Faculty Bibliography

Hepatic encephalopathy is a reversible progressive neuropsychiatric disorder that encompasses a wide clinical spectrum. Covert hepatic encephalopathy is defined as patients with minimal hepatic encephalopathy and Grade I encephalopathy by West-Haven Criteria. Terminology such as "sub-clinical", "latent", and "minimal" appear to trivialize the disease and have been replaced by the term covert. The lack of clinical signs means that covert hepatic encephalopathy is rarely recognized or treated outside of clinical trials with options for therapy based on patients with episodic hepatic encephalopathy. This review discusses the current available options for therapy in covert hepatic encephalopathy and focuses on non-absorbable disacharides (lactulose or lactitol), antibiotics (rifaximin), probiotics/synbiotics and l-ornithine-l-aspartate.

A 25-year-old black man presented with left-sided chest pain and cough for 3 days. His pain was pressure-like and nonradiating and was aggravated with movement and relieved when the patient lay at a 45° angle. The patient denied fevers, chills, night sweats, and swelling but reported gaining 4 to 6 kg (10 to 15 lbs) in the past few months. His cough had started 2 weeks prior with yellow mucus production but he denied facial swelling or tenderness. He had no chronic medical conditions and was not taking medications. He had no known exposure to chemicals, fumes, or dust and no history of tobacco or alcohol abuse.

OPINION STATEMENT/UNASSIGNED:The main issue with treating covert hepatic encephalopathy (HE) is to establish whether it is cost effective to reverse the neuropsychiatric abnormalities that define this mild form of HE. Until fairly recently, covert HE was rarely diagnosed, but advances in computerized psychometric testing have greatly simplified its detection. The many consequences of covert HE are now being identified, and most have been shown to be reversible with standard HE treatment. Perhaps the most enticing possibility will be the potential that standard HE therapies will postpone the onset of overt HE. This will require further evaluation with large placebo-controlled randomized trials.

OBJECTIVES/OBJECTIVE:Optimal administration of proton pump inhibitor (PPI) for the treatment of gastroesophageal reflux disease (GERD) requires consideration of meal timing. Since becoming available over the counter (OTC), no studies have assessed treatment patterns and symptom control in OTC consumers. The objective of this study was to survey dosing patterns and symptom control in OTC and prescription PPI users. METHODS:Patients at five clinics were surveyed regarding diagnosis of GERD, use of OTC or prescription PPIs, information on time of day dosing, demographics, and Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS; 2001, Johnson & Johnson). RESULTS:Of the 1,959 patients surveyed, 610 (31%) used PPIs for GERD. Of these, 190 (31%) and 223 (37%) received prescriptions from gastroenterologists (GIs) and primary care physicians (PCPs), respectively; 197 (32%) purchased OTC PPIs. Of the patients prescribed PPIs by GIs, 71% were optimal users, whereas 47% of patients receiving prescriptions from PCPs and 39% of consumers used PPIs optimally (P<0.001 compared with GIs). GSAS symptom, frequency, and severity scores were significantly better in patients prescribed PPIs by GIs (all P<0.001, GI compared with PCP and consumer). GSAS symptom, frequency, and severity scores were also significantly better in patients using PPIs optimally (P<0.001 for all parameters) compared with those taking PPIs suboptimally or excessively. CONCLUSIONS:Patients receiving prescription PPI from a GI are more likely to be optimal users with better symptom control. Conversely, consumers are more likely to be suboptimal users with inadequate symptom control.

INTRODUCTION/BACKGROUND:Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT. METHODS:A prospectively maintained LT database was retrospectively analyzed for patients with recurrent HCC following LT between 2001 and 2011-34 patients. Patients were divided into two groups based on whether they were prescribed sorafenib (n = 17) or not prescribed sorafenib (n = 17). The primary endpoint was overall survival. RESULTS:There were no significant differences between the two groups analyzed. Seventeen patients were on sorafenib for recurrent HCC, with a mean daily dose of ~444 mg. Mean duration of treatment was ~10 months. Side effects included: thrombocytopenia, diarrhea, rising transaminases, fatigue, hand-foot skin reaction, and nausea. Survival in the sorafenib vs. non-sorafenib group was greater at three-, six-, nine-, and 12-month intervals and overall survival. CONCLUSION/CONCLUSIONS:Sorafenib can be well tolerated and safe in patients with recurrent HCC following LT and may be associated with a modest survival benefit. To our knowledge, this is the largest single-center retrospective analysis of patients prescribed sorafenib for recurrent HCC after LT.

OBJECTIVE:To present a case series on biotin interference in parathyroid hormone (PTH) level measurement. METHODS:We review the presentation and management of patients at our institution evaluated for unexpectedly low PTH levels while taking biotin supplements in the setting of high or normal serum calcium. RESULTS:Two patients presented with surprising low parathyroid levels--one during preoperative evaluation for hyperparathyroidism and another during postoperative follow-up after subtotal parathyroidectomy. The patients were found to be taking 1,500 mcg and 5,000 mcg of biotin per day, respectively. The role of biotin interference was confirmed in one of the patients when she was retested off biotin, and PTH levels responded appropriately. Biotin supplements remain as unbound molecules in the serum, thus interfering with PTH enzyme-linked immunosorbent assay (ELISA) results and falsely depressing the PTH level. CONCLUSION/CONCLUSIONS:Biotin supplement use has expanded over the years, ranging from medically endorsed therapies to home remedies. Review of the 2 ELISA systems used at our institution demonstrates that free biotin mimics the biotinylated antibody used in the detection process. Screening for biotin use prior to PTH measurement and automatic biotin levels for clinically aberrant PTH levels provide the clinician with a true PTH level--lowering the disease burden of untreated hyperparathyroidism while avoiding unnecessary work-ups for other processes.

Hepatocellular carcinoma (HCC), one of the most common and lethal cancers, is a growing menace in modern society. Until recently, the majority of detected cases of liver cancer have been found in the developing nations of Asia and Africa; however, its occurrence has significantly increased in the United States. HCC occurs due to several etiologies, such as alcoholism, dietary carcinogens, iron overload, viral hepatitis, as well as several hepatic chronic diseases. In view of the limited treatment options, such as surgery and transplantation, a critical need exists to examine alternative approaches. The use of phytochemicals obtained from dietary sources provides a novel and fascinating preventive and therapeutic approach against HCC. Dietary phytochemicals possess potent antioxidant and anti-inflammatory properties which are extremely critical to combat the significant oxidative stress and inflammation implicated in liver cancer. An impressive number of phytochemicals have shown considerable promise as candidates for the prevention and treatment of HCC. In this article, we systematically review the in vivo pre-clinical evidence documenting the chemopreventive and therapeutic potential of several important dietary phytochemicals in HCC. This review critically examines the molecular mechanisms of the pharmacological effects of the aforementioned animal studies. Clinical and epidemiological studies are also highlighted in this review. Emerging issues such as bioavailability, dose optimization, targeted drug delivery, role of botanical extracts and synergy are also discussed. Finally, current challenges, limitations, future directions, innovative concepts and novel hypotheses for the use of dietary phytochemicals in the chemoprevention and amelioration of human HCC are presented.