Chronic Kidney Disease After Liver Transplantation.

Improved survival after liver transplantation has led to an aging cohort of recipients at risk of renal dysfunction. The etiology of renal dysfunction is typically multifactorial; calcineurin inhibitors nephrotoxicity, pretransplant renal dysfunction, and perioperative acute kidney injury are important risk factors. Metabolic complications such as hypertension, diabetes mellitus, and metabolic-associated fatty liver disease also contribute to the development of renal disease. Most LT recipients will eventually develop some degree of renal dysfunction. Criteria to select candidates for simultaneous liver and kidney transplantation have been established. Both delayed introduction of CNIs and renal-sparing immunosuppressive regimens may reduce progression of renal dysfunction.

Advances in the Management of Renal Dysfunction in Patients With Cirrhosis.

Renal dysfunction frequently develops in patients with advanced liver disease. Renal dysfunction in this setting is associated with adverse outcomes and an unfavorable prognosis. Hepatorenal syndrome (HRS), defined as worsening renal function in patients with advanced cirrhosis that can present either acutely (<3 months) or more indolently in the absence of other etiologies, remains a common cause of acute kidney injury. If reversal is not promptly achieved, rapid decline to mortality is common. Volume expansion and vasoconstrictors are the mainstays of therapy. Terlipressin, a vasopressin analogue licensed in several countries but not in the United States, is currently used for the treatment of HRS. Timely liver transplantation remains the only effective therapeutic option for a large group of patients with persistent renal dysfunction despite pharmacotherapy. In patients with underlying chronic renal dysfunction, simultaneous liver-kidney transplantation should be considered. The aim of this article is to present an overview of renal dysfunction in patients with cirrhosis, including diagnosis and management.

The Evolving Role of Advanced Endoscopic Techniques in Hepatology.

The role of advanced endoscopy in the field of hepatology has evolved rapidly over the last decade. Several novel diagnostic and therapeutic interventions can now be accomplished endoscopically both easily and safely in patients with liver disease; these include endoscopic ultrasound (EUS)-guided liver biopsy, EUS-guided measurement of the portal pressure gradient, EUS-guided therapy for gastric varices, and EUS elastography. This article highlights advances in endoscopic tools and techniques that can be applied in the field of hepatology.

Keeping Patients with End-Stage Liver Disease Alive While Awaiting Transplant: Management of Complications of Portal Hypertension.

Complications of portal hypertension such as gastroesophageal variceal hemorrhage, ascites, and spontaneous bacterial peritonitis, as well as pulmonary complications, are often responsible for diminished quality of life, excess morbidity and mortality, increased health care resource use and expenditure, and dropout from the liver transplant (LT) waiting list. Therefore, the care of LT candidates on the waiting list must be centered on anticipation and prompt intervention for these complications.

Safety of fibrates in cholestatic liver diseases.

BACKGROUND AND AIM: Off-label use of fibrates in patients with cholestatic liver diseases results in improved biochemical parameters and pruritus; however, their safety in this population has been a concern. This study summarizes safety data for fibrates when used for treatment of cholestatic liver diseases. METHODS: A systematic review of published studies evaluating the use of fibrates for treatment of primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) was performed. Electronic databases were searched up to December 2019 for published studies evaluating treatment outcomes associated to fibrates for these 2 diseases. RESULTS: A total of 37 studies were identified, including 31 for PBC and 6 for PSC, with a total of 1107 unique patients treated with fibrates ± ursodeoxycholic acid (UDCA). Most studies evaluated fenofibrate and bezafibrate, and only 1 study evaluated pemafibrate. There were no studies evaluating gemfibrozil or clofibrate. The most commonly reported adverse events (AEs) were gastrointestinal and musculoskeletal. Elevations of aminotransferases and serum creatinine were reported more commonly in patients treated with UDCA plus fibrates versus UDCA monotherapy. CONCLUSIONS: Fibrates appear to be safe and well tolerated in patients with PBC, with a low frequency of AEs. There are scarce data about the safety of these agents for treatment of PSC.

Evaluation of the diagnostic and therapeutic utility of retrograde through-the-scope balloon enteroscopy and single-balloon enteroscopy.

BACKGROUND: Retrograde single balloon enteroscopy (SBE) is a minimally invasive procedure which is less frequently performed compared with antegrade SBE. There are few studies on the retrograde through-the-scope enteroscopy (TTSE), a novel technique for evaluation of the small bowel. AIM: To compare the clinical utility and safety of retrograde TTSE with retrograde SBE. METHODS: Clinical data and complications of retrograde TTSE (2014-2018) and retrograde SBE (2011-2018) performed in a community hospital were reviewed and presented as mean ± SD or frequency (%) and compared using proper statistical tests. Technical success was defined as insertion of the enteroscope > 20 cm beyond ileocecal valve. RESULTS: Data obtained from 54 retrograde SBE in 49 patients and 27 retrograde TTSE in 26 patients were studied. The most common indication for retrograde enteroscopy was iron deficiency anemia (41 patients) followed by gastrointestinal bleeding (37 patients), and chronic diarrhea (7 patients). The duration of retrograde SBE procedure (91.9 ± 34.2 min) was significantly longer compared with retrograde TTSE (70.5 ± 30.7 min) (P = 0.04). Technical success was comparable in TTSE [23/27 (85.2%)] and SBE [41/54 (75.9%) (P = 0.33)]. The mean depth of insertion beyond the ileocecal valve in retrograde SBE (92.5 ± 70.0 cm) tended to be longer compared with retrograde TTSE (64.6 ± 49.0 cm) (P = 0.08). No complication was observed in this study. CONCLUSION: Both retrograde TTSE and retrograde SBE are feasible and safe. Retrograde TTSE takes a shorter time and has a comparable technical success with SBE. TTSE has a lower capacity of small bowel insertion.

Novel targeted therapies for the management of liver fibrosis.

Introduction: Prolonged liver injury results in tissue damage and replacement by extracellular matrix and fibrosis. Cirrhosis represents a leading cause of mortality worldwide and imposes a major financial burden on health-care systems. Fortunately, fibrogenesis has proven to be reversible if halted early, encouraging the development of novel anti-fibrotic agents that may accelerate histological restoration. Preclinical data have elucidated numerous potential therapeutic targets and many anti-fibrotic agents are currently at various stages of clinical research.Areas covered: The present review summarizes recent clinical data regarding anti-fibrotic drugs including monoclonal antibodies, targeted conjugates, and small molecule agents.Expert opinion: Although undeniable progress has been made in the development of anti-fibrotic agents in recent years, most data currently available are derived from preclinical and early clinical studies. The efficacy and safety of these agents will need to be corroborated by larger clinical trials, some of which are ongoing with results expected in the upcoming years. Combination therapy with agents targeting different pathways of fibrogenesis will also be of great interest for the future and will need to be explored in clinical trials.

Bacterial Infection in Patients with Cirrhosis: Don't Get Bugged to Death.

Bacterial infection remains a leading cause of mortality and morbidity for patients with cirrhosis, with hospitalization, alterations in the intestinal microbiota, and therapeutic drugs all implicated in its development. Bacterial infections also remain the most common precipitant of acute-on-chronic liver failure, with infection occurring as a direct consequence of the progression of this syndrome. Furthermore, recent epidemiological analyses have demonstrated that infections due to multidrug-resistant bacteria are occurring with increasing frequency in patients with cirrhosis. Despite significant advances in the understanding of the pathophysiological processes triggered by an infection in patients with cirrhosis, a demonstrable survival benefit for the sickest patients who require ICU admission has not yet occurred. Early diagnosis of infection and appropriate antimicrobial treatment is essential to ensuring optimal outcomes for these patients. This review provides an evidence-based analysis of both the current strategies for prevention and the recommended management of common bacterial infections in patients with cirrhosis.

Diagnosis and management of renal dysfunction in patients with cirrhosis.

Introduction: Renal dysfunction commonly occurs in patients with cirrhosis and is typically associated with poor prognosis. Several pathophysiologic mechanisms are responsible for renal disease in these patients, prompt identification permits individualized management.Areas covered: Pathophysiology, evaluation and differential diagnosis, management and prognosis of renal disease in patients with cirrhosis. Special focus on management of hepatorenal syndrome and indications for simultaneous liver-kidney transplantation.Literature search methodology: a detailed literature search was performed using PubMed without date restrictions. Published guidelines and position papers were also used and cross-referenced to identify additional studies.Expert opinion: The prognostic significance of renal dysfunction in patients with cirrhosis is highlighted by the inclusion of serum creatinine in the model for end-stage liver disease (MELD). Both acute and chronic renal dysfunction result in increased mortality in patients with cirrhosis, although there are marked differences related to the etiology of renal disease. Early recognition and prompt intervention determined by the most likely etiology are key in the management of these patients. Simultaneous liver-kidney transplantation improves patient survival compared to isolated liver transplantation in patients with cirrhosis and persistent renal impairment; however, selection of candidates must be judicious and individualized due to the ongoing shortage of donor kidneys.

Hepatic Complications of Inflammatory Bowel Disease.

Hepatobiliary disorders are commonly encountered in patients with inflammatory bowel disease (IBD). Although primary sclerosing cholangitis is the stereotypical hepatobiliary disorder associated with IBD, other diseases, including autoimmune hepatitis and nonalcoholic fatty liver disease, also are encountered in this population. Several agents used for treatment of IBD may cause drug-induced liver injury, although severe hepatotoxicity occurs infrequently. Furthermore, reactivation of hepatitis B virus infection may occur in patients with IBD treated with systemic corticosteroids and biologic agents.

Understanding and Treating Pruritus in Primary Biliary Cholangitis.

Pruritus is a common symptom with primary biliary cholangitis. Research has focused on refining understanding of the neurohumoral pathways involved in transduction of pruritus from peripheral cutaneous receptors to the central nervous system, and identifying modulating drugs. Current treatments have variable efficacy and safety. Because of the deleterious effects on quality of life or debilitation, many patients necessitate individualized therapeutic approaches; clinicians may need to consider invasive treatment options. This article highlights various therapeutic interventions, from general measures to invasive strategies, and novel agents under investigation, providing clinicians with the management tricks of the trade.

Non-Intensive Care Unit Management of Acute Liver Failure.

Acute liver failure (ALF) is an uncommon syndrome with a highly variable and unpredictable clinical course. The initial diagnostic evaluation is typically performed in a non-intensive care unit (ICU) setting, like the emergency department or general hospital ward. Prompt restoration of intravascular volume with intravenous fluids and correction of electrolyte, metabolic, and acid-base disturbances are important initial interventions in the management of ALF and can be safely accomplished in non-ICU settings in many patients. Similarly, therapies such as administration of N-acetylcysteine for acetaminophen-induced ALF and other cause-specific interventions can also be administered in non-ICU settings, thus minimizing delay.

Glecaprevir + pibrentasvir for treatment of hepatitis C.

INTRODUCTION: Glecaprevir/pibrentasvir is a fixed-dose combination regimen of a new generation NS3/4A inhibitor and an NS5A inhibitor with potent antiviral activity against all hepatitis C virus (HCV) genotypes. This regimen offers a shorter course of therapy (8 weeks) for selected patients regardless of genotype and has demonstrated high virological efficacy for retreatment of individuals who previously failed an NS5A containing regimen. Glecaprevir and pibrentasvir are minimally excreted by the kidneys; thus this regimen can safely be used in individuals with severe chronic kidney disease (CKD), including those undergoing hemodialysis. Areas covered: This review covers the mechanism of action, pharmacokinetics, clinical applications, efficacy, and safety profile of glecaprevir/pibrentasvir. It also covers key phase 2 and 3 clinical trials that led to licensure of this regimen. Expert opinion: Glecaprevir/pibrentasvir is the latest antiviral regimen licensed in the United States for treatment of HCV infection. Although several other direct-acting antiviral agents (DAAs) are currently available, glecaprevir/pibrentasvir has some unique characteristics that expand treatment options for HCV infection, including patients with comorbidities such as advanced stage CKD or prior treatment failure to antiviral regimens containing other DAAs.