Pharmacotherapy for primary biliary cholangitis: an assessment of medication candidacy and rates of treatment.

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis. METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review of medical records was performed to confirm the diagnosis of primary biliary cholangitis and determine which medications had been prescribed for treatment, as well as candidacy for second-line therapies. RESULTS: A total of 495 patients met inclusion criteria. Notably, 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy. In total, 8% of patients were taking obeticholic acid (either as combination or monotherapy). Only 3% would benefit from the addition of a second line therapy but had not yet been offered medication. Only 3% of patients were not on any medication for management of their primary biliary cholangitis. CONCLUSIONS: Ursodeoxycholic acid is a readily available and generally well-tolerated medication that should be offered to all patients with primary biliary cholangitis as first-line therapy. While prior investigations have suggested that up to 30% of patients with primary biliary cholangitis may never have received treatment for the disorder, the present study suggests that patients are generally being managed according to guidelines. Moreover, a significant proportion of patients with primary biliary cholangitis will qualify for second line therapies and prescribers should be aware of the indications to use these medications.

Striking Cholestatic Giant Cell Hepatitis Resulting in Fulminant Liver Failure After Garcinia Cambogia Use.

Garcinia cambogia, a weight control herbal, can cause mild liver toxicity with nonspecific histologic changes. Herein, we reported a case of herbal-induced fulminant cholestatic giant cell hepatitis due to garcinia cambogia use. A 65-year-old woman with breast cancer treated 18 years earlier was admitted for obstructive jaundice for 2 weeks. She started using garcinia cambogia 3 months ago for weight loss. Physical exam showed scleral icterus. Serum studies excluded Wilson's disease, systemic infection including COVID-19 (coronavirus disease 2019), autoimmune hepatitis, and metabolic or toxicologic causes. An urgent liver biopsy showed severe giant cell hepatitis in absence of HSV-1/2, cytomegalovirus, HBsAg and HBcAg (immunostain), and EBV (in situ hybridization). Despite supportive therapy, the patient developed grade 2-3 hepatic encephalopathy and necessitated liver transplant. The explanted liver was markedly atrophy, in which the most striking histologic finding was diffuse distribution of multinucleated giant hepatocytes with syncytial pattern in a background of extensive zone-1 accentuated, geographic, hemorrhagic, confluent hepatocytic necrosis, along with remarkable hepatocytic and canalicular cholestasis. Marked hepatocellular and sinusoidal iron orverload present. The patient recovered uneventfully.

Hepatitis B in Heart Transplant Donors and Recipients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Expanding the heart donor pool to include patients with hepatitis B virus (HBV) could help ameliorate the organ shortage in heart transplantation. We performed a systematic review and meta-analysis to evaluate the management and recipient outcomes of D+/R- and D-/R+ heart transplants. METHODS: An electronic search was performed to identify all relevant studies published on heart transplants involving HBV+ donors and/or HBV+ recipients. A comparison was performed between two groups where heart transplants were performed a) D+/R- (n = 98) versus b) D-/R+ (n = 65). RESULTS: Overall, 13 studies were selected, comprising 163 patients. Mean patient age was 55 y (95% CI: 39, 78) and 79% (69, 86) were male. Active post-transplant HBV infection requiring antiviral treatment occurred in 11% (1, 69) of D+/R- recipients and 33% (9, 71) of D-/R+ recipients. Post-transplant antiviral therapy was given to 80% (6, 100) of D+/R- recipients compared to 72% (42, 90) of D-/R+ recipients (P = 0.84). Hepatitis-related mortality was observed in no D+/R- recipients and 7% (2, 27) of D-/R+ recipients. Survival 1-y post-transplant was comparable between both groups at 83% (83, 92) and 81% (61, 92) for D+/R- and D-/R+ transplants, respectively. CONCLUSIONS: Our review found that HBV D+/R- heart transplantation was associated with fewer active hepatitis infections and lower hepatitis-related mortality than D-/R+ transplantation, with comparable survival at 1 y. Additional studies utilizing HBV nucleic acid testing (NAT) to compare outcomes with HBsAg+ and anti-HBc+ donors are crucial to reach more definitive conclusions about the risk of donor-derived infections in this context.

Acute Liver Failure Requiring Liver Transplantation due to Acute Hepatitis A Virus Infection.

INTRODUCTION: Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. METHODS: Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. RESULTS: All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King's College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. CONCLUSION: Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks.

Duodenal Perforation With Transplant Hepatic Artery Pseudoaneurysm.

A transplant hepatic artery pseudoaneurysm is a rare postorthotopic liver transplant complication. Bleeding is a common complication of posterior duodenal ulcer secondary to erosion into the gastroduodenal artery. We report the case of a post-transplant patient who presented with massive upper gastrointestinal hemorrhage in the setting of nonsteroidal anti-inflammatory drug use. Endoscopy demonstrated a duodenal ulcer with high-risk stigmata not amenable to hemostasis. Subsequently, an arteriogram revealed a hepatic artery pseudoaneurysm. Transplant professionals should be aware of the possibility of an ulcer eroding into the liver vasculature and in the differential diagnosis for bleeding and pseudoaneurysms in post-transplant patients.

A Head CT is Unnecessary in the Initial Evaluation of A Cirrhotic Patient with Recurrent Hepatic Encephalopathy.

INTRODUCTION AND AIM: The evaluation to determine the cause of hepatic encephalopathy consists primarily of laboratory testing to rule out infections and metabolic causes. Despite lack of evidence, it is a common practice amongst clinicians to obtain a head CT as part of their initial evaluation in a cirrhotic presenting with recurrent episodes of hepatic encephalopathy. MATERIAL AND METHODS: Medical records of all cirrhotic adults admitted to a tertiary care hospital from 2007 to 2010 with hepatic encephalopathy were reviewed. RESULTS: In 67 patients, there were 147 episodes of hepatic encephalopathy where a head CT was performed. Six CTs had intracranial findings explaining hepatic encephalopathy. Two patients had focal neurologic findings on physical exam with no history of trauma, one had a history of trauma with no focal neurologic deficits and two had both a history of trauma and focal neurologic findings. Only one case revealed an intracranial hemorrhage with neither a preceding history of trauma nor positive neurological signs. The overall prevalence of intracranial findings in hepatic encephalopathy was 4% (6/147) and 0.6% (1/142) in the absence of trauma or focal neurologic findings. Laboratory and clinical variables including mean levels of ammonia, sodium, creatinine, bilirubin, albumin, platelet count, INR, encephalopathy grade and MELD score did not have a statistically significant impact on head CT findings (P > .05). CONCLUSION: In conclusion, the yield of a head CT in determining the cause of change in mental status is extremely low in patients with cirrhosis who present with recurrent hepatic encephalopathy.

Pre-Liver Transplant Muscle Loss Is a Risk Factor for Post-Liver Transplantation Left Ventricular Systolic Dysfunction.

BACKGROUND The development of left ventricular systolic dysfunction (LVSD) after liver transplant (LT) can result in increased morbidity and mortality in the immediate period following liver transplant. The aim of this study was to evaluate low muscle mass due to chronic liver disease, as a potential risk factor for LVSD after LT. MATERIAL AND METHODS A retrospective chart review was completed for all adult patients who received a liver transplant between January 2002 and January 2015 at a single academic LT center. Collected data included patient demographics, medical history, laboratory data, radiology results, and pathology. Echocardiograms were reviewed for patients identified as having LVSD diagnosed within 1 year after LT (left ventricular ejection fraction <55%). The total psoas area (TPA), a marker of low muscle mass, was determined by measuring the average cross-sectional area of the psoas muscle on MRI or CT scans before transplant at the level of L4 vertebra. RESULTS Of the 503 post-LT patients reviewed, 144 (28.6%) had pre-and post-LT echocardiograms. Of these 144 patients, 17 developed LVSD, of which 15 (88.2%) occurred within 1 year after LT. The average age at transplant of those with LVSD was 58.9±6 years, with a mean MELD score of 30.7±6. The mean TPA normalized for height for patients with LVSD was 297.68±86.99 mm²/m² compared to 382.1±104.2 mm²/m² for those with normal EF (p= 0.002). BMI, MELD score, and etiology of cirrhosis were not significant risk factors for post-LT LVSD in our study population. During the study period, 35.2% (n=6) of LVSD patients died within 1 year after LT. CONCLUSIONS Although LVSD is thought to be a rare complication after LT, those with muscle loss as predicted by mean TPA measurements normalized for height may be at highest risk.

Distribution of serum concentrations reported for macroenzyme aspartate aminotransferase (macro-AST).

BACKGROUND: The presence of macroenzyme (M) is often the explanation of an isolated elevation of aspartate aminotransferase (AST). Where M is identified, it is reasonable for the clinician to ask where an individual patient's result fits in with known concentrations of M. In this context, we conducted a survey of literature to examine the distribution of reported serum concentrations of macro-AST. We also analyzed the distribution data to examine whether elevations were consistent with simple alteration of circulatory half-life (t1/2) of M relative to normal AST. METHODS: Distributions of M were compiled from the literature. These distributions were compared to predictions based on fixed changes in t1/2 applied to the reference interval for AST. RESULTS: There was a bimodal distribution of literature values for M (n =51), comprised roughly of populations A (M <200 U/L; 60% of total) and B (M >200 U/L; 40% of total). The two distributions were reasonably well characterized by a simple projection to the right of the reference interval for AST according to increased t1/2 (A: t1/2 =3.3 days; B: t1/2 =19.8 days) relative to AST (t1/2 =0.7 days). CONCLUSIONS: Knowledge of distributions for M may be useful in discussion with clinicians regarding significance of M for individual patients. Distributions for M were consistent with the simplest explanation for elevated AST due strictly to an extended circulatory lifetime for M. Caveats to analysis, however, include selection within literature data mainly for patients with various co-morbidities.

Listing Practices for Morbidly Obese Patients at Liver Transplantation Centers in the United States.

OBJECTIVES: The effect of morbid obesity on liver transplant outcomes has yielded mixed results. The aim of this study was to determine listing practices for morbidly obese patients at liver transplant centers in the United States. MATERIALS AND METHODS: A 19-item survey was created to assess liver transplant evaluation and listing practices for morbidly obese patients. All adult liver transplant medical and surgical directors in the United States were contacted by e-mail, which provided an Internet link to an online survey. RESULTS: We sent a total of 187 surveys by e-mail, with responses received from 46 physicians (24.7% response rate). A policy on evaluation and listing of obese patients was present at 70.5% of institutions, with most (54.5%) reporting that their body mass index cutoff for transplant was 40 kg/m2, but a range of 35 kg/m2 to unlimited was noted. Most respondents agreed that patients with high body mass index were less likely to be evaluated for transplant. Respondents reported increased complication rates among obese patients, with the most common being poor wound healing and increased infection rates. CONCLUSIONS: Most medical and surgical liver transplant directors have a strong appreciation of the possible morbidity risks associated with performing liver transplants in morbidly obese patients and have policies in effect to minimize these risks.

Liver and Kidney Transplantation: A Half-Century Historical Perspective.

This article describes the evolution of solid organ kidney and liver transplantation and expounds on the challenges and successes that the early transplant researchers and clinicians encountered. The article highlights the surgical pioneers, delves into the milestones of enhanced immunosuppression protocols, discusses key federal legislative and policy changes, and expounds on the ongoing disparities of organ supply and demand and the need for extended criteria and live donor organs to combat these shortages. Finally, recent changes in organ allocation and distribution policies are discussed. The authors also spotlight novel interventions that will further revolutionize abdominal transplantation in the next 50 years.

Granular Cell Tumor of the Common Hepatic Duct as an Unusual Cause of Jaundice in a Hepatitis C Patient.

A 33-year-old woman with a history of intravenous cocaine abuse presented with fatigue, nausea, and jaundice. Serologic testing revealed a positive hepatitis C virus (HCV) antibody and HCV RNA. Ultrasound and magnetic resonance imaging/magnetic resonance cholangiopancreatography showed a partially obstructing lesion in the common hepatic duct, which was confirmed by endoscopic retrograde cholangiopancreatography. Surgical excision revealed a granular cell tumor of the common hepatic duct, with immunohistochemical staining of tumor cells positive for S-100.

Acute autoimmune hepatitis presenting with peripheral blood eosinophilia.

 Peripheral blood eosinophilia has been described in a broad variety of allergic, infectious, neoplastic and autoimmune diseases. To the best of our knowledge blood eosinophilia has never previously been reported in association with isolated autoimmune hepatitis (AIH) in the absence of other autoimmune conditions. Herein we report an interesting case of an 18 year old man who presented to our hospital with an acute autoimmune hepatitis diagnosed on the basis of clinical features, serology and histopathology. He was noted to have a moderate peripheral eosinophilia at diagnosis which resolved within days of initiation of corticosteroids for treatment of the AIH. Given the absence of other systemic conditions or drugs which may have produced the eosinophilia and its rapid resolution with treatment of the underlying liver disease, we wished to highlight this rather novel presentation of AIH.

Liver transplantation in the 21st century: expanding the donor options.

Over the past decade, use of ECD organs for OLT has allowed many transplant programs to afford patients access to an otherwise scarce resource and to maintain center volume. Although overall posttransplant outcomes are inferior to results with optimal, whole-liver grafts, aggressive utilization of ECD and DCD organs significantly lowers median wait-times for OLT, MELD score at OLT, and death while awaiting transplantation. It is incumbent on the transplant community to provide continued scrutiny of the many factors involved in ECD organ utilization, evaluate the degree of risk and benefit such allografts may impart on particular recipients, and thereby provide suitable "matching" to maximize favorable outcomes. Transplant caregivers need to provide patients with evidence-based care decisions, be good stewards of a scarce resource, and maintain threshold survival results for their programs. This requires balancing the urgency with which a transplant is needed and the utility of such a transplant. There is a clear necessity to pursue additional donor research to improve use of these marginal grafts and assess interventions that enhance the safety of ECD livers.

The impact of biopsychosocial factors on quality of life: women with primary biliary cirrhosis on waiting list and post liver transplantation.

OBJECTIVES: Primary biliary cirrhosis (PBC) is the second most common reason for liver transplants among women in the USA. While survival rates are high, there is evidence of persistent problems post-transplant. This study aimed to identify significant contributors to quality of life (QOL) for women with PBC on waiting list (WL) and post-transplant (PT) and compare QOL in each group with US population norms. DESIGN: A cross-sectional, two-group study design was used. METHODS: WL and PT participants were recruited through medical centres and on-line. QOL was measured by the Short Form-36 and an indicator of Social QOL created for this study. A biopsychosocial model incorporating demographic, biomedical, psychological, and sociological factors guided choice of variables affecting QOL. Analyses examined (1) all factors for differences between WL and PT groups, (2) association between factors and QOL outcomes within each group, (3) multivariate regression of QOL on factors in the model for the sample as a whole, and (4) comparison of QOL outcomes with national norms. RESULTS: One hundred women with PBC participated in the study, 25 on WL and 75 PT. Group comparisons showed improvement for PT participants in most biomedical and psychological variables and in QOL outcomes. QOL was related to many, but not all, of the variables in the model. In multivariate analysis, Fatigue, Depression, Coping, and Education - but not Transplant Status - were identified as indicators of QOL. Physical QOL improved significantly after 5 years PT, when it was no longer worse than national norms. Mental QOL remained worse than national norms despite distance in time from transplant. CONCLUSIONS: The model proved useful in identifying a range of factors that contributed to QOL for women with PBC before and after transplant. Recommendations were made for clinical practice to improve QOL through a combination of treatment and self-management.

Liver disease in pregnancy.

This article briefly discusses gestational physiologic changes and thereafter reviews liver diseases during pregnancy, which are divided into 3 main categories. The first category includes conditions that are unique to pregnancy and generally resolve with the termination of pregnancy, the second category includes liver diseases that are not unique to the pregnant population but occur commonly or are severely affected by pregnancy, and the third category includes diseases that occur coincidentally with pregnancy and in patients with underlying chronic liver disease, with cirrhosis, or after liver transplant who become pregnant.

Uncertainty and liver transplantation: women with primary biliary cirrhosis before and after transplant.

Uncertainty is a frequent feature of chronic illness and can have a particularly important impact in the case of organ transplantation. This study of 100 women with primary biliary cirrhosis who were either waiting for or had already had a liver transplant focused on both changes in uncertainty with transplant and the correlates of uncertainty both pre- and post-transplant. While those who were post-transplant had significantly lower uncertainty scores (measured by the Mishel Uncertainty in Illness Scale-Adult Version-MUIS-A) than those on the waiting list, uncertainty was still persistent and associated with a reduced quality of life. The most significant factors in relation to uncertainty were fatigue, depression, anxiety, and dissatisfaction with medical information received. It is important for both patients and transplant team members to recognize the impact of uncertainty on a patient's well-being, both before and after a transplant, and to address the underlying factors that continue to compromise quality of life even after a life-saving procedure.