Kezer, Camille A.

Cirrhosis is a prevalent condition affecting more than 100 million people globally and carrying significant morbidity and mortality related to the development of portal hypertension and hepatic decompensation. Current treatment is primarily targeted at identifying chronic liver disease early and preventing the progression of fibrosis by treating the underlying etiology of liver disease. Treatment options for patients with advanced fibrosis are limited, and the only drug class approved for the prevention of hepatic decompensation remains nonselective beta-blockers. There are several pharmacological therapies being developed in both preclinical and clinical trials to explore their efficacy in preventing first hepatic decompensation. Most studies evaluate primary endpoints reflective of disease severity and portal hypertension, such as changes in HVPG or fibrosis stage based on histology or imaging. While many drugs are being investigated, much work is still needed to identify treatment targets with effective outcomes to move the needle in the field of cirrhosis management. This narrative review will address the current state of cirrhosis therapies, including potential new therapeutic targets, and provide direction on future advancements that will improve our current treatment paradigm and lead to better outcomes for those burdened with cirrhosis.

Abstract Background & Aims: Sarcopenia is common in patients with liver disease and both sarcopenia and short telomeres are associated with mortality, however their relationship in patients with liver disease remains unknown. Methods: A cohort of 16,072 adults from the National Health and Nutrition Examination Survey from 1999-2006 was analyzed. Liver disease was defined by aminotransferases and classified into etiology-based categories. Sarcopenia was defined by dual-energy x-ray absorptiometry. All analyses were conducted separately on each multiple imputation data set and combined via Rubin’s rules. P-values for group comparisons were calculated by testing logistic regression parameter estimates. Cox proportional hazards regression was used for mortality analysis with mortality data available until 2015. Results:Sarcopenia was present in 9.5% of patients with liver disease. Age, race, income, education, physical inactivity, and certain medical comorbidities were associated with sarcopenia. Patients with liver disease and sarcopenia had significantly shorter telomeres than patients with liver disease without sarcopenia when unadjusted for age. The interaction between telomere length and sarcopenia was significantly associated with all-cause mortality. Conclusions: The implications of telomere length on all-cause mortality in patients with liver disease varied by age and sarcopenia status. Shorter telomeres appear to be more highly associated with increased mortality in older patients without sarcopenia.

Background: Remote patient monitoring (RPM) is an emerging focus in health care, and specialized programs may reduce medical costs, supplement in-office visits, and improve patient satisfaction. In this study, we describe the development, feasibility, and early outcomes of an RPM program for patients with decompensated cirrhosis. Methods: Forty-six patients were offered enrollment at the time of hospital discharge in the cirrhosis RPM program (CiRPM), of which 41 completed at least 30 days of monitoring. Participants were mailed remote monitoring equipment and a tablet to be used for patient-reported outcomes. Alerts were continuously monitored by virtual nursing staff who could perform targeted interventions. A cohort of historical controls (n = 74) was created for comparison using inverse probability of treatment weighting. Results: Patients were enrolled in the program for a mean of 83.9 days, with 28 (68%) completing the full 90-day program. Participants uploaded vital signs and responded to symptom-based questionnaires on 93% of the monitored days. On end-of-program surveys, over 75% of patients expressed satisfaction with the program. Gender, age, and MELD-Na were similar between CiRPM and weighted control groups. The 90-day readmission rate was 34% in CiRPM and 47% in weighted controls. In the CiRPM group, 12% of subjects had 2 or more admissions, compared to 37% in the weighted control group. Conclusion: This study demonstrates the feasibility of a cirrhosis-specific RPM program. Overall, patient satisfaction and utilization of the CiRPM was high. Future studies are needed to confirm the impact of RPM on the reduction of hospital readmissions in decompensated cirrhosis.

AbstractBackgroundNodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non‐cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown.MethodsA retrospective cohort of consecutive patients diagnosed with pathology‐confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug‐associated, miscellaneous or idiopathic. Long‐term mortality was analysed using Kaplan‐Meier estimation and Cox regression models.ResultsOne hundred and sixty‐seven consecutive patients with pathology‐confirmed NRH were analysed over a 15‐year period and followed for a median time of 50 months (1–306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension‐related complications at diagnosis were common, with ascites present in one‐third of patients. Overall transplant‐free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not.ConclusionsThe rates of liver‐related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver‐related outcomes do not appear to differ based on associated, possibly causal, conditions.

Alcohol‐associated hepatitis (AAH) is a severe form of liver injury with mortality as high as 30%‐40% at 90 days. As a result of altered immune function in AAH, bacterial infections are common and are associated with poor outcomes. However, determining the risk and subsequent development of infection in patients with AAH remain challenging. We performed a retrospective study of consecutive patients admitted with a diagnosis of AAH at two independent tertiary centers from 1998 to 2018 (test cohort, n = 286) who developed infections following hospitalization. The diagnosis of AAH was confirmed by manual chart review according to the recent National Institute on Alcohol Abuse and Alcoholism definition. Infections were categorized by location and time of diagnosis as hospital‐acquired infection (48 hours after admission until discharge) and posthospital infections (up to 6 months following discharge). The cohort was 66% men, and the median age was 48 (21‐83) years. Corticosteroids were used in 32% of all patients with AAH. The overall infection rate was 24%. Of those with infections, 46% were hospital acquired and 54% were acquired after hospitalization. Variables found to be significant risk factors for bacterial infection included the presence of ascites on admission (hazard ratio [HR], 2.06), corticosteroid administration (HR, 1.70), Model for End‐Stage Liver Disease (MELD) >23 (HR, 2.61), and white blood cell (WBC) count on admission per point (HR, 1.02). Conclusion: In this multicenter cohort study of patients hospitalized with AAH, MELD score, ascites, WBC count, and use of corticosteroids were identified as significant predictors of the development of bacterial infection. We created a novel predictive equation that may be used to aid in the identification of patients with AAH at high risk of infection.