Robert S. Rahimi M.D.

Lai, J. C., J. L. Dodge, M. R. Kappus, M. A. Dunn, M. L. Volk, A. Duarte-Rojo, D. R. Ganger, R. S. Rahimi, C. E. McCulloch, C. E. Haugen, M. McAdams-DeMarco, D. Ladner, D. L. Segev and E. C. Verna (2020). “Changes in frailty are associated with waitlist mortality in patients with cirrhosis.” J Hepatol Mar 30. pii: S0168-8278(20)30191-4. [Epub ahead of print].

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BACKGROUND & AIMS: Frailty is predictive of death in patients with cirrhosis, but studies to date have been limited to assessments at a single time point. We aimed to evaluate changes in frailty over time (DeltaLFI) and its association with death/delisting for sickness. METHODS: Adults with cirrhosis listed for liver transplantation without hepatocellular carcinoma at 8 U.S. centers underwent ambulatory longitudinal frailty testing with the Liver Frailty Index (LFI). We used multilevel linear mixed effects regression to model and predict DeltaLFI per 3 months based on age, gender, MELDNa, ascites, and hepatic encephalopathy (HE) and categorize patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted DeltaLFI on death/delisting, with transplantation as the competing risk. RESULTS: We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe frailty worsening had worse baseline LFI and were more likely to have NAFLD, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted for sickness. The cumulative incidence of death/delisting increased by worsening DeltaLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELDNa, and albumin, a 0.1 unit change in DeltaLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI, 1.35-3.09). CONCLUSION: Changes in frailty were significantly associated with death/delisting independent of baseline frailty and MELDNa. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting than those who experienced worsening frailty. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.

Bajaj, J. S., M. Lauridsen, E. B. Tapper, A. Duarte-Rojo, R. S. Rahimi, P. Tandon, D. L. Shawcross, D. Thabut, R. K. Dhiman, M. Romero-Gomez, B. C. Sharma and S. Montagnese (2020). “Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus.” Am J Gastroenterol Mar 30. [Epub ahead of print].

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Management of hepatic encephalopathy (HE) remains challenging from a medical and psychosocial perspective. Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management focused on (i) driving, (ii) ammonia levels in clinical practice, (iii) testing strategies for covert or minimal HE, (iv) therapeutic options, and (v) nutrition and patient-reported outcomes. The consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice, laying the groundwork for future investigations.

Sundaram, V., S. Kogachi, R. J. Wong, C. J. Karvellas, B. E. Fortune, N. Mahmud, J. Levitsky, R. S. Rahimi and R. Jalan (2020). “Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival.” J Hepatol 72(3): 481-488.

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BACKGROUND & AIMS: Patients with acute-on-chronic liver failure (ACLF) can be listed for liver transplantation (LT) because LT is the only curative treatment option. We evaluated whether the clinical course of ACLF, particularly ACLF-3, between the time of listing and LT affects 1-year post-transplant survival. METHODS: We identified patients from the United Network for Organ Sharing database who were transplanted within 28 days of listing and categorized them by ACLF grade at waitlist registration and LT, according to the EASL-CLIF definition. RESULTS: A total of 3,636 patients listed with ACLF-3 underwent LT within 28 days. Among those transplanted, 892 (24.5%) recovered to no ACLF or ACLF grade 1 or 2 (ACLF 0-2) and 2,744 (75.5%) had ACLF-3 at transplantation. One-year survival was 82.0% among those transplanted with ACLF-3 vs. 88.2% among those improving to ACLF 0-2 (p <0.001). Conversely, the survival of patients listed with ACLF 0-2 who progressed to ACLF-3 at LT (n = 2,265) was significantly lower than that of recipients who remained at ACLF 0-2 (n = 17,631) at the time of LT (83.8% vs. 90.2%, p <0.001). Cox modeling demonstrated that recovery from ACLF-3 to ACLF 0-2 at LT was associated with reduced 1-year mortality after transplantation (hazard ratio0.65; 95% CI 0.53-0.78). Improvement in circulatory failure, brain failure, and removal from mechanical ventilation were also associated with reduced post-LT mortality. Among patients >60 years of age, 1-year survival was significantly higher among those who improved from ACLF-3 to ACLF 0-2 than among those who did not. CONCLUSIONS: Improvement from ACLF-3 at listing to ACLF 0-2 at transplantation enhances post-LT survival, particularly in those who recovered from circulatory or brain failure, or were removed from the mechanical ventilator. The beneficial effect of improved ACLF on post-LT survival was also observed among patients >60 years of age. LAY SUMMARY: Liver transplantation (LT) for patients with acute-on-chronic liver failure grade 3 (ACLF-3) significantly improves survival, but 1-year survival probability after LT remains lower than the expected outcomes for transplant centers. Our study reveals that among patients transplanted within 28 days of waitlist registration, improvement of ACLF-3 at listing to a lower grade of ACLF at transplantation significantly enhances post-transplant survival, even among patients aged 60 years or older. Subgroup analysis further demonstrates that improvement in circulatory failure, brain failure, or removal from mechanical ventilation have the strongest impact on post-transplant survival.

Fallahzadeh, M. A. and R. S. Rahimi (2020). “Hepatic Encephalopathy and Nutrition Influences: A Narrative Review.” Nutr Clin Pract 35(1): 36-48.

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Hepatic encephalopathy (HE) is a potentially reversible neurocognitive condition seen in patients with advanced liver disease. The overt form of HE has been reported in up to 45% of patients with cirrhosis. This debilitating condition is associated with increased morbidity and mortality and imposes a significant burden on the caregivers and healthcare system. After providing an overview of HE epidemiology and pathophysiology, this review focuses on the interaction of HE and frailty, nutrition requirements and recommendations in cirrhotic patients with HE, and current dietary and pharmacologic options for HE treatment.

Fallahzadeh, M. A. and R. S. Rahimi (2019). “Hepatic Encephalopathy and Nutrition Influences: A Narrative Review.” Nutr Clin Pract Dec 23. [Epub ahead of print].

Full text of this article.

Hepatic encephalopathy (HE) is a potentially reversible neurocognitive condition seen in patients with advanced liver disease. The overt form of HE has been reported in up to 45% of patients with cirrhosis. This debilitating condition is associated with increased morbidity and mortality and imposes a significant burden on the caregivers and healthcare system. After providing an overview of HE epidemiology and pathophysiology, this review focuses on the interaction of HE and frailty, nutrition requirements and recommendations in cirrhotic patients with HE, and current dietary and pharmacologic options for HE treatment.