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Acute liver failure is a unique clinical phenomenon characterized by abrupt deterioration in liver function and altered mentation. The development of high-grade encephalopathy and multisystem organ dysfunction herald poor prognosis. Etiologic-specific treatments and supportive measures are routinely employed; however, liver transplantation remains the only chance for cure in those who do not spontaneously recover. The utility of artificial and bioartificial assist therapies as supportive care—to allow time for hepatic recovery or as a bridge to liver transplantation—has been examined but studies have been small, with mixed results. Given the severity of derangements, intensive critical care is needed to successfully bridge patients to transplant, and evaluation of candidates occurs rapidly in parallel with serial reassessments of operative fitness. Psychosocial assessment is often suboptimal and relative contraindications to transplant, such as ventilator-dependence may be overlooked. While often employed to guide evaluation, no single prognostic model discriminates those who will spontaneously recover and those who will require transplant. The purpose of this review will be to summarize approaches in critical care, prognostic modeling, and medical evaluation of the acute liver failure transplant candidate.

Aim of the study Utilization of direct acting antiviral (DAA) therapy in candidates with well-compensated hepatitis C virus (HCV) cirrhosis and hepatocellular carcinoma (HCC) accruing end stage liver disease (MELD) exception points is highly variable among transplant centers based on center location, local organ procurement dynamics, HCV(+) organ availability, and patient preference. The association between DAA utilization prior to transplant and incidence of lymphovascular invasion on explant is unknown. Material and methods Retrospective evaluation from 2013-2017 of patients on a liver transplant (LT) waitlist with HCV-related cirrhosis, MELD-Na < 15, and HCC (within T2/Milan criteria). The cohort was divided into the pre-LT DAA treated group and untreated group with clinical/viral demographics collected. Tumor presenting characteristics, locoregional treatments, wait time to LT, dropout rates and explant pathology were compared. Results DAAs were used in 44 patients prior to LT (SVR12 of 37/44 [84%]) and 19 left untreated with LT performed in 81% (51/63) of the waitlisted cohort. No significant differences were found between groups with regards to clinical/viral demographics, local-regional therapy (LRT) sessions, or frequency of lymphovascular invasion on explant. The untreated cohort had a higher rate of dropout (6.3% vs. 3.2%) (p = 0.041). On subgroup analysis of 51 subjects undergoing LT, AFP > 250 ng/ml (p = 0.003) and multifocal HCC (> 1 lesion) (p = 0.006) were associated with lymphovascular invasion on explant while DAA therapy was not (p = 0.578). Conclusions DAA therapy for waitlist active HCV candidates accruing MELD exception points has no deleterious effects on bridging LRT, nor is it associated with increased frequency of lymphovascular invasion on explant. The latter appears driven by tumor related characteristics (AFP and number of lesions) irrespective of DAA utilization prior to LT.

Purpose To evaluate the rate and risk factors for hemorrhage in patients undergoing real-time, ultrasound-guided paracentesis by radiologists without correction of coagulopathy. Materials and Methods This was a retrospective study of all patients who underwent real-time, ultrasound-guided paracentesis at a single institution over a 2-year period. In total, 3116 paracentesis procedures were performed: 757 (24%) inpatients and 2,359 (76%) outpatients. Ninety-five percent of patients had a diagnosis of cirrhosis. Mean patient age was 56.6 years. Mean international normalized ratio (INR) was 1.6; INR was > 2 in 437 (14%) of cases. Mean platelet count was 122 x 103/μL; platelet count was Results Significant post-paracentesis hemorrhage occurred in 6 (0.19%) patients, and only 1 patient required an angiogram with embolization. No predictors of post-procedure bleeding were found, including INR and platelet count. Transfusion of 1125 units of fresh frozen plasma and 366 units of platelets were avoided, for a transfusion-associated cost savings of $816,000. Conclusions Without correction of coagulation abnormalities with prophylactic blood product transfusion, post-procedural hemorrhage is very rare when paracentesis is performed with real-time ultrasound guidance by radiologists.

Immune reconstitution syndrome is a recognized complication with initiation of highly active antiretroviral therapy for acquired immune deficiency syndrome patients co-infected with hepatitis B. Hepatitis B flares are seen in 20%-25% of patients after initiation of highly active antiretroviral therapy, an estimated 1%-5% of whom develop clinical hepatitis. We present a case of highly active antiretroviral therapy initiation for HIV that led to a flare of HBV activity despite antiviral therapy directed towards both. Liver biopsy and longitudinal serologic evaluation lend support to the hypothesis that the flare in activity was representative of IRIS. Importantly, we document eAg/eAb seroconversion with the IRIS phenomenon.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease–sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cystic lesions within the wall of the large intestine and presents along a spectrum of clinical severity ranging from benign to life threatening. Etiopathogenesis is multifactorial and postulated to result from either mechanical or bacterial causes. In this report, we present a patient with chronic abdominal pain evaluated with colonoscopy revealing segmental PCI isolated to the distal colon. Further investigation revealed an abdominal aortic aneurysm (AAA) compromising the inferior mesenteric artery takeoff. Endovascular repair of the AAA resulted in clinical resolution of abdominal pain and endoscopic resolution of PCI. To our knowledge, this is the first report to document endoscopic resolution of PCI with restoration of mesenteric arterial supply, highlighting vascular insufficiency as a predisposing and reversible pathogenic mechanism.

Intra-arterial or percutaneous locoregional therapies (LRT) are often employed to maintain potential liver transplant (LT) recipients with hepatocellular carcinoma (HCC) within T2/Milan criteria. Predictors of survival when LRT is used as destination therapy in those who are either ineligible or unwilling for LT remain poorly defined. We evaluated predictors of 3-year survival with destination LRT in a population of cirrhotic patients diagnosed with HCC, presenting within T2 criteria, and either ineligible or unwilling for LT. The cohort surviving 3 years had a significantly lower model for end-stage liver disease (MELD) score at HCC diagnosis (9.7 vs. 11.4, P=0.037) and MELD following initial locoregional therapy (10.7 vs. 13.3, P=0.008) compared to those not surviving three years despite similar demographic, tumor, and treatment variables. LRT as destination therapy results in modest intermediate term survival, with liver function at presentation and immediately following initiation of LRT predicting intermediate survival with this approach.

Background Low serum 25-Vitamin D levels are associated with advanced fibrosis in hepatitis C infection. Vitamin D supplementation has been hypothesized to augment response rates to interferon-based therapy. To date, no investigation has evaluated vitamin D levels during directacting antiviral therapy. We aimed to evaluate the prevalence of vitamin D deficiency in cirrhotic and non-cirrhotic cohorts, the predictive value of pretreatment levels for a sustained virologic response, and the changes in 25-OH vitamin D levels during direct-acting antiviral therapy. Methods Two hundred eighteen patients with chronic hepatitis C who completed directacting antiviral therapy were consecutively enrolled. Vitamin D levels were measured using chemiluminescence immunoassay, prior to initiation and at completion of therapy. Advanced liver fibrosis (cirrhosis) was determined by biopsy, FibroSURE blood test, or imaging. Results A sustained virologic response was achieved in 79% (n=172) of patients, with 19% (n=44) relapsing. A total of 123 (56.4%) patients were cirrhotic. The prevalence of Vitamin D deficiency (10-20 ng/mL) and severe deficiency (

Objectives Although no longer a contraindication to liver transplant, portal vein thrombosis may lead to longer operative time and complexities in venous reconstruction. Strategies to maintain preoperative patency include systemic anticoagulation and/or transjugular intrahepatic portosystemic shunt placement. The former may not be ideal in cirrhotic patients prone to luminal gastrointestinal tract bleeding, and factors that predict improvements in portal vein thrombosis with the latter have not been well defined. Our goal was to evaluate the effectiveness of transjugular intrahepatic portosystemic shunt placement as monotherapy to improve and/or resolve portal vein thrombosis in otherwise eligible liver transplant candidates with partial or complete portal vein thrombosis and to identify factors predicting success. Materials and methods We identified 30 patients from 2010 to 2015 who had transjugular intrahepatic portosystemic shunt placementfor primary indication to maintain portal vein patency. Results The main portal vein was completely thrombosed in 5 of 30 (16.6%), nearly completely thrombosed in 9 of 30 (30%), and partially thrombosed in 16 patients (53.3%). Twenty-four patients (80%) had improvement and/or resolution of portal vein thrombosis after transjugular intrahepatic portosystemic shunt placement, with 18 of these (75%) having complete resolution. All 5 patients (20.8%) with complete thrombosis had improvement/resolution of portal vein thrombosis. Nine patients (30%) required hospitalization within 3 months for hepatic encephalopathy. There were 3 deaths (10%) not related to transjugular intrahepatic portosystemic shunt placement (10%). Nine patients underwent liver transplant after shunt placement (median 2.9 mo; range, 0.3-32 mo); all 9 received endto-end anastomosis without need for intraoperative thrombectomy. Conclusions Transjugular intrahepatic portosystemic shunt placement may be effective as monotherapy for maintaining or restoring portal vein patency in selected livertransplant candidates, even in those with complete portal vein thrombosis. Further studies are needed to define potential responders to this approach.

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.

Budd-Chiari syndrome (BCS) refers to hepatic venous outflow obstruction that in severe cases can lead to acute liver failure prompting consideration of revascularization or transplantation. Here, a 22 year old female with angiographically proven BCS secondary to JAK2/V617F positive Polycythemia vera on therapeutic warfarin presented with acute liver failure (ALF). Imaging revealed a new, near complete thrombotic occlusion of the main portal vein with extension into the superior mesenteric vein. An emergent direct intrahepatic portocaval shunt (DIPS) was created and liver function promptly normalized. She has been maintained on rivaroxaban since that time. Serial assessment over 1 year demonstrated continued shunt patency and improved flow in the mesenteric vasculature on ultrasound as well as normal liver function. DIPS is a viable alternative in the treatment of ALF from BCS when standard recanalization is not feasible. Improved blood flow may also improve portal/mesenteric clot burden. While further investigation is needed, new targeted anticoagulants may be viable as a long term anticoagulation strategy.

Hepatic encephalopathy (HE) is a common complication of elective transjugular intrahepatic portosystemic shunt (TIPS) placement and is often successfully medically managed. Risk factors for refractory hepatic encephalopathy (RHE) necessitating revision of TIPS are not well defined. We evaluated the incidence, predictors, and outcomes of post-TIPS RHE necessitating TIPS revision. In a retrospective cohort study of 174 consecutive patients undergoing elective TIPS placement (2010–2015), we evaluated the incidence of post-TIPS RHE. Clinical demographics and procedural variables were collected. 1-year outcomes after revision were collected. Ten of 174 patients (5.7%) developed post-TIPS RHE requiring revision. Significant differences between RHE and non-refractory groups were shunt size > 8 versus ≤ 8 mm (18.5 vs. 3.4%, p = 0.001), history of HE (14 vs. 2%, p = 0.007), and serum albumin levels ≤ 2.5 versus > 2.5 g/dL (13.1 vs. 3.1%, p = 0.020). On multivariate analysis, shunt size > 8 mm (p = 0.001), history of HE prior to TIPS (p = 0.006), and low serum albumin (≤ 2.5 g/dL) (p = 0.022) remained independent predictors of RHE, controlling for age and Model for End-Stage Liver Disease score. RHE improved in 8 of 10 patients but survival at 1 year without liver transplantation (LT) was only 10%. While TIPS revision successfully improves RHE in most cases, 1-year mortality rates are high, limiting the value of revision in non-LT candidates. Patients with previous history of HE and low serum albumin levels prior to TIPS may benefit most from the use of shunt sizes

BACKGROUND/AIMS: Hepatic encephalopathy (HE) is a well-recognized complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. The aim of this investigation was to evaluate incidence and predictors of post-TIPS HE necessitating hospital admission in a non-clinical trial setting. METHODS: We performed a retrospective cohort study identifying 273 consecutive patients undergoing TIPS from 2010 to 2015 for any indication; 210 met inclusion/exclusion criteria. The primary endpoint was incidence of post-TIPS HE defined as encephalopathy with no other identifiable cause requiring hospitalization within 90 days of TIPS. Clinical demographics and procedural variables were collected and analyzed to determine predictors of readmission for post-TIPS HE. Categorical variables were analyzed using Fisher's exact test; continuous variables were compared using Levene's t-test and student's t-test; P 9 mmHg may require targeted follow up evaluation to prevent hospital readmission.

The development of aortic aneurysms in post-transplant patients is a rare but potentially lethal problem. De novo aortic aneurysm formation and rapid growth are postulated to result from an imbalance between pro- and anti-inflammatory vascular endothelial factors after transplant. Here, we present a case of de novo thoracic aneurysm formation within 2 months of orthotopic liver transplant. Prompt clinical recognition allowed for successful endovascular repair. Transplant clinicians should be aware of this potentially life-threatening complication and monitor at-risk recipients accordingly.

Background/Aim: The neutrophil–lymphocyte ratio (NLR) has gained attention as an index of inflammation in patients with chronic hepatitis B virus (HBV); however, changes with nucleoside analog therapy require investigation. Patients and Methods: We carried out a retrospective study identifying monoinfected HBV patients initiated on therapy with NLR follow-up over 1 year. Biochemistries recorded at treatment initiation and 1 year included alanine aminotransferase (ALT), Model for End Stage Liver Disease (MELD) score, and NLR. Results: A total of 67 patients were initiated on therapy and had baseline characteristics including e-antigen (eAg) (50, 74.6%) and cirrhosis (19, 28.4%). On subgroup analysis among those with HBV-associated cirrhosis, the NLR decreased over 1 year (3.08±0.39 vs. 1.77±0.18, p

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.

Hepatic arterioportal fistulae (APF) are abnormal communications between the hepatic artery and the portal vein. In this report, we present the second case in the literature of a symptomatic APF presenting as a gastric variceal bleeding. A 55-year-old female presented to our facility with hematemesis. Upper endoscopy revealed a bleeding gastric varix. A computed tomography scan identified a large left hepatic lobe APF between the left hepatic artery and the left portal vein. Through angiography coil embolization was performed and with resultant loss of arterial flow, the APF was decompressed. On hospital day 3, the patient developed new melena. Portovenogram was performed and a TIPS stent was deployed. The patient subsequently did well. Hepatic arterioportal fistulae can result in portal hypertension secondary to arterial blood flowing directly into the portal vein bypassing the hepatic sinusoids. Iatrogenic causes (e.g. percutaneous liver biopsy) represent more than 50% of published cases of APFs. Most APFs resolve spontaneously as they are small and peripherally located. In rare instances, when APFs are centrally located, clinical symptoms develop. There have been 30 reported cases of symptomatic intrahepatic APFs following percutaneous liver biopsy. Of those, only one case presented as a gastric variceal bleed. Digital subtraction angiography is the gold standard in the diagnosis and treatment of APFs. In addition to initial embolization, we elected to treat the patient with TIPS due to the magnitude of her bleed. Although rare, intrahepatic APF should be kept on the differential of a patient presenting with isolated gastric varices.

Primary Biliary Cholangitis is a progressive, autoimmune cholestatic liver disorder. Cholestasis with disease progression may lead to dyslipidemia, osteodystrophy and fat-soluble vitamin deficiency. Portal hypertension may develop prior to advanced stages of fibrosis. Untreated disease may lead to cirrhosis, hepatocellular cancer and need for orthotopic liver transplantation. Classically, diagnosis is made with elevation of alkaline phosphatase, demonstration of circulating antimitochondrial antibody, and if performed: asymmetric destruction/nonsupperative cholangitis of intralobular bile ducts on biopsy. Disease pathogenesis is complex and results from innate and adaptive (cell-mediated and humoral) responses that lead to inflammation of biliary duct epithelium. Ongoing damage is amplified and sustained through bile acid toxicity. Use of weight based (13-15mg/kg) ursodeoxycholic acid is well established in retarding disease progression and improving survival; however, is ineffective in achieving complete biochemical remission in many. Recently, a Farnesoid X Receptor agonist, obeticholic acid, has been approved for use. A number of ongoing clinical studies are underway to evaluate utility of fibric acid derivatives, biologics, antifibrotics, and stem cells as monotherapy or in combination with ursodeoxycholic acid for primary biliary cholangitis. The aim of this review is to discuss disease pathogenesis and highlight rationale/implications for both established and novel therapeutics.

Hepatitis C virus (HCV) infection and its recurrence after orthotopic liver transplantation (OLT) are associated with the remodeling of extracellular matrix (ECM) components [particularly collagen (Col)], which leads to fibrosis. Our aim was to determine whether the development of antibodies (Abs) to self-antigen Col in HCV-infected patients correlates with the fibrosis stage and the peripheral cytokine response. Patients with chronic HCV infection, patients with HCV recurrence after OLT who had undergone a biopsy procedure, and healthy control subjects were enrolled. The HCV subjects (n = 70) were stratified as follows: (1) a non-OLT group without fibrosis (Scheuer stages 0-2), (2) a non-OLT group with fibrosis (Scheuer stages 3-4), (3) a post-OLT group without fibrosis (Scheuer stages 0-2), and (4) a post-OLT group with fibrosis (Scheuer stages 3-4). Serum samples were analyzed for Abs against Col1, Col2, Col4, Col5, and vimentin with enzyme-linked immunosorbent assays. Serum levels of cytokines were measured with multiplex bead immunoassays. The levels of Abs to Col1 were higher in the fibrosis groups versus the no-fibrosis groups and the controls for both non-OLT patients (P < 0.001) and post-OLT patients (P = 0.01). There were increased levels of Abs to Col2, Col4, Col5, and vimentin in the non-OLT fibrosis group (Col2, P = 0.0001; Col4, P = 0.122; Col5, P < 0.0001; vimentin, P = 0.36) and in the post-OLT fibrosis group (Col2, P = 0.006; Col4, P = 0.19; Col5, P < 0.0001; vimentin, P = 0.24) in comparison with the no-fibrosis groups. The non-OLT and post-OLT fibrosis groups demonstrated significantly higher T helper 2 (T(h) 2) and T helper 17 (T(h) 17) cytokine levels and lower T helper 1 cytokine levels in comparison with the no-fibrosis groups. Our results demonstrate that in HCV-infected patients, the levels of Abs to ECM Col1, Col2, and Col5 positively correlate with liver fibrosis, which is associated with a predominantly T(h) 2 and T(h) 17 cytokine profile.

Treatment of chronic hepatitis B virus (HBV) infection currently involves the use of immunomodulators such as interferon and nucleoside or nucleotide analogues. Treatment aims to suppress levels of HBV DNA and induce clearance of the hepatitis B e antigen (HBeAg) or surface antigen (HBsAg) and seroconversion. At present, no single treatment has been shown to reliably suppress HBV DNA and induce durable HBsAg loss. Nucleoside or nucleotide analogues induce the production of HBV-resistant mutations that may lead to virologic and clinical breakthrough. Combination therapy, using either immunomodulators in combination or with nucleoside or nucleotide analogues, represents an emerging strategy for treating chronic HBV infection. The theoretical benefits of combining agents with varying mechanisms of action include more efficacious viral suppression and potentially durable HBsAg loss. Although combination therapy has proven successful in chronic hepatotropic viral infections and in chronic, noninfectious medical conditions, its benefits must be weighed against risks such as increased toxicity, resistance, and cost.

Background Exertional heat stroke (HS) with resultant acute liver failure (ALF) is a rare condition with high mortality. Diagnosis of ALF in the context of HS is confounded by numerous laboratory abnormalities related to multisystem organ dysfunction. Case Report We present the case of a 20-year-old male athlete with exertional HS who developed ALF and was treated successfully with orthotopic liver transplantation. He remained well after 1 year with normal liver function and no permanent neurologic impairment. Diagnosis and treatment was guided by serial monitoring of coagulation factors and intracranial pressure (ICP). Conclusions Currently, there are no well validated prognostic tools that predict the need for or survival with orthotopic liver transplantation for HS. We propose that serial monitoring of coagulation factors and, when safe and feasible, ICP monitoring may help to guide clinical decision making in this context.

Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management.