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Unlabelled: The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. Methods: A modified Delphi process was led by three large pan-national liver associations. Consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. Results: A total of 236 panellists from 56 countries participated in four online surveys and two hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83% and 78%, respectively. 74% of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms 'non-alcoholic' and 'fatty' were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease (SLD) was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least one of five cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic SLD. A new category, outside pure MASLD, termed MetALD was selected to describe those with MASLD who consume greater amounts of alcohol per week (140 to 350g/week and 210 to 420g/week for females and males respectively). Conclusions: The new nomenclature and diagnostic criteria are widely supported, non-stigmatising and can improve awareness and patient identification.

Split liver transplantation (SLT) emerged due to its potential to contribute to the organ pool and reduce organ shortage. However, SLT is technically challenging and has been associated with higher rates of postoperative complications leading to concerns about graft and patient survival. Moreover, there are few studies on matched-pair adult recipients of SLT and whole-liver transplant (WLT), with conflicting results.This retrospective study analyze outcomes among adults who underwent SLT at our institution from 2010 to 2019. A 1:1 propensity score matching analysis was performed based on important donor and recipient variables. Baseline characteristics and postoperative outcomes were analyzed and compared between groups. Actuarial graft and patient survival were analyzed by KM curves.Out of 592 adults receiving a LT in our institution, 21 SLT adult recipients were identified and matched with 21 adults undergoing WLT. As expected donor age was significantly lower in SLT recipients (16 (15-22) vs. 32 (17-47), P = .012). Additional donor characteristics, including anthropometrics, and ischemic times were similar between groups. Baseline recipient characteristics and postoperative outcomes, including length of stay, vascular complications, biliary complications, and re-transplantation were comparable between SLT and WLT recipients. Graft (95/95/95 vs. 100/94/94, P = .98) and patient (100/100/100 vs. 100/94/94, P = .30) survival at 1-, 3-, 5-years, were similar between the SLT- and WLT group, respectively.Split liver transplantation has the potential to increase the availability of organs for adult recipients without compromising individual outcomes.

Gastric and Ectopic varices are a rare complication of portal hypertension and represent a complex, heterogeneous system of vascular shunts. Bleeding from these shunts can be severe and life-threatening, with poorly standardized treatment algorithms to follow in their management. When bleeding occurs, it is important to follow standard diagnostic procedures for portal hypertensive bleeding and always obtain imaging of the underlying vascular anatomy to help guide therapy. Potential treatment methods will depend on these imaging findings as well as the location of the varix within the gastrointestinal tract. While gastric varices have more data to support specific treatment options, duodenal and rectal varices have only case reports and case series to guide their care. In addition, stomal varices are a very rare complication of portal hypertension and have limited data to support any one treatment modality. Gastric and ectopic varices are best approached in a multidisciplinary fashion after discussion with hepatologists and interventional radiologists to overcome the uncertainty in choosing a definitive therapy.

The use of pediatric grafts for liver transplantation (LT) into adult recipients is rare, and reported outcomes are conflicting. The aim of this study is to evaluate the outcomes in adult recipients following LT with grafts from deceased pediatric donors.A retrospective study identifying adult LT between 2010 and 2020 using pediatric deceased donor liver grafts was conducted. Adults undergoing LT with deceased donor pediatric grafts (age ≤ 12) were identified and matched 1:2 with adults receiving adult grafts (age ≥ 18) based on recipient age (±10 y), model for end-stage liver disease (MELD) score at transplant (±5 points) and etiology of liver disease. To assess real liver size differences between the pediatric-donor and adult-donor groups, patients receiving a graft from a donor between 13 and 17 y were excluded from the main analysis and studied independently. Outcomes between the groups were compared. Complication rates were identified and graded using Clavien-Dindo classification. Graft and patient survival were assessed by Kaplan-Meier curves.Twelve adult LT recipients with whole liver grafts from deceased pediatric donors were matched with 24 adult recipients of adult donors. Recipient age and MELD score were similar between groups. Recipients of pediatric grafts were more likely to be female (66.7% versus 16.7%,Excellent patient and graft survival is achievable with LT using young pediatric deceased donor grafts in smaller adult recipients. Outcomes are comparable with recipients of age and MELD-matched adult donors. Careful donor MELD-score recipient matching and close monitoring for potential biliary and vascular complications are crucial to achieve acceptable outcomes.

Supplemental Digital Content is available in the text., Background. There are limited data on liver transplant (LT) outcomes with grafts from super obese donors. The present study aims to evaluate a unique cohort of recipients following LT using grafts from donors with body mass index (BMI) ≥50. Methods. Patients receiving grafts from donors with BMI ≥50 and BMI

BACKGROUND AND AIMS Relative adrenal insufficiency (RAI) in patients with cirrhosis is associated with increased mortality. Although the pathogenesis of RAI remains unclear, disordered cholesterol metabolism may contribute. METHODS We performed a prospective cohort study of 96 non-critically ill subjects with decompensated cirrhosis at a tertiary care centre. Subjects were administered 250 µcg cosyntropin, with RAI defined as an increase in total cortisol

We report a case of recurrent gastrointestinal bleeding in the setting of diffuse duodenal and colorectal varices. These varices were secondary to either congenital absence of the portal vein or chronic occlusion of the portal vein leading to cavernous transformation of a collateral network of varices. He was acutely managed with injection of N-butyl-2-cyanoacrylate into a large complex of duodenal varices. His hospital course was complicated by a postprocedural gastrointestinal bleed within the first 24 hours after the procedure arising from a new duodenal ulcer at the site of injection, likely secondary to ischemia after obliteration of the varices.

The goal of our review is to provide a better understanding of the anatomy of gastric varices (GV) and to provide guidance regarding the management of bleeding GV. Despite a paucity of head-to-head controlled data in this field, there remain no further advances in therapy. Alterations to previous techniques, such as combining EUS-guided metallic coil injection with cyanoacrylate injection or approaching endovascular therapies such as balloon-occluded retrograde transvenous obliteration (BRTO) via different pathways, have been developed but not studied in a comparative manner. The primary therapy of GV is endoscopic cyanoacrylate injection and new studies have confirmed prior data suggesting this is effective with low complication and re-bleeding rates. Similarly, endovascular procedures such as BRTO continue to show robust results but no large, controlled, head-to-head trials exist to compare different modalities of therapy. Herein, we review the current literature for the therapy of bleeding GV and voice a call to action for future research endeavors in this field.

Ectopic varices (ECV) are a heterogeneous group of portosystemic shunts that occur in the presence of portal hypertension. The shunts occur throughout the abdomen and pelvis, including the gallbladder, the genitourinary system, and the retroperitoneal space, but they are most common within the bowel (small intestine and colon) and at the mucocutaneous junction of a stoma. Bleeding rates vary depending on the location, but overall, ECV account for 1%-5% of all variceal bleeding and can lead to significant morbidity and mortality. Management of these shunts can be very difficult owing to complex underlying vascular anatomy. Although there is a role for endoscopic intervention in these cases, definitive therapy by this modality is often unachievable, necessitating complex endovascular procedures to ultimately occlude the shunt. Understanding the anatomy, the reported success rates with various procedural interventions, and the complications of those interventions is of the utmost importance in the management of ECV and will be reviewed here in detail.

Non-alcoholic fatty liver disease (NAFLD) figures prominently into the clinical hepatology landscape. NAFLD represents a disease spectrum comprising simple steatosis, steatosis with elevated liver enzymes, and non-alcoholic steatohepatitis (NASH), the entity with clear potential for fibrosis progression. Risk factors associated with fibrosis progression in NASH include histologic findings of lobular inflammation and any fibrosis as well as clinical comorbidities that include type 2 diabetes, obesity, and metabolic syndrome. Liver biopsy remains the gold standard in evaluating NASH; however, noninvasive methods are accumulating evidence for a growing role in identifying patients at increased risk to develop NASH, fibrosis, and potentially cirrhosis.

With the passage of the Affordable Care Act, the Healthcare Readmissions Reduction Program (HRRP) was implemented, leading to significant reductions in readmissions for congestive heart failure, pneumonia, and myocardial infarction. Patients with cirrhosis have a complex and difficult to manage underlying disease process and are often left out of large policy decisions such as the HRRP although they represent a population at high risk for readmission and other negative outcomes. In this editorial, hospital readmissions in patients with cirrhosis are discussed in the context of the HRRP and evolving models of care.

Management of bleeding gastric varices (GV) presents a unique challenge for patients with portal hypertension. Despite over thirty years of diagnostic and treatment advances standardized practices for bleeding GV are lacking and unsupported by adequate evidence. There are no definitive natural history studies to help with risk assessment or prospective clinical trials to guide clinical decision making. Available literature on the natural history and management of gastric varices consists of case series, restricted cohort studies, and a few small randomized trials, all of which have significant selection biases. This review summarizes the available data and recommendations based on expert opinion on how best to diagnose and manage bleeding from gastric varices. Table 1 summarizes our recommendations.

There are 3 physiological phases of action in the modern view of hemostasis. Primary hemostasis begins with endothelial injury, exposure of von Willebrand factor (vWF), platelet activation and aggregation, and an initial thrombin “burst.” Coagulation then follows with activation of the coagulation cascade, through extrinsic and intrinsic pathways in a positive feedback loop activated by thrombin and the formation of the fibrin mesh and fortification of the classic clot. Lastly, fibrinolysis must occur through the action of anticoagulant proteins and enzymes to avoid pathologic thrombus formation. Primary hemostasis is typically measured through platelet counts, vWF levels, platelet function assays, and bleeding time. Coagulation is generally measured by prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) representing the intrinsic and extrinsic pathways of the clotting cascade, respectively. Although infrequently performed clinically, specific procoagulant factor levels can be measured. Fibrinolysis can generally be measured through fibrinogen levels, protein C and S levels, antithrombin III (ATIII) activity, euglobulin lysis time (ELT), and direct measurements of anticoagulant proteins (PAI-1, TAFI).1 There are also in vitro whole blood measures of the complete clotting system using thromboelastography (TEG), rotational thromboelastometry (ROTEM), and sonorheometry, which can give an overall assessment of the different stages of hemostasis, including the intrinsic fibrinolytic and antifibrinolytic pathways.2 In patients with cirrhosis every stage of hemostasis may be altered, putting them at risk for both bleeding and thrombosis. Classically, patients with cirrhosis have been thought of as “autoanticoagulated” because of an elevated INR and baseline thrombocytopenia owing to splenic sequestration and portal hypertension. Although routine tests such as platelet counts, INR, and aPTT may accurately reflect bleeding risk in general populations, multiple studies have shown that patients with cirrhosis have deficiencies in both the procoagulant and anticoagulant pathways, leading to a “rebalanced” coagulation system.3,4 In regard to primary hemostasis, patients with cirrhosis typically have a decreased number of circulating platelets. This is related to splenic sequestration, more rapid turnover and shorter half-life of platelets secondary to splenomegaly, and decreased production related to lower amounts of hepatic thrombopoetin.5,6 There may also be an immunologic component, although this appears to be a minor contributor.7 The decreased platelet count may be expected to increase the risk for bleeding, but patients with cirrhosis also have elevated levels of vWF, which increases in proportion to the severity of liver disease.8 In addition, there is a decrease in ADAMTS13, the vWF cleaving protein, and despite the underlying thrombocytopenia this increase in vWF may actually increase platelet adhesion.9,10 A study by Tripodi et al11 showed that in patients with cirrhosis a minimum platelet count of around 55×109/L is adequate for thrombin generation, allowing normal clot formation, and levels above 100×109/L have no increased benefit in primary hemostasis or in fibrin mesh formation when compared with controls. In some patients, these compensatory mechanisms may actually result in enhanced platelet adherence rather than dysfunctional primary hemostasis. In the second stage of hemostasis, clotting factors activate and begin to produce thrombin, predominantly on the surface of activated platelets, leading to subsequent deposition of the cross-linked fibrin mesh. In patients with cirrhosis, decreased levels of procoagulant proteins, such as factors II, V, VII, IX, X, and XI, suggest the potential for an anticoagulated state. In fact, 1 study showed a decrease in the activity of procoagulant proteins to as low as 20% to 46% in correlation with the severity of cirrhosis and portal hypertension.12 These deficiencies are easily seen in the standard clinical laboratory measurements of the INR and PT.

Nonalcoholic fatty liver disease (NAFLD) is an increasing public health threat with significant related morbidity and mortality. NAFLD is currently separated into two clinical entities, benign simple steatosis, and NASH, the more progressive form. Instead, NAFLD is likely a spectrum of disease that can progress regardless of the initial histologic findings. Risk factors associated with disease progression of NASH include the histologic findings of lobular inflammation, presence of NASH rather than simple steatosis, and most significant, the presence of fibrosis. In addition, comorbid metabolic conditions such as type 2 diabetes mellitus, obesity, and metabolic syndrome play a significant role in progression, and sometimes regression, of NAFLD. Currently liver biopsy remains the gold standard for diagnosis and staging of NAFLD, however noninvasive testing is garnering more interest in ongoing research trials and will hopefully prove to be a reliable means of evaluating patients with NAFLD in the future.

Background Hepatitis C is now curable for most individuals, and national goals for elimination have been established. Transmission persists, however, particularly in nonurban regions affected by the opioid epidemic. To reach goals of elimination, barriers to treatment must be identified. Methods In this open cohort of all individuals diagnosed with active hepatitis C from 2010 to 2016 at a large medical center, we identified patient and clinic characteristics associated with our primary outcome, sustained virologic response (SVR). We performed a subgroup analysis for those with documented substance misuse. Results SVR was achieved in 1544 (41%) of 3790 people with active hepatitis C. In a multivariable Poisson regression model, SVR was more likely in individuals diagnosed outpatient (incident rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5–2.0), living in close proximity to the medical center (IRR, 1.2; 95% CI, 1.1–1.3), with private insurance (IRR, 1.1; 95% CI, 1.0–1.3), and with cirrhosis (IRR, 1.4; 95% CI, 1.3–1.5). Achieving SVR was less likely in those qualifying as indigent (IRR, 0.8; 95% CI, 0.8–0.9) and those with substance misuse (IRR, 0.8; 95% CI, 0.7–0.9). In the subgroup analysis of those with substance misuse, SVR rates were higher in those linked to the infectious diseases clinic, which has embedded support services, than those linked to the gastroenterology clinic, which does not (IRR, 1.4; 95% CI, 1.1–1.9). Conclusions Social determinants of health including proximity to care and poverty impacted achievement of SVR. Those with substance misuse, a high-priority population for treatment of hepatitis C, had better outcomes when receiving care in a clinic with embedded support services.

To assess short- and long-term mortality and rebleeding with endoscopic cyanoacrylate (EC) versus balloon-occluded retrograde transvenous obliteration (BRTO).A retrospective cohort comparison was conducted of 90 EC patients and 71 BRTO patients from 1997 through 2015 with portal hypertension who presented due to endoscopically confirmed bleeding cardiofundal gastric varices. Patients underwent either endoscopic intra-varix injection of 4-carbon-n-butyl-2-cyanoacrylate or sclerosis with sodium tetradecyl sulfate with balloon occlusion for primary variceal treatment.Seventy-one BRTO patients and 90 EC patients, of whom 89% had cirrhosis and 35% were women, were included, with a respective average Model for End-Stage Liver Disease (MELD) score of 13.4 and 14.4, respectively. Mortality at 6 weeks was 14.4% for EC patients and 13.1% for BRTO patients (Kaplan-Meier/Wilcoxon, P = .85). No long-term mortality difference was observed (Cox hazard ratio [HR] = 0.89, P = .64). Also, 5.1% of EC patients and 3.5% of BRTO patients (Kaplan-Meier/Wilcoxon, P = .62) rebled at 6 weeks, but at 1 year, 22.0% of EC patients and 3.5% of BRTO patients had rebled (Kaplan-Meier/Wilcoxon, P.01). Lower rates of long-term rebleeding were found with BRTO (Cox HR = 0.25, P = .03). No difference was seen in the rate of new portal hypertensive complications (Cox HR = 1.21, P = .464). However, 16/71 patients who underwent BRTO had simultaneous transjugular intrahepatic portosystemic shunt. Age, sex, MELD score, and presence of cirrhosis were the primary predictors of mortality. One death in the EC group and 5 deaths in the BRTO group were deemed to be procedurally related (chi-square, P = .088).BRTO is associated with a lower rate of rebleeding but no change in mortality.

BACKGROUND: Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD). AIM: We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects. METHODS: Forty subjects (60% obese, 40% overweight) with biopsy-confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained. RESULTS: NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects’ fitness was comparable to the “least fit” tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs “least fit” 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs “least fit” 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT. CONCLUSIONS: Aerobic deconditioning was universally present in NASH subjects. NASH subjects’ fitness was similar to our laboratory’s “least fit” untrained, sedentary control subjects. Further research investigating NASH patients’ ability to improve low baseline aerobic fitness is warranted.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. "Lean" NAFLD represents a patient subpopulation with hepatic steatosis evident on imaging with normal BMI. This paper by Feldman and Eder et al. illustrates the mild but clear metabolic differences and genetic connections in Caucasian lean NAFLD patients compared with obese NAFLD and healthy controls. Their findings highlight key similarities of lean and obese NAFLD compared with lean healthy subjects. This paper characterizes "lean" NAFLD as a unique phenotype with specific genetic associations deserving of further investigation in the greater scheme of elucidating the pathophysiology of fatty liver.

Non-neoplastic portal vein thrombosis is common in cirrhosis. As our understanding of coagulopathy in cirrhosis evolves, clinicians are now recognizing that cirrhosis patients are not protected from thrombosis. In particular, factors innate to cirrhosis and portal hypertension promote a local environment conducive to portal vein thrombosis. Improvement in current diagnostic imaging has made diagnosis of portal vein thrombosis accurate, and we are now beginning to understand the incidence and prevalence. Development of occlusive portal vein thrombosis portends a worse outcome after transplant. Medical therapy for portal vein thrombosis in cirrhosis patients is effective and safe in certain circumstances. Furthermore, evidence is now emerging that prevention of portal vein thrombosis may reduce hepatic decompensation and progression of liver disease. Identifying patients that will benefit from therapy and improvement of diagnosis and prognostication should be the focus of future investigation.

Gastric varices (GV) present a challenge not always amenable to conventional approaches applied to esophageal varices (EV). Several types of GV classification systems exist including the familiar Sarin system and lesser-known vascular classifications which provide a foundation for management triage. While GV bleeding is less frequent than EV bleeding, it is often more pronounced. Initial management follows that for EV including very cautious volume replacement and early use of vasoactive medications. Urgent temporizing measures, if needed, may include balloon tamponade, sclerosants, banding, clipping and possibly procoagulants. Imaging is important in early management as optimal modalities such as balloon retrograde transvenous obliteration (BRTO), transhepatic porto-systemic shunts (TIPS), cyanoacrylate or combination modalities are contingent on the underlying vascular anatomy. Each of these is associated with particular advantages and disadvantages as discussed below.

Although often considered together, gastric and ectopic varices represent complications of a heterogeneous group of underlying diseases. Commonly, these are known to arise in patients with cirrhosis secondary to portal hypertension; however, they also arise in patients with noncirrhotic portal hypertension, most often secondary to venous thrombosis of the portal venous system. One of the key initial assessments is to define the underlying condition leading to the formation of these portal-collateral pathways to guide management. In the authors' experience, these patients can be grouped into distinct although sometimes overlapping conditions, which can provide a helpful conceptual basis of management.

BackgroundHospitalized patients with cirrhosis are at risk to develop venous thromboembolism. Although current guidelines support the routine administration of thromboprophylaxis to hospitalized patients, there is limited data regarding the safety or efficacy of this practice in hospitalized cirrhosis patients.AimsWe aimed to determine if administration of thromboprophylaxis was associated with increased complication rates for hospitalized cirrhosis patients.MethodsData were collected on patients admitted to the University of Virginia between 2007 and 2010. Study personnel systematically collected data on complications, including gastrointestinal bleed, venous thromboembolism and death directly from the medical record.ResultsA total of 235 patients (accounting for 355 discrete hospitalizations in which thromboprophylaxis was administered) met inclusion criteria accounting for 1660 person-days of thromboprophylaxis administered to patients. The mean age at admission was 58 (95% CI 57.1-59.2) years and 217 (61%) were male patients. The mean admission model for end-stage liver disease (MELD) score was 16.2 (95% CI 15.5-16.9). The mean hospital length of stay was 6.5 (95% CI 5.9-7.4) days. In patients who received thromboprophylaxis, the mean treatment length was 4.7days (95% CI 4.2-5.2). There were nine gastrointestinal bleeding events (2.5% of admissions), five venous thromboembolisms (1.4% of admissions), two cases of heparin-induced thrombocytopenia (0.5% of admissions) and 14 deaths overall (3.9% of admissions).ConclusionsThe use of thromboprophylaxis in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding or death.