Saab, Sammy

Abstract Purpose Albumin, the most abundant and arguably most important protein in the human body, plays a unique role in decompensated cirrhosis because its structure and function are quantitatively and qualitatively affected. A literature review was performed to provide insights into albumin use. The manuscript was developed using a multidisciplinary approach; 2 hepatologists, a nephrologist, a hospitalist, and a pharmacist, who are all members of or work closely with the Chronic Liver Disease Foundation, collaborated to write this expert perspective review. Summary Cirrhosis represents the potential end in the spectrum of all chronic liver diseases. Decompensated cirrhosis, defined by the overt manifestation of liver failure (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased mortality. Human serum albumin (HSA) infusion serves an important role in the treatment of advanced liver disease. The benefits of HSA administration in patients with cirrhosis are widely accepted, and its use has been advocated by several professional societies. However, inappropriate HSA use can lead to significant adverse patient events. This paper discusses the rationale for the administration of HSA in the treatment of complications of cirrhosis, analyzes the data on the use of HSA in cirrhosis, and streamlines practical recommendations set forth in published guidance. Conclusion Use of HSA in clinical practice needs to be improved. The objective of this paper is to empower pharmacists to facilitate and improve the use of HSA in patients with cirrhosis at their practice sites.

Acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]–AKI) is a severe and often fatal complication of end‐stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in patients who are critically ill. However, interventions have limited efficacy, and mortality rates remain high. In the United States, the mainstay of pharmacologic therapy consists of the off‐label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients because contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor short‐term prognosis in patients with HRS‐AKI and at best serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS‐AKI in the United States is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS‐AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS‐AKI and supported by recommendations for first‐line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS‐AKI and the potential benefits if terlipressin was approved in the United States.

AbstractBackgroundThere has been increasing interest in using protease inhibitors with pegylated interferon and ribavirin to treat recurrent hepatitis C (HCV) disease in liver transplant recipients.MethodsWe retrospectively evaluated the safety and efficacy in liver transplant recipients treated for recurrent hepatitis C genotype 1 with the combination of peginterferon, ribavirin and boceprevir.ResultsTwenty liver transplant recipients were treated for recurrent hepatitis C. Baseline alanine aminotransferase, total bilirubin and HCV RNA values (± SD) were 67.5 (±50.9) mg/dl, 1.78 (±1.99) U/L, and 16 955 510 (±21 620 675) IU/ml. Anaemia was a common adverse event requiring epoetin in 16 of 20 recipients and ribavirin dose reductions in 17 of 20 recipients. One‐third of recipients required a blood transfusion. Filgrastim was used in 11 of 20 patients (55%) and eltrombopag in two of 20 recipients (10%) over the course of treatment. Serum creatinine level increased significantly from a baseline value of 1.33 mg/dl to 1.59 mg/dl at week 20 of boceprevir (P < 0.005). The overall sustained viral response (SVR) was 50%. Of the 14 patients who had a viral load less than 1000 IU/ml at week 4 of boceprevir, the SVR was 71%. The SVR was 83% of the 11 patients who had undetectable viral levels at week 4 of boceprevir.ConclusionsAntiviral therapy utilizing boceprevir in liver transplant recipients requires close monitoring. Anaemia and neutropenia were common requiring growth factors in most recipients. On‐treatment viral responses appear promising but long‐term data are needed.

SummaryBackgroundInfection with the hepatitis C virus (HCV) has been considered a major cause of mortality, morbidity and resource utilisation in the US. In addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent developments in the diagnosis and treatment of HCV, including new recommendations pertaining to screening for HCV by the Centers for Disease Control and Prevention and newer treatment regimens with high efficacy, short duration and the potential for interferon‐free therapies, have energised the health care practitioners regarding HCV management.AimTo assess the full impact of HCV burden on clinical, economic and patient‐reported outcomes.MethodsAn expert panel was convened to assess the full impact of HCV burden on a number of important outcomes using an evidence‐based approach predicated on Grading of Recommendations Assessment, Development and Evaluation methodology. The literature was summarised, graded using an evidence‐based approach and presented during the workshop. Workshop presentations were intended to review recent, relevant evidence‐based literature and provide graded summary statements pertaining to HCV burden on topics including the relationships between HCV and the development of important outcomes.ResultsThe associations of HCV with cirrhosis, HCC, liver‐related mortality, type 2 diabetes mellitus, rheumatological diseases and quality of life impairments are supported by strong evidence. Also, there is strong evidence that sustained viral eradication of HCV can improve important outcomes such as mortality and quality of life.ConclusionsThe current evidence suggests that HCV has been associated with tremendous clinical, economic and quality of life burden.