James F. Trotter, M.D.

Asrani, S. K., L. W. Jennings, J. F. Trotter, J. Levitsky, M. K. Nadim, W. R. Kim, S. A. Gonzalez, B. Fischbach, R. Bahirwani, M. Emmett and G. Klintmalm (2018). “A model for Glomerular filtration Rate Assessment In Liver disease (GRAIL) in the presence of renal dysfunction.” Hepatology Oct 19. [Epub ahead of print].

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Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in presence of renal dysfunction. We developed a model for GFR Assessment In Liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction. Measured GFR (mGFR) by iothalamate clearance (n=12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR<30ml/min/1.73m(2) . Prediction of development of chronic kidney disease (mGFR < 20ml/min/1.73m(2) , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n=785) and external validation (n=68,217, 2001-2015). GRAIL had less bias, was more accurate and precise as compared to CKD-EPI, MDRD-4 and MDRD-6 at time points before/after LT for low GFR. For mGFR<30ml/min/1.73m(2) , the median difference (eGFR-mGFR) was GRAIL: 5.24 [9.65] ml/min/1.73m(2) as compared to CKD-EPI: 8.70 [18.24]ml/min/1.73m(2) , MDRD-4: 8.82 [17.38]ml/min/1.73m(2) , and MDRD-6: 6.53[14.42] ml/min/1.73m(2) . Prior to LT, GRAIL correctly classified 75% as having mGFR<30ml/min/1.73m(2) vs. 36.1% (CKD-EPI), 36.1%(MDRD-4), and 52.8%(MDRD-6).(p<0.01) An eGFR<30ml/min/1.73m(2) by GRAIL predicted development of CKD (26.9% vs. 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% vs. 22.0% CKD-EPI vs. 23.1% MDRD-4 vs. 48.3% MDRD-6, p<0.01) in national data within 5 years after LT. CONCLUSION: GRAIL may serve as an alternative model to estimate GFR amongst patients with liver disease before and after LT at low GFR.

Asrani, S. K., L. Hall, M. Hagan, S. Sharma, S. Yeramaneni, J. Trotter, J. Talwalkar and F. Kanwal (2018). “Trends in Chronic Liver Disease-Related Hospitalizations: A Population-Based Study.” Am J Gastroenterol Oct 17. [Epub ahead of print].

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OBJECTIVES: In a population-based study, we examined time trends in chronic liver disease (CLD)-related hospitalizations in a large and diverse metroplex. METHODS: We examined all CLD-related inpatient encounters (2000-2015) in Dallas-Fort Worth (DFW) using data from the DFW council collaborative that captures claims data from 97% of all hospitalizations in DFW (10.7 million regional patients). RESULTS: There were 83,539 CLD-related hospitalizations in 48,580 unique patients across 84 hospitals. The age and gender standardized annual rate of CLD-related hospitalization increased from 48.9 per 100,000 in 2000 to 125.7 per 100,000 in 2014. Mean age at hospitalization increased from 54.0 (14.1) to 58.5 (13.5) years; the proportion of CLD patients above 65 years increased from 24.2% to 33.1%. HCV-related hospitalizations plateaued, whereas an increase was seen in hospitalizations related to alcohol (9.1 to 22.7 per 100,000) or fatty liver (1.4 per 100,000 to 19.5 per 100,000). The prevalence of medical comorbidities increased for CLD patients: coronary artery disease (4.8% to 14.3%), obesity (2.8% to 14.6%), chronic kidney disease (2.8% to 18.2%), and diabetes (18.0% to 33.2%). Overall hospitalizations with traditional complications of portal hypertension (ascites, varices, and peritonitis) remained stable over time. However, hospitalization with complications related to infection increased from 54.7% to 66.4%, and renal failure increased by sevenfold (2.7% to 19.5%). CONCLUSION: CLD-related hospitalizations have increased twofold over the last decade. Hospitalized CLD patients are older and sicker with multiple chronic conditions. Traditional complications of portal hypertension have been superseded by infection and renal failure, warranting a need to redefine what it means to have decompensated CLD.

Soape, M. P., R. S. Rahimi, C. W. Spak and J. F. Trotter (2018). “Case Report of a Rare Presentation of Isolated Cytomegalovirus Hepatitis After Renal Transplantation.” Prog Transplant 28(3): 296-298.

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Although CMV infection and disease are recognized complications of renal transplant, CMV hepatitis is distinctly uncommon. A recent study showed kidney transplant recipients receiving CMV prophylaxis, and CMV disease incidence was 19.2%. Thus, CMV disease was not surprising in this case, given the multiple risk factors. Thymoglobulin induction alone increased the risk of CMV infection by 4 times. With these risk factors, the transplanted kidney was uncharacteristically spared. Our case reemphasizes the significance for CMV prophylaxis, which was not optimized with our patient, and stopping valganciclovir certainly contributed to disease progression. Prophylaxis is defined as administration of antiviral agents at the onset of the transplantation. Our institutional protocol outlines the prophylactic use of valganciclovir in all liver and kidney transplantations. Another form of preventive CMV therapy is preemptive, which involves periodic monitoring of viremia to allow for prompt treatment. It has been shown that any form of preventive treatment for any CMV serology status has decreased CMV-associated mortality, all-cause mortality, and clinically important diseases due to opportunistic infections. To our knowledge, it has been 20 years since an isolated CMV hepatitis in renal transplantation was reported in the United States and none since the advent of current CMV prophylaxis regimens. In conclusion, this case illustrates the importance of CMV prophylaxis while presenting a rare case of isolated CMV hepatitis. (Excerpt from text, p. 298; no abstract available.)

Asrani, S. K., M. Kouznetsova, G. Ogola, T. Taylor, A. Masica, B. Pope, J. Trotter, P. Kamath and F. Kanwal (2018). “Increasing Health Care Burden of Chronic Liver Disease Compared With Other Chronic Diseases, 2004-2013.” Gastroenterology 155(3): 719-729.e714.

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BACKGROUND & AIMS: Chronic liver disease (CLD) is a common and expensive condition, and studies of CLD-related hospitalizations have underestimated the true burden of disease. We analyzed data from a large, diverse health care system to compare time trends in CLD-related hospitalizations with those in congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). METHODS: We collected data from a large health care system in Texas on hospitalizations related to CLD (n = 27,783), CHF (n = 60,415), and COPD (n = 34,199) from January 1, 2004 through December 31, 2013. We calculated annual hospitalization rates (per 100,000) and compared hospital course, inpatient mortality, ancillary services, and readmissions. RESULTS: Compared with patients with CHF (median age, 71 years) or COPD (median age, 69 years), patients with CLD were significantly younger (median age, 57 years) (P < .01 vs CHF and COPD). Higher proportions of patients with CLD were uninsured (11.7% vs 5.4% for CHF and 5.4% for COPD, P < .01) and Hispanic (17% for CLD vs 9.3% for CHF and 5.0% for COPD, P < .01). A lower proportion of patients with CLD had Medicare (41.5% vs 68.6% with CHF and 70.1% with COPD, P < .01). From 2004 through 2013, the rate of CLD-related hospitalization increased by 92% (from 1295/100,000 to 2490/100,000), compared with 6.7% for CHF (from 3843/100,000 to 4103/100,000) and 48.8% for COPD (from 1775/100,000 to 2642/100,000). During this time period, CLD-related hospitalizations covered by Medicare increased from 31.8% to 41.5%, whereas hospitalizations covered by Medicare did not change for CHF (remained at 70%) or COPD (remained at 70%). Patients with CLD had longer hospital stays (7.3 days vs 6.2 days for CHF and 5.9 days for COPD, P < .01). A higher proportion of patients with CLD died or were discharged to hospice (14.2% vs 11.5% of patients with CHF and 9.3% of patients with COPD, P < .01), and a smaller proportion had access to postacute care (13.2% vs 23.2% of patients with CHF and 27.4% of patients with COPD, P < .01). A higher proportion of patients with CLD were readmitted to the hospital within 30 days (25% vs 21.9% of patients with CHF and 20.6% with COPD, P < .01). CONCLUSIONS: Patients with CLD, compared with selected other chronic diseases, had increasing rates of hospitalization, longer hospital stays, more readmissions, and, despite these adverse outcomes, less access to postacute care. Disease management models for CLD are greatly needed to manage the anticipated increase in hospitalizations for CLD.

Asrani, S. K., G. Saracino, J. G. O’Leary, S. Gonzales, P. T. Kim, G. J. McKenna, G. Klintmalm and J. Trotter (2018). “Recipient characteristics and morbidity and mortality after liver transplantation.” J Hepatol 69(1): 43-50.

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BACKGROUND AND AIMS: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. We sought to identify an easily applicable set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within five years after liver transplantation. METHODS: We collected national (n=31,829, 2002-2015) and center-specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (five patients; hazard ratio [HR] 1.59; 95% CI 1.48-1.72); recipient age >60years (three patients; HR 1.29; 95% CI 1.23-1.36); hemodialysis (three patients; HR 1.26; 95% CI 1.16-1.37); diabetes (two patients; HR 1.20; 95% CI 1.14-1.27); or serum creatinine >/=1.5mg/dl without hemodialysis (two patients; HR 1.15; 95% CI 1.09-1.22). RESULTS: Graft survival within five years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with >8points, graft survival was 42% (model for end-stage liver disease [MELD] score <25) and 50% (MELD score 25-35) in recipients receiving grafts from donors with a donor risk index >1.7. In center-specific data within the first year, subjects with >/=5points (vs. 0-4) had longer hospitalization (11 vs. 8days, p<0.01), higher admissions for rehabilitation (12.3% vs. 2.7%, p<0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p<0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p=0.03) within five years. CONCLUSION: The impact of co-morbidities in an MELD-based organ allocation system need to be reassessed. The proposed clinical tool may be helpful for center-specific assessment of risk of graft failure in non-HCV patients and for discussion regarding relevant morbidity in selected subsets. LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age >60years, ventilator status, diabetes, hemodialysis and creatinine >1.5mg/dl) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics leads to lower survival.