Risk of Cardiovascular Events in Patients with Primary Biliary Cholangitis - Systematic Review.

Background and Aims: Hypercholesterolemia is a common finding in patients with primary biliary cholangitis (PBC) and is a well-defined risk factor for cardiovascular disease. However, studies have been mixed on whether PBC patients do, in fact, have higher cardiovascular risk. The aim of this study is to review the current literature and provide an evidence-based assessment of cardiovascular risk in PBC patients. Methods: We performed a systematic literature search on PubMed regarding patients with PBC and cardiovascular events from the database inception to July 1, 2017. A total of 33 articles fulfilling our inclusion criteria were found. Results: The majority of the studies evaluated yielded no statistically significant difference in cardiovascular disease in the PBC population compared to the general public. However, some reports found a statistically significantly increase in coronary artery disease. Several studies have looked at the specific lipid profile of patients with PBC with hypocholesteremia. While these lipid abnormalities differ by stage of disease, there is evidence to suggest that the specific lipid profile in PBC may have lower atherogenicity than in patients with hypercholesterolemia without PBC. Studies looking at patients with PBC with other risk factors for cardiovascular disease, such as hypertension and metabolic syndrome, have consistently found a higher risk for cardiovascular disease in these patients. Statin treatment is effective in reducing lipid levels and possibly improving endothelial inflammation in patients with PBC with hypercholesterolemia. Conclusions: There is not enough evidence to suggest an increased risk of cardiovascular disease in patients with PBC with hypercholesterolemia, except for those individuals with concomitant features of metabolic syndrome. In patients with PBC with no additional cardiovascular risk factors, individual risk/benefit discussion on lipid-lowering treatment should be considered.

Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders: A systematic review.

BACKGROUND: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been the primary medication for the treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. The aim of this systematic review is to provide an evidence based assessment of the medications that have been studied in patients who are refractory to UDCA. METHODS: We performed a systematic literature search on MEDLINE and the Cochrane Database of Systematic Reviews of the published literature. A total of 23 articles fulfilling our inclusion criteria were found. RESULTS: Several studies have shown an improvement in liver biochemistries with the use of obeticholic acid in conjunction with UDCA. Fibrates, including fenofibrate and bezafibrate, have evidence supporting benefit in this population but need more robust studies to confirm these observational results. Neither obeticholic acid nor fibrates have shown to increase transplant free survival. While there may be some benefit with methotrexate, colchicine, budesonide, mycophenolate mofetil and azathioprine, these findings were not consistent and the benefits were marginal. Further investigation is needed. CONCLUSION: In patients with PBC refractory to UDCA, obeticholic acid or a fibrate is a reasonable choice as an adjunctive treatment to UDCA. Further investigation with randomized controlled trials is needed to provide high quality evidence to formulate standardized therapies in this difficult to treat population.

Bariatric Surgery and Liver Transplantation.

Obesity is an important public health and medical concern in the United States. The rate of obesity has steadily risen for the past several decades. Obesity is associated with the development of nonalcoholic steatohepatitis, which is one of the leading indications for liver transplantation. After liver transplantation, recipients tend to gain weight and develop recurrent fatty liver. Over time, recurrent fatty liver may impact patient and graft survival. A bariatric surgical approach may be beneficial in select patients.

Liver Transplantation and Bariatric Surgery: Best Approach.

Obesity has become increasingly prevalent, and the number of obese patients in need of liver transplant is expected to continue to increase. In addition, liver disease due to nonalcoholic fatty liver disease is expected to become the leading cause of liver transplantation in the near future. However, obesity remains a relative contraindication in liver transplant. New strategies in managing this patient population are clearly needed. To this end, the authors review the current literature on the efficacy of bariatric surgery in the setting of liver transplantation in obese patients.

A Rare Case of Digital Ischemia and Gangrene in ANCA-Associated Vasculitis with Review of the Literature.

This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases.

Age-related Morbidity and Mortality After Transjugular Intrahepatic Portosystemic Shunts.

AIM: To compare age-related morbidity and mortality after transjugular intrahepatic portosystemic shunts (TIPS). METHODS: We performed a retrospective chart review of patients who underwent TIPS at the University of California Los Angeles Medical Center between 2008 to 2014. Elderly patients (65 y and older) were matched with nonelderly patients (controls, below 65 y) by model for end-stage liver disease (MELD) score (±3), indication for TIPS (refractory ascites vs. variceal bleeding), serum sodium level (±5), in a ratio of 1:1. Endpoints measures were hospital stay post-TIPS, rifaximin, or lactulose use, TIPS failure at 30 days, readmission at 90 days, MELD at 90 days, and mortality at 90 days. RESULTS: A total of 30 patient matches were included in this study: 30 control and 30 elderly patients. The median [interquartile (IQR)] MELD scores for controls and elderly were 11 (9, 13.8) for the controls and 11.5 (9, 14.8) for elderly patients (P=0.139). There were no significant differences in serum sodium and indication for TIPS. Thirty and 90-day follow-up laboratory test results were also similar between elderly and control patients. Event-free survival at 90 days was similar between controls and elderly patients [odds ratio (OR), 0.86; 95% confidence interval (CI), 0.3-2.5; P>0.05]. There was a trend toward greater hospitalization (OR, 1.76; 95% CI, 0.52-5.95; P=0.546) and mortality (OR, 3.3; 95% CI, 0.3-14.01; P=0.182). CONCLUSIONS: The results of this study suggest event-free survival is similar between nonelderly and elderly patients. Although statistically significant, there is a tendency toward greater mortality and hospitalization in the elderly.

Spotlight on grazoprevir-elbasvir once-daily combination and its potential in the treatment of hepatitis C.

Chronic hepatitis C virus (HCV) infection is a leading cause of health care utilization in the USA. Incidence of cirrhosis from HCV is expected to rise in the near future, further increasing this burden. There is a high medical need for effective, tolerable, safe, all-oral, short-duration therapy. To this end, several new direct-acting antiviral agents have been developed and have shown excellent sustained virologic response rates. However, patients who have previously failed treatment or who have developed cirrhosis, renal failure, or human immunodeficiency virus coinfection remain difficult-to-treat subgroups. An all-oral agent that is effective in many of these subgroups would simplify treatment of HCV greatly. Here we review currently available data on the efficacy, treatment duration, tolerability, and safety of combination of grazoprevir and elbasvir.

Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions.

Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy.

Treatment of Hepatitis C Virus Infection in Liver Transplant Recipients.

Chronic hepatitis C virus (HCV) infection is the leading cause of liver transplantation in adults. Although the recurrence of HCV infection after liver transplantation is nearly universal, the recent advances in direct-acting antiviral (DAA) agents have revolutionized the management of HCV infection in the posttransplant setting. A number of these agents have been evaluated in recent clinical trials and have shown high sustained virologic response rates, shorter durations of treatment, and decreased adverse events when compared with the previous treatment of pegylated interferon and ribavirin. This article will review the current literature on the efficacy, tolerability, and potential drug interactions of various DAA agents in patients with recurrent HCV infection posttransplant.

Timing of Hepatitis C Antiviral Therapy in Liver Transplant Recipients With Direct-acting Agents.

Chronic hepatitis C virus infection is a substantial health care burden worldwide and is the leading cause of liver transplant in adults. In patients with detectable hepatitis C virus RNA at the time of transplant, interferon-based therapies for hepatitis C virus were poorly tolerated with low virologic response rates. Although reinfection after transplant is inevitable, the recent advent of direct-acting antiviral agents has revolutionized treatment of hepatitis C virus in the pre- and posttransplant settings. These antiviral agents have been shown to have high-sustained virologic response rates, shorter courses of treatment, and decreased frequencies of adverse effects. Here, we review the current literature on the use of direct-acting agents for treatment of patients with hepatitis C virus before and after liver transplant.

Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials.

BACKGROUND: Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization. AIM: The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose. METHODS: The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I(2) statistic. RESULTS: Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47-2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42-1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25-6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33-0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26-0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52-1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52-1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73-2.10, P = 0.42). CONCLUSIONS: Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates.

Alcoholic hepatitis: The pivotal role of Kupffer cells.

Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis (AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides (LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called toll-like receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis.

Multiple pancreatic pseudocysts treated with endoscopic transpapillary drainage.

Management of a solitary pancreatic pseudocyst with endoscopic transpapillary stent drainage is a well recognized treatment modality. Endoscopic options are however limited in the presence of multiple pancreatic pseudocysts. Conventionally surgery has been the mainstay of treatment in this situation. In this case report, we present a patient with multiple pancreatic pseudocysts who was successfully treated via transpapillary placement of pancreatic duct stent.