African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

Development and scale-up of rVSV-SARS-CoV-2 vaccine process using single use bioreactor.

The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the Coronavirus Disease 2019 (COVID-19) has spread through the globe at an alarming speed. The disease has become a global pandemic affecting millions of people and created public health crises worldwide. Among many efforts to urgently develop a vaccine against this disease, we developed an industrial-scale closed, single use manufacturing process for V590, a vaccine candidate for SARS-CoV-2. V590 is a recombinant vesicular stomatitis virus (rVSV) genetically engineered to express SARS-CoV-2 glycoprotein. In this work, we describe the development and optimization of serum-free microcarrier production of V590 in Vero cells in a closed system. To achieve the maximum virus productivity, we optimized pH and temperature during virus production in 3 liters (L) bioreactors. Virus productivity was improved (by ∼1 log) by using pH 7.0 and temperature at 34.0 °C. The optimal production condition was successfully scaled up to a 2000 L Single Use Bioreactor (SUB), producing a maximum virus titer of ∼1.0e+7 plaque forming units (PFU)/mL. Further process intensification and simplification, including growing Vero cells at 2 gs per liter (g/L) of Cytodex-1 Gamma microcarriers and eliminating the media exchange (MX) step prior to infection helped to increase virus productivity by ∼2-fold.

Impact of Pruritus on Quality of Life and Current Treatment Patterns in Patients with Primary Biliary Cholangitis.

BACKGROUND AND AIMS: Patients with primary biliary cholangitis (PBC) often suffer with pruritus. We describe the impact of pruritus on quality of life and how it is managed in a real-world cohort. METHODS: TARGET-PBC is a longitudinal observational cohort of patients with PBC across the USA. Data include information from medical records for three years prior to the date of consent up to 5 years of follow-up. Enrolled patients were asked to complete patient-reported outcome surveys: PBC-40, 5-D itch, and the PROMIS fatigue survey. Kruskal-Wallis tests were used to compare differences in symptoms between groups. RESULTS: A total of 211 patients with completed PRO surveys were included in the current study. PRO respondents were compared with non-respondents in the TARGET-PBC population and were broadly similar. Pruritus was reported in 170 patients (81%), with those reporting clinically significant pruritus (30%) scoring worse across each domain of the PBC-40 and 5-D itch, more frequently having cirrhosis, and having significantly greater levels of fatigue. Patients reporting clinically significant pruritus were more likely to receive treatment, but 33% had never received treatment (no itch = 43.9%, mild itch = 38.3%). CONCLUSIONS: The prevalence of pruritus was high in this population, and those reporting clinically significant pruritus had a higher likelihood of having advanced disease and worse quality of life. However, this study found that pruritus in PBC is under-treated. This may be due in part to ineffectiveness of current treatments, poor tolerance, or the lack of FDA-approved medications for pruritus.

Sarcopenic visceral obesity is associated with increased post-liver transplant mortality in acutely ill patients with cirrhosis.

"Sarcopenic obesity" refers to a condition of low muscle mass in the context of obesity, though may be difficult to assess in patients with cirrhosis who are acutely ill. We aimed to define sarcopenic visceral obesity (SVO) using CT-based skeletal muscle index (SMI) and visceral-to-subcutaneous adipose tissue ratio (VSR) to examine its association with post-transplant mortality. We analyzed 116 adult inpatients with cirrhosis who were urgently listed and transplanted between 1/2005 and 12/2017 at 4 North American transplant centers. SVO was defined as patients with sarcopenia (SMI <50 cm2 /m2 in men and <39 cm2 /m2 in women) and visceral obesity (VSR ≥ 1.54 in men and ≥1.37 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 45%, 42%, and 20%, respectively. Cumulative rates of post-transplant mortality were higher in patients with SVO compared to patients with sarcopenia or visceral obesity alone at 36 months (39% vs. 14% vs. 8%) [logrank p = .01]. In univariable regression, SVO was associated with post-transplant mortality (HR 2.92, 95%CI 1.04-8.23) and remained significant after adjusting for age, sex, diabetes, encephalopathy, hepatocellular carcinoma, and MELD-Na (HR 3.50, 95%CI 1.10-11.15). In conclusion, SVO is associated with increased post-transplant mortality in acutely ill patients with cirrhosis.

A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis.

The purpose of this pilot study was to explore the efficacy, safety, and tolerability of vidofludimus calcium (VC) in the treatment of primary sclerosing cholangitis (PSC). This was a single-arm open-label pilot study with a cohort of 18 patients with PSC. Study patients received VC for a period of 6 months. The study was undertaken at two sites, Mayo Clinic, Rochester, MN, and Mayo Clinic, Phoenix, AZ. The primary endpoint of the study was improvement of serum alkaline phosphatase (ALP) at the end of the study. Secondary endpoints included assessment of other liver biomarkers (bilirubin, alanine aminotransferase, and aspartate aminotransferase). Of 18 patients enrolled, 11 completed the 6 months of study treatment. Patients who completed treatment versus those who did not were similar other than a significantly higher direct bilirubin at baseline in the group that completed treatment (mean ± SD, 0.4 ± 0.3 versus 0.1 ± 0.1, p = 0.04). By intent to treat analysis, the primary outcome was met in 16.7% (3/18) of patients. By per-protocol analysis, including only patients who completed treatment, normalization of ALP occurred in 27.7% (3/11) at week 24 (95% confidence interval, 6.0% to 61.0%). VC was well tolerated with no drug-related serious adverse events. Conclusion: This proof of concept study provides support for further exploration of VC in patients with PSC.

Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score.

BACKGROUND AND AIMS: The NASH Clinical Research Network histologic scoring system, the gold-standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS). APPROACH AND RESULTS: Four liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80-0.85) and interrater (0.60-0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68-0.79), including those extending scores from 0-2 to 0-4. Steatosis measures (interrater ICCs, 0.72-0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory-Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70-0.87. CONCLUSIONS: After extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required.

Recommendations for intraoperative mesh brachytherapy: Report of AAPM Task Group No. 222.

Mesh brachytherapy is a special type of a permanent brachytherapy implant: it uses low-energy radioactive seeds in an absorbable mesh that is sutured onto the tumor bed immediately after a surgical resection. This treatment offers low additional risk to the patient as the implant procedure is carried out as part of the tumor resection surgery. Mesh brachytherapy utilizes identification of the tumor bed through direct visual evaluation during surgery or medical imaging following surgery through radiographic imaging of radio-opaque markers within the sources located on the tumor bed. Thus, mesh brachytherapy is customizable for individual patients. Mesh brachytherapy is an intraoperative procedure involving mesh implantation and potentially real-time treatment planning while the patient is under general anesthesia. The procedure is multidisciplinary and requires the complex coordination of multiple medical specialties. The preimplant dosimetry calculation can be performed days beforehand or expediently in the operating room with the use of lookup tables. In this report, the guidelines of American Association of Physicists in Medicine (AAPM) are presented on the physics aspects of mesh brachytherapy. It describes the selection of radioactive sources, design and preparation of the mesh, preimplant treatment planning using a Task Group (TG) 43-based lookup table, and postimplant dosimetric evaluation using the TG-43 formalism or advanced algorithms. It introduces quality metrics for the mesh implant and presents an example of a risk analysis based on the AAPM TG-100 report. Recommendations include that the preimplant treatment plan be based upon the TG-43 dose calculation formalism with the point source approximation, and the postimplant dosimetric evaluation be performed by using either the TG-43 approach, or preferably the newer model-based algorithms (viz., TG-186 report) if available to account for effects of material heterogeneities. To comply with the written directive and regulations governing the medical use of radionuclides, this report recommends that the prescription and written directive be based upon the implanted source strength, not target-volume dose coverage. The dose delivered by mesh implants can vary and depends upon multiple factors, such as postsurgery recovery and distortions in the implant shape over time. For the sake of consistency necessary for outcome analysis, prescriptions based on the lookup table (with selection of the intended dose, depth, and treatment area) are recommended, but the use of more advanced techniques that can account for real situations, such as material heterogeneities, implant geometric perturbations, and changes in source orientations, is encouraged in the dosimetric evaluation. The clinical workflow, logistics, and precautions are also presented.

Azathioprine Monotherapy Is Equivalent to Dual Therapy in Maintaining Remission in Autoimmune Hepatitis.

BACKGROUND: Standard of care treatment for AIH includes prednisone monotherapy or dual therapy prednisone-azathioprine. However, many hepatologists alternatively use azathioprine monotherapy to avoid side effects of long-term corticosteroids. AIMS: To determine whether azathioprine monotherapy is comparable to dual prednisone-azathioprine for maintenance of remission in AIH. METHODS: A retrospective chart review of 260 individuals with AIH from a single institution was performed; 45 individuals were included. Exclusion criteria included concomitant PBC or PSC, use of alternative treatment regimen, and/or failure to reach remission. Treatment regimen received was guided by clinician standard of practice, not patients' clinical factors. Initial remission was defined as normalization of serum ALT for at least two consecutive blood draws. Data were analyzed for 5 years post-remission, recording outcome and dose of prednisone and/or azathioprine. RESULTS: 83% of individuals were female, and average age was 65 years. Median dose of prednisone and azathioprine for the dual-therapy group was 5 mg and 100 mg, respectively, while median azathioprine dose for the monotherapy group was 75 mg. Considering overall outcome, 93% of all patients maintained remission. 80% of the dual-therapy group, and 95% of the azathioprine monotherapy group maintained remission. Using Chi-square analysis to compare the maintenance of remission between dual therapy and azathioprine monotherapy, a p value of 0.28 was calculated. CONCLUSIONS: AASLD guidelines recommend dual prednisone-azathioprine as standard of care for maintenance of remission in AIH. Our results suggest that azathioprine monotherapy is equivalent to prednisone-azathioprine. Azathioprine monotherapy offers a significant advantage in mitigating risks of long-term corticosteroid therapy.

Development of a High Yielding Bioprocess for a Pre-fusion RSV Subunit Vaccine.

Respiratory syncytial virus (RSV) is a highly contagious virus causing severe infection in infants and the elderly. Various approaches are being used to develop an effective RSV vaccine. The RSV fusion (F) subunit, particularly the cleaved trimeric pre-fusion F, is one of the most promising vaccine candidates under development. The pre-fusion conformation elicits the majority of neutralizing antibodies during natural infection. However, this pre-fusion conformation is metastable and prone to conversion to a post-fusion conformation, thus hindering the potential of this construct as a vaccine antigen. The Vaccine Research Center (VRC) at the National Institutes of Health (NIH) designed a structurally stabilized pre-fusion F glycoprotein, DS-Cav1, that showed high immunogenicity and induced a neutralizing response in animal studies. To advance this candidate to clinical manufacturing, a production process that maintained product quality (i.e. a cleaved trimer with pre-fusion conformation) and delivered high protein expression levels was required. This report describes the development of the vaccine candidate including vector design and cell culture process development to meet these challenges. Co-transfection of individual plasmids to express DS-Cav1 and furin (for DS-Cav1 cleavage and activation) demonstrated a superior protein product expression and pre-fusion conformation compared to co-expression with a double gene vector. A top clone was selected based on these measurements. Protein expression levels were further increased by seeding density optimization and a biphasic hypothermia temperature downshift. The combined efforts led to a high-yield fed-batch production of approximately 1,500 mg/L (or up to 15,000 doses per liter) at harvest. The process was scaled up and demonstrated to be reproducible at 50 L-scale for toxicity and Phase I clinical trial use. Preliminary phase I data indicate the pre-fusion antigen has a promising efficacy (Crank et al., 2019).

Bile Acid Profiles in Primary Sclerosing Cholangitis and Their Ability to Predict Hepatic Decompensation.

BACKGROUND AND AIMS: Altered bile acid (BA) homeostasis is an intrinsic facet of cholestatic liver diseases, but clinical usefulness of plasma BA assessment in primary sclerosing cholangitis (PSC) remains understudied. We performed BA profiling in a large retrospective cohort of patients with PSC and matched healthy controls, hypothesizing that plasma BA profiles vary among patients and have clinical utility. APPROACH AND RESULTS: Plasma BA profiling was performed in the Clinical Biochemical Genetics Laboratory at Mayo Clinic using a mass spectrometry based assay. Cox proportional hazard (univariate) and gradient boosting machines (multivariable) models were used to evaluate whether BA variables predict 5-year risk of hepatic decompensation (HD; defined as ascites, variceal hemorrhage, or encephalopathy). There were 400 patients with PSC and 302 controls in the derivation cohort (Mayo Clinic) and 108 patients with PSC in the validation cohort (Norwegian PSC Research Center). Patients with PSC had increased BA levels, conjugated fraction, and primary-to-secondary BA ratios relative to controls. Ursodeoxycholic acid (UDCA) increased total plasma BA level while lowering cholic acid and chenodeoxycholic acid concentrations. Patients without inflammatory bowel disease (IBD) had primary-to-secondary BA ratios between those of controls and patients with ulcerative colitis. HD risk was associated with increased concentration and conjugated fraction of many BA, whereas higher G:T conjugation ratios were protective. The machine-learning model, PSC-BA profile score (concordance statistic [C-statistic], 0.95), predicted HD better than individual measures, including alkaline phosphatase, and performed well in validation (C-statistic, 0.86). CONCLUSIONS: Patients with PSC demonstrated alterations of plasma BA consistent with known mechanisms of cholestasis, UDCA treatment, and IBD. Notably, BA profiles predicted future HD, establishing the clinical potential of BA profiling, which may be suited for use in clinical trials.

Liver Stiffness Measured by Either Magnetic Resonance or Transient Elastography Is Associated With Liver Fibrosis and Is an Independent Predictor of Outcomes Among Patients With Primary Biliary Cholangitis.

GOALS: We aimed to describe the diagnostic and prognostic performance of transient elastography (TE) and magnetic resonance elastography (MRE) in patients with primary biliary cholangitis (PBC). BACKGROUND: The diagnostic performance of TE and MRE in detecting advanced fibrosis in PBC and in predicting outcomes independent of existing serologic prognostic markers is incompletely understood. MATERIALS AND METHODS: Five hundred thirty-eight consecutive patients with PBC at 3 centers with liver stiffness (LS) measurements by TE (n=286) or MRE (n=332) were reviewed. LS cutoffs for predicting fibrosis stages were determined by receiver operating characteristic curves among those with a liver biopsy (TE, n=63; MRE, n=98). Cox proportional hazard regression modeling was used to identify associations between covariates and hepatic decompensation. RESULTS: The optimal LS thresholds for predicting histologic stage F4 were 14.40 kPa (area under the curve=0.94) for TE and 4.60 kPa (area under the curve=0.82) for MRE. Both TE and MRE outperformed biochemical markers for the prediction of histologic advanced fibrosis. Optimal LS thresholds to predict hepatic decompensation were 10.20 kPa on TE and 4.30 kPa on MRE. LS by TE and MRE (respectively) remained predictors of hepatic decompensation after adjusting for ursodeoxycholic acid responsiveness [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.24 and HR, 1.68; 95% CI, 1.28-2.19] and the GLOBE score (HR, 1.13; 95% CI, 1.07-1.19 and HR, 2.09; 95% CI, 1.57-2.78). CONCLUSION: LS measurement with either TE or MRE can accurately detect advanced fibrosis and offers additional prognostic value beyond existing serologic predictive tools.

The long-term outcomes of patients with immunoglobulin G4-related sclerosing cholangitis: the Mayo Clinic experience.

BACKGROUND: The long-term outcomes of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are not well known. METHODS: The outcomes of patients with IgG4-SC at Mayo Clinic (1999-2018) were compared to an age- and gender-matched (1:1 ratio) group of patients with primary sclerosing cholangitis (PSC). RESULTS: We identified 89 patients with IgG4-SC; median age at diagnosis was 67 years, 81% were males, and the median follow-up was 5.7 years. Seventy-eight patients received prednisone for induction of remission, and 53 received at least one other immunosuppressive agent for maintenance of remission. Of the IgG4-SC group, 10 died (median time from diagnosis until death was 6.5 years): 2 due to cirrhosis, 3 due to cholangiocarcinoma (CCA), and 5 due to non-hepatobiliary causes. Eleven patients in the PSC group underwent liver transplantation, while none did in the IgG4-SC group. The incidence of a hepatobiliary adverse event (cirrhosis or CCA) was 3.4 times greater in the PSC compared to the IgG4-SC group (events per 1000 person-years: 52.6; 95% CI 38-73; vs. 15.6; 95% CI 7-32). The probability of development of a hepatobiliary adverse event within 10 years was 11% in the IgG4-SC compared to 45% in the PSC group (P = 0.0001). The overall survival tended to be higher in the IgG4-SC compared to the PSC group (10-year: 79% vs. 68%, respectively; P = 0.11). CONCLUSIONS: In a cohort of IgG4-SC patients, 88% of whom were treated with immunosuppressive drugs, the risk of cirrhosis and CCA was significantly lower compared to an age- and gender-matched group with PSC.

Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis.

BACKGROUND: Oral vancomycin (OV) in primary sclerosing cholangitis (PSC) has been evaluated as a potential therapeutic agent. We report the long-term biochemical course and outcomes of patients with PSC treated with OV. METHODS: Patients were enrolled in 2 open-label clinical trials (ClinicalTrials.gov Identifier: NCT01802073 and NCT01322386) and offered OV at 50 mg/kg/day in 3 divided doses if weight <30kg, and 500 mg 3 times/day if weight ≥30kg. Patients with biliary strictures requiring stenting or awaiting liver transplant were excluded. Liver biochemistry, MRCP and histology were documented at baseline and while on OV. The primary outcome was a decrease in elevated gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and/or alanine aminotransferase (ALT) from baseline. RESULTS: 30 subjects were enrolled, and 29 additional subjects who learned of the clinical trial requested OV (total n = 59; median age was 13.5 years [range, 1.5-44 years]; 64.4% were male; and 94.9% had inflammatory bowel disease [IBD]). The median treatment duration was 2.7 years (range, 0.2-14 years). Ninety-six percent (57/59), 81.3% (48/59), and 94.9% (56/59) experienced reduction of GGT, ALP, and ALT, respectively. Furthermore, 39% (23/59), 22% (13/59), and 55.9% (33/59) experienced normalization of GGT, ALP, and ALT, respectively, within the first 6 months of OV treatment. One patient underwent liver transplantation 8 years after beginning OV treatment, and one developed biliary strictures requiring endoscopic intervention. OV was well-tolerated by patients, and no patient developed treatment-related adverse events. CONCLUSION: In PSC, OV was well-tolerated and was associated with improvement in liver chemistry. A randomized placebo-controlled clinical trial is warranted.

Gender Differences in Hepatology Medical Literature.

BACKGROUND: Studies suggest that gender differences in academic medicine exist. Men frequently have better measures of performance such as number of publications, number of citations, remuneration, and funding. AIMS: To evaluate whether a gender disparity in authorship exists. METHODS: We recorded the gender of first and senior authors of original papers, editorials/reviews from liver-related manuscripts in Gastroenterology, Hepatology, Transplantation, American Journal of Gastroenterology, and Liver Transplantation from January 2014 to 2016. RESULTS: Of 2424 articles reviewed, we excluded 232 (10%) due to inability to determine gender. Among papers analyzed, 72.0% were original and 28.1% reviews/editorials with 65.1% of first authors being male and 34.9% female. Only 20.3% of papers with multiple authors had a female senior author. The proportion of male first and senior authorship between original papers and reviews/editorials was comparable. 72% of original papers had a male as first or senior author, but only 28% females. 71% of review/editorial papers had a male as first or senior author, but only 29% females. When the senior author of an original paper was female, 47.1% of first authors were male and 52.9% female. When the senior author was male, 67.1% of first authors were male and 32.9% female (p < 0.00001). CONCLUSIONS: A significant gender difference exists in Hepatology publications. Female authorship mirrors the percentage of female AASLD membership; however, female senior authorship remains disproportionate. In general, funding for male authors is greater. Fewer women are first authors when the senior author is male, highlighting the importance of female mentorship in Hepatology.

A North American Expert Opinion Statement on Sarcopenia in Liver Transplantation.

Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut-off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best-studied technique for assessing sarcopenia in patients with cirrhosis. Cut-off values for sarcopenia, defined as SMI < 50 cm2 /m2 in male and < 39 cm2 /m2 in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.