Liver Transplantation for Nonalcoholic Steatohepatitis: Pathophysiology of Recurrence and Clinical Challenges.

Nonalcoholic steatohepatitis is the fastest-growing indication for the liver transplant and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the USA. Post-transplant nonalcoholic hepatic steatosis and steatohepatitis are frequent complications of liver transplantation. Nonalcoholic steatohepatitis poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome, coronary artery disease, chronic kidney disease, and obstructive sleep apnea. While optimal therapy is not yet available in the post-liver transplant setting, lifestyle interventions continue to remain as the mainstay of therapy for post-transplant nonalcoholic steatohepatitis. Early recognition with protocol biopsies and noninvasive modalities, along with modification of known risk factors, are the most effective methods to curtail the progression of nonalcoholic steatohepatitis in the absence of FDA-approved pharmacologic therapy.

Hepatitis C virus direct-acting antiviral nonadherence: Relationship to sustained virologic response and identification of at-risk patients.

OBJECTIVES: There is a dearth of literature on effects of nonadherence to hepatitis C virus (HCV) direct-acting antiviral (DAA) regimens; thus, the objective of our study was to assess the impact of adherence on sustained virologic response (SVR) and evaluate factors associated with nonadherence, such as race, psychiatric comorbidities, and therapy length. METHODS: We conducted a retrospective cohort study of patients completing DAA treatment between January 2014 and May 2016 within an interdisciplinary hepatology clinic. Adherence was defined a priori as 95% or greater of DAA doses taken within the prescribed treatment period. Post hoc analyses were done with adherence thresholds ≥ 90%, ≥ 85%, and ≥ 80% and adherence as a continuous percentage. Patients lost to follow-up before completing therapy or that discontinued therapy early were excluded from analyses. The association between adherence and SVR rates was assessed using Fisher exact test (for adherence thresholds) and the Wilcoxon rank-sum test (for continuous adherence). Factors associated with adherence were assessed similarly using Fisher exact and Wilcoxon rank-sum tests and multivariable logistic regression. RESULTS: Overall adherence was high, with an average of 97.8% of DAA doses taken within the prescribed treatment period. Achievement of SVR was not significantly different in adherent and nonadherent patients, at an adherence threshold of 95% or greater (93.4% vs. 88.5%; P = 0.246) or any of the post hoc adherence thresholds (≥ 90% [93.3% vs. 84.0%; P = 0.098], ≥ 85% [92.8% vs. 91.7%; P = 0.601], ≥ 80% [92.9% vs. 80.0%; P = 0.315], or as a continuous percentage [P = 0.328]). Black patients were significantly more likely to be nonadherent to DAAs than non-black patients at each adherence threshold (P < 0.05). No other factors evaluated were associated with nonadherence. CONCLUSION: A numerically higher but not statistically significant SVR failure rate was noted in nonadherent patients, although the gold standard definition for adherence remains to be established. Black patients may require additional adherence support.

Disseminated Histoplasmosis Involving Soft Palate, Duodenum, Sigmoid Colon and Bone Marrow in a Patient With Isolated CD4+ T-Lymphocytopenia.

Idiopathic CD4 T-lymphocytopenia (ICL) is a rare entity that is associated with decreased immunity which predisposes affected individuals to opportunistic infections and malignancies. Autoimmune conditions are common in patients with ICL and they are considered part of its clinical spectrum as well. Treatment of ICL includes treatment of opportunistic infections and prophylaxis against them. Some cases are self-limited while others require long-term monitoring. We present a case of a 60-year-old man who was diagnosed with disseminated histoplasmosis involving soft palate, duodenum, colon and bone marrow in the setting of idiopathic CD4 T-lymphocytopenia.

Peri-transplant management of nonalcoholic fatty liver disease in liver transplant candidates .

The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly growing, affecting 25% of the world population. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD and affects 1.5% to 6.5% of the world population. Its rising incidence will make end-stage liver disease (ESLD) due to NASH the number one indication for liver transplantation (LT) in the next 10 to 20 years, overtaking Hepatitis C. Patients with NASH also have a high prevalence of associated comorbidities such as type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), which must be adequately managed during the peritransplant period for optimal post-transplant outcomes. The focus of this review article is to provide a comprehensive overview of the unique challenges these patients present in the peritransplant period, which comprises the pre-transplant, intraoperative, and immediate postoperative periods.

Similarities and Differences Between Nonalcoholic Steatohepatitis and Other Causes of Cirrhosis.

Nonalcoholic fatty liver disease includes a spectrum of liver disorders that range from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Risk factors such as obesity, hypertension, hyperlipidemia, chronic kidney disease, and smoking status increase risk of progression to cirrhosis among patients with NASH. Cirrhosis derived from non-NASH causes may share similar features with patients with NASH but embody distinct pathogenetic mechanisms, genetic associations, prognosis, and outcomes. This article discusses in detail the comparison of clinical, genetic, and outcome characteristics between patients with NASH cirrhosis as opposed to alternative causes of chronic liver disease.

Systematic review with meta-analysis: abnormalities in the international normalised ratio do not correlate with periprocedural bleeding events among patients with cirrhosis.

BACKGROUND: Cirrhotic coagulopathy is a delicate interplay comprising deficiencies of both procoagulant and anticoagulant factors. AIM: To identify the relationship between international normalised ratio [INR] with periprocedural bleeding risk among patients with cirrhosis. METHODS: Following a thorough database search of the primary literature, 29 studies were targeted for analysis, including 13 276 patients with cirrhosis undergoing indicated procedures. RESULTS: There was no significant association between periprocedural bleeding events and pre-procedural INR [pooled odds ratio 1.52; 95% CI 0.99, 2.33; P = 0.06]. Furthermore, there was no significant difference in mean INR [pooled mean difference 0.05; 95% CI -0.03, 0.13; P = 0.23] upon comparison of patients who either did or did not experience a periprocedural bleeding event. Significant heterogeneity among some studies was primarily fuelled by significant subgroup effects of both specific procedure types performed. Additionally, there were markedly inconsistent transfusion practices across studies. CONCLUSIONS: INR fails to serve as a significant correlate for periprocedural bleeding events among patients with cirrhosis. Ideally, these new findings will help serve as a springboard for future studies, as well as to minimize transfusion of blood products, which command a myriad of adverse effects among patients with cirrhosis.