Clinical outcomes of hepatitis C treatment before and after kidney transplantation and its impact on time to transplant: A multicenter study.

Waitlist time for kidney transplantation is long but may be shortened with the utilization of hepatitis C positive allografts. We retrospectively reviewed the course of 36 hepatitis C positive patients awaiting kidney transplantation at 2 large centers within the same health system, with near-identical care delivery models with the exception of timing of hepatitis C treatment, to determine the impact of timing of hepatitis C treatment on access to transplant, waitlist time, and treatment efficacy and tolerability. The majority of patients had hepatitis C genotype 1a or 1b, and all received direct acting antiviral therapy with 100% treatment response. One patient underwent transplantation in the pretransplant treatment group. The 1-year transplantation rate was 12.5% vs 67.9% (P = .0013) in those treated posttransplantation. The median waitlist time in the posttransplant group was 122 (interquartile range [IQR] 21.5, 531.0) days, which was significantly shorter than the center's regional and national wait time. Pathologic review revealed no difference in allograft quality. Overall treatment related adverse events were not different between the 2 groups. A strategy of posttransplant hepatitis C treatment increased access to transplant and reduced waitlist time. Delaying treatment until after transplant did not appear to adversely affect recipients' kidney allograft or overall survival.

Tuberculous hepatitis in renal transplant recipients following alemtuzumab induction therapy.

Mycobacterium tuberculosis infection is one of many opportunistic infections in renal transplant recipients, arising either from reactivation of latent infection or de novo infection, occasionally donor derived. M. tuberculosis hepatitis has never been reported in patients who have received alemtuzumab as part of their renal transplant management. We describe 2 patients who underwent deceased-donor renal transplantation following alemtuzumab induction therapy and presented with a febrile syndrome, subsequently diagnosed as tuberculous hepatitis, one with disseminated disease. Both responded well to treatment without significant side effects, resulting in excellent graft function. The importance of chemoprophylaxis should be emphasized to minimize the risk of developing active tuberculosis in patients with latent tuberculosis infection undergoing solid organ transplantation.

Evaluation of risk factors for cytomegalovirus infection and disease occurring within 1 year of liver transplantation in high-risk patients.

BACKGROUND: Recent studies have demonstrated that cytomegalovirus (CMV) infection and disease are associated with increased risk of graft loss and death in high-risk (donor CMV seropositive/recipient CMV seronegative) liver transplant recipients (LTR) despite effective antiviral chemoprophylaxis. Predictors of CMV infection and disease in this important population are incompletely defined. METHODS: A retrospective cohort study of 227 high-risk first LTR who received primary anti-CMV chemoprophylaxis during the first 100 days after transplant was performed. A large number of patient, donor, operative, and post-transplant potential risk factors were collected. Associations of potential risk factors for CMV infection or disease that occurred during the first year after transplant were assessed using Cox regression models. After Bonferroni adjustment for multiple testing, P-values ≤0.00125 (associations with CMV infection) and ≤0.00122 (associations with CMV disease) were considered as statistically significant. RESULTS: CMV infection and disease occurred in 91 (40%) and 43 (19%) of LTR, respectively. In multivariable analysis, increased risk of CMV infection was observed for patients with lower model for end-stage liver disease (MELD) score (P = 0.025), lower total bilirubin (P = 0.014), and longer operative time (P = 0.038), whereas increased risk of CMV disease was seen in patients with lower MELD score (P = 0.026), lower total bilirubin (P = 0.044), and lower international normalized ratio (P = 0.043). However, after adjustment for multiple testing, none of these findings approached statistical significance. CONCLUSION: Our results suggest that interventions designed to prevent CMV infection and disease should be applied to all high-risk LTR until more definitive predictors of these complications are identified.

Association of cytomegalovirus infection and disease with death and graft loss after liver transplant in high-risk recipients.

In the era of effective antiviral chemoprophylaxis, cytomegalovirus (CMV) disease has been inconsistently associated with increased mortality in liver transplant (LT) recipients. A retrospective study evaluating the association of CMV infection and disease occurring within 1 year of transplant with the endpoints of death or the combined endpoint of graft loss or death was undertaken in a cohort of 227 CMV donor seropositive, recipient seronegative first LT recipients. Associations were evaluated using Cox proportional hazards regression models. CMV infection and disease occurred in 91 (40%) and 43 (19%) patients, respectively. Forty-eight (21%) died while 58 (26%) sustained graft loss or death. In multivariable analysis, CMV infection was associated with an increased risk of death (RR: 2.24, p = 0.008) and graft loss or death (RR: 2.85, p < 0.001). CMV disease was also associated with an increased risk of death (RR: 2.73, p = 0.003) and graft loss or death (RR: 3.04, p = 0.001). CMV infection and disease occurring within the first year after LT in high-risk recipients is associated with increased risk of death and of graft loss or death. Investigation of strategies to further reduce the risk of CMV infection and disease in high-risk LT recipients is warranted.

The role of surveillance endoscopy and endosonography after endoscopic ablation of high-grade dysplasia and carcinoma of the esophagus.

Barrett's esophagus (BE) with high-grade dysplasia (HGD) or early carcinoma treated with surgery or photodynamic therapy (PDT) is at risk of recurrence. The efficacy of endoscopic ultrasound (EUS) for surveillance after PDT is unknown. Our objective was to determine if EUS is superior to esophagogastroduodenoscopy (EGD) and/or CT scan for surveillance of BE neoplasia after PDT. The study was designed as a retrospective review with the setting as a tertiary referral center. Consecutive patients with BE with HGD or carcinoma in situ treated with PDT were followed with EUS, CT scan and EGD with jumbo biopsies every 1 cm at 3, 4, or 6-month intervals. Exclusion criteria was < 6 months of follow up and/or < 2 EUS procedures. Main outcome measurements were residual or recurrent disease discovered by any method. Results showed that 67/97 patients met the inclusion criteria (56 men and 11 women). Median follow-up was 16 months. Recurrent or residual adenocarcinoma (ACA) was detected in four patients during follow-up. EGD with random biopsies or targeted nodule biopsies detected three patients. EUS with endoscopic mucosal resection of the nodule confirmed T1 recurrence in one of these three. In the fourth patient, CT scan revealed perigastric lymphadenopathy and EUS-FNA (fine needle aspiration) confirmed adenocarcinoma. There were two deaths, one related to disease progression and one unrelated. The rate of recurrent/persistent ACA after PDT was 4/67 = 6%. EUS did not detect disease when EGD and CT were normal. Limitations of this study include non-blinding of results and preferential status of non-invasive imaging (CT) over EUS. Our experience suggests that EUS has little role in the surveillance of these patients, unless discrete abnormalities are found on EGD or cross-sectional imaging.

Accuracy and interobserver agreement of small-caliber vs. conventional esophagogastroduodenoscopy for evaluating esophageal varices.

BACKGROUND AND STUDY AIMS: Advances in endoscope design have allowed high-quality imaging using small-caliber endoscopes (< 6 mm), and these have been proposed as providing an accurate modality for evaluating esophageal varices in several small studies. We aimed to evaluate the accuracy and interobserver agreement of small-caliber esophagogastroduodenoscopy (EGD) compared with conventional EGD for evaluating esophageal varices in a large prospective cohort. PATIENTS AND METHODS: A total of 115 patients with end-stage liver disease and/or portal hypertension were prospectively enrolled into the study. EGD procedures were performed using conventional (8.6-mm) and small-caliber (4.9-mm) endoscopes, back to back and under standard sedation, by two different endoscopists. Esophageal varices were graded at the time of EGD (the "real-time" grade); and by retrospective review of photographs by three endoscopists, when a "consensus" grade (i. e. a grading agreed by two out of the three endoscopists) was used as the final result. RESULTS: Of the 115 patients, 33 patients (29 %) were classified as Child's class A, 47 patients (41 %) as Child's class B, and 35 patients (30 %) as Child's class C. The mean model for end-stage liver disease (MELD) score was 13.6. Thirty-six patients (31 %) had undergone previous ligation of esophageal varices. Compared with conventional EGD, the accuracy of small-caliber EGD for esophageal varices grading was 94 % (consensus grade) and 95 % (real-time grade). Excellent concordance was demonstrated between real-time grade and consensus grade, with a kappa of 0.95 for both types of EGD. There was excellent interobserver agreement between endoscopists, regardless of the type of EGD. The severity of hepatic dysfunction and the presence or absence of a history of previous esophageal varices ligation did not have any impact on the accuracy or interobserver agreement. CONCLUSIONS: Small-caliber EGD performed under sedation via oral intubation is a highly accurate and reliable modality for evaluating esophageal varices in patients with end-stage liver disease and/or portal hypertension, regardless of the degree of hepatic dysfunction or history of previous esophageal varices ligation.

Choice of Partial Splenic Embolization Technique in Liver Transplant Recipients Correlates With Risk of Infectious Complications.

BACKGROUND: Complications of cirrhosis may persist after liver transplantation. When indicated, partial splenic embolization (PSE) is an alternative to splenectomy but can cause severe infection. The identification of modifiable risk factors when performing PSE in immunocompromised liver transplant recipients may help reduce the risk of severe infection. METHODS: Data were collected retrospectively for all PSE performed after liver transplantation at a single institution and included demographics, etiology of liver disease, indication for PSE, vaccination status, laboratory findings, procedural details, extent and pattern of splenic infarction, hospital length-of-stay, readmissions, procedural complications, and mortality. Statistical analysis included 2-tailed t test, Fisher exact test, and Kaplan-Meier survival curves, with significance defined as P < .05. RESULTS: Sixteen patients received 22 embolizations, with 11 patients undergoing a single session and 5 patients undergoing multiple sessions. Indications included hypersplenism, gastrointestinal hemorrhage, ascites, and autoimmune hemolytic anemia. PSE produced significant and sustained cell count increases, improved ascites, and controlled hemorrhage. Splenic abscess, septic shock, need for splenectomy, and PSE-related mortality were seen in the group with large confluent splenic infarction but not in peripheral/wedge-shaped infarction. Multiple-session PSE exclusively using particles for embolization correlated with the pattern of peripheral/wedge-shaped infarction and avoided severe infection and PSE-related mortality. CONCLUSIONS: PSE in the immunosuppressed liver transplant recipient is an effective alternative to splenectomy, but carries substantial infectious risk. The risk is decreased when PSE performed with polyvinyl alcohol particles results in a pattern of peripheral/wedge-shaped infarction, which correlates with smaller infarction volumes, favorable length-of-stay, and minimal risk of abscess, sepsis, and mortality.

The risk of occupational HIV exposure among Thai healthcare workers.

To analyze the incidence of occupational exposure to HIV in a large group of healthcare workers at the 2 Thai Red Cross hospitals, prospectively collected during a seven-year period in order to find out the causes and circumstances that prone to exposure, the interventions that may minimize the exposure and the consequences of the accidents. The first 200 incident reports from 198 hospital workers of the Thai Red Cross Society who had occupational exposure to HIV-infected blood and body fluids during 1991-1997 were analyzed. We analyzed the demographic data, the timing and place of exposure, the nature and cause of exposure, HIV status at baseline and at follow-up at 3, 6 and 12 months as well as the received antiretroviral prophylaxis. All of the 198 HCW had negative anti-HIV at baseline and remained negative throughout the one-year follow-up although only 55% submitted the results of their anti-HIV testing at 6 months. However, none claimed for work-related life insurance against HIV during those 7 years indicating that nosocomial rate of transmission is less than 1 in 200 or less than 0.5%. Analysis of the incidents indicated that the risk group was the 20-40 years old nursing personnel who worked in the medical wards during the regular working hours. The procedures that were responsible for most of the injuries were venepuncture, intravenous access, injection and waste collection. Most of the injuries could be prevented if the work place safety guidelines were strictly followed and if personnel were more careful at work. The results can be used to implement more effective preventive measures for hospitals in Thailand. Postexposure management at the Thai Red Cross hospitals conformed with the international guidelines. However, only 78% of those who should receive postexposure prophylaxis were recommended for treatment and only 69% of those recommended actually took the treatment. This emphasizes the need to educate clinicians involved in postexposure care as well as to ensure them and the injured subjects about the safety of the antiretroviral prophylaxis.

Abatacept use in graft-versus-host disease after orthotopic liver transplantation: a case report.

BACKGROUND: Graft-versus-host disease (GVHD) is a rare, serious, fatal disease that occurs after orthotopic liver transplantation (OLT). CASE REPORT: We treated a 60-year-old man who underwent OLT owing to familial amyloidosis. The patient developed fever on postoperative day 16. The fever was persistent and did not respond to antibiotic therapy. Cultures and radiologic studies were done and excluded infection as a potential cause. On postoperative day 26, a skin rash appeared on his chest, accompanied by diarrhea and persistent fever. The rash spread all over the trunk, neck, and arms, but spared the palms of his hands and soles of his feet. In the meantime, his blood cell count revealed pancytopenia. Skin biopsy was done and showed interface lymphocytic infiltrate that are largely centered on the dermal-epidermal junction, is consistent with GVHD (this pattern of rash distribution is unique and different from the rash of GVHD after hematopoietic stem cell transplant, which is confined to palms of the hands and soles of the feet; Fig 1). The diagnosis was confirmed by colonoscopy and multiple forceps biopsies, which revealed extensive crypt loss. After hematology consultation, the patient was treated by withdrawal of all immunosuppressive therapy coupled with abatacept infusion. Abatacept is a chimeric protein that inhibits T-lymphocytes and is approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis. Interestingly, after second dose of abatacept the patient showed marked clinical and laboratory improvement. The patient was discharged after 47 days in a stable condition. CONCLUSION: Because of the lack of a consensus for treatment of these patients, we report our experience with a male patient who had post-OLT GVHD and showed a marked improvement in response to abatacept.

Liver transplantation in patients with atrial fibrillation.

In this study we described survival and incidence of perioperative and postoperative complications in liver transplant recipients with known atrial fibrillation. A total number of 717 patients underwent liver transplantation between January 2005 and December 2008 at our institution. In this population, preoperative paroxysmal or chronic-persistent atrial fibrillation was diagnosed in 32 patients (4.5%). Of these, 12 patients died during follow-up and 4 patients required liver retransplantation. Perioperative cardiac complications occurred in 10 patients (31%) resulting in 3 cardiac-related deaths. Median patient survival was 1613 days (range, 22-2492) and median graft survival was 1524 days (range, 10-2492). Twenty patients are still alive with a median survival of 1861 days (range, 1189-2492) after liver transplantation.

The impact of diabetes and obesity on liver histology in patients with hepatitis C.

AIM: An association between diabetes mellitus and HCV has been recognized previously. No study has examined whether there is an independent association between the degree of hepatic fibrosis and the incidence of diabetes in HCV patients when controlling for other risk factors. METHODS: We reviewed the charts of 264 consecutive patients with chronic HCV infection at a referral liver centre from January 1991 to December 1999. Demographic background, medical history, laboratory and liver biopsy results were retrieved. RESULTS: The prevalence of diabetes was 16.3%. Gender, intravenous drug use, steatosis scores, aminotransferase levels and iron studies were similarly distributed in patients with and without diabetes (all p > 0.05). In contrast, mean age was greater in the diabetic group (49.8 vs. 44.3, p = 0.003). The prevalence of diabetes was substantially higher in African-Americans (p = 0.001) and those with BMI > 30 (p = 0.015). Although the fibrosis score was higher in diabetics (rho = 0.14, p = 0.03), that association did not remain significant when controlling for diabetes risk factors (p > 0.3). The degree of steatosis and fibrosis both tended to increase with increasing BMI (rho = 0.47, p < 0.001 and rho = 0.13, p = 0.03, respectively). Even after controlling for diabetes, age, gender, race, and current alcohol use, those associations remained (both p < 0.001). CONCLUSIONS: The prevalence of diabetes in our group of HCV patients was high, consistent with other studies. Diabetes is not an independent predictor of degree of fibrosis. Body mass index is an independent predictor of both fibrosis and steatosis in HCV patients.