Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome.

BACKGROUND: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe. METHODS: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons. RESULTS: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group. CONCLUSIONS: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.).

Region 11 MELD Na exception prospective study.

INTRODUCTION: Hyponatremia complicates cirrhosis and predicts short term mortality, including adverse outcomes before and after liver transplantation. MATERIAL AND METHODS: From April 1, 2008, through April 2, 2010, all adult candidates for primary liver transplantation with cirrhosis, listed in Region 11 with hyponatremia, were eligible for sodium (Na) exception. RESULTS: Patients with serum sodium (SNa) less than 130 mg/dL, measured two weeks apart and within 30 days of Model for End Stage Liver Disease (MELD) exception request, were given preapproved Na exception. MELD Na was calculated [MELD + 1.59 (135-SNa/30 days)]. MELD Na was capped at 22, and subject to standard adult recertification schedule. On data end of follow-up, December 28, 2010, 15,285 potential U.S. liver recipients met the inclusion criteria of true MELD between 6 and 22. In Region 11, 1,198 of total eligible liver recipients were listed. Sixty-two (5.2%) patients were eligible for Na exception (MELD Na); 823 patients (68.7%) were listed with standard MELD (SMELD); and 313 patients (26.1%) received HCC MELD exception. Ninety percent of MELD Na patients and 97% of HCC MELD patients were transplanted at end of follow up, compared to 49% of Region 11 standard MELD and 40% of U.S.A. standard MELD (USA MELD) patients (p < 0.001); with comparable dropout rates (6.5, 1.6, 6.9, 9% respectively; p = 0.2). MELD Na, HCC MELD, Region 11 SMELD, and USA MELD post-transplant six-month actual patient survivals were similar (92.9, 92.8, 92.2, and 93.9 %, respectively). CONCLUSION: The Region 11 MELD Na exception prospective trial improved hyponatremic cirrhotic patient access to transplant equitably, and without compromising transplant efficacy.

Differences in NAFLD/NASH Management by Provider Specialty: Opportunities for Optimizing Multidisciplinary Care.

Purpose: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are a part of a complex metabolic disease process requiring a multi-faceted and multidisciplinary management approach. This study was conducted to identify areas where medical education across a multidisciplinary team could be optimized in providing optimal care of patients with NAFLD/NASH. Methods: A survey instrument including a patient case vignette was developed to understand approaches of US clinicians to diagnosis and management of patients with NAFLD/NASH. The survey was fielded via email in December 2020-January 2021. Analysis was conducted using embedded Qualtrics analytic software. Results: There were 629 survey respondents: 318 PCPs, including physicians, NPs, and PAs, 57 hepatologists, 156 gastroenterologists, and 98 endocrinologists. Survey results demonstrated variation in likelihood to screen patients for NAFLD/NASH among specialists and PCPs as well as in the types of clinicians that respondents would involve in the initial management of a patient diagnosed with NASH. Notably, between 15% and 33% across respondent clinician types would not include any other clinicians or medical specialists in initial management. For a patient with newly diagnosed NASH, the most likely initial management recommendations included drug therapy to improve control of diabetes and therapy to lower lipids and were less likely to recommend drug therapy for weight loss, drug therapy for NASH, or bariatric surgery. Respondents rated "poor patient adherence to lifestyle modifications" and "lack of approved therapies for NASH" as the most significant barriers to optimal management of patients with NASH. Conclusion: Variation in the evaluation and management of patients with NAFLD/NASH across PCPs and medical subspecialists was identified in this study. Education aimed at multidisciplinary roles in optimally managing patients with NAFLD/NASH, can be beneficial, particularly if focused on increasing screening, implementing guideline updates as they emerge, and incorporating new therapies as they gain approval for clinical practice.

COMPASS: A Pilot Trial of an Early Palliative Care Intervention for Patients With End-Stage Liver Disease.

CONTEXT: Palliative care interventions have shown promise in improving quality of life and reducing health-care utilization among patients with chronic organ failure. OBJECTIVES: To evaluate the effect of a palliative care intervention for adults with end-stage liver disease. METHODS: A randomized controlled trial of patients with end-stage liver disease admitted to the hepatology service at a tertiary referral center whose attending hepatologist indicated they would not be surprised if the patient died in the following year on a standardized questionnaire was performed. Control group patients received usual care. Intervention group patients received inpatient specialist palliative care consultations and outpatient phone follow-up by a palliative care nurse. The primary outcome was time until first readmission. Secondary outcomes included days alive outside the hospital, referral to hospice care, death, readmissions, patient quality of life, depression, anxiety, and quality of end-of-life care over 6 months. RESULTS: The trial stopped early because of difficulties in accruing patients. Of 293 eligible patients, only 63 patients were enrolled, 31 in the intervention group and 32 in the control group. This pace of enrollment was only 25% of what the study had planned, and so it was deemed infeasible to complete. Despite stopping early, intervention group patients had a lower hazard of readmission (hazard ratio: 0.36, 95% confidence interval: 0.16-0.83, P = 0.017) and greater odds of having more days alive outside the hospital than control group patients (odds ratio: 3.97, 95% confidence interval: 1.14-13.84, P = 0.030). No other statistically significant differences were observed. CONCLUSION: Logistical obstacles hindered completion of the trial as originally designed. Nevertheless, a preemptive palliative care intervention resulted in increased time to first readmission and more days alive outside the hospital in the first six months after study entry.

Physician predictions of graft survival following liver transplantation.

INTRODUCTION: Due to the scarcity of cadaveric livers, clinical judgment must be used to avoid futile transplants. However, the accuracy of human judgment for predicting outcomes following liver transplantation is unknown. The study aim was to assess expert clinicians' ability to predict graft survival and to compare their performance to published survival models. MATERIALS AND METHODS: Pre-transplant case summaries were prepared based on 16 actual, randomly selected liver transplants. Clinicians specializing in the care of liver transplant patients were invited to assess the likelihood of 90-day graft survival for each case using (1) a 4-point Likert scale ranging from poor to excellent, and (2) a visual analog scale denoting the probability of survival. Four published models were also used to predict survival for the 16 cases. RESULTS. Completed instruments were received from 50 clinicians. Prognostic estimates on the two scales were highly correlated (median r=0.88). Individual clinicians' predictive ability was 0.61+/-0.13, by area under the receiver operating characteristic curve. The performance of published models was MELD 0.59, Desai 0.66, Ghobrial 0.61, and Thuluvath 0.45. For three cases, clinicians consistently overestimated the probability of survival (87+/-10%, 89+/-9%, 86+/-9%); these patients had early graft failures caused by postoperative complications. DISCUSSION. Clinicians varied in their ability to predict survival for a set of pre-transplant scenarios, but performed similarly to published models. When clinicians overestimated the chance of transplant success, either sepsis or hepatic artery thrombosis was involved; such events may be hard to predict before surgery.

Benign Neoplasms of the Liver.

Tumors of the liver often are discovered incidentally in asymptomatic individuals during diagnostic imaging or exploratory laparotomy performed for alternative reasons. Hemangiomas are the most common benign liver tumors, followed in prevalence by focal nodular hyperplasia (FNH); other benign tumors are rare. The growth and development of hemangiomas, FNH, and hepatic adenomas especially, have been linked to hormonal (eg, estrogen) stimulation. Differentiating between benign and malignant neoplasms of the liver can be challenging. Radiologic imaging is essential for preliminary identification and classification of hepatic tumors, but tissue biopsy or surgical excision sometimes is required for a definitive diagnosis. Individuals with hemangioma or FNH usually are asymptomatic, have a benign course, and can be managed conservatively. In contrast, hepatic adenomas need to be followed more carefully and often are excised to provide symptomatic relief, remove the risk of rupture, and avoid potential malignant transformation. Liver transplantation in patients with benign hepatic neoplasms is exceedingly uncommon, and is recommended only when alternative methods of treatment are not feasible or have failed to control significant symptoms.

Nutrition and chronic liver disease.

Nutritional abnormalities almost uniformly accompany the metabolic disturbances of severe chronic liver disease and may adversely affect patient well-being and survival, especially surrounding liver transplantation surgery. The exact metabolic alterations responsible for malnutrition and its consequences in these patients have been debated and are a focus of this review. Disturbances in energy production and utilization, as well as macro- and micronutrient metabolism have been appreciated but are not always easily identified or quantifiable. Interestingly, the manifestations of poor nutritional status can vary substantially between patients, even in those having the same etiology and severity of illness. Proper assessment of patients with liver disease for malnutrition carries its own challenges, but some of the more easily applied techniques, such as anthropometry, can be comparable in accuracy to more sophisticated measuring tools. Gaining an appreciation and understanding of how nutritional disturbances develop and can contribute to morbidity and mortality will help combat inappropriate nutritional losses in this specialized group of patients. In many instances, simple adjustments in diet can offset losses and stabilize or improve the patient's nutritional status.

Ultrasound-assisted percutaneous liver biopsy performed by a physician assistant.

OBJECTIVE: Percutaneous liver biopsy is an essential diagnostic tool utilized in the management of patients with liver disease. This procedure is generally performed by a physician and has a small but well-defined complication rate. We report on the complication rate and efficiency of ultrasound-assisted percutaneous liver biopsy performed by an experienced physician assistant. METHODS: One thousand eighty-six consecutive outpatient liver biopsies (847 hepatic allografts and 239 native livers) were performed at a single center by a physician assistant between June, 1996 and June, 2000. Patients with hepatic mass lesions, unusual hepatic anatomy, and uncorrectable coagulopathy (international normalized ratio > 1.7, platelet count < 50 x 10(9)/L) were excluded. Bedside ultrasonography was used to determine the optimal site for the liver biopsy. Liver biopsies were performed with a 15-gauge Jamshidi aspiration biopsy needle. Patients were observed for 3 h after biopsy, followed by dismissal with subsequent contact in 24 h to assess outcome and complications. RESULTS: Adequate tissue was obtained in 1084 cases (99.8%), with a mean tissue length of 3.2 cm. After the procedure, narcotic analgesia was necessary in 116 (10%) of the patients undergoing liver biopsies. The overall complication rate requiring hospitalization was 0.6%. Major complications requiring intervention occurred in four patients (0.4%). There were no deaths resulting from liver biopsies. CONCLUSION: We conclude that outpatient percutaneous liver biopsy can be safely and effectively performed by a trained physician assistant.