Adnan Said

Quality of life after liver transplantation. A systematic review

BACKGROUND/AIMS Although many studies have reported significant improvements in quality of life (QOL) after liver transplantation (LT), consistent data on areas of improvement are lacking. To perform a systematic review on medical literature of QOL after LT paying particular attention to studies that utilized the most commonly adopted study instrument, Short Form-36 (SF-36). METHODS To collect studies focused on QOL in adult LT recipients, from 1963 to 2007, cited in Pub Med, Embase or Cochrane databases. From an initial identification of 613 articles, we selected 44 longitudinal studies with pre- and post-LT data that we assessed using a sign test, and 19 used SF-36, which we analyzed separately. RESULTS Longitudinal data showed remarkable improvement of common domains of QOL comparing pre- and post-transplant items. However, analysis of 16 SF-36 cross-sectional studies comparing post-LT patient domains with control population showed significantly higher ratings for controls in six while no differences were found in two. CONCLUSIONS This review suggests that whereas general QOL improves after LT, when compared with healthy controls, LT recipients have significant deficits in QOL. Consequently, the previously reported QOL benefits after LT may have been overstated.

The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: a systematic review and meta-analysis.

Selective digestive decontamination (SDD) refers to the use of antimicrobials to reduce the burden of aerobic gram‐negative bacteria and/or yeast in the intestinal tract to prevent infections caused by these organisms. Liver transplant patients are highly vulnerable to bacterial infection particularly with gram‐negative organisms within the first month after transplantation, and SDD has been proposed as a potential measure to prevent these infections. However, the benefit of this procedure remains controversial. We undertook a systematic review and meta‐analysis to determine whether SDD is beneficial in reducing infections overall and those caused by gram‐negative bacteria in patients following liver transplantation. All studies that evaluated the efficacy of SDD in liver transplant patients were included. Randomized trials that included liver transplant patients given SDD versus either placebo or no treatment or minimal treatment (e.g., oral nystatin alone), and that provided adequate data to calculate a relative risk ratio, were included in the meta‐analysis. Our review shows that most studies found SDD to be effective in reducing gram‐negative infection. The nonrandomized and uncontrolled trials also showed benefit with SDD in reducing overall infection; however, the effect on overall infection was limited in the 4 randomized trials, in which the pooled relative risk was 0.88 (95% CI, 0.7‐1.1), indicating no statistically significant reduction in infection with the use of SDD. The summary risk ratio for the association between SDD and gram‐negative infection was 0.16 (95% CI, 0.07‐0.37), indicating an 84% relative risk reduction in the incidence of infection caused by gram‐negative bacteria in patients receiving SDD in randomized trials. In conclusion, the available literature supports a beneficial effect of SDD on gram‐negative infection following liver transplantation; however, the risk of antimicrobial resistance must be considered. Larger multicenter randomized trials in this patient population to assess the effect of SDD in reducing infection and mortality, while assessing the risk of antimicrobial resistance, are needed. (Liver Transpl 2004;10:817–827.)

Predictors of early recurrence of benign esophageal strictures

OBJECTIVE:In the era of liberal proton pump inhibitor (PPI) use, benign esophageal strictures remain a significant management problem, with 30–40% of patients experiencing symptomatic recurrence within 1 yr of successful dilation. We therefore sought to examine predictors of early recurrence of benign esophageal strictures after endoscopic dilation.METHODS:Predictors for stricture recurrence were examined in 87 consecutive outpatients undergoing initial dilation over a 1-yr period. Patients with symptomatic recurrence of dysphagia requiring repeat dilation within 1 yr of initial successful dilation (cases) were compared to patients who did not require redilation (controls). Predictors were assessed by univariate and multivariate analysis. Kaplan-Meier analysis of significant predictors using time to first redilation was also performed.RESULTS:Of the patients, 36 required repeat dilation within 1 yr, whereas 51 did not (median follow-up, 33 months). Of all strictures, 67 (77%) were peptic, with the remainder caused by radiation, drug-related injury, or congenital stenosis, among other causes. In multivariate analysis, nonpeptic strictures were significant predictors for early recurrence, as was a narrower stricture diameter. For peptic strictures, the persistence of heartburn after dilation and the presence of a hiatal hernia were significant predictors. Of all peptic strictures, 84% of patients were on PPIs after dilation, with no difference between cases and controls. Of all patients with persistent heartburn after dilation, 90% were on PPIs.CONCLUSIONS:The persistence of heartburn after dilation is a strong predictor for early symptomatic recurrence of benign esophageal peptic strictures, despite a high rate of PPI use. This may suggest persistent acid reflux requiring optimization of acid reduction therapy. Alternatively, combined acid and alkaline reflux may account for progressive injury despite PPI therapy. Esophageal pH studies may be invaluable in making the distinction between acid and non-acidic (alkaline) reflux. Nonpeptic strictures are also more likely to have early recurrences and are therefore more difficult to manage.

Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome.

Introduction Few therapeutic modalities exist for the treatment of hepatorenal syndrome (HRS). The combination of octreotide, midodrine, and albumin has shown possible benefit in small preliminary studies in improving renal function and short-term survival. Methods We examined the effect of octreotide, midodrine, and albumin on survival (censored for liver transplantation) and renal function in patients with HRS type 1 and type 2, compared with a historical cohort that did not receive this therapy (control group). Results Seventy-five patients with HRS received octreotide, midodrine, and albumin and 87 did not constitute the control group. HRS type 1 was present in 102 individuals and HRS type 2 in 60. Transplantation was performed in 45% of patients in the treatment group as compared with 26% of patients in the control group although a significant difference in transplantation rate was seen in only HRS type 2. In the treatment arm, transplant-free survival was higher compared with the control arm (median survival 101 d vs. 18 d, P<0.0001). Survival was significantly better in the treatment arm in both HRS type 1 (P=0.0003) and HRS type 2 (P=0.009). In multivariable analysis, treatment with octreotide, midodrine, and albumin (P=0.0001) and HRS type 2 (P=0.05) were independently associated with improved survival. Renal function was significantly improved at 1 month (glomerular filtration rate 48 mL/min) in the treatment group compared with the control group (34 mL/min), P=0.03. Conclusions The therapeutic regimen of octreotide, midodrine, and albumin significantly improved short-term survival and renal function in both HRS type 1 and type 2. This may provide a significant benefit as a bridge to liver transplantation in HRS type 1 and may prevent progression of HRS type 2 to HRS type 1.

NAFLD recurrence in liver transplant recipients.

Background and Aims. Nonalcoholic fatty liver disease (NAFLD) is a common indication for liver transplantation and can recur in the graft. To describe this recurrence, we performed a cohort study of individuals undergoing liver transplantation for NAFLD-related cirrhosis between 1993 and 2007. Predictors of NAFLD recurrence and outcomes in this cohort were also studied. Methods. Eighty-eight liver transplant recipients were included in this study. NAFLD recurrence was described by performing a blinded reevaluation of posttransplant liver biopsies and classified according to histologic activity (NAFLD activity score) and fibrosis. Results. Recurrent NAFLD was seen in 34 (39%) recipients with isolated steatosis in 9 and steatohepatitis in 25 recipients. Severe recurrence was seen in 3 of 34 recipients (NAFLD activity score ≥5) and advanced fibrosis in 3 recipients. NAFLD recurrence correlated with higher pretransplant (P=0.001) and posttransplant body mass index (P<0.0001) and increased triglyceride levels posttransplantation. Serum triglyceride levels at 6 and 12 months were 280±129 and 324±265 mg/dL, respectively, in those with NAFLD recurrence versus 206±96 mg/dL at 6 months and 190±103 mg/dL in those without NAFLD recurrence (P=0.007 at 6 months and P=0.005 at 12 months). Average steroid dose at 6 months posttransplant was also higher in those with NALFD recurrence than those without (11±8.5 and 7.2±5.7 mg/day, P=0.04). Posttransplant survival did not differ between those with and without NAFLD recurrence during the entire follow-up period (P=0.78). Posttransplant cardiovascular disease was significantly and adversely correlated with posttransplant survival. Conclusions. NAFLD recurrence is common in the first 5 years postliver transplantation and is associated with features of the metabolic syndrome. Although NAFLD recurrence was not associated with higher mortality in our cohort, cardiovascular mortality and morbidity were common, suggesting that the metabolic syndrome is an important link to NAFLD recurrence and cardiovascular deaths posttransplantation.

The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation

Patients with clinical acute alcoholic hepatitis (AAH) are not considered suitable candidates for orthotopic liver transplantation (OLT). The histological correlates of AAH are often seen in the explanted liver at the time of transplantation. The importance of these findings remains inconclusive regarding their role as a prognostic marker for patient or allograft health. Our aim was to examine the explanted liver of patients with purely alcoholic liver disease (ALD) for findings of histologic AAH and to correlate these to patient and graft outcomes. We compared patients with and without histological AAH with patients transplanted for non‐ALD. Of 1,097 liver transplant recipients, 148 had ALD and 125 were non‐ALD control patients with similar demographics. Thirty‐two of 148 ALD patients had histologic AAH, and 116 had bland alcoholic cirrhosis (BAC). Twenty‐eight percent of the ALD patients reported <6 months abstinence, and 54% reported <12 months abstinence. There was a statistically significant relationship between the presence of histologic AAH and abstinence durations <12 months (P = 0.009), but not <6 months. Overall, posttransplantation patient and graft survival between the ALD and non‐ALD groups was not significantly different (P = 0.53). Furthermore, patient and graft survival between ALD patients with histologic AAH and BAC were similar (P = 0.13 and P = 0.11, respectively). The rate of posttransplantation relapse among ALD patients was 16%; however, there was no increase in graft loss, nor was there decreased survival compared with controls. The patients with histologic AAH and those with BAC had no differences in posttransplantation relapse (P = 0.13). In multivariate analysis, patient and graft survival was not influenced by pretransplantation abstinence or posttransplantation relapse. In conclusion, histological alcoholic hepatitis in the explant did not predict worse outcome regarding relapse, and allograft or patient survival for liver transplant recipients. Caution should be exercised when liver histology is used to discriminate among suitable candidates for OLT concerning alcoholic patients. Liver Transpl 13: 1728–1735, 2007.

Impact of a CT Colonography Screening Program on Endoscopic Colonoscopy in Clinical Practice

OBJECTIVEThe potential effect of CT colonography (CTC) on endoscopic colonoscopy (EC) has been the topic of much speculation. The aim of this study was to evaluate the impact of a CTC screening program on colonoscopy in clinical practice.METHODSAt our institution a third-party reimbursed CTC colorectal cancer (CRC) screening program was established in 2004. The number of CTC monthly exams performed, monthly EC total and screening exams performed, EC with polypectomy performed, and the number of referrals for EC screening exams requested were prospectively examined in the first 33 months after introduction of a CTC CRC screening program.RESULTSThe mean number of overall (378.5 vs 413.1) and screening (150.7 vs 162.9) colonoscopy exams performed per month did not change significantly after screening CTC was introduced. The mean number of monthly CTC exams performed rose significantly throughout the first year of the study from 39 initially to a peak of 147.6 cases per month but decreased slightly to 114.3 monthly exams at the end of 2006. A mean 10.0 patients per month were sent for EC after a positive CTC exam. The mean number of monthly colonoscopies with polypectomy remained constant after the introduction of CTC (197.0 vs 180.2). Monthly referrals for screening EC exams initially decreased but were unchanged 3 yr after institution of a CTC screening program (255.0 vs 253.5).CONCLUSIONS(a) In our tertiary care center the initiation of a screening CTC program did not result in a decrease in the number of total colonoscopy exams, screening colonoscopy exams performed, nor requests for screening colonoscopy. (b) Only a small number of CTC exams were referred for EC with polypectomy, therefore a CTC screening program may not increase the overall number of therapeutic colonoscopies performed.

Liver transplantation: an update 2009

Purpose of review Recent attention in liver transplantation has focused on equity in organ allocation and management of posttransplant complications. Recent findings Adoption of the model for end-stage liver disease for liver allocation has been successful in implementing a system based on medical urgency rather than waiting time. Refinements are being studied in improving the prediction of mortality and improving transplant benefit by balancing pretransplant mortality and posttransplant survival. Emerging literature is examining expansion of the current criteria for transplantation of hepatocellular carcinoma and the role of neoadjuvant therapy. Chronic renal dysfunction after liver transplantation is a source of considerable morbidity. Nephron-sparing immunosuppression regimens are emerging with encouraging results. Hepatitis C virus infection is difficult to differentiate histologically from rejection, although newer markers are being developed. Antiviral and immunosuppressive strategies for reducing the severity of hepatitis C virus recurrence are discussed. Alcohol relapse is common after liver transplant in alcoholic liver disease patients and can lead to worse outcomes. Summary Organ allocation tends to evolve under the model for end-stage liver disease with a focus on maximizing transplant benefit. Hepatitis C virus, hepatocellular carcinoma, chronic renal dysfunction and alcohol relapse are major challenges, and continued research in these areas will undoubtedly lead to better outcomes for transplant recipients.

Infected Bilomas in Liver Transplant Recipients, Incidence, Risk Factors and Implications for Prevention

Bilomas, infected hepatic fluid collections, are a frequent complication of liver transplantation. We report a case‐control cohort study to determine the incidence and microbiologic profile of bilomas and risk factors for biloma formation in 492 patients undergoing liver transplantation from 1994 to 2001. Fifty‐seven patients (11.5%) developed one or more bilomas; 95% in the first year post‐transplantation. The most common initial infecting pathogens were enterococci (37%), one‐half resistant to vancomycin (VRE); coagulase‐negative staphylococci (26%); and Candida species (26%). Infection by coagulase‐negative staphylococci was strongly associated with the presence of a T‐tube (OR 9.60, p = 0.02). In stepwise logistic regression multivariable analyses, hepatic artery thrombosis (OR 90.9, p < 0.0001), hepatic artery stenosis (OR 13.2, p < 0.0001) and Roux‐en‐Y choledochojejunostomy (OR 5.8, p = 0.03) were independent risk factors for biloma formation; ursodeoxycholic acid use was highly protective (OR 0.1, p = 0.002). Strategies to prevent biloma formation must focus on measures to prevent hepatic artery thrombosis and colonization of liver transplant patients by multiresistant nosocomial pathogens. T‐tube drainage post‐transplantation bears reassessment. The protective effect of ursodeoxycholic acid found in this study warrants confirmation in a prospective multicenter, randomized trial.

Risk of de novo hepatitis in liver recipients from hepatitis-B core antibody-positive grafts – a systematic analysis

Skagen CL, Jou JH, Said A. Risk of de novo hepatitis in liver recipients from hepatitis‐B core antibody‐positive grafts – a systematic analysis.
Clin Transplant 2011: 25: E243–E249.