Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post‐LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post‐LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.

INTRODUCTION: The prevalence of cirrhosis is increasing despite advances in therapeutics, and it remains an expensive medical condition. Studies examining the healthcare burden of inpatient cirrhosis-related care regardless of etiology, stage, or severity are lacking. This study aims to describe the current drivers of cost, length of stay (LOS), and mortality in hospitalized patients with cirrhosis. METHODS: Using the National Inpatient Sample (NIS) data from 2008 to 2014, we categorized admissions into decompensated cirrhosis (DC), compensated cirrhosis (CC), and NIS without cirrhosis. Descriptive statistics and regression analysis were used to analyze the association between patient characteristics, comorbidities, complications, and procedures with costs, LOS, and mortality in each group. RESULTS: The hospitalization costs for patients with cirrhosis increased 30.2% from 2008 to 2014 to $7.37 billion. Cirrhosis admissions increased by 36% and 24% in the DC and CC groups, respectively, compared with 7.7% decrease in the NIS without cirrhosis group. DC admissions contributed to 58.6% of total cirrhotic admissions by 2014. Procedures increased costs in both DC and CC groups by 15%–152%, with mechanical ventilation being associated with high cost increase and mortality increase. Complications are also key drivers of costs and LOS, with renal and infectious complications being associated with the highest increases in the DC group and infections and nonportal hypertensive gastrointestinal bleeding for the CC group. DISCUSSION: Economic burden of hospitalized patients with cirrhosis is increasing with more admissions and longer LOS in DC and CC groups. Important drivers include procedures and portal hypertensive and nonportal hypertensive complications.

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.

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IMPORTANCE Changes in the characteristics of patients with cirrhosis are likely to affect future outcomes and are important to understand in planning for the care of this population. OBJECTIVE To identify changes in demographic and clinical characteristics and outcomes in patients with newly diagnosed cirrhosis. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of patients with a new diagnosis of cirrhosis was conducted using the Indiana Network for Patient Care, a large statewide regional health information exchange, between 2004 and 2014. Patients with at least 1 year of continuous follow-up before the cirrhosis diagnosis were followed up through August 1, 2015. The analysis was conducted from December 2018 to January 2019. EXPOSURES Age, cause of cirrhosis, and year of diagnosis. MAIN OUTCOMES AND MEASURES Overall rates for mortality, liver transplant, hepatocellular carcinoma, and hepatic decompensation (composite of ascites, hepatic encephalopathy, or variceal bleeding). RESULTS A total of 9261 patients with newly diagnosed cirrhosis were identified (mean [SD] age, 57.9 [12.6] years; 5109 [55.2%] male). A 69% increase in new diagnoses occurred over the course of the study period (620 in 2004 vs 1045 in 2014). The proportion of those younger than 40 years increased by 0.20% per year (95% CI, 0.04% to 0.36%; P for trend = .02), and the proportion of those aged 65 years and older increased by 0.81% per year (95% CI, 0.51% to 1.11%; P for trend < .001). The proportion of patients with alcoholic cirrhosis increased by 0.80% per year (95% CI, 0.49% to 1.12%), and the proportion with nonalcoholic steatohepatitis increased by 0.59% per year (95% CI, 0.30% to 0.87%), whereas the proportion with viral hepatitis decreased by 1.36% per year (95% CI, −1.68% to −1.03%) (P < .001 for all). In patients younger than 40 years, 40 to 64 years, and 65 years and older, mortality rates were 6.4 (95% CI, 5.4 to 7.6), 9.9 (95% CI, 9.5 to 10.4), and 16.2 (95% CI, 15.2 to 17.2) per 100 person-years, respectively (P < .001). Mortality rates decreased during the study period (11.9 [95% CI, 10.7-13.1] per 100 person-years in 2004 vs 10.0 [95% CI, 8.1-12.2] per 100 person-years in 2014; annual adjusted hazard ratio, 0.87 [95% CI, 0.86 to 0.88]) and were lower in those with alcoholic cirrhosis compared with patients with viral hepatitis (adjusted hazard ratio, 0.89 [95% CI, 0.80 to 0.98]). Rates of hepatocellular carcinoma were low in patients younger than 40 years (0.5 [95% CI, 0.2 to 0.9] per 100 person-years). Liver transplant rates were low throughout the study period (0.3 [95% CI, 0.3-0.4] per 100 person-years). In patients with compensated cirrhosis, rates of hepatic decompensation were lower in patients younger than 40 years (adjusted subhazard ratio 0.78; 95% CI, 0.62 to 0.99) and in patients with nonalcoholic steatohepatitis (adjusted subhazard ratio, 0.51; 95% CI, 0.43 to 0.60).

Summary Background Metformin may protect against hepatocellular carcinoma and mortality among patients with type 2 diabetes. Aim To investigate whether long‐term use of metformin improves survival and reduces liver‐related outcomes among patients with type 2 diabetes and non‐alcoholic steatohepatitis. Methods A total of 191 diabetic patients with biopsy‐proven non‐alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis were retrospectively identified at Indiana University Medical Center between October 2004 and January 2016. Of them, 110 were users and 81 never‐users of metformin. Primary outcomes were transplant‐free survival, development of hepatocellular carcinoma or a first event of hepatic decompensation. Results Cirrhosis was present in 85% of metformin users and 88% of nonusers. Metformin dose was greater than or equal to 1 g/d in 104 out of 110 users and its median duration of use was 6 (95% CI: 4.4‐7.9) years. The mean follow‐up was 6.92 and 6.80 years for metformin users and non‐users, respectively. During follow‐up, 28 patients developed hepatocellular carcinoma (metformin users: 7, nonusers: 21), and 52 died (metformin users: 7, nonusers: 24) or were transplanted (metformin users: 13, non‐users: 13). Metformin use was associated with lower risk of overall mortality or transplant (HR: 0.42; 95% CI: 0.24‐0.74, P = 0.003) and hepatocellular carcinoma (sHR: 0.25; 95% CI: 0.11‐0.58, P = 0.001), and remained independently associated with both outcomes after propensity‐score and covariate‐adjusted analyses. No instances of hepatotoxicity or lactic acidosis were observed. Conclusion Our study demonstrated an association between long‐term metformin use and reduced the risk of all‐cause mortality/transplant and hepatocellular carcinoma in diabetics with non‐alcoholic steatohepatitis and advanced fibrosis.

Background. Recurrence of hepatocellular carcinoma (HCC) is an important predictor of survival after liver transplantation (LT). Recent studies show that early diagnosis, aggressive treatment, and surveillance may improve outcomes after HCC recurrence. We sought to determine the current practices and policies regarding surveillance for HCC recurrence after LT. Methods. We conducted a web-based national survey of adult liver transplant centers in the United States to capture center-specific details of HCC surveillance post-LT. Responses were analyzed to generate numerical and graphical summaries. Results. Of 101 eligible adult liver transplant centers, 48 (48%) centers across the United States responded to the survey. Among the participating centers, 79% stratified transplant recipients for HCC recurrence risk, while 19% did not have any risk stratification protocol. Explant microvascular invasion (mVI) was the most common factor used in risk stratification. Use of pretransplant serum biomarkers such as alpha-fetoprotein (AFP) was variable, with only 48% of the participating centers reporting specific “cutoff” values. While a majority of centers (88%) reported having a routine imaging protocol for HCC recurrence surveillance, there was considerable heterogeneity in terms of frequency and duration of such surveillance. Of the centers that did risk stratify patients to identify those at higher risk of HCC recurrence, about 50% did not change their surveillance protocol. Conclusions. Our study affirms significant variability in center practices, and our results reflect the need for high-quality studies to guide risk stratification and surveillance for HCC recurrence.

These results support co-management between hospitalists and hepatologists as a superior model of care for hospitalized patients with SBP. Furthermore, this study adds to the growing literature indicating that efforts are needed to improve the quality of care delivered to CLD patients.