Robert S. Rahimi M.D.

Posted July 15th 2017

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

Robert S. Rahimi M.D.

Robert S. Rahimi M.D.

Elwir, S. and R. S. Rahimi (2017). “Hepatic encephalopathy: An update on the pathophysiology and therapeutic options.” J Clin Transl Hepatol 5(2): 142-151.

Full text of this article.

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.


Posted April 15th 2016

Acute on chronic liver failure: definitions, treatments and outcomes.

Robert S. Rahimi M.D.

Robert S. Rahimi, M.D.

Rahimi, R. S. and D. C. Rockey (2016). “Acute on chronic liver failure: definitions, treatments and outcomes.” Curr Opin Gastroenterol. 2016 May;32(3):172-81.

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PURPOSE OF REVIEW: Acute on chronic liver failure (ACLF) causes significant morbidity and mortality in patients with cirrhosis and/or chronic liver disease (CLD). The purpose of this review is to highlight recent studies that have better defined ACLF, and to highlight current outcomes and treatment strategies. RECENT FINDINGS: Currently, there are no clear definitions for ACLF; however, ACLF requires a precipitating event that occurs in the setting of cirrhosis and/or CLD, and progresses rapidly to multiorgan failure with high mortality. Most precipitants of ACLF are due to infections, leading to inflammatory cascades, hence early treatment with antibiotics in these cases might show benefit. Prognosis in ACLF typically depends on the number of extrahepatic organs affected. Potential biomarkers in ACLF may result in early detection and risk stratification; however, further research is needed. ACLF portends a poor prognosis; however, rescue therapy with liver transplantation has been considered in selected cases. SUMMARY: ACLF is a common and devastating complication of cirrhosis or CLD. ACLF usually requires a precipitating event and rapid progression to multiorgan failure with high mortality. Although signs and symptoms might overlap in patients with ACLF and those with decompensated cirrhosis, the two entities should be distinguished separately (although it is challenging to differentiate these in certain cases). Furthermore, diagnosing each entity should be based on a variety of clinical indicators, laboratory data and precipitating factors, in order to determine the best possible targeted treatment strategies. Refinement in the clinical definitions for ACLF may lead to better management and possibly better outcomes if recognized early.


Posted March 15th 2016

Hepatic Encephalopathy: Pharmacological Therapies Targeting Ammonia.

Robert S. Rahimi M.D.

Robert S. Rahimi, M.D.

Rahimi, R. S. and D. C. Rockey (2016). “Hepatic Encephalopathy: Pharmacological Therapies Targeting Ammonia.” Semin Liver Dis 36(1): 48-55.

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Hepatic encephalopathy (HE) is a major complication in patients with decompensated cirrhosis, leading to higher readmission rates causing a profound burden of disease and considerable health care costs. Because ammonia is thought to play a crucial role in the pathogenesis of HE, therapies directed at reducing ammonia levels are now being aggressively developed. Ammonia scavengers such as AST-120 (spherical carbon adsorbent), glycerol phenylbutyrate, sodium phenylacetate or sodium benzoate, and ornithine phenylacetate have been used to improve HE symptoms. A new approach, bowel cleansing with polyethylene glycol 3350, appears to be a promising therapy, with a recent study demonstrating a more rapid improvement in overt HE (at 24 hours after treatment) than lactulose. Extracorporeal devices, although now used primarily in research settings, have also been utilized in patients with refractory HE, but are not approved for clinical management.


Posted February 19th 2016

Transfusing common sense instead of blood products into coagulation testing in patients with cirrhosis: Overtreatment not equal safety.

Robert S. Rahimi M.D.

Robert S. Rahimi, M.D.

Rahimi, R. S. and J. G. O’Leary (2016). “Transfusing common sense instead of blood products into coagulation testing in patients with cirrhosis: Overtreatment not equal safety.” Hepatology 63(2): 368-370.

Full text of this article.

In patients with cirrhosis the imbalance of procoagulants and anticoagulants combined with potential alterations in fibrinolysis and platelet number and function can alter standard laboratory coagulation testing. Prothrombin time and platelet count are frequently abnormal and, in our risk-averse health care system, often result in preprocedure transfusions to achieve “safer” thresholds. But what are we actually achieving: a risk of portal hypertensive bleeding, transfusion reaction, transfusion-related acute lung injury, infection transmission, human leukocyte antigen (HLA) antibody development, superior test results, or improved coagulation? According to the International Symposium on Coagulopathy and Liver Disease, rebalanced hemostasis is what we need to measure, which stems from both the prohemostatic and antihemostatic pathways working in concert. Disproportionately fewer nonportal hypertension-related bleeding complications occur in patients with cirrhosis relative to their prothrombin time and platelet values. This results from relatively rebalanced hemostasis. Despite this, many health care professionals continue to transfuse blood products (i.e., fresh frozen plasma [FFP] and platelets) prophylactically to improve laboratory profiles, regardless of function and prior data demonstrating a low risk of bleeding complications in patients with cirrhosis, especially for inimally invasive procedures like paracentesis. Fortunately, the study by De Pietri and colleagues in this issue of Hepatology offers an alternative to unnecessary preprocedural use of blood products in patients with cirrhosis with an elevated international normalized ratio (>1.8) and/or thrombocytopenia (<50 × 103/µL) using thromboelastography (TEG) to guide transfusions.4 TEG was adopted into clinical practice in 1985, more than 35 years after the procedure was first pioneered for research purposes. Using approximately 0.35 mL of whole blood in an oscillating cup at 37oC, this test uses mechanically transduced waves at different rates to graphically illustrate the patient's coagulation function. TEG is already used clinically in liver transplant, cardiovascular, trauma, and obstetric surgery where dynamic changes in blood volume and coagulation occur. This semiautomated bedside instrument easily yields an overall coagulation assessment in 30 minutes, with prolonged times resulting in blood product transfusions. A prolonged reaction time measures clot formation, indicative of coagulation factor function and results in transfusion (i.e., usually FFP), while a prolonged maximum amplitude measures clot strength, indicative of platelet function and results in transfusion. The authors of this open-label, intention-to-treat trial randomized patients to TEG-guided transfusion where patients only received transfusion if their functional coagulation was altered versus standard of care preprocedural prophylactic transfusion therapy.4 Of note, only 16.7% of TEG-guided patients received transfusions compared to 100% of patients in the standard of care arm (P = 0.009). Although platelet levels >50,000/µL have sufficient thrombin production, the use of FFP and platelet transfusions in patients with cirrhosis rarely, if ever, achieves complete normalization of coagulation parameters by standard testing. Of note, although allogenic transfusions at times are necessary, their cost and more importantly risk must also be taken into account (Table 1). The risk of overtransfusion was highlighted in a recent randomized controlled trial comparing liberal (hemoglobin <9 g/dL) versus restrictive (hemoglobin <7 g/dL) pack red blood cell (RBC) transfusion strategies in acute upper gastrointestinal bleeding. This trial subsequently resulted in a lower hemoglobin threshold (<7 g/dL) for RBC transfusion in general clinical care. Furthermore, liberal blood transfusions in patients with cirrhosis, compared to restrictive strategies, had the additional risk of worsening portal hypertension (P = 0.03) and resulted in higher bleeding complication rates (P = 0.01), a longer length of stay (P = 0.01), and more adverse events (P = 0.02; especially transfusion associated overload, P = 0.001), culminating in an increased all-cause 45-day mortality (P = 0.02).