Simultaneous Liver Kidney Transplant in Elderly Patients With Chronic Kidney Disease: Is There an Appropriate Upper Age Cutoff?

BACKGROUND: The aging of liver transplant (LT) recipients, the weighting of the model for end-stage liver disease score, and the increased prevalence of nonalcoholic steatohepatitis has led to an increased number of older LT recipients with pre-LT chronic kidney disease (CKD). There are limited data on the impact of increased recipient age on post-simultaneous liver-kidney (SLK) transplant outcomes among patients with CKD, leading some centers to employ subjective age cutoffs for potential SLK recipients. METHODS: We evaluated United Network for Organ Sharing data of adult SLK recipients from February 27, 2002, to December 31, 2018, restricted to recipients with ≥90 days of waiting time and CKD (estimated glomerular filtration rate persistently <60 mL/min/1.73 m2 for ≥90 d using the modification of diet in renal disease-4 equation). We fit mixed-effects Cox regression models (center as random effect) to evaluate the association of recipient age and patient survival. RESULTS: Among 3146 SLK recipients with CKD, nearly two-thirds were 50-64 years of age, while 465 (14.8%) and 93 (3.0%) were 65-69 years and ≥70 years, respectively. Compared with nondiabetic SLK recipients aged 50-59 years, SLK recipients ≥70 years of age without diabetes (hazard ratio, 1.97; 95% CI, 1.20-3.23; P = 0.007) and with diabetes (hazard ratio, 1.90; 95% CI, 1.16-3.09; P = 0.01) had higher mortality compared with the reference group. In absolute terms, SLK recipients ≥70 years of age had 25% lower patient survival at 5 years compared to recipients aged 40-49 years. CONCLUSIONS: Although careful selection is required of any SLK recipient, especially those with increased comorbidities, there are no objective data to justify a specific age cutoff <70 years among potential SLK recipients with CKD.

Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial of Synthetic Preimplantation Factor in Autoimmune Hepatitis.

Preimplantation factor (PIF) is an evolutionary conserved peptide secreted by viable embryos which promotes maternal tolerance without immune suppression. Synthetic PIF (sPIF) replicates native peptide activity. The aim of this study was to conduct the first-in-human trial of the safety, tolerability, and pharmacokinetics of sPIF in patients with autoimmune hepatitis (AIH). We performed a randomized, double-blind, placebo-controlled, prospective phase I clinical trial. Patients were adults with documented AIH with compensated chronic liver disease. Diagnosis of AIH was confirmed by either a pretreatment International Criteria for the Diagnosis of AIH score of 15 or more, or a posttreatment score of 17 or more. Patients were divided into three dosing cohorts (0.1, 0.5, or 1.0 mg/kg) of 6 patients in each group. Three patients in each group had normal liver tests and 3 patients had abnormal liver tests. They were randomized to receive a single, subcutaneous dose of either sPIF or a matching placebo. Eighteen patients were enrolled, and all successfully completed the trial. There were no clinically significant adverse events and all doses were well tolerated. Ascending doses of sPIF produced a linear increase in the respective serum levels with a half-life of 90 minutes. There were no grade 2, 3 or 4 laboratory abnormalities. No patient developed detectable anti-sPIF antibodies. Conclusion: This first-in-human trial of the safety and pharmacokinetics of sPIF (a novel biologic immune modulatory agent) demonstrated both excellent safety and tolerability. The data support further studies of multiple ascending doses of sPIF in autoimmune hepatitis and potentially other autoimmune disorders.

Transplantation of kidneys from hepatitis C-positive donors into hepatitis C virus-infected recipients followed by early initiation of direct acting antiviral therapy: a single-center retrospective study.

The availability of direct acting antiviral agents (DAA) has transformed the treatment of hepatitis C virus (HCV) infection. The current study is a case series that reports the outcomes from a cohort of twenty-five HCV-infected ESRD patients who received a kidney from an anti-HCV-positive deceased organ donor followed by treatment with DAAs in the early post-transplant period. Time to transplantation and the efficacy of DAA therapy as measured by sustained viral response at 12 weeks were assessed. The median waiting time from original date of activation on the United Network Organ Sharing (UNOS) waiting list until transplantation was 427 days; however, the median time from entering the patient into UNetsm for a HCV-positive offer until transplantation was only 58 days. The 25 patients were started on antiviral treatment early post-transplant (median 125 days) and 24 of 25 (96%) achieved a sustained virologic response at 12 weeks. Tacrolimus dose adjustments were required during antiviral treatment in 13 patients to maintain therapeutic levels. Accepting a kidney from an anti-HCV-positive deceased donor shortened the waiting time for HCV-infected kidney transplant candidates. We recommend that kidneys from anti-HCV-positive donors should be considered for transplant into HCV-infected recipients followed by early post-transplant treatment with DAA agents.

Clinical Features of Chronic Hepatitis B in Treatment-naive Asian Patients With Positive HBeAg and Coexisting Precore and/or Basal Core Promoter Mutations.

BACKGROUND: Precore or/and basal core promoter (PC/BCP) mutations are frequently detected in hepatitis B e antigen (HBeAg)-negative patients, but little is known about their clinical significance in HBeAg-positive patients. AIM: To characterize and report the clinical features of treatment-naive chronic hepatitis B patients who are HBeAg positive and harbor PC and/or BCP mutations. PATIENTS AND METHODS: Consecutive treatment-naive patients with chronic hepatitis B between 2004 and 2014 were enrolled. Clinical characteristics were compared based on the stratification of HBeAg status and the presence of PC/BCP mutations. In addition, subset analysis in HBeAg-positive cohort was performed to compare clinical features of patients with and without PC/BCP mutations RESULTS:: Of the 267 patients enrolled from 3 centers, 177 were HBeAg positive and 90 HBeAg negative. When compared with HBeAg-negative patients, HBeAg-positive patients were significantly younger in mean age (37.93 vs. 44.40; P<0.001), had higher levels of median ALT (51 vs. 30.5 U/mL; P<0.001), higher levels of mean HBV DNA (7.50±1.48 vs. 5.10±1.44 log10 copies/mL; P<0.001), and lower frequency of detectable PC/BCP mutations (60.45% vs. 93.33%; P<0.001), but had significantly higher frequency of BCP when mutations were detected (37.85% vs. 22.22%; P=0.013). Among HBeAg-positive patients, when compared with patients with wild type, those with PC/BCP mutations were significantly older (30.63 vs. 42.71; P<0.001), had higher median ALT levels (29.5 vs. 73 U/mL; P<0.001), but there was no significant association with mean HBV DNA levels (7.96 vs. 7.20 log10 copies/mL; P=0.865) or HBV genotype (P=1.000). In the multivariate analysis, only age and ALT were independently associated with PC/BCP mutations in HBeAg-positive patients, but there was no association with HBV genotype or DNA. CONCLUSIONS: PC/BCP mutants were frequent (up to 60%) in treatment-naive HBeAg-positive patients and were associated with distinct clinical characteristics when compared with patients with wild type or HBeAg negative. Future large studies are needed to substantiate the long-term clinical outcomes when PC/BCP mutations are detected in HBeAg-positive patients as it may impact the natural history or treatment response in such patients.

A Rare Case of Hepatitis C-Associated Cryoglobulinemic Duodenal Vasculitis.

Intestinal involvement of cryoglobulinemia is an uncommon manifestation and marker of severe vasculitis. We describe the case of a woman admitted to our service for management of acute renal failure and progressive gastrointestinal symptoms after initiating hepatitis C virus treatment with ribavirin and sofosbuvir 4 weeks prior. With an undetectable hepatitis C viral load and persistent symptoms despite hepatitis C virus therapy cessation, an upper endoscopy revealed duodenal sloughing, erythema, and bleeding, sparking suspicion for recurrence of cryoglobulinemic vasculitis.

Noninvasive Markers to Assess Liver Fibrosis.

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. Their prognosis and management greatly depends on the amount and progression of liver fibrosis with time and the risk of development of cirrhosis. Historically, liver biopsy was considered to be the gold standard for the detection of fibrosis. Nevertheless, liver biopsy is an invasive procedure that has limitations in terms of patient acceptance, risk-benefit ratio, cost-effectiveness, and its availability in various geographic regions. Moreover, it is a questionable gold standard due to significant sampling error and intraobserver and interobserver variability. These limitations have led to the development of noninvasive techniques for assessing the presence and the degree of liver fibrosis. This review aims to revise the most recent data from the literature about noninvasive methods useful in the evaluation of liver fibrosis.

Endoscopic and histological features of mycophenolate mofetil colitis in patients after solid organ transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunosuppressive agent commonly used after organ transplantation. Gastrointestinal side effects occur in approximately 45% of patients. The spectrum of histologic features associated with MMF colitis has been well described, but data on the endoscopic features is lacking. The aim of the study was to describe the endoscopic features of MMF colitis in solid organ transplant recipients (SOTRs) as well as the frequency of histologic features and identify associated risk factors. METHODS: A retrospective review of all SOTRs taking MMF and who underwent colonoscopy between 2000 and 2010 was performed. 36 cases of MMF colitis were identified and 361 patients served as controls. Descriptive statistics and data analysis looking for associated risk factors were performed. RESULTS: Among SOTRs taking MMF who underwent colonoscopy, MMF colitis was diagnosed in 9%. Endoscopic findings ranged from erythema (33%) to erosions/ulcers (19%). 47% of patients had a normal colonoscopy and everyone had rectal sparing. Histological findings included acute colitis-like findings (50%), inflammatory bowel disease-like characteristics (36%), ischemia-like findings (5.6%), and graft-versus-host disease-like features (8.3%). Diarrhea occurred in 83%. Kidney transplantation was associated with a higher risk of MMF colitis (OR 5.8 [2.86-11.86], P<0.0001) whereas liver transplantation was associated with a lower risk (OR 0.06 [0.03-0.16], P<0.0001). CONCLUSION: MMF colitis is fairly prevalent in SOTRs taking MMF who undergo colonoscopy. Diarrhea is the most common reason for colonoscopy referral (83%) and up to 47% of patients have normal colonoscopy, suggesting the need for routine biopsies to help confirm the diagnosis.

Factors predicting early discharge and mortality in post-percutaneous endoscopic gastrostomy patients.

BACKGROUND: The aim of our study was to ascertain factors that favor early discharge and predict mortality in post-percutaneous endoscopic gastrostomy (PEG) patients. METHODS: Successive patients who underwent successful PEG placement during a 10-year period in a single New York City hospital were included in the study. Data was retrospectively extracted from hospital electronic medical records. RESULTS: Two hundred and eighty-four patients underwent successful PEG placement. Forty-six patients (16%) were discharged within 3 days of PEG placement (early discharge). Two hundred and thirty six patients (84%) remained in hospital from 4 to 244 days (median 13.5) after PEG insertion (late discharge). Twenty-six (9%) patients died in-house after PEG placement. A serum albumin level <2.2 g/dL (P=0.007) and presence of 2 or more co-morbidities (P=0.019) were predictors of late discharge. A dementia indication was twice as likely to result in an early discharge compared to a stroke indication (OR 2.39; 95% CI 1.07-5.36; P=0.033). Female sex, positive urine cultures and low serum albumin levels were independent predictors of in-house mortality. CONCLUSION: Clinical and laboratory markers may predict post-PEG mortality as well as early patient discharge.

Hispanics with primary biliary cirrhosis are more likely to have features of autoimmune hepatitis and reduced response to ursodeoxycholic acid than non-Hispanics.

BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a cholestatic disease that predominantly affects middle-aged Caucasian women. Studies have suggested that PBC has a more aggressive course in individuals of Hispanic ancestry. We investigated the clinical presentation and progression of PBC in an ethnically diverse population. METHODS: We performed a cross-sectional study, analyzing data from Hispanic (n = 70) and non-Hispanic patients (n = 134) with PBC seen at the University of Miami/Jackson Memorial Hospital from January 1, 2000, through December 31, 2011. We compared demographics, clinical presentation, response to therapy, and outcomes between the groups. RESULTS: Age at diagnosis, antimitochondrial antibody positivity, frequency of advanced histologic stage, use and dose of ursodeoxycholic acid (UDCA), and the presence of pruritus or fatigue were similar between groups. Hypothyroidism was less frequent among Hispanics (16% vs 29% in non-Hispanics; P = .04). Hispanic subjects were more likely to have overlap syndrome of PBC and autoimmune hepatitis than non-Hispanics (31% vs 13%; P = .002). After a median follow-up period of 3.65 years, a greater percentage of Hispanics had ascites (24% vs 12%; P = .03) and variceal bleeding (20% vs 7%; P = .01), although there were no differences in the number of deaths or liver transplants. Of 204 total patients, 180 received UDCA for at least 1 year. A lower proportion of Hispanic patients had a biochemical response to treatment (60% vs 88%; P < .0001). Independent predictors of poor biochemical response were younger age at diagnosis and Hispanic ethnicity. CONCLUSIONS: In a cross-sectional study, patients of Hispanic ethnicity with PBC had an increased prevalence of overlap syndrome, reduced response to UDCA treatment, and more frequent complications of portal hypertension than non-Hispanic patients.

An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus.

BACKGROUND & AIMS: Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We analyzed methods of risk assessment and interventions for MTCT. METHODS: We reviewed 63 articles and abstracts published from 1975-2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database. RESULTS: Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6-12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%-30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (10(6) copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT. CONCLUSIONS: HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT.