Non-hepatic Malignancy Research Articles

Association of hepatitis delta virus infection and hepatocellular carcinoma, hepatic decompensation, all-cause and liver-related death in a national cohort.

Hepatitis Delta Virus (HDV) infection is the most severe form of chronic hepatitis. However, studies on outcomes and causes of death in a United States-born population, with primarily horizontal transmission of HDV, are lacking. The aim of this study was to conduct a national study of patients with hepatitis D to understand the natural history and outcomes compared to patients with hepatitis B virus (HBV). infection. In a national cohort of 4,817 HBV infected veterans tested for HDV (99.6% US-born, 3.3% HDV positive) over a 23-year period, we used multivariable models to identify the factors associated with a composite outcome of hepatocellular carcinoma (HCC), decompensation, and liver-related mortality (LRM), as well as all-cause mortality of patients with HDV compared to HBV mono-infection. HDV coinfection (vs. HBV monoinfection) was associated with a significantly higher incidence of composite liver-related outcomes at both 5 (23.84 vs. 7.98, p<0.001), and 10 years (19.14 vs. 10.18, p<0.001) respectively. The most common cause of death was liver-related (33.8% for HDV vs. 24.7% for HBV), followed by non-hepatic malignancies, (15.6 vs. 14.8%),cardiac (11.7 vs. 15.2%), and lung disease (5.2 vs. 3.7%). In multivariable models, HDV was associated with an increased risk of composite liver outcomes (aHR 2.57, 95% CI 1.87-3.52, p<0.001), and all-cause mortality (aHR 1.52, 95% CI 1.20-1.93, p<0.001). In a predominantly U.S born cohort of Veterans, HDV co-infection was associated with an increased risk of liver-related outcomes and all-cause mortality. Our findings support widespread testing for early identification of HDV.

Innovations in Image-Guided Procedures: Unraveling Robot-Assisted Non-Hepatic Percutaneous Ablation.

Interventional oncology is routinely tasked with the feat of tumor characterization or destruction, via image-guided biopsy and tumor ablation, which may pose difficulties due to challenging-to-reach structures, target complexity, and proximity to critical structures. Such procedures carry a risk-to-benefit ratio along with measurable radiation exposure. To streamline the complexity and inherent variability of these interventions, various systems, including table-, floor-, gantry-, and patient-mounted (semi-) automatic robotic aiming devices, have been developed to decrease human error and interoperator and intraoperator outcome variability. Their implementation in clinical practice holds promise for enhancing lesion targeting, increasing accuracy and technical success rates, reducing procedure duration and radiation exposure, enhancing standardization of the field, and ultimately improving patient outcomes. This narrative review collates evidence regarding robotic tools and their implementation in interventional oncology, focusing on clinical efficacy and safety for nonhepatic malignancies.

Bariatric surgery post-liver transplantation: A Belgian nationwide study.

Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. We conducted a national retrospective analysis in 5 Belgian transplant centers and included 25 patients with an LT followed by a bariatric procedure. A total of 187 LT patients without BS were included for comparison. Clinical, biochemical, and outcome data were retrospectively retrieved. In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared with the non-BS population (54.5 vs. 60.6, p <0.001). Weight loss was significant and sustained, with a decrease in body mass index from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS ( p <0.001) and 31.1±5.8 3-5 years post-BS ( p <0.001). Three pre-BS (12.0%) patients presented with recurrent and one (4.0%) de novo metabolic dysfunction-associated steatotic liver disease after LT, with 100% resolution post-BS ( p =0.016). Notable reductions were observed in alanine transaminase levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p =0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p <0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a nonhepatic malignancy and one (4.0%) due to liver failure. SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent metabolic dysfunction-associated steatotic liver disease post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival.

Neoadjuvant and Adjuvant Systemic Therapies in Loco-Regional Treatments for Hepatocellular Carcinoma: Are We at the Dawn of a New Era?

Despite maximizing techniques and patient selection, liver resection and ablation for HCC are still associated with high rates of recurrence. To date, HCC is the only cancer with no proven adjuvant or neoadjuvant therapy used in association to potentially curative treatment. Perioperative combination treatments are urgently needed to reduce recurrence rates and improve overall survival. Immunotherapy has demonstrated encouraging results in the setting of adjuvant and neoadjuvant treatments for non-hepatic malignancies. Conclusive data are not yet available in the context of liver neoplasms. However, growing evidence suggests that immunotherapy, and in particular immune checkpoint inhibitors, could represent the cornerstone of an epochal change in the treatment of HCC, improving recurrence rates and overall survival through combination treatments. Furthermore, the identification of predictive biomarkers of treatment response could drive the management of HCC into the era of a precision medicine. The purpose of this review is to analyze the state of the art in the setting of adjuvant and neoadjuvant therapies for HCC in association with loco-regional treatments in patients not eligible for liver transplantation and to hypothesize future scenarios.

Relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer.

The liver is the largest organ in the abdomen and is often irradiated in radiotherapy for non-hepatic malignancies. As most of the studies on changes in liver volume are on hepatocellular carcinoma based on liver dysfunction, there are few studies on healthy liver. In this study, we investigated the relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer in patients without apparent pre-treatment liver dysfunction. Liver volume was compared between pre-treatment, acute (< 4months) and late post-treatment (≥ 4 and < 13months) phases in 12 patients using abdominal plain CT images. Volume changes were evaluated separately for the right and left lobes. We investigated the relationship between the volume change and VxGy (percentage of volume received x Gy or more dose). In addition, volume change for each absorbed dose was investigated using deformable image registration. The volume of the left lobe showed a significant decrease between pre-treatment and acute post-treatment phases (p < 0.001), while the volume of right lobe and between acute and late post-treatment phase of left lobe did not. The mean value of the volume reduction rate of the left lobe was 51.1% and equivalent to the mean value of V30Gy. As a result of the volume change for each absorbed dose, the volume reduction rate increased as the absorbed dose increased, and a significant volume loss was observed at doses above 11Gy. Volume of the liver significantly decreased only in the acute phase after chemoradiotherapy for esophageal cancer. The tolerable dose for a healthy liver is generally considered to be 30Gy, but attention should be paid to lower doses to avoid radiation-induced liver injury.

A215 CAUSE-SPECIFIC MORTALITY IN PATIENTS WITH CIRRHOSIS: A POPULATION-BASED COHORT STUDY

BackgroundCirrhosis is a major global health concern with increasing mortality secondary to cirrhosis and chronic liver diseases observed both in the United States and Canada. However, population-level causes of death among patients with cirrhosis in North America have not been reported.AimsThe aim of this study was to describe cause-specific mortality in patients with cirrhosis stratified by cirrhosis etiology.MethodsRetrospective cohort study using linked administrative healthcare data from Ontario, Canada. Adult patients with cirrhosis 2000/01/01-2017/12/31 were identified and etiology of liver disease was assigned as hepatitis C (HCV), hepatitis B (HBV), alcohol-associated liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), or autoimmune liver disease (AI)/other using validated algorithms for cirrhosis (sensitivity [sn] 99%, specificity [sp] 79%) and cirrhosis etiology (sn 75%-97%, sp 95%-100%). Patients were followed until death, liver transplant, or end of study. The primary outcome of cause of death was defined based on the top 10 causes of death reported by Statistics Canada; however, hepatocellular carcinoma and cholangiocarcinoma were included in liver-related deaths as opposed to malignant neoplasms. The proportion of deaths by each cause was described, stratified by cirrhosis etiology. The cumulative incidence of death with liver transplant and hepatocellular carcinoma as competing risks were calculated at 1, 5 and 10 years.Results202,022 patients with cirrhosis were identified (60% male sex, median age 56 years [IQR 46–67], 52% NAFLD, 26% ALD, 11% HCV, 5% HBV, 6% AI/Other). Overall, 81,428 (40%) patients died after a median follow-up of 5 years (IQR 2–12) and 3,024 (2%) patients received liver transplant. The overall leading cause of death was liver-related (32%) but varied substantially by cirrhosis etiology. Liver-related deaths were highest among those with viral hepatitis (HBV 56%, HCV 52%), and lowest in NAFLD (20%). In NAFLD cirrhosis, the most common causes of death were non-hepatic malignancy (26%), followed by a composite of cardiovascular disease, cerebrovascular disease, or diabetes (22%).ConclusionsAlthough the overall leading cause of death in patients with cirrhosis is liver-related, the most common causes of mortality in patients with NAFLD cirrhosis is non-hepatic malignancy, cerebrovascular disease, and diabetes. This supports the involvement of multidisciplinary teams and healthcare providers for patients with NAFLD cirrhosis to optimize appropriate cancer screening and management of co-morbid cardiovascular and metabolic conditions.Funding AgenciesNone

Incidence of Malignancies Among Patients With Chronic Hepatitis B in US Health Care Organizations, 2006-2018.

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

Muscle-Invasive Bladder Cancer in Patients with Liver Cirrhosis: A Review of Pertinent Considerations.

The incidence of liver cirrhosis is increasing worldwide. Patients with cirrhosis are generally at a higher risk of harbouring hepatic and non-hepatic malignancies, including bladder cancer, likely due to the presence of related risk factors such as smoking. Cirrhosis can complicate both the operative and non-surgical management of bladder cancer. For example, cirrhotic patients undergoing abdominal surgery generally demonstrate worse postoperative outcomes, and chemotherapy in patients with cirrhosis often requires dose reduction due to its direct hepatotoxic effects and reduced hepatic clearance. Multiple other considerations in the peri-operative management for cirrhosis patients with muscle-invasive bladder cancer must be taken into account to optimize outcomes in these patients. Unfortunately, the current literature specifically related to the treatment of cirrhotic bladder cancer patients remains sparse. We aim to review the literature on treatment considerations for this patient population with respect to perioperative, surgical, and adjuvant management.

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors.

SummaryImmune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

Underutilization of Hospice in Inpatients with Cirrhosis: The NACSELD Experience.

Little is known about patients discharged to hospice following hospitalization for complications of cirrhosis. We sought to understand the current pattern of hospice utilization in patients with cirrhosis by evaluating the North American Consortium for the Study of End-stage Liver Disease (NACSELD) cohort. Patients with cirrhosis from 14 tertiary-care hepatology centers across North America non-electively hospitalized and prospectively enrolled were evaluated. Exclusion criteria included HIV infection, transplantation or non-hepatic malignancy. Random computer-based propensity score matching was undertaken in a 1:2 ratio based on admission MELD score ± 3 points. Totally, 2718 patients were enrolled, 5% (N = 132) were discharged to hospice, 6% (N = 171) died, and the rest were discharged alive. Patients discharged to hospice were older (60 vs. 57years, p = 0.04), less likely to have had SBP (13% vs. 28%, p = 0.002) and be listed for liver transplantation (11% vs. 26%, p = 0.0007). Features, on multivariable modeling, associated with increased probability of discharge to hospice as opposed to being discharged alive: grade-3-4 hepatic encephalopathy, a higher Child-Turcotte-Pugh (CTP) score, and a higher discharge serum creatinine; however, a higher serum sodium, being listed for transplant and being prescribed rifaximin or a statin were protective from hospice discharge. Patients with more advanced liver disease, hepatic encephalopathy, renal dysfunction, and those not candidates for liver transplantation were more likely to be discharged to hospice. However, in this sick multinational cohort of cirrhotic inpatients, it seems that hospice is markedly underutilized (5%) since 25% of patients not discharged to hospice died within 6months.

Long-term outcomes of living donor liver transplantation in patients with a prior history of nonhepatic malignancy.

Posttransplant malignancy has become a significant cause of mortality. Data on the long-term outcomes of patients with pretransplant nonhepatic malignancy (PTM) after living donor liver transplantation (LDLT) are scarce, although the recipients of other organs with PTM have been reported to have a poor survival. Fifteen patients with PTM (4.4%) among the 342 adult recipients were identified in our LDLT programs. The outcomes of the patients with PTM after LDLT were compared to those of patients without PTM in terms of the all-cause mortality and cancer-specific mortality (defined as mortality related to malignancy expect for hepatocellular carcinoma, cholangiocarcinoma, or neuroendocrine tumor). The sites of PTM included the breast in six, stomach in two, and colon, lung, kidney, uterine, thyroid, larynx, and acute myelogenous leukemia in one each. The median interval from the PTM treatment to LDLT was 57 months (range, 2-298). The patients who received the curative treatment for PTM were selected as the recipients. No patients with PTM had recurrence during the follow-up period. The 1-, 5-, and 10-year patient survival rates were 100%, 92.9%, and 92.9% in the PTM group and 86.2%, 76.7%, and 68.5% in the non-PTM group, respectively (p = 0.142). Likewise, there was no significant difference between the two groups in the cancer-specific mortality. In conclusion, the patients with PTM had comparable outcomes with regard to mortality and cancer-specific mortality compared with those without PTM. This study showed that the patients with PTM can obtain an acceptable outcome after LDLT when carefully selected.

556P - Surgery for non-hepatic malignancy in cirrhotic patients: 5 year single center experience in India

556P - Surgery for non-hepatic malignancy in cirrhotic patients: 5 year single center experience in India

Treating Hepatic Steatosis and Fibrosis by Modulating Mitochondrial Pyruvate Metabolism.

A hepatic comorbidity of metabolic syndrome, known as nonalcoholic fatty liver disease (NAFLD), is increasing in prevalence in conjunction with the pandemics of obesity and diabetes. The spectrum of NAFLD ranges from simple hepatic fat accumulation to a more severe disease termed nonalcoholic steatohepatitis (NASH), involving inflammation, hepatocyte death, and fibrosis. Importantly, NASH is linked to a much higher risk of cirrhosis, liver failure, and hepatocellular carcinoma, as well as an increased risk for nonhepatic malignancies and cardiovascular disease. Interest in the understanding of the disease processes and search for treatments for the spectrum of NAFLD-NASH has increased exponentially, but there are no approved pharmacologic therapies. In this review, we discuss the existing literature supporting insulin-sensitizing thiazolidinedione compounds as potential drug candidates for the treatment of NASH. In addition, we put these results into new context by summarizing recent studies suggesting these compounds alter mitochondrial metabolism by binding and inhibiting the mitochondrial pyruvate carrier.

Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study

Little is known about the natural course of nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis. We describe long-term outcomes and evaluate the effects of clinical and histologic parameters on disease progression in patients with advanced NAFLD. We conducted a multi-national study of 458 patients with biopsy-confirmed NAFLD with bridging fibrosis (F3, n= 159) or compensated cirrhosis (222 patients with Child-Turcotte-Pugh scores of A5 and 77 patients with scores of A6), evaluated from April 1995 through November 2013 and followed until December 2016, death, or liver transplantation at hepatology centers in Spain, Australia, Hong Kong, and Cuba. Biopsies were re-evaluated and scored; demographic, clinical, laboratory, and pathology data for each patient were collected from the time of liver biopsy collection. Cox proportional and competing risk models were used to estimate rates of transplantation-free survival and major clinical events and to identify factors associated with outcomes. During a mean follow-up time of 5.5 years (range, 2.7-8.2 years), 37 patients died, 37 received liver transplants, 88 had initial hepatic decompensation events, 41 developed hepatocellular carcinoma, 14 had vascular events, and 30 developed nonhepatic cancers. A higher proportion of patients with F3 fibrosis survived transplantation-free for 10 years (94%; 95% confidence interval [CI], 86%-99%) than of patients with cirrhosis and Child-Turcotte-Pugh A5 (74%; 95% CI, 61%-89%) or Child-Turcotte-Pugh A6 (17%; 95% CI, 6%-29%). Patients with cirrhosis were more likely than patients with F3 fibrosis to have hepatic decompensation (44%; 95% CI, 32%-60% vs 6%, 95% CI, 2%-13%) or hepatocellular carcinoma (17%; 95% CI, 8%-31% vs 2.3%, 95% CI, 1%-12%). The cumulative incidence of vascular events was higher in patients with F3 fibrosis (7%; 95% CI, 3%-18%) than cirrhosis (2%; 95% CI, 0%-6%). The cumulative incidence of nonhepatic malignancies was higher in patients with F3 fibrosis (14%; 95% CI, 7%-23%) than cirrhosis (6%; 95% CI, 2%-15%). Death or transplantation, decompensation, and hepatocellular carcinoma were independently associated with baseline cirrhosis and mild (<33%) steatosis, whereas moderate alcoholconsumption was associated with these outcomes onlyin patients with cirrhosis. Patients with NAFLD cirrhosis have predominantly liver-related events, whereas those with bridging fibrosis have predominantly nonhepatic cancers and vascular events.

Cancer and liver cirrhosis: implications on prognosis and management

Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies.

Time-varying impact of comorbidities on mortality after liver transplantation: a national cohort study using linked clinical and administrative data

ObjectiveWe assessed the impact of comorbidity on mortality in three periods after liver transplantation (first 90 days, 90 days–5 years and 5–10 years).DesignProspective cohort study using records from the UK...

Severe morbidity according to sex in the era of combined antiretroviral therapy: the ANRS CO3 Aquitaine Cohort.

ObjectiveTo describe trends and determinants of severe morbidity in HIV-infected women and men.DesignA French prospective cohort of HIV-infected patients of both sexes and all transmission categories.MethodsWe used hospital admission data from January 2000 to December 2008. A severe morbid event (SME) was defined as a clinical event requiring hospitalization for ≥48 h, several events could be reported during hospitalization. Yearly incidence rates of SME were estimated and compared using Generalized Estimating Equations.ResultsAmong 4,987 patients (27% women), followed for a median of 8.7 years, 1,473 (30%) were hospitalized (3,049 hospitalizations for 5,963 SME). The yearly incidence rate of hospitalization decreased in men, from 155 in 2000 to 80/1,000 person-years (PY) in 2008 and in women, from 125 to 71/1,000 PY, (p<0.001). This trend was observed for all SME except for hepatic events, stable in men (15 to 13/1,000 PY) and increasing in women (2.5 to 11.5), cardiovascular events increasing in men (6 to 10/1,000 PY) and in women (6 to 14) and non-AIDS non-hepatic malignancies increasing in men (4 to 7/1,000 PY) and stable in women (2.5). Intraveneous drug users, age >50 years, HIV RNA >10,000 copies, CD4 <500/mm3, AIDS stage, hepatitis C co-infection and cardiovascular risk factors (diabetes, high blood pressure, and tobacco use) were associated with SME.ConclusionsHIV-infected individuals in care in France require less and less frequently hospitalization. Women are now presenting with severe hepatic and cardio-vascular events. Disparities in SME between men and women are primarily explained by different exposure patterns to risk factors. Women should be targeted to benefit cardiovascular prevention policies as well as men.

PTH-038 Albumin As A Plasma Expander During Large Volume Paracentesis: Are We Following The Guidelines?

IntroductionAscites is a major complication of cirrhosis occurring in more than 50% of patients within 10 years. Tense ascites is treated with large volume paracentesis (LVP) with human albumin solution...

NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients

To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease (NAFLD) fibrosis score can predict all-cause mortality, cardiac complications, and/or liver complications of patients with NAFLD over long-term follow-up. A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project. The NAFLD fibrosis score (NFS) was used to separate NAFLD patients with and without advanced liver fibrosis. We used the NFS score to classify the probability of fibrosis as < -1.5 for low probability, > -1.5 to < 0.67 for intermediate probability, and > 0.67 for high probability. Primary endpoints included all-cause death and cardiovascular- and/or liver-related mortality. From the 479 patients with NAFLD assessed, 302 patients (63%) greater than 18 years old were included. All patients were followed, and medical charts were reviewed until August 31, 2009 or the date when the first primary endpoint occurred. By using a standardized case record form, we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period. A total of 302/479 (63%) NAFLD patients (mean age: 47 ± 13 year) were included with a follow-up period of 12.0 ± 3.9 year. A low probability of advanced fibrosis (NFS < -1.5 at baseline) was found in 181 patients (60%), while an intermediate or high probability of advanced fibrosis (NSF > -1.5) was found in 121 patients (40%). At the end of the follow-up period, 55 patients (18%) developed primary endpoints. A total of 39 patients (13%) died during the follow-up. The leading causes of death were non-hepatic malignancy (n = 13/39; 33.3%), coronary heart disease (CHD) (n = 8/39; 20.5%), and liver-related mortality (n = 5/39; 12.8%). Thirty patients had new-onset CHD, whereas 8 of 30 patients (27%) died from CHD-related causes during the follow-up. In a multivariate analysis, a higher NFS at baseline and the presence of new-onset CHD were significantly predictive of death (OR = 2.6 and 9.2, respectively; P < 0.0001). Our study showed a significant, graded relationship between the NFS, as classified into 3 subgroups (low, intermediate and high probability of liver fibrosis), and the occurrence of primary endpoints. The use of metformin or simvastatin for at least 3 mo during the follow-up was associated with fewer deaths in patients with NAFLD (OR = 0.2 and 0.03, respectively; P < 0.05). Additionally, the rate of annual NFS change in patients with an intermediate or high probability of advanced liver fibrosis was significantly lower than those patients with a low probability of advanced liver fibrosis (0.06 vs 0.09, P = 0.004). The annual NFS change in patients who died was significantly higher than those in patients who survived (0.14 vs 0.07, P = 0.03). At the end of the follow-up, we classified the patients into 3 subgroups according to the progression pattern of liver fibrosis by comparing the NFS at baseline to the NFS at the end of the follow-up period. Most patients were in the stable-fibrosis (60%) and progressive-fibrosis (37%) groups, whereas only 3% were in the regressive fibrosis. A higher NAFLD fibrosis score at baseline and a new onset of CHD were significantly predictive of death in patients with NAFLD.

Non-Cirrhotic Splanchnic Vein Thrombosis: When Is Anticoagulation Enough?

Abstract 3390 Background:In the absence of primary liver disease, thrombosis of the splanchnic vessels (portal, mesenteric, and splenic veins) is a rare occurrence with variable etiologies. Early diagnosis of non-cirrhotic splanchnic vein thrombosis (SVT) and prompt treatment with anticoagulation therapy (ACT) has consistently led to high recanalization rates, symptom relief, and improved survival. For ongoing prothrombotic risk factors, prolonged ACT prevents symptom progression and recurrence. We aim to describe our centre's experience with managing non-cirrhotic SVT, and to identify factors associated with the need for further interventions beyond ACT alone. Methods:We reviewed all consecutive adult patients referred to the Thrombosis clinics at our institution between 2008 and 2011 for first-episode non-cirrhotic SVT. The primary efficacy outcome studied was SVT symptom resolution or no need for additional medical, endoscopic, or surgical treatments beyond ACT. The secondary efficacy outcome was recanalization of splanchnic vessels on follow-up imaging. Patients were categorized as resolved or unresolved based on achievement of the primary efficacy outcome. The measured safety outcome of ACT was major bleeding according to standard definitions. Results:We included 22 patients (mean age 51±12; 9 female). Nine patients had multi-vessel thrombosis involving combinations of the portal vein, superior mesenteric vein (SMV), splenic vein, and/or concurrent non-splanchnic vein thrombosis, while 13 had isolated vessel involvement (7 portal vein, 6 SMV). The portal vein was involved in 73% of patients, SMV in 59%, and splenic vein in 27%. Nine patients had completely occluded vessels, and 4 also demonstrated portal vein cavernomatous transformation on initial imaging.Upon diagnosis, all patients received ACT with either unfractionated heparin or low molecular weight heparin, followed by oral vitamin K antagonists. Four patients were not suitable for oral therapy and were maintained on low molecular weight heparin throughout their course of treatment. Long-term ACT was indicated in 3 patients with SVTs of unknown etiology and in 8 patients with isolated or combined systemic thrombophilias, including Factor V Leiden (n=4), JAK2V617Ftyrosine kinase mutation or overt myeloproliferative disorder (MPD) (n=6), and prothrombin gene variant (n=2). The remaining 11 patients with local or transient risk factors, such as recent abdominal surgery or non-hepatic malignancy, were treated with ACT for 3 to 6 months.Fifteen patients (68%) achieved complete symptom resolution with ACT alone. In the remaining 7 patients that comprised the unresolved group, there was an increased frequency of completely occluded vessels (P=0.03) and the Jak2V617F mutation or an overt MPD (P=0.004). Signs of either portal hypertension (including ascites and gastroesophageal varices) or cavernomatous transformation at the time of diagnosis tended to be more frequent among the unresolved group (P=0.005 and 0.06, respectively). Four patients in the unresolved group required invasive interventions including variceal band ligation, splenectomy, bowel resection and liver transplantation.Among the resolved group, radiographic recanalization of vessels was observed in 9 cases. The 6 remaining patients had persistent but asymptomatic vessel thrombosis in follow-up. Recanalization was more likely to occur in patients with non-occlusive thrombi (P<0.001) and local/transient etiologies (P=0.002).One patient experienced recurrent non-major gastrointestinal bleeding that ceased upon the completion of a 6-month course of ACT. Variceal hemorrhage occurred in 1 patient who subsequently underwent variceal band ligation prior to resuming prolonged ACT due to recurrent thrombosis. Conclusions:Our data, albeit limited, suggests that ACT is a safe and effective first-line treatment for patients with SVT. Short-term ACT is appropriate for patients with a clear mechanical or transient eliciting factor and non-occlusive thrombi, as recanalization rates are high in these cases. The presence of the Jak2 mutation or overt MPD, occlusive vessel thrombosis, or portal hypertensive pathology at presentation might help to identify patients who are less likely to respond to ACT and might require additional interventions. Disclosures:Lazo-Langner:Leo Pharma: Honoraria; Pfizer: Honoraria.