Sumeet K. Asrani M.D.

Kanwal, F., Khaderi, S., Singal, A. G., Marrero, J. A., Loo, N., Asrani, S. K., Amos, C. I., Thrift, A. P., Gu, X., Luster, M., Al-Sarraj, A., Ning, J. and El-Serag, H. B. (2022). “Risk Factors for Hepatocellular Cancer in Contemporary Cohorts of Patients with Cirrhosis.” Hepatology.

Full text of this article.

BACKGROUND & AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed hepatocellular cancer (HCC) risk. APPROACH & RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven U.S. centers and followed until HCC diagnosis, transplant, death or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on the risk of HCC. We included 2733 patients with cirrhosis (mean age 60.1 years, 31.3% women). At enrollment, 19.0% had active HCV, 23.3% cured HCV, 16.1% had alcoholic liver disease, and 30.1% had nonalcoholic fatty liver disease (NAFLD). During 7,406 person-years follow up, 135 patients developed HCC at an annual incidence rate of 1.82% (95% confidence interval [CI]=1.51-2.13). The annual HCC incidence rate was 1.71% in patients with cured HCV, 1.32% in patients with alcoholic liver disease, and 1.24% in patients with NAFLD cirrhosis. Compared to patients with NAFLD, the risk of progression to HCC was 2-fold higher in patients with cured HCV (hazard ratio [HR]=2.04, 95% CI, 1.24-3.35). Current smoking (HR=1.63, 95%CI, 1.01-2.63) and overweight/obesity (HR=1.79, 95% CI 1.08, 2.95) were also associated with HCC risk. CONCLUSIONS: HCC incidence among patients with cirrhosis was lower than previously reported. HCC risk was variable across etiologies, with higher risk in patients with HCV cirrhosis and lower in those with NAFLD cirrhosis. Current smoking and overweight/obesity increased HCC risk across etiologies.

Serper, M., Parikh, N. D., Thiele, G., Ovchinsky, N., Mehta, S., Kuo, A., Ho, C., Kanwal, F., Volk, M., Asrani, S. K., Ghabril, M. S., Lake, J. R., Merriman, R. B., Morgan, T. R. and Tapper, E. B. (2022). “Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.” Hepatology.

Full text of this article.

BACKGROUND AND AIMS: HCC is a leading cause of mortality in patients with advanced liver disease and is associated with significant morbidity. Despite multiple available curative and palliative treatments, there is a lack of systematic evaluation of patient-reported outcomes (PROs) in HCC. APPROACH AND RESULTS: The American Association for the Study of Liver Diseases Practice Metrics Committee conducted a scoping review of PROs in HCC from 1990 to 2021 to (1) synthesize the evidence on PROs in HCC and (2) provide recommendations on incorporating PROs into clinical practice and quality improvement efforts. A total of 63 studies met inclusion criteria investigating factors associated with PROs, the relationship between PROs and survival, and associations between HCC therapy and PROs. Studies recruited heterogeneous populations, and most were cross-sectional. Poor PROs were associated with worse prognosis after adjusting for clinical factors and with more advanced disease stage, although some studies showed better PROs in patients with HCC compared to those with cirrhosis. Locoregional and systemic therapies were generally associated with a high symptom burden; however, some studies showed lower symptom burden for transarterial radiotherapy and radiation therapy. Qualitative studies identified additional symptoms not routinely assessed with structured questionnaires. Gaps in the literature include lack of integration of PROs into clinical care to guide HCC treatment decisions, unknown impact of HCC on caregivers, and the effect of palliative or supportive care quality of life and health outcomes. CONCLUSION: Evidence supports assessment of PROs in HCC; however, clinical implementation and the impact of PRO measurement on quality of care and longitudinal outcomes need future investigation.

Panchani, N., Schulz, P., Van Zyl, J., Felius, J., Baxter, R., Yoon, E.T., Baldawi, H., Bindra, A. and Asrani, S.K. (2021). “Liver stiffness and prediction of cardiac outcomes in patients with acute decompensated heart failure.” Clin Transplant Nov 24;e14545. [Epub ahead of print]. e14545.

Full text of this article.

BACKGROUND: In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however, it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF. METHODS: In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death. RESULTS: The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 – 63.4] vs 13.8 [9.5 – 40.3] kPa, p = .049). Moreover, the risk of composite outcome was highest in the 3rd tertile (> 39.8 kPa compared to 1(st) and 2(nd) combined, HR 2.83, 95% CI 1.20- 6.67, p = .02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = .01). CONCLUSIONS: LSM may serve as a novel noninvasive tool to determine LVAD, HT, or death in patients with ADHF.

Asrani, S.K., Ghabril, M.S., Kuo, A., Merriman, R.B., Morgan, T., Parikh, N.D., Ovchinsky, N., Kanwal, F., Volk, M.L., Ho, C., Serper, M., Mehta, S., Agopian, V., Cabrera, R., Chernyak, V., El-Serag, H.B., Heimbach, J., Ioannou, G.N., Kaplan, D., Marrero, J., Mehta, N., Singal, A., Salem, R., Taddei, T., Walling, A. and Tapper, E.B. (2021). “Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.” Hepatology Nov 15. [Epub ahead of print].

Full text of this article.

BACKGROUND AND AIMS: The burden of hepatocellular carcinoma (HCC) is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes along the HCC care continuum. APPROACH AND RESULTS: We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate patient-reported outcomes (PRO) based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. CONCLUSIONS: The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.

Shankar, N., A. Ramani, C. Griffin, U. Agbim, D. Kim, A. Ahmed and S. K. Asrani (2021). “Extrahepatic causes of death in cirrhosis compared to other chronic conditions in the United States, 1999-2017.” Ann Hepatol: 100565.

Full text of this article.

INTRODUCTION AND OBJECTIVES: Cirrhosis- related mortality is underestimated and is increasing; extrahepatic factors may contribute. We examined trends in cirrhosis mortality from 1999-2017 in the United States attributed to liver-related (varices, peritonitis, hepatorenal syndrome, hepatic encephalopathy, hepatocellular carcinoma sepsis) or extrahepatic (cardiovascular disease, influenza and pneumonia, diabetes, malignancy) causes, and compared mortality trends with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) populations. MATERIALS AND METHODS: A national mortality database was used. Changes in age-standardized mortality over time were determined by joinpoint analysis. Average annual percentage change (AAPC) was estimated. RESULTS: Cirrhosis cohort: From 1999-2017, both liver-related (AAPC 1.3%; 95% confidence interval [CI] 0.7-1.9) and extrahepatic mortality (AAPC 1.0%; 95% CI 0.7-1.2) increased. Cirrhosis vs other chronic disease cohorts: changes in all-cause mortality were higher in cirrhosis (AAPC 1.0%; 95% CI 0.7-1.4) than CHF (AAPC 0.1%; 95% CI -0.5- 0.8) or COPD (AAPC -0.4%; 95% CI -0.6- -0.2). Sepsis mortality was highest in cirrhosis (AAPC 3.6%, 95% 3.2- 4.1) compared to CHF (AAPC 0.6%, 95% CI -0.5- 1.7) or COPD (AAPC 0.8%, 95% CI 0.5- 1.2). Cardiovascular mortality increased in cirrhosis (AAPC 1.3%, 95% CI 1.1- 1.5), declined in CHF (AAPC -2.0%, 95% CI -5.3- 1.3) and remained unchanged in COPD (AAPC 0.1%, 95% CI -0.2- 0.4). Extrahepatic mortality was higher among women, rural populations, and individuals >65 years with cirrhosis. CONCLUSIONS: Extrahepatic causes of death are important drivers of mortality and differentially impact cirrhosis compared to other chronic diseases.