Ross A. Dierkhising

Frequency and Outcomes of Liver Transplantation for Nonalcoholic Steatohepatitis in the United States

BACKGROUND & AIMS The relative frequency of nonalcoholic steatohepatitis (NASH) as an indication for liver transplantation and comparative outcomes following transplantation are poorly understood. METHODS We analyzed the Scientific Registry of Transplant Recipients for primary adult liver transplant recipients from 2001 to 2009. RESULTS From 2001 to 2009, 35,781 patients underwent a primary liver transplant, including 1959 for who NASH was the primary or secondary indication. The percentage of patients undergoing a liver transplant for NASH increased from 1.2% in 2001 to 9.7% in 2009. NASH is now the third most common indication for liver transplantation in the United States. No other indication for liver transplantation increased in frequency during the study period. Compared with other indications for liver transplantation, recipients with NASH are older (58.5±8.0 vs 53.0±8.9 years; P<.001), have a larger body mass index (>30 kg/m2) (63% vs 32%; P<.001), are more likely to be female (47% vs 29%; P<.001), and have a lower frequency of hepatocellular carcinoma (12% vs 19%; P<.001). Survival at 1 and 3 years after liver transplantation for NASH was 84% and 78%, respectively, compared with 87% and 78% for other indications (P=.67). Patient and graft survival for liver recipients with NASH were similar to values for other indications after adjusting for level of creatinine, sex, age, and body mass index. CONCLUSIONS NASH is the third most common indication for liver transplantation in the United States and is on a trajectory to become the most common. Outcomes for patients undergoing a liver transplant for NASH are similar to those for other indications.

Incidence, Prevalence, and Survival of Chronic Pancreatitis: A Population-Based Study

OBJECTIVES:Population-based data on chronic pancreatitis (CP) in the United States are scarce. We determined incidence, prevalence, and survival of CP in Olmsted County, MN.METHODS:Using Mayo Clinic Rochesters Medical Diagnostic Index followed by a detailed chart review, we identified 106 incident CP cases from 1977 to 2006 (89 clinical cases, 17 diagnosed only at autopsy); CP was defined by previously published Mayo Clinic criteria. We calculated age- and sex-adjusted incidence (for each decade) and prevalence rate (1 January 2006) per 100,000 population (adjusted to 2000 US White population). We compared the observed survival rate for patients with expected survival for age- and sex-matched Minnesota White population.RESULTS:Median age at diagnosis of CP was 58 years, 56% were male, and 51% had alcoholic CP. The overall (clinical cases or diagnosed only at autopsy) age- and sex-adjusted incidence was 4.05/100,000 person-years (95% confidence interval (CI) 3.27–4.83). The incidence rate for clinical cases increased significantly from 2.94/100,000 during 1977–1986 to 4.35/100,000 person-years during 1997–2006 (P<0.05) because of an increase in the incidence of alcoholic CP. There were 51 prevalent CP cases on 1 January 2006 (57% male, 53% alcoholic). The age- and sex-adjusted prevalence rate per 100,000 population was 41.76 (95% CI 30.21–53.32). At last follow-up, 50 patients were alive. Survival among CP patients was significantly lower than age- and sex-specific expected survival in Minnesota White population (P<0.001).CONCLUSIONS:Incidence and prevalence of CP are low, and ∼50% are alcohol related. The incidence of CP cases diagnosed during life is increasing. Survival of CP patients is lower than in the Minnesota White population.

The insensitivity of endoscopic markers in celiac disease

Abstract OBJECTIVES: Celiac disease (CD) is characterized by small intestinal inflammation and mucosal atrophy. Endoscopic markers of villous atrophy are reported to be present in 88–100% of untreated celiac patients. In patients being evaluated for iron deficiency anemia (IDA), we examined whether endoscopic markers could predict histological results consistent with CD. METHODS: One hundred thirteen patients without histories of CD had small bowel biopsies to evaluate IDA using videoendoscopy. Markers suggesting villous atrophy were noted at endoscopy. Biopsy specimens were reviewed for consistency with CD. Endoscopic and histological findings were compared. RESULTS: Seventeen patients were diagnosed with CD, both clinically and histologically. Loss of folds was the most sensitive marker of villous atrophy, present in 47% with CD, with 97% specificity. The mosaic pattern was much less sensitive (12%), with 100% specificity. Nodularity and scalloping had low sensitivities (6%), but specificities of 95% and 100%, respectively. A finding of any endoscopic marker yielded a sensitivity of 59% and specificity of 92% for CD. CONCLUSIONS: Although endoscopic markers have been guides for directing small bowel biopsies in patients suspected of having CD, we found sensitivities of these markers to be low and conclude that they should not be relied upon for detecting CD in patients presenting with IDA.

Single-Center Experience With Drug-Induced Liver Injury From India: Causes, Outcome, Prognosis, and Predictors of Mortality

OBJECTIVES:Although drug-induced liver injury (DILI) is rare, it may result in significant morbidity or death. The causes and outcome vary according to regions, with acetaminophen and complementary medicines common in the West and the Far East, respectively. This study evaluates the causes, outcomes, predictors, and models for 90-day mortality from DILI from India.METHODS:Consecutive patients with DILI from 1997 to 2008 based on International Consensus Criteria from a medical college hospital setting were studied.RESULTS:Of the 313 patients, 58% were males. Leading causes were a combination of four anti-tuberculous drugs (ATDs) (58%), anti-epileptics (11%), olanzapine (5.4%), and dapsone (5.4%). The overall 90-day mortality of 17.3% was significantly higher for ATD hepatitis (21.5%) vs. those without (11.4%) (P=0.02). The highest mortality was for leflunomide (75%). Seventy-eight percent of patients received more than one drug. Fulminant hepatic failure developed more commonly in females than in males (23% vs. 17%). Of the 66% of cases with jaundice and/or icterus, mortality was 26%. Multivariable models for mortality using a combination of encephalopathy, ascites, and bilirubin, or a combination of albumin, prothrombin time, and white blood cell count yielded a C-statistic of at least 0.86 by recursive partitioning and 0.92 by logistic regression. Model for end stage liver disease (MELD) scores of 38 and 46 yield probabilities of death of 0.90 (confidence interval (CI): 0.71–0.97) and 0.99 (CI: 0.90–1.00), respectively.CONCLUSIONS:DILI results in significant overall mortality (17.3%). ATDs, anti-convulsants, sulphonamides, and olanzapine are the leading causes of DILI. Although common in males, more females developed fulminant hepatic failure. High-MELD score or a combination of ascites, encephalopathy, high bilirubin, prothrombin time, and leukocyte count are predictive of mortality.

Delayed-onset primary cytomegalovirus disease after liver transplantation

Clinical practice guidelines recommend antiviral prophylaxis to cytomegalovirus (CMV) donor‐positive/recipient‐negative (D+/R−) liver transplant recipients. We assessed the outcome of this strategy by determining the incidence, clinical features, and risk factors of CMV disease among CMV D+/R− liver transplant recipients who received antiviral prophylaxis. Sixty‐seven CMV D+/R− liver transplant recipients (mean age ± standard deviation: 49.5 ± 11.4 years; 75% male) received oral ganciclovir [n = 9 (13%)] or valganciclovir [n = 58 (87%)] prophylaxis for a median duration of 92 days (interquartile range: 91‐100). No breakthrough CMV disease was observed during antiviral prophylaxis. However, primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1, 3, 6, 12, and 24 months, respectively, after antiviral prophylaxis was stopped. The incidence of delayed‐onset primary CMV disease was similar between those who received oral ganciclovir and valganciclovir. Nine (47%) patients had CMV syndrome, 8 (42%) had gastrointestinal CMV disease, and 2 (11%) had CMV hepatitis. Female patients (P = 0.01) and younger age at transplant (P = 0.03) were associated with an increased risk, whereas diabetes mellitus (P < 0.001) was significantly associated with a lower risk of delayed‐onset primary CMV disease. Allograft loss or mortality occurred in 8 (12%) patients during the median follow‐up period of 3.31 (range: 0.8‐5.9) years. No significant association was observed between CMV disease and patient and allograft survival. In conclusion, CMV disease remains a common complication in CMV D+/R− liver transplant patients during the contemporary era of antiviral prophylaxis. Female patients and younger patients are at increased risk of delayed‐onset primary CMV disease. Liver Transpl 13: 1703–1709, 2007.

Occurrence of and risk factors for complications after endoscopic dilation in eosinophilic esophagitis

BACKGROUND Several small series have suggested an increased risk of complications associated with esophageal dilation in patients with eosinophilic esophagitis (EoE). OBJECTIVE To quantitate the risk and identify risk factors for esophageal complications in dilation in EoE patients. DESIGN Retrospective, uncontrolled, single-center study. SETTING Tertiary referral hospital. PATIENTS A total of 161 EoE patients (mean ± standard deviation age 44.3 ± 15.3 years, 112 men, 49 women, 150 white patients, 10 unknown, 1 Asian). INTERVENTIONS Through-the-scope balloon or Savary dilation of EoE. MAIN OUTCOME MEASUREMENTS The rate of complications defined as deep mucosal tear, major bleeding, or perforation, and determination of risk factors for complications. RESULTS A total of 293 dilations were performed in 161 patients. Complications reported were deep mucosal tear in 9.2% (n = 27), major bleeding in 0.3% (n = 1), and immediate perforation in 1.0% (n = 3). All patients with perforations were successfully treated medically without surgery (mean ± standard deviation hospital stay 5.3 ± 3.2 days). Factors associated with an increased risk of complications were luminal narrowing in the upper (odds ratio [OR], 5.62; 95% CI, 2.07-15.26; P < .001) and middle third of the esophagus (OR, 4.93; 95% CI, 1.64-14.83; P < .005) compared with lower third, luminal stricture unable to be traversed with a standard upper endoscope (OR, 2.48; 95% CI, 1.06-5.83; P = .037), and use of Savary dilator (OR, 2.63; 95% CI, 1.18-5.83; P = .018). LIMITATIONS Retrospective design, uncontrolled study. CONCLUSIONS Deep mucosal tears are common after dilation (9%), but the risk of immediate transluminal perforation with EoE is approximately 1%. The risk of severe complications is increased in patients with more proximal stricture and strictures that initially prevent endoscope passage.

The usefulness of Routine small bowel biopsies in evaluation of iron deficiency anemia

Background Iron deficiency anemia (IDA) may be the sole manifestation of celiac disease. The role of routine small bowel biopsies obtained during endoscopy in the evaluation of IDA is unclear. This study assessed the usefulness of routine small bowel biopsies in patients presenting with IDA. Study Evaluation of 103 consecutive patients with IDA undergoing panendoscopy with routine small bowel biopsies was performed. All patients had a diagnosis of IDA with either a ferritin less than 15 μg/L or iron saturation less than 8%. Celiac disease was defined as total or partial villous atrophy with intraepithelial lymphocytosis, histologically, and a clinical response to gluten free diet. Gastrointestinal symptoms were recorded. Results Nine patients (8.7%) were diagnosed with celiac disease. Of these patients, endoscopic lesions potentially responsible for IDA were found in 33%. We found no statistically significant difference when comparing reports of diarrhea, weight loss, abdominal pain, nausea or vomiting, aspirin or NSAID use, or menopausal status with celiac disease status. Conclusions Routine small bowel biopsies to evaluate for celiac disease are indicated in the evaluation of patients with IDA. The finding of endoscopic lesions that may otherwise explain IDA should not preclude small bowel biopsy.

Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features.

OBJECTIVES To estimate the prevalence of cellac disease (CD) in pediatric and adult type 1 diabetes melitus in a defined population and to describe clinical features and HLA class II genotypes predictive of CD in screened patients with type 1 diabetes. PATIENTS AND METHODS All residents of Olmsted County, Minnesota, with type 1 diabetes mellitus on the prevalence date January 1, 2001, were identified with the use of an established medical records linkage system (Rochester Epidemiology Project) and defined clinical criteria. Consenting patients underwent serologic screening with endomyslal antibody and tissue transglutaminase antibody testing and Intestinal biopsies to confirm the diagnosis of CD. A subset of screened patients also underwent HLA class II genotyping. Quality-of-life screening (Medical Outcomes Study 36-Item Short-Form Health Survey) was completed in a subset of patients at the time of serologic screening. RESULTS Overall, 392 Olmsted County residents with type 1 diabetes on January 1, 2001, were Identified. A total of 158 patients with type 1 diabetes were tested, representing 40% (158/392) of the enumerated diabetic population, and 11 had biopsy-proven CD for an estimated point prevalence of 7.0% (95% confidence Interval, 3.5%-12.1%). Most CD-positive diabetic patients were asymptomatic and expressed an at-risk CD haplotype with at least one of but not both HLA DQ2 or DQ8. CONCLUSIONS Celiac disease Is not rare In North American patients with type 1 diabetes, and most CD-positive diabetic patients are asymptomatic Irrespective of age at screening.

Incidence of and Risk Factors for Skin Cancer After Heart Transplant

OBJECTIVE To examine the incidence, tumor burden, and risk factors for nonmelanoma and other skin cancer types in this heart transplant cohort. DESIGN Retrospective review of patient medical records. SETTING Tertiary care center. Patients All heart transplant recipients at Mayo Clinic from 1988 to 2006. MAIN OUTCOME MEASURES Cumulative incidence of skin cancer and tumor burden, with Cox proportional hazards regression models used to evaluate risk factors for posttransplant primary and secondary nonmelanoma skin cancer. RESULTS In total, 312 heart transplant patients had 1395 new skin cancers in 2097 person-years (mean, 0.43 per year per patient) with a range of 0 to 306 for squamous cell carcinoma (SCC) and 0 to 17 for basal cell carcinoma (BCC). The cumulative incidence rates of any skin cancer were 20.4%, 37.5%, and 46.4% at 5, 10, and 15 years after heart transplant, respectively. Cumulative incidence of SCC after the first BCC was 98.1% within 7 years. Multivariate analysis showed that posttransplant nonskin cancer, increased age, and heart failure etiologic factors other than idiopathic disease were associated with increased risk of SCC. Posttransplant herpes simplex viral infection, increased age, and use of mycophenolate mofetil for immunosuppression were associated with increased risk of BCC. CONCLUSIONS With prolonged survival, many heart transplant patients have numerous skin cancers. Vigilant sun protection practices, skin cancer education, and regular skin examination are appropriate interventions in these high-risk patients.

Hepatopulmonary syndrome: Favorable outcomes in the MELD exception era

Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality, regardless of the cause or severity of liver disease. Liver transplantation (LT) improves survival in HPS. We present the largest consecutive series of HPS patients specifically addressing long‐term survival relative to the degree of hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan‐Meier methodology. LT was accomplished in 49 HPS patients. Post‐LT survival (1, 3, 5, and 10 years) did not differ between groups based on baseline partial pressure of arterial oxygen (PaO2) obtained at the time of HPS diagnosis. Improvements in overall survival at 1, 3, and 5 years post‐LT in those HPS patients transplanted after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively) did not reach statistical significance (5‐year P = 0.09). Model for Endstage Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since January 1 2002 with post‐LT survival of 19/21 patients and one wait‐list death. Conclusion: Long‐term outcome after LT in HPS is favorable, with a trend towards improved survival in the MELD exception era since 2002 as compared to earlier HPS transplants. Survival after LT was not associated with PaO2 levels at the time of HPS diagnosis. (HEPATOLOGY 2012)