Or Orthotopic Liver Transplantation Research Articles

Association of Serum Albumin Levels and Long-Term Prognosis in Patients with Biopsy-Confirmed Nonalcoholic Fatty Liver Disease.

The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation (OLT), liver-related death, and liver-related events (hepatocellular carcinoma [HCC], decompensated cirrhosis, and gastroesophageal varices/bleeding). 1383 Japanese patients with biopsy-confirmed NAFLD were analyzed. They were divided into 3 groups based on serum albumin: high (>4.0 g/dL), intermediate (3.5-4.0 g/dL), and low (<3.5 g/dL). Unadjusted hazard ratio [HR] of the intermediate albumin group, compared with the high albumin group, were 3.6 for death or OLT, 11.2 for liver-related death, 4.6 for HCC, 8.2 for decompensated cirrhosis, and 6.2 for gastroesophageal varices (all risks were statistically significant). After adjusting confounding factors, albumin remained significantly associated with death or OLT (intermediate vs. high albumin group: HR 3.06, 95% confidence interval [CI] 1.59-5.91, p < 0.001; low vs. high albumin group: HR 22.9, 95% CI 8.21-63.9, p < 0.001). Among biopsy-confirmed NAFLD patients, those with intermediate or low serum albumin had a significantly higher risk of death or OLT than those with high serum albumin.

Surgical Outcome of Children with a Malignant Liver Tumour in The Netherlands: A Retrospective Consecutive Cohort Study.

Introduction: Six to eight children are diagnosed with a malignant liver tumour yearly in the Netherlands. The majority of these tumours are hepatoblastoma (HB) and hepatocellular carcinoma (HCC), for which radical resection, often in combination with chemotherapy, is the only curative treatment option. We investigated the surgical outcome of children with a malignant liver tumour in a consecutive cohort in the Netherlands. Methods: In this nationwide, retrospective observational study, all patients (age < 18 years) diagnosed with a malignant liver tumour, who underwent partial liver resection or orthotopic liver transplantation (OLT) between January 2014 and April 2021, were included. Children with a malignant liver tumour who were not eligible for surgery were excluded from the analysis. Data regarding tumour characteristics, diagnostics, treatment, complications and survival were collected. Outcomes included major complications (Clavien–Dindo ≥ 3a) within 90 days and disease-free survival. The results of the HB group were compared to those of a historical HB cohort. Results: Twenty-six children were analysed, of whom fourteen (54%) with HB (median age 21.5 months), ten (38%) with HCC (median age 140 months) and one with sarcoma and a CNSET. Thirteen children with HB (93%) and three children with HCC (30%) received neoadjuvant chemotherapy. Partial hepatic resection was possible in 19 patients (12 HB, 6 HCC, and 1 sarcoma), whilst 7 children required OLT (2 HB, 4 HCC, and 1 CNSET). Radical resection (R0, margin ≥ 1.0 mm) was obtained in 24 out of 26 patients, with recurrence only in the patient with CNSET. The mean follow-up was 39.7 months (HB 40 months, HCC 40 months). Major complications occurred in 9 out of 26 patients (35% in all, 4 of 14, 29% for HB). There was no 30- or 90-day mortality, with disease-free survival after surgery of 100% for HB and 80% for HCC, respectively. Results showed a tendency towards a better outcome compared to the historic cohort, but numbers were too small to reach significance. Conclusion: Survival after surgical treatment for malignant liver tumours in the Netherlands is excellent. Severe surgical complications arise in one-third of patients, but most resolve without long-term sequelae and have no impact on long-term survival.

Natural History of Cirrhosis of Liver after First Decompensation: A Prospective Study in India

As liver cirrhosis is a dynamic condition, it is possible to improve survival in decompensated cirrhosis. Hence, we planned a prospective study to determine the natural history of cirrhosis after first decompensation. We enrolled all patients of liver cirrhosis who presented with first episode of decompensation defined by the presence of ascites, either overt or detected by Ultrasonography (UD), Gastroesophageal Variceal Bleeding (GEVB), and Hepatic Encephalopathy (HE). All patients were followed up to death/liver transplant or at least for the period of 1 year. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or Orthotopic Liver Transplantation (OLT)). In total of 110 cirrhotic patients (93 males, mean age 50±11 years), the most frequent etiology was alcohol (48%), followed by nonalcoholic steatohepatitis/cryptogenic (26%), hepatitis B (10%), autoimmune hepatitis (7%), and hepatitis C (6%). The distribution of CTP classes was: 4%, 56%, and 41% in class A, B, and C, respectively. Ascites was the most common decompensation found in 88 patients (80%) followed by HE (14%) and GEVB (6%). At 1-year follow up, transplant free survival was 78%, 2 underwent OLT, 4 developed hepatocellular carcinoma, and 24 died. Cumulative incidence of failure (death or OLT) by type of decompensation after 1 year was: 22% overt ascites, 50% GEVB, 28% UD ascites, 20% HE, and 33% ascites and GEVB concomitant. Patients with UD ascites do not have a negligible mortality rate as compared to overt ascites. Patients with cirrhosis after first decompensation have better transplant free survival with treatment of etiology and complications than previously mentioned in literature.

Sorafenib use for recurrent hepatocellular cancer after resection or transplantation: Observations from a US regional analysis of the GIDEON registry

Treatment of unresectable recurrent hepatocellular carcinoma (HCC) in patients who recur after resection or orthotopic liver transplantation (OLT) remains a clinical challenge. One option is sorafenib, although little is known about its safety and tolerance in this unique patient population; therefore, we analyzed patients who underwent prior surgical resection and/or OLT and were treated with sorafenib in US cohort of GIDEON registry. In US, 645 patients were enrolled; 553 for intent to treat and 563 for safety. Data were analyzed in the safety population of 479 patients no surgery and 56 for resection or OLT. Forty-one patients underwent resection prior to the initiation of sorafenib, 15 patients had previously received an OLT, and 6 patients had both resection and OLT. Initial low starting doses (400 mg/day) were observed for more patients with prior OLT (71%) than prior resection (36%), resection and OLT (50%), concomitant OLT (25%), and no surgery (36%). Most AEs occurred in the first 4 weeks of treatment. Drug-related AEs were higher in patients with prior resection (87%), prior OLT (100%), or both (100%) than in patients with concomitant OLT (63%) or no surgery (70%). However, incidence of AEs resulting in permanent discontinuation were similar in all groups (19–38%).

Long term results of hepatic resection or orthotopic liver transplantation in patients with liver metastases from gastrointestinal neuroendocrine tumors.

Hepatic metastases are one of the most important prognostic factors for survival among patients affected by gastrointestinal neuroendocrine tumors (NETs). The present study aims to evaluate the impact of surgery, including hepatic resection or orthotopic liver transplantation (OLT), on the outcome of patients affected by hepatic metastases from NETs, in terms of overall survival (OS). In this multicentric retrospective study, data was collected on 26 patients, who underwent surgery for hepatic metastases from NETs in two Italian University Clinics between January 1990 and December 2012; of which, 22 patients underwent hepatic resective surgery and 4 patients OLT. Hepatic metastases were synchronous in the 53.8% of cases and metachronous in the 46.2% of cases. The median number of resected hepatic metastases was 3. Surgical radicalness (R0) was reached in the 84.6% of cases. In total, 57.7% of patients had a recurrence, 66.7% of which were intra- and 33.3% extra-hepatic. The OS of patients that underwent hepatic resections and OLT was 44.9% [95% confidence interval (CI95), 26.0-77.7%] and 50% (CI95, 12.5-100.0%) at 5 years, respectively. Although the data regarding the survival of patients receiving surgery for hepatic metastases from NETs are encouraging, randomized clinical trials are necessary to more adequately evaluate the effect of surgery on survival of this group of patients.

Radio-frequency ablation-based studies on VX2rabbit models for HCC treatment.

Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with high morbidity, mortality and increasing incidence. It is of note that the main curative therapies for HCC are hepatic resection and transplantation although the majority of patients at the time of presentation are not eligible for resection or orthotopic liver transplantation (OLT) due to the underlying cirrhosis. Currently, a variety of loco-regional therapies, including radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT), transarterial chemoembolization (TACE) and others, have been developed as alternative treatment options for HCC. Among these techniques, RFA is currently the most widely used treatment, due to its several advantages, such as safety and efficacy. To date, the effectiveness of RFA for HCC is reduced by the presence of residual tumor as a consequence of insufficient treatment. In order to ameliorate the effects of RFA on HCC, several in vivo studies, have been performed on its application as single or in combination treatment with drugs or others loco-regional therapies, by using rabbit VX2 liver model. This represents an ideal model of liver cancers and is widely used for imaging and other experimental studies due to the rapid growth of these tumors and their similarity to human hepatocellular carcinoma. In order to elucidate the therapeutic potential of RFA with adjuvant treatments for HCC, we reviewed the latest findings on the RFA-based studies in rabbit VX2 hepatocarcinoma models.

Type 2 diabetes: a risk factor for liver mortality and complications in hepatitis B cirrhosis patients.

The effect of type 2 diabetes mellitus (DM) on morbidity and mortality among hepatitis B virus (HBV) cirrhosis patients is poorly defined. We assess the effect of DM on the HBV cirrhosis outcomes and survival. A retrospective study of HBV cirrhosis patients who sought care at a sole public hospital in a geographically defined region, from year 2000 to 2012. Cirrhosis complications, liver transplantations, and mortality were reviewed. Primary outcome is the composite of liver-related and overall mortality or orthotopic liver transplantation (OLT). Two hundred twenty-three patients entered into the final analysis; 50 patients (22.4%) have DM at cirrhosis diagnosis. Seventy-two percent of DM patients have DM for more than 5 years at cirrhosis diagnosis. The incidence of hepatocellular carcinoma (HCC) was 25.4 and 60.5 per 1000 patient-years for non-DM and DM patients, respectively (P = 0.006). In multivariate analysis, DM was a predictor of HCC (hazard ratio [HR] 2.36, [1.14-4.85], P = 0.02), hepatic complications (HR 2.04, [1.16-3.59], P = 0.01), liver mortality or OLT (HR 2.26, [1.05-4.86], P = 0.04), and overall mortality or OLT (HR 2.25, [1.96-4.22], P = 0.01). Insulin and/or sulphonylurea use and poor diabetic control (glycosylated hemoglobin ≥ 7.0%) were predictors of HCC and cirrhosis complications (all P < 0.05). The 5-year liver-related mortality or OLT rate was 23.4% for DM patients and 9.4% for non-DM patients, respectively (P = 0.009). The presence of DM and poor diabetic control at cirrhosis diagnosis significantly increase the rate of cirrhosis complications and reduced survival in patients with HBV cirrhosis. Improving diabetic control should be essential part of the cirrhosis care in these patients.

Mortality Risk According to Different Clinical Characteristics of First Episode of Liver Decompensation in Cirrhotic Patients: A Nationwide, Prospective, 3-Year Follow-Up Study in Italy

The occurrence of decompensation marks a crucial turning point in the course of cirrhosis. The purpose of this study was to assess the risk of mortality according to the clinical characteristics of first decompensation, considering also the impact of acute-on-chronic liver failure (AoCLF). We conducted a prospective nationwide inception cohort study in Italy. Decompensation was defined by the presence of ascites, either overt or detected by ultrasonography (UD), gastroesophageal variceal bleeding (GEVB), and hepatic encephalopathy (HE). AoCLF was defined according to the Asian Pacific Association for the Study of the Liver criteria. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or orthotopic liver transplantation (OLT)). A total of 490 consecutive cirrhotic patients (314 males, mean age 60.9±12.6 years) fulfilled the study criteria. AoCLF was identified in 59 patients (12.0%). Among the remaining 431 patients, ascites were found in 330 patients (76.6%): in 257 (77.8%) as overt ascites and in 73 (22.2%) as UD ascites. GEVB was observed in 77 patients (17.9%) and HE in 30 patients (7.0%). After a median follow-up of 33 months, 24 patients underwent OLT and 125 died. The cumulative incidence of failure (death or OLT) after 1, 2, and 3 years was, respectively, 28, 53, and 62% in patients with AoCLF; 10, 18, and 25% in patients with UD ascites; 17, 31, and 41% in patients with overt ascites; and 8, 12, and 24% in patients with GEVB (P<0.0001). AoCLF is responsible for a relevant proportion of first decompensation in cirrhotic patients and is associated with the poorest outcome. Patients with UD ascites do not have a negligible mortality rate and require clinical monitoring similar to that of patients with overt ascites.

The impact of ulcerative colitis on the long‐term outcome of patients with primary sclerosing cholangitis

The impact of ulcerative colitis (UC) on the outcome of primary sclerosing cholangitis (PSC) outcome remains unclear. To investigate whether the presence of UC is associated with a worse clinical of associated PSC. A total of 222 patients with PSC (167 with UC and 55 without UC) seen and followed at a single centre from 1985 to 2011 were included. Clinical and demographic variables were obtained and patients were followed until the date of their last clinic visit. The median age at presentation of PSC with associated UC was 38 vs. 47 years without UC (P < 0.001). At presentation, median serum bilirubin (2.1 vs. 4.5, P < 0.001) and the Mayo PSC Risk Score (0.95 vs. 1.69, P < 0.001) were lower in those with UC vs. those without UC. A total of 55 of 167 (32.9%) patients with PSC-UC developed colon neoplasia in contrast to 1 of the 55 (1.8%) patients with PSC. (P < 0.001) On proportional hazards analysis, UC (hazard ratio (HR) = 0.90 [95% confidence interval (CI): 0.60-1.34, P = 0.60] was not associated with death or orthotopic liver transplantation (OLT), when adjusting for gender, Mayo risk score and year of PSC diagnosis; whereas the revised Mayo risk score [HR = 5.08, 95% CI: (2.62-9.86), P < 0.001] was associated with a greater risk of OLT or death. Primary sclerosing cholangitis often is recognised at an early stage in patients with concurrent ulcerative colitis; ulcerative colitis has no impact on long-term prognosis in terms of liver-related outcomes when adjusted for the severity of liver disease.

Building a Comprehensive Genomic Program for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, causing approximately 660,000 deaths worldwide annually. The preferred treatment of HCC is surgical resection or orthotopic liver transplantation (OLT) for patients meeting specific criteria. For patients outside these criteria, options are limited and include medical therapy, radiofrequency ablation, chemoembolization, or palliative measures, and these result in poor outcomes. Various centers at Baylor are elucidating the genomics of HCC to improve treatment options, with a focus on three etiologies: hepatitis C virus, hepatitis B virus, and non-viral. Through collaborative efforts, we have established an effective specimen biobanking protocol, and we are using several techniques to analyze HCC, including whole genome sequencing, whole exome sequencing, gene-specific analysis, gene expression, and epigenetic analysis. We have completed whole genome sequencing on two patient samples, whole exome sequencing on 47 patient samples, gene-specific analysis on 94 patient samples, gene expression on 4 patient samples, and epigenetic analysis on 1 patient sample. We hope to use these results to define novel genetic therapeutic strategies that may work in conjunction with surgical approaches to improve long-term patient and graft survival rates in patients with HCC. We also aim to provide a functional framework of a comprehensive program for genomic analysis that may be imitated by other institutions and for other tumors in the global quest toward personalized genomic medicine.

A 2010 update on occult hepatitis B infection

Occult hepatitis B virus infection is a challenging issue whose virological and clinical relevance has been a source of long-lasting debate. By definition, OBI is characterized by the persistence of HBV-DNA in the liver tissue (and in some cases also in the serum) in absence of HBsAg. According to the HBV serological profile, OBI may be antibody (anti-HBc alone or together with anti-HBs) positive (seropositive OBI) or antibody negative (seronegative OBI). OBI is a complex biological entity with possible relevant clinical implications, mainly related to the intrahepatic persistence of viral cccDNA and to a strong suppression of viral replication and gene expression. Clinical observations suggest that OBI carriers may be a source of HBV transmission through blood transfusion or orthotopic liver transplantation (OLT). The state of suppression of viral replication and gene expression may be discontinued when an immunosuppressive status occurs, leading to typical hepatitis B with severe – and some times – fulminant course. The long-lasting persistence of the virus in the liver may provoke a very mild but continuing necro-inflammation that (if other causes of liver damage cohexist) may contribute over time to the progression of the chronic liver damage towards cirrhosis. In addition, OBI is supposed to be an important risk factor to HCC development since it maintains the pro-oncogenic properties typical of the overt infection.

Beta-Catenin Activation Promotes Liver Regeneration after Acetaminophen-Induced Injury

Acute liver failure (ALF) remains a disease with poor patient outcome. Improved prognosis is associated with spontaneous liver regeneration, which supports the relevance of exploring 'regenerative' therapies. Therefore, the role of the Wnt/beta-catenin pathway in liver regeneration following ALF was investigated. ALF was induced in mice by acetaminophen overdose, which is also a leading cause of liver failure in patients. beta-catenin distribution was also studied in liver sections from acetaminophen-induced ALF patients. A nonlethal dose of acetaminophen, which induces liver regeneration, led to stabilization and activation of beta-catenin for 1 to 12 hours. These data were also verified by increased expression of the beta-catenin surrogate target glutamine synthetase. Beta-catenin activation occurred secondary to the inactivation of glycogen synthase kinase-3beta and an increase in levels of casein kinase 2alpha, and led to increased cyclin-D1, another known beta-catenin target. These observations were next substantiated in beta-catenin conditional-null mice (beta-catenin-null), which show dampened regeneration after acetaminophen injury following induction of CYP2e1/1a2 expression. In light of decreased acetaminophen injury in beta-catenin-null mice despite CYP induction, equitoxic studies in control mice were performed. Significant differences in regeneration persisted following comparable injury in beta-catenin-null and control animals. Retrospective analysis of liver samples from acetaminophen-overdose patients demonstrated a positive correlation between nuclear beta-catenin, proliferation, and spontaneous liver regeneration. Thus, our studies demonstrate early activation of beta-catenin signaling during acetaminophen-induced injury, which contributes to hepatic regeneration.

Early Bacteremia After Solid Organ Transplantation

Bloodstream infections (BSI) are a major cause of morbidity and mortality after solid organ transplantation. Our aim was to analyze early BSI after solid organ transplantation. A prospective cohort study included patients undergoing a kidney, simultaneous kidney-pancreas (SPK), or orthotopic liver transplantation (OLT) from 2003-2007. We prospectively collected demographic variables, underlying chronic diseases, transplantation procedures, and posttransplant complications. Recorded cases of BSI were defined as significant according to CDC criteria. Early BSIs were considered to be those appearing within 30 days posttransplantation. During the study period, we performed 902 transplantations: 474 renal, 340 liver, and 88 pancreas. Seventy episodes of early BSI were diagnosed in 67 patients (7.4%). The incidences of BSI according to the type of transplantation were: 4.8% in renal, 4.5% in SPK, and 12% in OLT (P < .001). Sixty-three percent of the bacteria isolated were gram-negative, the most frequent being Escherichia coli, of which 18 (54%) were extended-spectrum beta-lactamase-producing (ESBL), and Pseudomonas aeruginosa, of which 18 (31%) were multidrug-resistant. The most frequent gram-positive bacteria were coagulase-negative staphylococci (20%). The urinary tract was a frequent source of BSI (27%), followed by a catheter (18%). Two patients (3%) died, both liver recipients, but neither death was related to the BSI. In our setting, the incidence of early BSI among solid organ transplant recipients was high, especially liver recipients, but with low associated mortality. The most frequent sources of infection were urinary tract and catheter. Gram-negative BSI showed a high rate of multidrug resistance.

Preoperative Portal Venous and Hepatic Arterial Embolization of Tumor

Although the goal of embolization is usually to create therapeutic ischemia or hemostasis without surgery, the rationale for preoperative embolotherapy is different in several respects. First, the aim is to prepare patients for definitive surgical resection rather than cure or palliation, and, thus, the goals and expectations are limited and defined by close communication between the interventionalist and the surgeon. Second, when considering segmental resection, the normal liver should be protected from procedural damage. Third, the search for extrahepatic disease is crucial for these patients because resection is typically abandoned in favor of alternative therapies for patients with systemic disease. Finally, intraoperative ultrasound should always be considered to survey the future liver remnant for unsuspected small tumors and allow ablation of these lesions to maximize the success of partial hepatectomy. This article describes preoperative hepatic arterial and portal venous embolization in patients with or without cirrhosis complicated by tumors judged eligible for surgical resection or orthotopic liver transplantation (OLT). Each type of embolization will be reviewed in terms of indications and contraindications, technique, and complications. Finally, the outcomes will be evaluated in terms of morbidity, mortality, and tumor recurrence rates.

Phase I Trial of Stereotactic Body Radiation Therapy for Primary Hepatocellular Carcinoma

Phase I Trial of Stereotactic Body Radiation Therapy for Primary Hepatocellular Carcinoma

Comparison of Social Support and Psychosocial Stress After Heart and Liver Transplantation

We studied social support, psychological symptoms, and subjective appraisal of quality of life among 233 patients at 1 to 3 years after heart (HTX) or orthotopic liver transplantation (OLT): 78 HTX in 62.8% men and 155 OLT in 51% men. Patients after OLT versus HTX were more often single or divorced (14.4% and 12.3% vs 3.9% and 7.7%), had better school education (68.4% vs 37.8%), and were more often employed (25.5% vs 11.8%). Among the HTX patients, 40.3% had more than 3 inpatient treatments due to complications after transplantation vs only 9.3% of OLT patients. HTX patients had more rejection reactions (55.4% vs 21%). Asked for their appraisal of quality of life, HTX and OLT patients gave comparably good “school grades” (2.6 vs 2.7), describing similar scores of social support in the F-SozU (4.4 vs 4.2). OLT patients, women in particular, reported a significantly higher grade of global psychological stress than HTX patients (67.4 vs 55.1; P < .001). Our results indicated that social support, employment status, and degree of somatic complications cannot sufficiently explain the degree of emotional distress after transplantation. Subjective factors such as making sense of the transplantation in terms of regarding it as a worthwhile operation within the life course are important mediators of psychological stress and perceived quality of life.

Long-Term Outcome of Liver Resection and Transplantation for Caroli Disease and Syndrome

To assess the preoperative disease characteristics as well as the rate of postoperative complications, patient survival, and course of symptoms after liver resection or orthotopic liver transplantation (OLT) for Caroli disease (CD) or syndrome (CS). The clinical course of monolobar or diffuse CD or CS is often characterized by multiple conservative treatment attempts and interventions with recurrent episodes of cholangitis and a serious reduction in quality of life. The role and effectiveness of surgical treatment is still not well defined. Between June 1989 and December 2002, we treated 44 consecutive patients with CD or CS who had failure of conservative treatment before and were referred for surgical intervention. Demographic and clinical data, operative procedures and related morbidity, course of symptoms, and long-term follow-up were reviewed. Four patients with palliative resection for cholangiocarcinoma and incidental diagnosis of CD were excluded from the analysis. Twenty-two women and 18 men had a median period of 26.5 months from onset of symptoms to surgical therapy. Their median age at therapy was 49 years and 80% of the patients had monolobar disease with a left-right ratio of 2.6 to 1. Thirty-three (82.5%) patients underwent liver resection, while 4 (10%) patients received OLT for diffuse disease. Biliodigestive anastomosis alone was performed in 3 (7.5%) patients with contraindications to OLT. Patients (37.5%) had minor postoperative complications, which were treated conservatively, while 2 (5%) transplanted patients had a reoperation due to intraperitoneal bleeding. After a median follow-up of 86.5 months, we observed a favorable patient and graft survival. Three deaths during follow-up were not related to treatment or disease complications. Follow-up of disease-related symptoms, biliary complications, and antibiotic treatment revealed a significant improvement. Our data show that liver resection for monolobar CD or CS and OLT for diffuse manifestations can achieve excellent long-term patient survival with marked symptom relief. Because of life-threatening long-term complications such as biliary sepsis and development of cholangiocarcinoma, timely indication for surgical treatment is crucial.

Hepatic Epithelioid Hemangioendothelioma 15 Years Later

Purpose: Epithelioid hemangioendothelioma (EHE) is an uncommon cause of increased alkaline phosphatase. Few cases have been described; none of them in Latin Americans or with a 15 year retrospective follow up. This vignette presents a 34 y/o Hispanic male who presented in 1991 with a one-month history of lightheadedness and weight loss. Physical exam was remarkable for coarse, non-tender hepatomegaly. Initial laboratory data revealed microcytic anemia, and an elevated alkaline phosphatase. Abdominal sonogram showed hepatomegaly with multiple calcifications. A liver biopsy demonstrated minute areas of fibrosis and microcalcifications. Endoscopy, colonoscopy and small bowel series were normal. Tumor markers including; AFP, CEA and HCG were normal. Repeat liver biopsy was positive for Factor VIII immunoperoxidase stains consistent with EHE. Chest CT showed evidence of bilateral lung metastasis. As of 2006 the patient shows no evidence of disease progression and is being followed with periodical CT scans. EHE is a vascular tumor of endothelial origin that preferentially arises in soft tissues of the extremities and in the lung. Liver involvement occurs as metastasis or as a primary tumor. Common presenting symptoms are upper abdominal pain, anorexia and weight loss. Jaundice, fever, and variceal bleeding are rarely seen. Liver function tests are usually normal, except for alkaline phosphatase. Imaging usually reveals peripheral multifocal hypovascular lesions, multiple calcifications, and fibrotic indentations of the liver capsule. Diagnosis is established by histology with a multifocal pattern of liver involvement, evidence of vascular differentiation, fibrotic centers, and involvement of adjacent sinusoids. This tumor is relatively avascular. Weibel-Palade bodies (cytoplasmic inclusions) may be seen. Immunochemistry, CD31, CD34, Factor VIII and anticytokeratins have been used for identification of this tumor. EHE has a low propensity to metastasize. Therapeutic options include observation, chemotherapy, radiotherapy or orthotopic liver transplantation (OLT). Surgical resection of amenable lesions should be considered. OLT has been shown to prolong survival even in the presence of metastatic disease. Prognosis is unpredictable. Most patients experience long survival. Important prognostic features include: younger age, disparity between the presence of multiple lesions and patients overall well-being, and presence of intramural calcifications.

Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis: review of indications and problems.

The aim of this study was to evaluate the role of transjugular intrahepatic portosystemic shunt (TIPS) in patients who present with portal vein thrombosis (PVT) or Budd-Chiari Syndrome (BCS). Nine patients with recent PVT and four patients with BCS underwent TIPS. The diagnosis was confirmed by color Doppler ultrasound and by angiogram in most patients. Patients were followed clinically and had TIPS checked periodically for patency. The end point was mortality, subsequent surgical shunting or orthotopic liver transplantation (OLT). TIPS was placed in 13 of 15 (87%) patients with BCS or PVT. The mean decrease in pressure gradient was 56%. Median and mean follow-up were 14 months and 16.9 months. Procedure related complications occurred in two of 13 (15%), both in the PVT group. Direct procedural mortality was one of 13 (8%). The majority of patients with PVT (five of eight) underwent OLT. Of the remaining three, one patient subsequently developed a cavernous transformation of portal vein but is stable, one patient is stable, without further variceal bleeding, and one patient died because of multiple organ failure. In patients with BCS, three of four (75%) did well with TIPS, but one patient required immediate surgical shunting after occlusion of the TIPS. Two patients underwent OLT and the fourth patient is stable 2 yr later but has cirrhosis on biopsy. In patients with BCS, TIPS placement is effective and can be used as a bridge to liver transplantation. TIPS in the noncavernous PVT group should only be recommended when cirrhosis and uncontrollable variceal bleeding are present.

Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari Syndrome or portal vein thrombosis: Review of indications and problems

OBJECTIVE: The aim of this study was to evaluate the role of transjugular intrahepatic portosystemic shunt (TIPS) in patients who present with portal vein thrombosis (PVT) or Budd-Chiari Syndrome (BCS). METHODS: Nine patients with recent PVT and four patients with BCS underwent TIPS. The diagnosis was confirmed by color Doppler ultrasound and by angiogram in most patients. Patients were followed clinically and had TIPS checked periodically for patency. The end point was mortality, subsequent surgical shunting or orthotopic liver transplantation (OLT). RESULTS: TIPS was placed in 13 of 15 (87%) patients with BCS or PVT. The mean decrease in pressure gradient was 56%. Median and mean follow-up were 14 months and 16.9 months. Procedure related complications occurred in two of 13 (15%), both in the PVT group. Direct procedural mortality was one of 13 (8%). The majority of patients with PVT (five of eight) underwent OLT. Of the remaining three, one patient subsequently developed a cavernous transformation of portal vein but is stable, one patient is stable, without further variceal bleeding, and one patient died because of multiple organ failure. In patients with BCS, three of four (75%) did well with TIPS, but one patient required immediate surgical shunting after occlusion of the TIPS. Two patients underwent OLT and the fourth patient is stable 2 yr later but has cirrhosis on biopsy. CONCLUSIONS: In patients with BCS, TIPS placement is effective and can be used as a bridge to liver transplantation. TIPS in the noncavernous PVT group should only be recommended when cirrhosis and uncontrollable variceal bleeding are present.