James F. Trotter, M.D.

Alsahhar, J. S., D. Hansen, J. Page, U. Sandkovsky, S. Burdick, J. Trotter and R. S. Rahimi (2019). “An Atypical Biliary Fistula In A Liver Transplant Recipient.” Liver Transpl Jan 28. [Epub ahead of print].

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A 55-years-old Caucasian male presented with chest pain, dyspnea and hypotension four-months after simultaneous liver and kidney transplantation. His post-transplant course was complicated with only one episode of acute cellular rejection one month prior to presentation, successfully treated with steroids. His immunosuppression consisted of tacrolimus and mycophenolic acid. Transthoracic echocardiogram (TTE) in the emergency room showed a large pericardial effusion and tamponade physiology. Emergent pericardiocentesis removed 560 mL of bloody fluid (red blood cell count of 6.74 million) and a pericardial drain was placed. Fluid studies including bacterial, fungal, and acid-fast bacilli cultures, viral PCR (herpes simplex, adenovirus, human herpesvirus 6, cytomegalovirus), histoplasma, coccidioides antigens, and cytology were negative.

Asrani, S. K., L. Hall, M. Hagan, S. Sharma, S. Yeramaneni, J. Trotter, J. Talwalkar and F. Kanwal (2019). “Trends in Chronic Liver Disease-Related Hospitalizations: A Population-Based Study.” Am J Gastroenterol 114(1): 98-106.

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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%). CONCLUSIONS: 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.

O’Brien, A., P. S. Kamath and J. Trotter (2018). “MACHT – Outpatient albumin infusions do not prevent complications of cirrhosis in patients on the liver transplant waiting list.” J Hepatol 69(6): 1217-1218.

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Albumin has long been an important option in the treatment of patients with cirrhosis and ascites. Albumin improves circulatory function; and is widely recommended for use in inpatients with cirrhosis complicated by hepatorenal syndrome and spontaneous bacterial peritonitis, as well as to prevent post paracentesis circulatory dysfunction following large volume paracentesis (LVP). Albumin has beneficial immunomodulatory and endothelial effects.5 Therefore, many centres use albumin as an unproven, but seemingly effective agent as an adjuvant to chronic diuretic therapy for ascites in patients with cirrhosis. In particular, patients regarded to have the greatest potential benefit are those with chronic renal insufficiency who tolerate diuretic therapy poorly. Midodrine, an α‐adrenergic agonist, has been shown to improve systemic and renal hemodynamics in patients with ascites. However, a meta‐analysis of 10 trials using midodrine to treat ascites showed no beneficial effect on survival and when used as an alternative to albumin in LVP, the mortality was higher for midodrine than albumin. Furthermore, the addition of the somatostatin analogue, octreotide to midodrine was not superior to albumin in preventing ascites recurrence compared to albumin. In the current issue of this Journal, Sola et al. report on the MACHT trial (midodrine and albumin for cirrhotic patients in the waiting list for liver transplantation) conducted by the centre with the best record of performing clinically important trials in advanced liver disease. This study showed that in patients with cirrhosis awaiting liver transplantation, outpatient treatment with midodrine and albumin (40 g every 2 weeks) slightly suppressed the vasoconstrictor activity, but neither prevented complications of cirrhosis nor improved survival. This was a double blinded placebo-controlled trial using opaque bags and intravenous sets to administer albumin or placebo. However, only 9 patients were treated for the entire year, the median length of treatment was actually only 80 days and the mortality rate in both arms was very low. This demonstrates how challenging these studies are, in particular “natural history” studies in liver transplant candidates as transplantation frequently interrupts the course of the patients’ disease. Therefore, the results of this important study should be considered in light of these qualifications. (Excerpt from this commentary on the MACHT trial, p. 1217; no abstract available.)

O’Brien, A., P. S. Kamath and J. Trotter (2018). “MACHT – Outpatient albumin infusions do not prevent complications of cirrhosis in patients on the liver transplant waiting list.” J Hepatol Oct 9. [Epub ahead of print].

Full text of this article.

Albumin has long been an important option in the treatment of patients with cirrhosis and ascites. Albumin improves circulatory function; and is widely recommended for use in inpatients with cirrhosis complicated by hepatorenal syndrome and spontaneous bacterial peritonitis, as well as to prevent post paracentesis circulatory dysfunction following large volume paracentesis (LVP). Albumin has beneficial immunomodulatory and endothelial effects.5 Therefore, many centres use albumin as an unproven, but seemingly effective agent as an adjuvant to chronic diuretic therapy for ascites in patients with cirrhosis. In particular, patients regarded to have the greatest potential benefit are those with chronic renal insufficiency who tolerate diuretic therapy poorly. Midodrine, an α‐adrenergic agonist, has been shown to improve systemic and renal hemodynamics in patients with ascites. However, a meta‐analysis of 10 trials using midodrine to treat ascites showed no beneficial effect on survival and when used as an alternative to albumin in LVP, the mortality was higher for midodrine than albumin.7 Furthermore, the addition of the somatostatin analogue, octreotide to midodrine was not superior to albumin in preventing ascites recurrence compared to albumin. In the current issue of this Journal, Sola et al. report on the MACHT trial (midodrine and albumin for cirrhotic patients in the waiting list for liver transplantation) conducted by the centre with the best record of performing clinically important trials in advanced liver disease. This study showed that in patients with cirrhosis awaiting liver transplantation, outpatient treatment with midodrine and albumin (40 g every 2 weeks) slightly suppressed the vasoconstrictor activity, but neither prevented complications of cirrhosis nor improved survival. (Excerpt from text, p. 1-2.)

Idriss, R., J. Hasse, T. Wu, F. Khan, G. Saracino, G. McKenna, T. Giuliano, J. Trotter, G. Klintmalm and S. K. Asrani (2018). “Impact of prior bariatric surgery on perioperative liver transplant outcomes.” Liver Transpl Oct 28. [Epub ahead of print].

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Bariatric surgery (BS) is effective in treating morbid obesity but the impact of prior BS on candidacy for liver transplantation (LT) is unclear. We examined 78 cirrhotic patients with prior BS compared with a concurrent cohort of 156 patients matched by age, MELD score, and underlying liver disease. We compared rates of transplant denial after evaluation, delisting on the waitlist (WL) and survival after LT. The median time from BS to LT evaluation was 7 years. Roux-en-Y gastric bypass was the most common BS procedure performed (63% of cohort). Nonalcoholic fatty liver disease was the leading etiology for liver cirrhosis (47%). Delisting/death on WL was higher among patients with BS (33.3% vs 10.1% P = 0.002) and transplantation rate was lower (48.9% vs 65.2% P =0.03). Intent-to-treat survival from listing to 1 year after LT was lower in the BS vs. concurrent cohort (1-year survival 84% vs 90%, p=0.05). On adjusted analysis, history of BS was associated with an increased risk of death on the WL (HR 5.7, 95% CI 2.2-15.1) but this impact was attenuated (HR, 4.9, 95% CI 1.8-13.4) by presence of malnutrition. When limited to matched controls by gender, mortality attributed to BS was no longer significant for women (p=0.37) but was significant for males (p=0.046). Sarcopenia, as captured by skeletal muscle index, was calculated in a subset of patients (n=49). The total skeletal surface area was lower in the BS group (127cm(2) (105-141) vs 153cm(2) (131-191) p = 0.005). Rates of sarcopenia were higher among patients delisted after listing (71.4% vs. 16.7%, p=0.04). Conclusion History of BS was associated with higher rates of delisting on the WL as well as lower survival from time of listing on intent-to-treat analysis. Presence of malnutrition and sarcopenia among patients with BS may contribute to worse outcomes.