Search

Background: Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. Aims: To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. Methods: Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. Results: Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). Conclusions: Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.

Background: Lenvatinib is approved for patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, its clinical outcomes in patients experiencing HCC recurrence after liver transplantation (LT) remain unclear. Thus, we investigated the efficacy and safety of lenvatinib in patients with recurrent HCC after LT.Methods: This multinational, multicenter, retrospective study included 45 patients with recurrent HCC after LT who received lenvatinib at six institutions in three countries (Korea, Italy, and Hong Kong) from June 2017 to October 2021.Results: At the time of lenvatinib initiation, 95.6% (n = 43) of patients were Child–Pugh A, with 35 (77.8%) and 10 (22.2%) patients classified as albumin-bilirubin (ALBI) grades 1 and 2, respectively. The objective response rate was 20.0%. With a median follow-up duration of 12.9 months (95% confidence interval [CI]: 11.2–14.7), median progression-free survival and overall survival (OS) were 7.6 (95% CI: 5.3–9.8) months, and 14.5 (95% CI: 0.8–28.2) months, respectively. Patients with ALBI grade 1 showed significantly better OS (52.3 months, [95% CI: not assessable]) than patients with ALBI grade 2 (11.1 months [95% CI: 0.0–30.4 months], p = 0.003). The most common adverse events were hypertension (n = 25, 55.6%), fatigue (n = 17, 37.8%), and anorexia (n = 14, 31.1%).Conclusion: Lenvatinib showed consistent efficacy and toxicity profiles in patients with recurrent HCC after LT compared to the results of previous studies of non-LT HCC patients. The baseline ALBI grade was correlated with better OS in lenvatinib-treated patients with LT.

There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013–2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42–56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p&nbsp

Worldwide, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) significantly increases mortality and morbidity. The Coronavirus Disease 2019 (COVID-19) outbreak has had a considerable impact on healthcare systems all around the world, having a significant effect on planned patient activity and established care pathways, in order to meet the difficult task of the global pandemic. Patients with hepatocellular carcinoma (HCC) are considered a particularly susceptible population and conceivably at increased risk for severe COVID-19 because of two combined risk factors: chronic advanced liver disease and HCC itself. In these challenging times, it is mandatory to reshape clinical practice in a prompt way to preserve the highest standards of patient care and safety. However, due to the stay-at-home measures instituted to stop the spread of COVID-19, HCC surveillance has incurred a dramatic drop, and care for HCC patients has been rearranged by refining the algorithm for HCC treatment to the COVID-19 pandemic, permitting these patients to be safely managed by identifying those most at risk of neoplastic disease progression.

Background: Monoprophylaxis with third-generation nucleos(t)ide analogues (NAs) can be safely adopted in hepatitis B virus (HBV)-positive, liver transplantation (LT) patients after at least 6 months of HBV immunoglobulin (HBIg)+NA. We investigated the efficacy of earlier initiation of post-LT entecavir (ETV) or tenofovir (TDF) monoprophylaxis. Methods: Between September 2011 and January 2017, all consecutive hepatitis B surface antigen (HBsAg)-positive transplanted patients were scheduled to receive HBIg with ETV or TDF for a period related to the risk for HBV reinfection: 1. low-risk patients (HBeAg-negative and HBV DNA < 12 IU/mL before LT) were due to withdraw from HBIg once HBsAg had become negative after a minimum of 7 days of HBIg+NA; 2. high-risk patients were due to receive HBIg for at least 6 months, after which they continued with third-generation NA monotherapy, only. Results: Twenty patients with a median interquartile range (IQR) follow-up of 46 (64-39) months were enrolled in the study (40% receiving ETV, 60% receiving TDF). Two low-risk patients refused early HBIg withdrawal and were therefore treated and analyzed along with the high-risk group. Eventually, there were 2 groups: group A, which included 12 low-risk patients, and group B, which included 8 patients (six high-risk, 2 low-risk). After transplantation, group A and B patients received HBIg+NA for a median (IQR) time of 7 (9-7) days and 9 (13-5) months, respectively. All 20 recipients demonstrated HBV DNA < 12 IU/mL and stable graft function during follow-up. Two patients (10%), 1 from each group, had HBsAg relapse. Notably, both patients who relapsed had hepatocellular carcinoma (HCC) diagnosed before LT and showed very low levels (< 0.25 IU/mL) of HBsAg after recurrence. Conclusion: In low-risk HBsAg-positive recipients, HBIg may be safely discontinued within 2 weeks of LT and replaced by ETV or TDF monotherapy.

The majority of patients undergoing Orthotopic Liver Transplantation (OLT) have increased in age, therefore chronological age may have become an unreliable parameter for supporting clinical decisions. The age-related deficit accumulation model measuring frailty proposed by Rockwood et al., may propose an alternative in providing an estimate of an individual’s biological age. No Frailty Index (FI) tailored specifically for OLT patients exists to date. Forty-three consecutive OLT patients with ≥ 20 years of survival with a functioning graft were included in our study. The FI was computed taking to account 39 items (FI-39), meeting the standard criteria for internal validation. Endpoints were polypharmacy, and recent Emergency Room admission. The mean age of our population was 69 (sd 9) years. The mean FI-39 was 0.23 (sd 0.1). The FI-39 was associated with polypharmacy [odds ratio (OR) 1.13; Confidence interval (95%CI) 1.03–1.24; p = 0.01], and recent Emergency Room admission [beta coefficient + 1.98; 95%CI + 0.26, + 3.70; p = 0.03], independent for age and sex. This study demonstrates that an FI can be derived from data collected during routine clinical follow-up and allows for improved differentiation related to the OLT clinical complexity in OLT patients, independent of chronological age. This may lead to the adoption of FI-39 to improve personalized OLT patient care.

Optimal involvement of palliative care (PC) services in the management of patients with decompensated cirrhosis and end-stage liver disease (ESLD) is limited. This may result from both ignorance and the failure to recognize the spectrum and unpredictability of the underlying liver condition. Palliative care is a branch of medicine that focuses on quality of life (QoL) by optimizing symptom management and providing psychosocial, spiritual, and practical support for both patients and their caregivers. Historically, palliative care has been underutilized for patients with decompensated liver disease. This review provides an evidence-based analysis of the benefits of the integration of palliative care into the management of patients with ESLD. Liver Transplantation 24 961-968 2018 AASLD.

Objectives To evaluate the efficacy and tolerability of direct‐acting antiviral (DAA) therapy in individuals aged 65 and older. Design Retrospective review between June 2014 and January 2017. Setting Viral hepatitis outpatient clinic. Participants Individuals aged 65 and older treated with DAA therapy for hepatitis C virus (HCV) during the study period (N=113) divided into 2 cohorts: aged 65 to 74 (n=88) and aged 75 and older (n=25). Measurements Drug‐drug interactions (DDIs), adverse events (AEs), and rates of sustained virologic response with DAA therapy were assessed. Results Sustained virologic response rate was 97.7% in individuals aged 65 to 74 and 95.8% in those aged 75 and older. Individuals aged 75 and older were more likely to be taking more than 2 medications per day for chronic conditions (84% vs 62%, p=.02) and more likely to have clinically significant DDIs necessitating cessation or adjustment of medications before commencement of DAA therapy (80% vs 36%, p=.001). Moreover, individuals aged 75 and older were more likely to experience an AE during therapy (50% vs 26%, p=.03) and were more susceptible to developing anemia secondary to ribavirin (60% vs 20%, p=.02). Conclusion DAA therapy is highly efficacious for the treatment of HCV in older adults, but those aged 75 and older are more likely to have clinically significant pretreatment DDIs and experience AEs, including ribavirin‐induced anemia, during therapy.

This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.

Autoantibodies are frequently detected after liver transplantation (LT), but their role is unclear. This study was designed to address three points: autoantibody prevalence pre-LT and over time up to five yr after LT, identification of possible predictors of autoantibody formation, and correlation between autoantibodies and graft dysfunction. To these aims, we retrospectively evaluated 92 consecutive LT recipients for whom prospectively stored frozen sera were available for autoantibodies assessment by immunofluorescence. The overall autoantibody prevalence resulted significantly higher after LT than before LT (64% vs. 27%, p < 0.001 and 35.9% vs. 8.7%, p < 0.001 considering cutoff titer of ≥ 1:80 and ≥ 1:160, respectively). Recipient gender, donor age and gender, and indication for LT and main immunosuppressant (cyclosporine vs. tacrolimus) were not associated with the presence of autoantibodies. Patients with graft dysfunction had a significantly higher autoantibody prevalence irrespective of the etiology of liver injury as compared to those patients with persistently normal liver biochemistry, but only for cutoff titers ≥ 1:160 (p = 0.004). No cases of de novo autoimmune hepatitis were observed. In conclusion, autoantibodies are very frequently detected after LT also at high titers and their association with graft dysfunction likely represents an aspecific indicator of liver injury.

Different strategies of DAAs treatment are currently possible both pre- and postliver transplantation (LT). Clinical and economic consequences of these strategies still need to be adequately investigated; this study aims at assessing their cost-effectiveness. A decision analytical model was created to simulate the progression of HCV-infected patients listed for decompensated cirrhosis (DCC) or for hepatocellular carcinoma (HCC). Three DAAs treatment strategies were compared: (i) a 12-week course of DAAs prior to transplantation (PRE-LT), (ii) a 4-week course of DAAs starting at the time of transplantation (PERI-LT) and (iii) a 12-week course of DAAs administered at disease recurrence (POST-LT). The population was substratified according to HCC presence and, in those without HCC, according to the MELD score at listing. Data on DAAs effectiveness were estimated using a cohort of patients still followed by 11 transplant centres of the European Liver and Intestine Transplant Association and by data available in the literature. In this study, PRE-LT treatment strategy was dominant for DCC patients with MELD20 and for those with HCC. Sensitivity analyses confirmed PRE-LT as the cost-effective strategy for patients with MELD≤20. In conclusion, PRE-LT treatment is cost-effective for patients with MELD≤20 without HCC, while treatments after LT are cost-effective in cirrhotic patients with MELD>20 and in those with HCC. It is worth reminding, though, that the final choice of a specific regimen at the patient level will have to be personalized based on clinical, social and transplant-related factors

Background & Aims Notwithstanding evidences implicating the lipopolysaccharides (LPS)/toll-like receptor-4 (TLR4) axis in the pathogenesis of NAFLD, there are no studies aimed to characterize hepatic TLR4 expression in NAFLD patients. We aimed to analyse hepatic TLR4 expression and to verify its relationship with disease activity/evolution in NAFLD patients. Methods Liver tissue from 74 patients with NAFLD and 12 controls was analysed by immunohistochemistry (IHC) for TLR4, α–smooth muscle actin (α–SMA) and cytokeratin-7. IHC for α–SMA was used to evaluate activation of fibrogenic cells (hepatic stellate cells and portal/septal myofibroblasts), that for cytokeratin-7 to count hepatic progenitor cells and bile ducts/ductules, and that for CD68, in a subgroup of 27 patients, for detecting macrophages. Serum LPS-binding protein (LBP), a sensitive marker of LPS activity, was determined in 36 patients and 32 controls. Results As confirmed by double-labelling experiments, the highest level of TLR4 expression was observed in hepatic progenitor cells, biliary cells and portal/septal macrophages. TLR4-positive hepatic progenitor cells and bile ducts/ductules correlated with portal/interface inflammation, activity of fibrogenic cells and fibrosis (P

Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening.Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption.The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P0.001,36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P0.001 and HR: 5.4 (95% CI: 2.2-13.2), P0.001 respectively].In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.

To determine the single or combined effect ofboth rs12979860 and rs8099917 SNPs on HCV treatmentresponse, these variants were genotyped in samples from acohort of 170 patients infected with different HCV genotypes(HCVGT). The favourable rs12979860 CC genotype wasfound only in patients with sustained or rapid virologicalresponses (SVR/RVR) and at significantly high proportionsin HCVGT1/4 SVR patients. A significant association wasalso found between the rs8099917 TT genotype and SVR inboth HCVGT1/4 and HCVGT2/3 groups of patients. Incontrast, we found that there was significantly more of thers8099917 GG genotype in nonresponders (NR) than in SVRpatients which suggests a good association of the minorhomozygote GG with the lack of treatment response. Thecombination of rs12979860/rs8099917 CC/TT favourablegenotypes was found only in SVR patients and matched thefrequency observed for their rs12979860 CC genotypesalone. By contrast, the inverse unfavourable correlaters12979860/rs8099917 TT/GG genotype was seen more inNR than in SVR patients as observed for the single GGgenotype. This study confirms the impact of bothrs12979860 and/or rs8099917 IL-28B SNPs on treatment-induced clearance of HCV-RNA and demonstrates that thers12979860 CC genotype is stronger than rs8099917 TTgenotype in predicting a positive treatment response inHCVGT1/4 patients. The unfavourable rs8099917 GGgenotype seems to be more important in predicting the fail-ure of treatment response independently from HCV geno-type.Keywords: HCV, IFN, IL-28B, RBV, SVR.

Interruption or hypoplasia of the inferior vena cava, with associated azygos continuation, is an uncommon congenital vascular malformation (Ellis et al, Comput Radiol 1986;10:15-22). Although this anomaly causes venous stasis, few patients present with history of deep vein thrombosis (DVT). The exact role of coexisting thrombophilic gene mutations, also heterozygotic, is far from being completely understood. However, in these cases, because of a probable additive effect, treatment of complications and careful prophylaxis for recurrent DVT are recommended lifelong. The authors report a case of inferior vena cava interruption with azygos continuation in a 30-year-old woman who presented with a history of recurrent lower limb DVT. In addition, heterozygosis for the H1299R polymorphism of the factor V gene (Factor V HR2), for the C677T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR C677T) and for the 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene (PAI-1 4G/5G) was found in DNA analyses.

Haemorrhoidal disease is a common finding in cirrhotic patients (40–44%) [1, 2], as haemorrhoidal plexus is a possible site of porto-systemic venous anastomosis. Portal hypertension (PH) can both exacerbate pre-existent essential haemorrhoidal varices (HV) and cause secondary vascular pathologies, called ano-rectal varices (ARV), particularly in conditions of severely increased hepatic vein pressure gradient (HVPG). Coexisting in up to 30% of cases, ARV are different from HV: as they are mainly due to portal pressure, they usually do not benefit from local therapies, requiring instead a corrective strategy for the underlying PH. Here we report a case of a 45-year-old man, known to have alcoholic Child-B liver cirrhosis, who was admitted to our clinic in March 2011 for severe anaemization (haemoglobin 5.8 g/dl) secondary to persistent rectorrhagia. On admission, he was haemodynamically stable and physical examination evidenced pale skin, tachycardia and tachypnoea, while laboratory results showed microcytic anaemia and severe thrombocytopenia (46 000/µl), and mild elevation of hepatic tests. On anamnestic deepening, he underwent an haemorrhoidal prolapsectomy 15 years earlier and a haemorrhoidal ligature 6 years earlier for persistent symptomatic bleeding haemorrhoids. Moreover, he had a 25-year history of severe alcohol consumption but he had been in a relatively good condition until August 2010, when he received the diagnosis of liver cirrhosis because of the first episode of hepatic decompensation (ascites and encephalopathy). Clinical examination evidenced third-degree haemorrhoids and a pancolonoscopy documented ARV excluding other colonic bleeding lesions, while upper endoscopy showed congestive gastropathy in absence of oesophageal varices. Doppler ultrasonography revealed an increased diameter of the main portal tract (13.5 mm), with preserved hepatopetal flow at reduced mean velocity (10 cm/s). An abdominal computed tomography scan with contrast medium detected a patent ectatic superior mesenteric vein with congestion of the rectal venous plexus and mild perihepatic ascites and splenomegaly (Figure 1). Repeated blood transfusions were prescribed to raise haemoglobin and propranolol in increasing dosage was started to reduce portal hypertension. However, severe rectorrhagia continued so we opted for reducing portal system congestion with a transjugular intrahepatic portosystemic shunt (TIPS). The initial portal venous pressure was 22 mm Hg and the estimated HVPG was 18 mm Hg. Despite reduction of the pressure gradient from 18 mm Hg to 4 mm Hg, rectorrhagia persisted, so surgical intervention for haemorrhoids was suggested. Transanal haemorrhoidal dearterialization (THD) was performed through a dedicated proctoscope, which incorporates a Doppler probe that allows one to identify and to ligate haemorrhoidal arteries and arteriovenous shunts. Transanal haemorrhoidal dearterialization is an innovative mini-invasive technique that has gradually gained in popularity among surgeons since the encouraging initial results reported by Morinaga et al. [3] in 1995. It consists of the Doppler-guided ligation of the terminal branches of the superior rectal artery, which solely contribute to the blood supply of the haemorrhoidal plexus [4, 5], thereby reducing the congestion [6]. The postoperative course was uneventful and the patient was discharged after 5 days. After a 15-month follow-up period, the patient is in good clinical condition, complying with his medical treatment, and the ano-rectal blood loss has not recurred. Figure 1 Coronal contrast-enhanced CT image showing ectatic superior mesenteric vein (white arrow) This case highlights how difficult it can be to diagnose and treat haemorrhoidal disease in cirrhotic patients with severe portal hypertension. The presence of persistent bleeding HV, relapsing after previous local therapies, and of endoscopic-evident ARV, suggested that the severely increased portal hypertension was the real cause of bleeding and of persistence of varices. So, we first reduced portal hypertension with both medical (β-blockers) and interventional (TIPS) techniques, probably achieving a reduction in ARV degree and, when we observed that rectorrhagia persisted, it was clear that blood loss was due to coexistent essential HV, this time. Thus, we treated them with a local mini-invasive technique (THD, previously described). Conventional surgical approaches are usually considered unsuitable in this context [7]: they can worsen portal hypertension after surgical removal of the venous porto-caval shunts, as well as having an increased risk of complications in cirrhotic patients. In conclusion, our experience sheds further light on the relevance of managing portal pressure in case of persistent bleeding and relapsing HV in presence of ARV: TIPS could be performed as the first approach in order to reduce the degree of portal hypertension and to plan, in case of ineffective resolution of ano-rectal bleeding, a mini-invasive surgical procedure with reduced operative risk.

Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory disturbances. More flexibility in classification should derive from this etiopathogenic background.

During chronic liver disease (CLD), angiogenesis participates in the fibrogenic process. Herein, we aimed at verifying the on-treatment kinetics of serum vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in hepatitis C virus (HCV) patients undergoing antiviral therapy. Forty-three HCV patients treated with pegylated-interferon/ribavirin and 26 controls were studied. Serum VEGF and Ang-2 were determined before treatment, at different time points during treatment, and at follow-up after treatment. Thirty and 13 patients were sustained virological responder (SVR) and No-SVR, respectively. Patients showed increased Ang-2 levels [504 (368-720) versus 449 (389-483) pg/mL, P0.05], and equivalent VEGF levels [271 (193-377) versus 274 (199-324) pg/mL, P = 0.6], with respect to controls. By univariate analysis, stage of fibrosis was associated with Ang-2 levels (odds ratio 4.25, P0.05). In SVR patients VEGF levels showed a progressive reduction (P0.05) but returned to pretherapy levels at follow-up, and Ang-2 levels showed an opposite progressive increase, being significantly reduced at follow-up (P0.01). No significant modifications in VEGF and Ang-2 levels were observed in No-SVR. We conclude that, in patients with HCV-CLD, Ang-2 serum levels are associated with fibrosis and reduced at follow-up in SVR patients. On-treatment, VEGF and Ang-2 serum levels undergo different-sided modifications only in SVR patients, possibly expressing the vascular remodeling occurring early after viral clearance.

A 67-year-old-man with advanced alcoholic cirrhosis presented with progressive dyspnea. Chest radiography showed findings suggestive of a large right pleural effusion.

in the pathogenesis of cirrhosis. Therapeutic options to target these factors are currently limited to long-term antibiotics. Nanoporous carbons are non-absorbable, synthetic materials which are safe with porosity manipulated for adsorption of middle and high molecular weight molecules and surface chemistry modified to alter adsorption capacity for biological molecules such as cytokines and endotoxin. The aims of this study were to determine whether oral administration of these carbons would prevent the complications of cirrhosis. Methods: 131 male Sprague-Dawley rats underwent bile ductligation or sham biliary surgery. Animals were pair fed with or without oral carbon therapy two weeks from surgery until completion of the experiment at 4–5 weeks. Intraperitoneal lipopolysaccharide (LPS) was administered to 4 subgroups 3.5 hours prior to completion of study. The following groups were studied: Sham (n=16), Sham + carbon (n =15), Sham + LPS (n =11), Sham+LPS+carbon (n =10), BDL (n =27), BDL + carbon (n =26), BDL+LPS (n =10), BDL+LPS+carbon (n =16). Portal haemodynamics were performed on 93 rats and Kupffer cell population and ROS production were performed by flow cytometry in a subgroup of animals. Biochemistry and portal venous cytokines were measured. Results: A significant reduction in portal pressure was observed in BDL+LPS (mean 18.1mmHg (0.88) untreated, 10.2mmHg (1.07) with carbon, p = 0.0007) and BDL (mean 12.6mmHg (0.43) untreated, 11.0mmHg (0.28) with carbon, p = 0.004) groups following carbon treatment. A significant reduction in ALT was observed in the carbon treated BDL+LPS (p =0.01) and BDL groups (p = 0.04). Carbon treatment in BDL rats was associated with a significant reduction in LPS-induced ROS production by the Kupffer cells. A trend towards reduction in portal venous IL-4 and IL-10 were observed in carbontreated BDL rats. A significant increase in final body mass was observed in the BDL carbon-treated group (p =0.03). Conclusions: The data from this study suggests that nanoporous carbon is a novel approach to reducing gut translocation which prevents Kupffer cell activation thereby preventing portal hypertension.