Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation.

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Prediction of long-term morbidity and mortality after liver transplantation using two-dimensional shear wave elastography compared with liver biopsy.

The role of noninvasive liver disease assessment by two-dimensional shear wave elastography (2D-SWE) to diagnose fibrosis is well described in patients with chronic liver disease. However, its role in prognosis, especially after liver transplantation (LT) has not been adequately examined. We hypothesized that elevated liver stiffness measurement (LSM) as measured by 2D-SWE after LT predicts future morbidity and mortality independent of fibrosis by liver biopsy. In a prospective cohort study, consecutive LT recipients underwent concomitant protocol 2D-SWE and protocol liver biopsy (2012-2014), with the assessor blinded to biopsy findings. We examined the baseline correlation of LSM with fibrosis stage and the association between elevated LSM and the development of subsequent clinical outcomes and all-cause mortality. A total of 187 LT recipients (median age 58 years, 38.5% women, median body mass index 26.5 kg/m2 , 55.1% hepatitis C virus, 17.6% nonalcoholic steatohepatitis/cryptogenic) were examined. Median time between LT and biopsy/2D-SWE assessment was 4.0 years, and the median follow-up time after LSM determination was 3.5 years. Median LSM was 9 kPa (8 kPa [F0/F1], 11.5 kPa [F2], 12 kPa [F3/F4]). There was a positive correlation between LSM and fibrosis stage (rs  = 0.41; p < 0.001). LSM ≥11 kPa was associated with lower survival within 3 years (84.8 vs. 93.7%; p = 0.04). After adjusting for age, sex, and fibrosis stage, LSM ≥11 kPa was independently associated with mortality (hazard ratio, 2.45; 95% confidence interval, 1.08-5.60). Elevated LSM by 2D-SWE is associated with increased mortality after LT independent of hepatic fibrosis. Given the overall decrease in the use of liver biopsy in the current era, 2D-SWE may serve as a novel noninvasive prognostic tool to predict relevant outcomes late after LT.

Barriers in Hepatitis C Treatment in Somali Patients in the Direct Acting Antiviral Therapy Era.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) treatment has changed dramatically in the last few years. Our observations suggest that a minority of HCV infected Somalis are treated. In this study, we aimed to evaluate for treatment and health outcome disparities between Somali and non-Somali patients during the direct acting antiviral (DAA) era. METHODS: Patients with HCV seen in the gastroenterology clinic in 2015 were included in the study. Patients were identified using ICD9 and 10 codes. Electronic medical records were analyzed to evaluate for treatment candidacy, acceptance and reasons for refusal of treatment. RESULTS: Genotype 4 followed by 3 were the most common genotypes in the Somalis while genotype 1 was the most common in the non-Somalis. Majority of patients were offered treatment, active alcohol and substance abuse was a common reason for not offering treatment in non-Somalis while the presence of hepatocellular carcinoma was the most common reason in Somalis. Somalis had higher rates of declining treatment given the asymptomatic nature of their disease and the feeling that treatment is not needed. Sustained virologic response rates were comparable in both groups. CONCLUSIONS: Disparities in acceptance of HCV treatment persist in the DAA era. The asymptomatic nature of the infection and potential cultural mistrust makes patients hesitant to undergo treatment. Healthcare providers must find interventions aimed at reducing barriers to treatment and increasing acceptance of HCV treatment.

Endoscopic Management of Biliary Leaks and Strictures After Living Donor Liver Transplantation: Optimizing Techniques for Successful Management.

BACKGROUND AND AIMS: Biliary complications (BCs) occur in up to 40% of living donor liver transplant (LDLT) recipients. The aim of this study was to evaluate the efficacy of endoscopic therapy in the management of LDLT-related BCs. METHODS: A retrospective study of 100 LDLT recipients at a single transplant center over a 9-year period was conducted. BC was defined as a biliary leak and/or a stricture. Patient records were used to identify time to diagnosis, type of intervention, and time to resolution. RESULTS: BCs occurred in 46 (46%) patients; median follow-up was 4.6 years (range 5 days-9.3 years); and median time to diagnosis was 37.5 days (range 1 day-3.5 years). BCs were classified as a leak in 6 (6%), stricture in 22 (22%), and a leak + stricture in 18 (18%). ERCP was the initial treatment modality in 43/46 (93%) patients and was completed in 42/43 (98%). Three (6.5%) patients with a leak underwent surgery as the primary treatment approach. The median time to resolution of BCs was 91.5 days (range 21-367). Thirteen patients had a recurrence which was managed with endoscopic therapy alone. CONCLUSIONS: Endoscopic therapy was successful in almost all patients (98%) and ERCP alone resulted in successful treatment in a higher proportion of patients (93%) than traditionally reported. Advanced endoscopic techniques obviate the need for PTC and/or surgery and allow successful management in almost all LDLT recipients presenting with BC and in patients with recurrence of strictures.

Ischemic Gastritis: A Multicenter Case Series of a Rare Clinical Entity and a Review of the Literature.

GOALS: To report a case series of ischemic gastritis and discuss its etiology, management, and associated mortality according to our results and the published English literature. BACKGROUND: Ischemic gastritis is rare, given the rich blood supply of the stomach. It has been reported in isolated case reports and small case series. Most cases are vascular in origin and associated with a high mortality. STUDY: Pathology databases from 3 hospitals affiliated with the University of Minnesota Medical School were searched for cases of ischemic gastritis in the last 10 years. Patients' demographics, clinical course, and 1-month and 1-year mortalities were collected from electronic medical records. RESULTS: A total of 12 patients were identified (age range, 32.1 to 83.2), the largest series reported to date. The presenting symptom was gastrointestinal bleeding (8), abdominal pain (2), nausea (1), and symptomatic anemia (1). The etiology included postinterventional radiology embolization (2), hemodynamic changes in the setting of celiac axis stenosis (2), vasculitis (1), systemic hypotension (1), and unknown (6). Treatment included steroid therapy, revascularization by interventional radiology, surgery, or supportive treatment. Thirty-day and 1-year mortalities were 33% and 41%, respectively. CONCLUSIONS: Ischemic gastritis is rare, but associated with a high mortality. Evaluation for treatable etiologies should be sought and corrected if present.

Risk Stratification for Chronic Kidney Disease After Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Cirrhosis: Results From the NailMASH Consortium.

BACKGROUND: Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. METHODS: A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. RESULTS: Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups (P < 0.0001). CONCLUSIONS: The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.

Biliary stenting in patients with malignant biliary obstruction: comparison of double layer, plastic and metal stents.

BACKGROUND AND AIM: The double layer stent (DLS) has a unique design and has been used for palliation of malignant biliary obstruction, but literature on this stent is limited. Our aim was to compare plastic (PS), DLS and metal stents (MS) in terms of complication rates, time to occlusion, and patency rate in patients with malignant biliary obstruction (MBO). METHODS: A retrospective review of stents placed for MBO at our institution in the period between January 2009 and April 2011 was conducted. A total of 114 stents were identified, of which 44 were MS (39 %), 37 DLS (32 %), and 33 PS (29 %). A stent was considered occluded when an unplanned stent removal or intervention occurred due to clinical suspicion of biliary obstruction. RESULTS: Stents remained patent for 95 days (range 7-359 days) in the DLS group and 59 days (range 7-228 days) in the PS group (P = 0.014) and 128.7 days (range 4-602 days) in the metal stent group. Twenty-seven percent (n = 9) of PS occluded after a mean of 60 days while 16 % (n = 7) of MS occluded after a mean of 87 days and 5 % (n = 2) of DLS occluded after a mean of 85 days (DLS vs. PS P = 0.012, DLS vs. MS P = 0.13, MS vs. PS P = 0.22). CONCLUSIONS: DLS are superior to PS in patients with MBO and appear to be comparable to MS. MS had a longer patency rate but were comparable to DLS in early and late complications. We speculate that the less expensive DLS may be a cost effective alternative in the palliation of MBO.

Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options.

Hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities, seen in patients with liver dysfunction and/or portosystemic shunting. One of the most debilitating complications of cirrhosis, encephalopathy affects 30-45% of cirrhotics. In addition to significantly affecting the lives of patients and their caregivers, it is also associated with increased morbidity and mortality as well as significant utilization of health care resources. In this paper, we provide an overview on the pathophysiology, diagnosis, management and newer therapies of hepatic encephalopathy.

Variability in, and factors associated with, sizing of polyps by endoscopists at a large community practice.

BACKGROUND AND AIMS: Accurate sizing of polyps at time of colonoscopy is critical for determining surveillance intervals. Endoscopists routinely over- or underestimate the size of polyps at colonoscopy. We evaluated the variability in sizing of polyps among multiple endoscopists, and the effect of patient and physician related factors on polyp size estimation in a large community-based practice. METHODS: Adult patients who underwent a colonoscopy with polypectomy at five endoscopy centers in Minneapolis/St. Paul by one of 52 endoscopists in 2013 were included in this study. Association of patient, physician, and procedure related factors on polyp sizing was assessed. RESULTS: In the study time frame, 38 624 colonoscopies were performed at five ambulatory endoscopy centers. Of these, 16 336 had one or more polyp removed with size information available, and were included in this analysis. There was significant inter-physician variation for estimating polyp sizes larger than 5 mm (intraclass correlation coefficient [ICC] 0.13). Older patient age (OR 1.08, 95 %CI 1.06 - 1.11), and male physician gender (OR 1.92, 95 %CI 1.26 - 2.94) were associated with increased odds of physicians sizing polyps as larger in size. Surveillance procedures had a higher odds of larger polyp sizing compared to screening (OR 0.91, 95 %CI 0.86 - 0.97) and diagnostic procedures (OR 0.86, 95 %CI 0.78 - 0.94). CONCLUSION: In a large community setting, variation of polyp sizing estimates exists between physicians. Male physicians were more likely to size polyps as larger in size. Older patients and patients undergoing surveillance procedures were more likely to have polyps that were sized as larger in size.

Pancreatitis of ectopic pancreatic tissue: a rare cause of gastric outlet obstruction.

Inflammation in ectopic pancreatic tissue can clinically present with pain or obstructive symptoms, depending on the location of the ectopic tissue. We present a rare case of gastric outlet obstruction secondary to pancreatitis of ectopic pancreatic tissue in the pylorus.

Current Status of Liver Allocation in the United States.

The liver transplant allocation system is currently based upon the Model for End-Stage Liver Disease (MELD) score and allocates organs preferentially to patients with the highest scores (ie, the sickest patients) within a defined geographic unit. In addition, certain patient populations, such as patients with hepatocellular carcinoma and portopulmonary hypertension, receive MELD exception points to account for their increased waitlist mortality, which is not reflected by their MELD score. Significant geographic variation in the access to liver transplantation exists throughout the United States. Both the Organ Procurement and Transplant Network Board of Directors and the Health Resources and Services Administration have determined these geographic disparities to be unacceptable. The liver transplant community has worked to develop methods to reduce these geographic disparities and to reexamine how MELD exception points are granted to certain patient populations. As a result, numerous policy changes have been adopted throughout the years that have broadened the sharing of organs through wider geographic sharing. Despite all of these changes, variation in access to liver transplantation continues to exist, and, thus, the liver transplant community continues to examine new ways to address geographic disparities. This paper reviews several of the key changes to the liver allocation system that have occurred since the implementation of MELD allocation in 2002 and provides an overview of potential changes to the system.

Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient's clinical profile. METHODS: A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P < 0.05) were analysed by a multivariate logistic regression model. RESULTS: A total of 117 patients met the inclusion criteria and were divided into a hepatic encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. CONCLUSION: A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy.