IFI occurring among SOT recipients in a university hospital from 2008 to 2011. To determine risk factors for IFI we carried out a matched case-control study (1:2 ratio). Control subjects were matched for transplant type and timing. RESULTS: We documented 20 episodes of IFI among 744 SOT recipients (2.7%). Sixty-five percent of cases were proven IFI and 35% were probable IFI. The types of IFI documented were aspergillosis in 8 cases, candidiasis in 7, pneumocystosis in 3, Emmonsia species in infection 1, and disseminated cryptococcosis in 1. Ninety-nine percent of the patients had received a prior antibiotic therapy (3 months), 40% presented allograft rejection (3 months), and 40% had prior kidney injury. Complications of IFI included septic shock (50%), respiratory failure (55%), multiple-organ dysfunction (55%), and intensive care unit (ICU) admission (50%). Median days from transplantation to diagnosis was 103 for candidiasis (range, 27-4644) and 1195 for aspergillosis (range, 0-4319). In a comparison of case patients with 40 matched control subjects, case patients more frequently presented prior ICU stay (3 months; P = .05), hemodialysis requirement (P = .02), receipt of high-dose prednisone (6 months; P = .006), and prior antibiotic therapy (P < .001). Prior use of antibiotic treatment was the only risk factor for IFI (odds ratio [OR] 93; 95% confidence interval [CI], 8.3-1042). Case-fatality rate was 60%. CONCLUSIONS: In our recent experience, 2.7% of SOT recipients developed IFI, mainly aspergillosis followed by candidiasis. Prior ICU admission, hemodialysis, receipt of high-dose prednisone, and prior antibiotic use were more frequent in cases when compared with control subjects, with the latter factor being the only independent risk factor for developing IFI. Case-fatality rate was high (60%).

Surgical treatment of biliary tract complications after liver transplantation.

OBJECTIVE: Biliary strictures are the most common biliary tract complication after liver transplantation. There are scarce data on the results of hepaticojejunostomy (HJ) in the management of biliary complications after orthotopic liver transplantation (OLT). Thus, the role of surgery in this setting remains to be established. The aim of this study was to evaluate the results of surgical treatment of patients with biliary complications at our institution. PATIENTS AND METHODS: We reviewed 1000 consecutive liver transplantations performed at our institution from 1984 to 2007. We used a prospectively recorded database to identify patients who underwent HJ to treat any biliary tract complication. RESULTS: Overall, 62 patients (6.2%) underwent HJ, 40 for an anastomotic and 7 for a non-anastomotic stricture as well as 15 for biliary leaks. Postoperative morbidity was 16%, and postoperative mortality 1.6%. There were 7 cases of anastomotic stenosis (11.3%). Four patients (5%) required retransplantation. CONCLUSIONS: HJ is a safe procedure to manage biliary complications after OLT. It may be the first treatment choice especially for cases with anastomotic strictures.