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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., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., Competing Interests: Disclosures: Dr Martin has consulted for Mallinckrodt. The other authors have no relevant conflicts of interest to disclose., (Copyright © 2021, Gastro-Hep Communications, Inc.)

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., Competing Interests: The authors have no relevant conflicts of interest to disclose., (Copyright © 2021, Gastro-Hep Communications, Inc.)

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., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict-of-interest statement: The authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

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 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.

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.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Introduction: The combination of elbasvir and grazoprevir in a single co-formulated tablet is highly effective for treatment of hepatitis C virus (HCV) infection. This regimen affords profound inhibition of NS3/4A protease and NS5A activity, resulting in potent activity against HCV genotypes 1, 4, and 6 with high rates of sustained virological response., Areas Covered: This review covers the mechanism of action, pharmacokinetics, clinical applications, efficacy and safety profile of elbasvir/grazoprevir including special populations such as individuals with compensated and decompensated cirrhosis, HCV/HIV co-infection, advanced chronic kidney disease, and those that previously failed antiviral therapy., Expert Opinion: Elbasvir/grazoprevir is an effective antiviral regimen for treatment of genotypes 1 and 4 and has a very favorable safety profile based on extensive data from several pre-licensure clinical trials that included patient subgroups at increased risk of toxicity. This regimen is currently the only one licensed for use in individuals with advanced chronic kidney disease requiring hemodialysis.

Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3-7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between different specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a 'bridge' therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE.

Transjugular intrahepatic portosystemic shunt has evolved into an important option for management of complications of portal hypertension. The use of polytetrafluoroethylene covered stents enhances shunt patency. Hepatic encephalopathy (HE) remains a significant problem after TIPS placement. The approach to management of patients with refractory hepatic encephalopathy typically requires collaboration between different specialties. Patient selection for TIPS requires careful evaluation of risk factors for HE. TIPS procedure-related technical factors like stent size, attention to portosystemic pressure gradient reduction and use of adjunctive variceal embolization maybe important. Conservative medical therapy in combination with endovascular therapies often results in resolution or substantial reduction of symptoms. Liver transplantation is, however, the ultimate treatment., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recurrent hepatitis C virus (HCV) infection occurs universally in the allograft in the absence of effective antiviral therapy before liver transplantation (LT). Antiviral therapy with sofosbuvir and simeprevir has proven to be highly effective and well tolerated in the nontransplant setting for treatment of HCV genotype 1 infection; therefore, we sought to evaluate the efficacy and safety of this regimen in LT recipients with recurrent HCV infection. This was a retrospective analysis of a single-center treatment protocol of patients with HCV genotype 1 infection who received a 12-week combination regimen of sofosbuvir and simeprevir. Sixty-one patients (35 with genotype 1a and 26 with genotype 1b) completed treatment with simeprevir and sofosbuvir. Three patients received additional ribavirin. Laboratory data and clinical assessments performed at the baseline, on treatment, at the end of treatment, and 12 weeks after the completion of antiviral therapy [sustained virological response at 12 weeks (SVR12)] were analyzed. The median time after LT was 5.4 years [interquartile range (IQR), 1.9-8.4 years], and tacrolimus was the most commonly used immunosuppressive agent (80.3%). Overall, SVR12 was achieved in 93.4% [95% confidence interval (CI), 84%-97%] of LT recipients treated with 12 weeks of sofosbuvir and simeprevir. When they were analyzed according to the HCV subtype, LT recipients with genotype 1b had a 100% SVR12 rate (95% CI, 87%-100%), whereas SVR12 was 89% (95% CI, 74%-95%) for those with genotype 1a. Advanced fibrosis (METAVIR F3-F4) was associated with diminished antiviral efficacy in LT recipients with genotype 1a [SVR12, 67% (95% CI, 39%-86%); P = 0.01]. Overall, the incidence of adverse events (AEs) was low, and no severe AEs occurred during treatment. In conclusion, treatment with a 12-week regimen of sofosbuvir and simeprevir was well tolerated and resulted in a high SVR12 rate for LT recipients with recurrent HCV genotype 1 infection. Genotype 1a patients with advanced fibrosis of the allograft were more likely to relapse., (© 2015 American Association for the Study of Liver Diseases.)

Introduction: Hepatitis C virus (HCV) therapy continues to evolve rapidly. ABT-450 is a novel potent inhibitor of the non-structural 3/4A protease that has been studied in combination with several agents, allowing shorter duration of therapy and interferon-free/ribavirin-free all-oral regimens. Preliminary data from studies evaluating these new regimens are impressive with sustained virological response (SVR) rates of 88 - 100% after 12 weeks of therapy in patients with previously untreated HCV genotype 1 infection. SVR rates in treatment-experienced patients are also encouraging., Areas Covered: Efficacy and tolerability of antiviral regimens containing ABT-450 boosted with ritonavir (ABT-450/r). Results from published studies and abstracts from recent meetings are presented., Expert Opinion: Newer direct-acting antiviral agents such as ABT-450 promise effective and durable suppression of HCV with interferon/ribavirin-free all-oral regimens. This agent also allows for shorter duration of treatment and has tolerable side effects. Results of clinical trials including a broader spectrum of individuals with HCV infection are eagerly awaited.

Improved outcomes in liver transplant recipients reflect advances in surgical technique, post-operative care, immunosuppression as well as better selection of potential candidates. The pre-transplant evaluation is a multidisciplinary process intended to recognize and treat important comorbid conditions that may impair outcomes during the peri- and post-transplant periods. Important psychosocial issues should also be ascertained and tackled early during the pre-transplant evaluation with an overarching intention to improve the success of liver transplantation.

Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Here we describe a patient with a rare movement disorder, hemichorea-hemiballismus, which is described as a complication of non-ketotic hyperglycaemia. This complication may be seen in individuals with poorly controlled long-standing diabetes mellitus. Proper diagnosis is established with CT and MRI of the brain, which typically show classic findings in the basal ganglia. Treatment focuses on improvement of glycaemic control and usually results in rapid resolution of the movement disorder. Nevertheless, recurrent episodes of hemichorea-hemiballismus, and even more ominous complications such as ischaemic stroke may occur.

Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment.

As life expectancy continues to rise, elderly adults represent a rapidly growing proportion of the population. The likelihood of complications of acute and chronic liver disease and overall mortality are higher in elderly populations. Several physiological changes associated with aging, greater prevalence of co-morbid conditions, and cumulative exposure to hepatotropic viruses and environmental hepatotoxins may contribute to worse outcomes of viral hepatitis in the elderly. Although pharmacotherapy for hepatitis B and C continues to evolve, the efficacy, tolerability, and side effects of these agents have not been studied extensively in elderly adults. Immunization against hepatitis A and B in naïve elderly adults is an important public health intervention that needs to be revised and broadened.

Chronic liver disease is a major cause of morbidity and mortality among Hispanic people living in the United States. Environmental, genetic, and behavioral factors, as well as socioeconomic and health care disparities among this ethnic group have emerged as important public health concerns. We review the epidemiology, natural history, and response to therapy of chronic liver disease in Hispanic patients. The review covers nonalcoholic fatty liver disease, viral hepatitis B and C, coinfection of viral hepatitis with human immunodeficiency virus, alcoholic cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, and primary biliary cirrhosis. For most of these disorders, the Hispanic population has a higher incidence and more aggressive pattern of disease and overall worse treatment outcomes than in the non-Hispanic white population. Clinicians should be aware of these differences in caring for Hispanic patients with chronic liver disease., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Diarrhea is a common side effect of chemotherapy. Pseudomembranous colitis is a well known complication of antibiotic treatment that can also be observed, albeit rarely, with certain chemotherapeutic agents. We present four cases of severe colitis in patients undergoing treatment with taxane-based chemotherapy for pancreatic, lung and breast cancer. None of them had recently received antibiotics. One patient presented with a bowel perforation and three had endoscopic findings of pseudomembranous colitis. Two of these three patients had negative stool toxin assays for Clostridium difficile. In the patient presenting with perforation, an emergency left hemicolectomy was performed and the pathological findings in the colon were acute inflammation and ischemic necrosis; the other three patients were treated with oral vancomycin and/or oral or intravenous metronidazole leading to complete resolution of the symptoms. Apart from pseudomembranous colitis, we describe patients presenting with neutropenic enterocolitis as well as ischemic colitis after docetaxel use. These cases provide some insight into the spectrum and varied clinical presentations of severe colitis associated with taxane-based chemotherapy.