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.

Ulcer bleeding after band ligation of esophageal varices: Risk factors and prognosis.

BACKGROUND: Post-banding ulcer bleeding is a rare complication of endoscopic band ligation of esophageal varices with high morbidity and mortality. There exist no management guidelines for this complication. AIMS: To determine the incidence, outcome and risk factors of post-banding ulcer bleeding. METHODS: Data for cirrhotic patients with acute variceal bleeding during a six-year period were prospectively collected, and all band ligation sessions performed were retrospectively analyzed. Demographic, analytic and endoscopic data were recorded, as well as complications, outcome and management of each episode of post-banding ulcer bleeding. RESULTS: The study includes 521 band ligation sessions performed on 175 patients. There were 24 cases of post-banding ulcer bleeding in 21 patients (incidence 4.6%). Independent risk factors for post-banding ulcer bleeding were MELD score, hepatocellular carcinoma and total beta-blocker dose. Mortality during the bleeding episode was 23.8%. Active bleeding or adherent clots at the time of endoscopy was associated with treatment failure or death. CONCLUSIONS: Post-banding ulcer bleeding is an uncommon but severe complication of esophageal banding. Patients with hepatocellular carcinoma, poor liver function and a low beta-blocker dose have higher risk of post-banding ulcer bleeding. An aggressive treatment should be considered in case of active bleeding at endoscopy.

Efficacy and Safety of Delayed Prolonged-Release Tacrolimus Initiation in De Novo Hepatitis C Virus-Negative Orthotopic Liver Transplant Recipients: A Single-Center, Single-Arm, Prospective Study.

BACKGROUND Delaying initiation of tacrolimus after liver transplantation (LT) is a potential renal-sparing strategy. We assessed safety and efficacy of delayed initiation of prolonged-release tacrolimus (PR-T) in de novo LT. MATERIAL AND METHODS This was a single-center, single-arm, prospective, 12-month observational study of hepatitis C virus-negative orthotopic LT patients. Immunosuppression included PR-T (initially 0.1 or 0.2 mg/kg/day) initiated on Day 3 post LT, basiliximab (20 mg) on post-transplantation Day 0 and Day 4, and intraoperative corticosteroids (500 mg). Patients received maintenance corticosteroids and mycophenolate mofetil (MMF) according to center protocol. MMF dose was adjusted according to thrombocyte count. The primary endpoint was the estimated glomerular filtration rate (eGFR) measured using the Modification of Diet in Renal Disease 4-variable formula at 12 months. Secondary endpoints included biopsy-confirmed acute rejection (BCAR) and dialysis requirement. Adverse events were recorded. RESULTS Sixty-nine patients (mean age 55.0 years) were included. Most patients started MMF on Day 1 (60.9%) or Day 2 (10.1%), and PR-T on Day 3 (55.1%) or Day 4 (29.0%). Mean tacrolimus trough levels (ng/mL) were: Day 7, 9.5±6.3; Day 10, 9.4±5.4; Month 1, 8.0±3.1; Month 3, 7.8±3.7; Month 6, 8.0±4.1; and Month 12, 7.2±3.1. Mean 12-month eGFR was 77.2±24.5 mL/min/1.73 m2; 72.5% of patients had eGFR >60 mL/min/1.73 m² at 12 months; 89.9% had no eGFR measurements <40 mL/min/1.73 m² during the study. Renal insufficiency (any eGFR <60 mL/min/1.73 m²) was diagnosed in 27.5% of patients; one patient required dialysis. There were no BCAR episodes; the infection rate was 36.2%, and 3 patients died. Overall, 19 patients (27.5%) developed de novo diabetes mellitus, 18 patients (26.1%) had hypercholesterolemia, and 12 patients (17.4%) had hypertriglyceridemia. CONCLUSIONS Quadruple therapy with delayed administration of PR-T was well tolerated and efficacious, and was associated with acceptable renal function over 12 months.

Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study.

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients.

Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation.

BACKGROUND & AIMS: Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients. METHODS: Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain. RESULTS: In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p=0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT. CONCLUSIONS: Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need. LAY SUMMARY: Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need.

Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: a prospective cohort study.

BACKGROUND & AIMS: The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. METHODS: This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. RESULTS: Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. CONCLUSIONS: The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly.

Single-session endosonography and endoscopic retrograde cholangiopancreatography for biliopancreatic diseases is feasible, effective and cost beneficial.

BACKGROUND: Endoscopic ultrasonography (EUS) and Endoscopic Retrograde Cholangiopancreatography (ERCP) are often required in patients with pancreaticobiliary disorders. AIMS: To assess the clinical impact and costs savings of a single session EUS-ERCP. METHODS: Patient and intervention data from April 2009 to March 2012 were prospectively recruited and retrospectively analyzed from a database at a tertiary hospital. Indications, diagnostic yield, procedure details, complications and costs were evaluated. RESULTS: Fifty-five scheduled combined procedures were done in 53 patients. The accuracy of EUS-fine needle aspiration for malignancy was 90%. The main clinical indication was a malignant obstructing lesion (66%). The ERCP cannulation was successful in 67%, and in 11/15 failed ERCP (73%), drainage was completed thanks to an EUS-guided biliary drainage: 6 transmurals, 5 rendezvous. Eight patients (14%) had related complications: bacteremia (n = 3), pancreatitis (n = 2), bleeding (n = 2) and perforation (n = 1). The mean duration was 65 ± 22.2 min. The mean estimated cost for a single session was €3437, and €4095 for two separate sessions. The estimated cost savings using a single-session strategy was €658 per patient, representing a total savings of €36,189. CONCLUSION: Combined EUS and ERCP is safe, technically feasible and cost beneficial. Furthermore, in failed ERCP cases, the endoscopic biliary drainage can be completed with EUS-guided biliary access in the same procedure.

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.

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.

Liver transplantation in patients with hepatic hydrothorax.

Hepatic hydrothorax is a uncommon complication of cirrhotic patients and the results of liver transplantation (OLT) in patients with this complication are not well defined. We studied postoperative complications and survival of 28 patients with hepatic hydrothorax transplanted at our center during a period of 12 years, comparing them with a control group of 56 patients transplanted immediately before and after each case. There were no differences between hydrothorax group and control group in days of mechanical ventilation after surgery, transfusion requirements, postoperative mortality and long-term survival (70% vs. 55% at 8 years, P = 0.11). Long-term evolution was similar between patients with refractory hepatic hydrothorax or spontaneous bacterial empyema and those with noncomplicated hepatic hydrothorax. Hepatic transplantation is an excellent therapeutic option for patients with hepatic hydrothorax. Presence of hepatic hydrothorax does not imply more postoperative complications, and long-term survival is similar to other indications of hepatic cirrhosis.

Liver transplantation without steroid induction in HIV-infected patients.

Until recently, human immunodeficiency virus (HIV) infection was considered an absolute contraindication for liver transplantation in Spain. We present the first 4 cases of liver transplantation (LT) carried out in our center in patients infected with HIV and coinfected by the hepatitis C virus (HCV), immunosuppressed with cyclosporine A (CyA) and basiliximab, but without steroids. The 4 patients were male, with a mean age of 38.25 +/- 4.5 years. Mean time of HIV infection was 114 +/- 62.3 months and all patients were receiving highly active antiretroviral therapy (HAART). HCV genotypes of the 4 patients were 4, 1b, 1b, and 1a. Two patients were classified as Child-Turcotte-Pugh C (10 and 11 points), 1 was B (8 points), and the patient with hepatocellular carcinoma was A (5 points). Immunosuppression consisted of basiliximab and monotherapy with CyA. There were no postoperative infections. With a follow-up of 17 +/- 8 months, all patients are alive. There was only 1 acute rejection episode, and this was solved with steroid pulses. Three patients showed HCV recurrence with enzymatic and histological changes and were treated with interferon and ribavirin. One patient had negative HCV-ribonucleic acid after 6 months of treatment. In conclusion, HIV infection should not be considered an absolute contraindication for liver transplantation. The evolution of this type of patients will probably depend on the HCV infection. Immunosuppression without steroids may reduce opportunistic infection.

Low complement levels and opsonic activity in hepatic hydrothorax: its relationship with spontaneous bacterial empyema.

GOALS: To analyze the pleural fluid factors that might cause spontaneous bacterial empyema (SBEM) in patients with cirrhotic hydrothorax. BACKGROUND: Pathogenic mechanism of SBEM of cirrhotic patients is probably similar to that of spontaneous bacterial peritonitis, but local factors affecting pleural fluid have not been studied. STUDY: Determination of C3, C4, and opsonic activity levels of pleural fluid in a cohort of patients with pleural effusions of different causes. RESULTS: Forty-eight patients had hepatic hydrothorax; 8, heart failure and 45, exudates (9, tuberculosis; 21, malignancies; 10, other). Of the 48 cirrhotic patients, 15 developed SBEM on admission. The pleural fluid of cirrhotic patients showed significantly lower levels of total protein, complement, and opsonic activity than did the fluids of patients with other causes of SBEM. Patients who developed SBEM had lower concentrations of pleural fluid total protein and C3 and had a higher Child-Pugh score than patients who did not develop the infection. CONCLUSION: Cirrhotic patients with hepatic hydrothorax have lower pleural fluid opsonic activity and C3 levels than those found in the pleural fluid of patients with other causes. Patients who develop SBEM have lower levels of pleural fluid C3, pleural fluid total protein, and a higher Child-Pugh score than those who do not develop SBEM.

Is MELD really the definitive score for liver allocation?

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.

[Surgical treatment of hepatocellular carcinoma. Long term results]. / Resultados a largo plazo del tratamiento quirúrgico del hepatocarcinoma.

BACKGROUND: Surgical treatment for hepatocellular carcinoma remains controversial due to a lack of prospective randomized studies. MATERIAL AND METHOD: Between January 1990 and December 2000, 121 liver transplantations (group 1) and 52 hepatectomies (group 2) were performed for hepatocellular carcinoma. Each surgical treatment was carried out depending on patients' and tumor's characteristics. RESULTS: Patients from group 1 had a more advanced tumoral grade, with higher involvement of two lobes (19 vs 4%; p = 0.015) and higher number of nodules (1.9 DE [2] vs 1.2 [0.6]; p = 0.001); yet the mean tumor size was lower (3 cm [1.5] vs 4.2 [3.2]; p = 0.006). Operative mortality (4% vs 2%; p = 0.66) and 5- and 10-years survival (68% and 42% vs 63% and 45%; p = 0.23) were similar between both groups. Nevertheless, 5- and 10-years recurrence rates (10.6% and 10.6% vs 50% and 65.5%; p < 0.0001) were more favourable in group 1. Prognostic factors of recurrence included microscopic vascular invasion (RR = 12.12; CI, 2.02-75.52) and alpha-fetoprotein levels higher than 300 ng/mL (RR = 7.12; 95% CI, 1.08-47.02) in group 1, and the pT3-4 stage (RR = 3.86; 95% CI, 1.06-14.03) in group 2. Mean time on waiting lists for liver transplantation was 3.06 (2.66) months and it has increased significantly in last years, especially among blood group 0 patients. However, this fact has not been associated with a worsening of survival rates (p = 0.98). CONCLUSIONS: After a good patient selection, either liver transplantation or hepatectomy achieve excellent long term survival rates in patients with hepatocellular carcinoma, though the former allows a better control of the tumoral disease. The increase of mean time on waiting lists for liver transplantation during the last years has not led to a worsening of survival results.