Search

We report the case of a female patient who was referred to our unit because of a solid liver tumor, suggestive of metastasis. After biopsy, the patient was diagnosed with epithelioid hemangioendothelioma of the liver. Epithelioid hemangioendothelioma is a rare entity with an unpredictable, potentially fatal, clinical course and outcome. Due to its rarity, this entity should be considered when a solitary hepatic lesion is detected and should be included in the differential diagnosis with liver metastases. We highlight the infrequency of this tumor, its presentation as a solitary hepatic lesion and the indication of surgical treatment. We describe the clinical and pathological characteristics of epithelioid hemangioendothelioma of the liver and report a new case of this entity. The distinct therapeutic options are discussed.

We hypothesized that antiviral efficacy [sustained virologic response (SVR)] has improved in recent years in the transplant setting. Our aim was to assess whether the efficacy of pegylated interferon (PegIFN)–ribavirin (Rbv) has improved over time. One hundred seven liver transplant patients [74% men, 55.5 years old (range: 37.5–69.5), 86% genotype 1a or 1b] were treated with PegIFN-Rbv for 355 (16–623) days at 20.1 (1.7–132.6) months after transplantation. Tacrolimus was used in 61%. Sixty-seven percent had baseline F3–F4 (cirrhosis: 20.5%). Donor age was 49 (12–78) years. SVR was achieved in 39 (36.5%) patients, with worse results achieved in recent years (2001–2003: n = 27, 46.5%; 2004: n = 23, 43.5%; 2005: n = 21, 35%; 2006 to January 2007: n = 36, 24%; P = 0.043). Variables associated with SVR in the univariate analysis included donor age, baseline viremia and cirrhosis, bilirubin levels, rapid virologic response and early virologic response (EVR), premature discontinuation of PegIFN or Rbv, and accumulated Rbv dose. In the multivariate analysis, the variables in the model were EVR [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.016–0.414, P = 0.002] and donor age (OR: 1.039, 95% CI: 1.008–1.071, P = 0.01). Variables that had changed over time included donor age, baseline viremia, disease severity (cirrhosis, baseline bilirubin, and leukocyte and platelet counts), interval between transplantation and therapy, and use of growth factors. In the multivariate analysis, variables independently changing were donor age (OR: 1.041, 95% CI: 1.013–1.071, P = 0.004), duration from transplantation to antiviral therapy (OR: 1.001, 95% CI: 1.000–1.001, P = 0.013), and baseline leukocyte count (OR: 1.000, 95% CI: 1.000–1.000, P = 0.034). In conclusion, the efficacy of antiviral therapy with PegIFN-Rbv has worsened over time, at least in our center. The increase in donor age and greater proportion of patients treated at advanced stages of disease are potential causes. Liver Transpl 15:738–746, 2009. © 2009 AASLD.

Hepatitis C virus (HCV)-related liver disease is enhanced by alcohol consumption. Of HCV-related liver transplantation (LT) recipients, 25% have a history of alcohol intake. The purpose of this research was to determine whether LT outcome differs between patients with cirrhosis of mixed etiology compared to HCV or alcohol alone. Of 494 LT (1997-2001), recipient/donor features, post-LT histological, metabolic complications [hypertension, diabetes-diabetes mellitus (DM)], and de novo tumors were compared in 3 groups [HCV-related cirrhosis = 170 (HCV group), alcohol-related cirrhosis (alcohol group) = 107, and cirrhosis of mixed etiology (mixed group) = 60]. Protocol biopsies were done in HCV patients. Severe recurrent HCV disease was defined as: 1-year fibrosis >1, cholestatic hepatitis, recurrent cirrhosis, or HCV-related liver retransplantation (reLT) within 5 years. Patients in the mixed group were younger (mean age: HCV group = 59 years; mixed group = 49 years; alcohol group = 53 years; P < 0.05) and mainly men (% men: HCV group = 51%; mixed group = 97%; alcohol group = 87%). Hepatocellular carcinoma (HCC) was more frequent in HCV patients (HCV group = 44%; mixed group = 35%; alcohol group = 18%; P = 0.05). Five-year survival was lowest in the HCV group (HCV group = 49% versus mixed group = 73% versus alcohol group = 76%; and P < 0.01 for the HCV group versus the alcohol group or the HCV group versus the mixed group; P = 0.74 for the alcohol group versus the mixed group). Metabolic complications and de novo tumors were more frequent in the alcohol groups. Severe HCV disease was similar in the HCV+ groups (HCV group = 45%; mixed group = 45%; P = 0.66). Patients with in the mixed group were more frequently treated with antivirals (32% versus HCV group = 18%; P = 0.03). In HCV patients, factors independently associated with lower survival were older donor age, LT indication (HCV alone), and increased body mass index (BMI). Antiviral therapy was a protective factor. Post-LT survival was lower in the isolated HCV group compared to the alcohol or mixed groups despite a similar recurrence of HCV disease. A greater use of antiviral therapy in the mixed group may explain these differences. The incidence of metabolic complications and de novo tumors was greater in the alcohol groups.

Pegylated interferon (pegIFN) and ribavirin eradicates hepatitis C virus (HCV) in one third of liver recipients with recurrent disease. Side effects are frequent and potentially life threatening. Our aim was to define the long-term benefits of antiviral therapy in recurrent HCV. Eighty-nine (89) recipients (genotype 1: 86.5%) were treated with IFN (n = 31) or pegIFN (n = 58) plus ribavirin and 75 untreated contemporaneous disease-matched controls. The major end point was survival from transplantation. Survival, progression to cirrhosis and clinical decompensation since start of therapy were compared between sustained virologic responders (SVRs) and nonresponders (NRs). Results revealed 44 patients died during the follow-up (20% treated vs. 35% controls; p = 0.05). Patient survival was higher in treated compared to controls (7 years: 74% vs. 62%; p = 0.04). Among treated patients, an SVR was achieved in 37% (IFN 16% vs. peg-IFN 48%; p = 0.03). About 2/33 SVRs and 16/56 NRs died (p = 0.01) due to HCV-disease (56%), IFN-induced rejection (11%), both causes (11%) or others (22%). Five-year survival was greater in SVRs than in NRs (93% vs. 69%, p = 0.032). In patients without baseline cirrhosis, progression to cirrhosis occurred more frequently in NRs (27/42 vs. 6/16; p = 0.06). The 5-year risk of graft decompensation was higher in NRs (33% vs. 16%; p = 0.04). Antiviral therapy is associated with improved long-term outcome in recurrent HCV.

SUMMARY. The effect of hepatitis C virus (HCV) genetic heterogeneity on clinical features of post-transplantation hepatitis C is controversial. Different regions of the HCV genome have been associated with apoptosis, fibrosis, and other pathways leading to liver damage in chronic HCV infection. Besides, differences in immunodominant regions, such as NS3, may influence HCV-specific immune responses and disease outcome. In the liver transplant setting, a recent study has reported a positive association between HCV-1b Core region genetic relatedness 5-year post-transplantation and histological severity of recurrent hepatitis C. We have compared nucleotide sequences of HCV Core, NS3 and NS5b regions in HCV-1b-infected patients 3 years post-transplantation (n ¼ 22). A cohort of nontransplanted patients (n ¼ 22) was used as control of natural chronic HCV-1b infection. Histological evaluation was used to define the rate of fibrosis progression. Molecular variance analysis did not show significant differences in HCV sequences between transplanted and nontransplanted patients, or between those with fast or slow fibrosis progression. The same results were obtained when analysing phylogenetic trees for Core, NS3 and NS5b regions. A more appropriate clustering method (using minimum spanning networks) revealed a significant positive relationship between HCV genetic similarity in Core (r ¼ 0.550, P < 0.01) and NS5b regions (r ¼ 0.847, P < 0.01) and the yearly rate of fibrosis progression in nontransplanted patients which, in contrast, was not observed in transplanted patients. Our results indicate that some strains of HCV-1b might be more pathogenic in the natural course of chronic infection by this virus subtype. In the liver transplant setting, when the immune response is severely compromised, other mechanisms are probably more important in determining hepatitis C progression.

Although histological hepatitis occurs in the majority of hepatitis C virus (HCV)-infected liver transplant recipients, the natural history is highly variable. Whereas progression to cirrhosis occurs in up to 30% after 3 to 7 years, the disease remains stable in another third of patients, in whom protocol liver biopsies might be avoided. However, there is recent concern that with prolonged follow-up, some patients with initial benign recurrence may develop a late-onset aggressive course. Aims of the study are to determine the incidence and factors associated with this event. Based on yearly protocol biopsies (median, five biopsies; range, three to seven biopsies), we evaluated the histological outcome of 57 HCV type 1b-infected transplant recipients with initial benign recurrence, defined as stable histological state (fibrosis stage F0 or F1) during the first 3 years posttransplantation. Severe late-onset liver damage is defined as progression to F3 or F4 in patients with previous benign recurrence. Potential predictors of this event include demographics, donor-related factors, liver enzyme levels at 1 and 3 (or baseline) years posttransplantation, activity grade and fibrosis stage at 1 and 3 years posttransplantation, nonalcoholic steatohepatitis-related variables occurring within the first 3 years posttransplantation (diabetes, hyperlipidemia, obesity), use of some drugs (renin-angiotensin inhibitors, ursodeoxycholic acid), and the advent of any unusual event. The incidence of severe late-onset liver damage was 35% (n = 20). Twelve transplant recipients progressed to F3, whereas 8 transplant recipients progressed to F4. Sudden histological deterioration was observed on postoperative biopsy 5 in 12 patients; biopsy 6 or 7, in 7 patients; and biopsy 4, in 1 patient. Variables associated with this event in univariate analysis were fibrosis stage and activity grade (and its components) at baseline (P < .0001), recipient female gender (P = .04), alanine aminotransferase (ALT) level at 1 year posttransplantation (P = .02), and aspartate aminotransferase (AST) and ALT levels at baseline (P = .008 and P = .005, respectively). By multivariate analysis, only one variable was retained in the model: fibrosis stage at baseline (relative risk, 11; 95% confidence interval, 3 to 41; P = .0007), whereas AST level almost reached statistical significance (P = .07). In conclusion, delayed HCV-related severe liver damage is not infrequent in transplant recipients with initial benign recurrence, occurring in approximately one third of them. The presence of some degree of fibrosis at baseline appears to predict this sudden change in the natural history of recurrent hepatitis C. Based on these findings, we recommend continuing protocol biopsies and evaluating potential antiviral therapy in transplant recipients with evidence of some fibrosis (even if it is only portal).

Background: Hibernoma or lipoma of brown fat is a rare benign tumor, representing 1.6% of the neoplasms of this tissue. Because of its histological characteristics can be wrongly classified as liposarcoma, therefore a correct differential diagnosis is necessary to provide appropriate treatment.Case presentation: The patient on which this case study is based is a 44-year-old male with a painless soft mass in his axilla located by his 4th and 5th ribs. The resected specimen did not have the classic macroscopic features of lipoma or fibrolipoma. Microscopically, the report described a proliferation of unilocular adipocytes with eccentric nucleus and, in less frequency, multilocular adipocytes with central nucleus. He had no recurrence after excision.Conclusions: Despite radiology studies and other technologies such as magnetic resonance imaging, computerized axial tomography (CAT), etc., the clinical diagnosis of hibernoma could be difficult. Lipoma-like hibernoma only have a few multilocular cells and can be wrongly classified as liposarcoma. Well-differentiated liposarcoma resembles it on low-power examination. Due to this it is especially important to perform a differential diagnosis with lipoma, fibroma, and even with liposarcoma. In this study we describe the histological features, the molecular markers and cytogenetic aspects that contribute to differentiate hibernoma from others tumors.

Background/Aims: The natural history and predictors of HCV-related disease severity post-transplantation are uncertain. The aims of this study were to define the natural history of post-transplantation HCV infection by assessing the rate of fibrosis progression, to determine if the post-transplantation natural history differs from that observed pre-transplantation, and to identify predictors of post-transplantation disease progression. Methods: Post-transplantation biopsies (mean: 3+/-1.6/patient) from 284 patients were scored according to histologic stage, using the method of Desmet et al. Change in fibrosis score (fibrosis progression/year) post-transplantation was used as the primary outcome. Predictors analyzed included viral factors (genotype and viral load at transplantation), patient demographics, year of transplantation, country of transplantation, pre-transplantation fibrosis progression, immunosuppression and laboratory data. Results: There was a linear association between change in fibrosis score and time from transplantation, with a median rate of fibrosis progression per year of 0.3 (0.004-2.19/year). Using parametric time-to-event analysis, the expected median duration to cirrhosis was 10 years. The rate of post-transplantation fibrosis progression was significantly higher than pretransplantation (0.2/year (0.09-0.8) p

Primary anorectal melanoma is a rare malignancy with an extremely aggressive biological behaviour. The main clinical presentations are local symptoms such as rectal bleeding, anal mass or pain, or a change in bowel habits. The tumour is frequently mistaken for benign conditions as haemorrhoids or rectal polyps. Many treatments can be used: surgery, chemotherapy, radiotherapy, immunotherapy and even biotherapy. Despite this, the disease has a very poor prognosis and 5 years.

Therapeutic options for treating unresectable hepatic metastases of leiomyosarcomas were scarce until a few years ago. Recent advances in the study of the biology of intestinal tumours have radically changed our knowledge of their pathogenesis. Many of the tumours previously considered as leiomyosarcomas are now identified as gastrointestinal stromal tumours (GISTs). The introduction of imatinib (an antineoplasic drug that specifically acts on the pathogenesis of these tumours) has shown promising results in patients with advanced GISTs. We present three patients with the initial diagnosis of unresectable hepatic metastases of leiomyosarcomas. They received liver transplants. All three had tumour recurrences after transplantation. Histological re-evaluation identified a stromal origin of the tumours, and the patients were treated with imatinib therapy (400 mg/day). Recurrence occurred in all patients after a mean of 38.3 months, but imatinib treatment achieved control of the tumours. The current survival times with the combination of transplantation and imatinib are 92, 48 and 46 months for the three patients. This series is small and inconclusive, but imatinib treatment showed promising results. The treatment options for patients with unresectable metastases of GISTs must be defined, as in these three patients liver transplantation achieved a disease-free status but all had tumour recurrences before starting the imatinib treatment.

Recently, hypoglycemia with endogenous hyperinsulinemia has been described after undergoing bariatric surgery because of morbid obesity. It has been theorized that after a gastric bypass surgery, some trophic factors affecting pancreatic β cells could emerge. The authors present a case of morbidly obese patient with severe hypoglycemia 3 months after bariatric surgery. An abdominal helicoidally computed tomography scan showed a 1.7 cm tumor in the tail of the pancreas. Histopathology revealed an insulinoma with well-defined contours surrounded by pancreatic tissue with atrophic signs and with hyperplasia and hypertrophic phenomena compatible with nesidioblastosis in adjacent islets of the pancreatic duct. Authors hypothesize that maintenance of the stimulus produces hyperplasia/hypertrophy of the pancreatic islets and reemphasizes the dynamic qualities of pancreatic β cells and the possibility of producing hyperplasia from the extreme resistance to insulin present in morbidly obese patients.

The goal of the study was to determine the incidence and variables associated with post-liver transplantation (LT) de novo internal neoplasms development, excluding skin tumors and hepatocellular carcinoma. Medical records were reviewed for recipient/donor demographics, viral serology, cause of liver disease, interval from LT to tumor diagnosis, predisposing factors, immunosuppression and survival. Forty-one neoplasms (31 solid and 10 hematologic) developed in 772 recipients (5.3%) transplanted between 1991 and 2001. Time to tumor diagnosis was longer in patients transplanted before 1995 than in those transplanted afterwards (58 vs. 22 months; p

Ten cases of Budd-Chiari syndrome associated with coeliac disease have been reported in the literature, most of them in North African subjects. Supporting this association, we report a new case in a young Spanish Caucasian man in whom the cause of the syndrome was the membranous obstruction of the inferior vena cava, an infrequent cause of Budd-Chiari syndrome in Western countries. A percutaneous balloon angioplasty was performed, with satisfactory outcome.

Background Recurrent hepatitis C is very common leading to graft cirrhosis in a significant proportion of patients. Preliminary reports of combination therapy with interferon-ribavirin have been promising but generally applied to selected patients with chronic mild disease. Little is known, however, about the efficacy and risk of adverse effects when it is used in general clinical practice. Aims To analyse the efficacy (biochemical, virological and histological response) and tolerance of combination therapy in patients with recurrent hepatitis C genotype 1 b. Methods Twenty-four patients (mean age 54 years; range 37-67 years; 75% male) with recurrent hepatitis C virus (histology at baseline: acute hepatitis (n = 3); chronic hepatitis (n = 21) with F3 or 4 in 77%) were treated with 12 months interferon (1.5-3 MU thrice weekly) + ribavirin (600-1200 mg daily) followed by 6 months ribavirin (58%), at a median of 427 days (56-2812) after transplantation. Results Seven patients (29%) discontinued therapy due to side effects, mainly anaemia, at a median of 3 months since initiation. Dose modifications were required in 88% of those completing the whole course of therapy. Overall, the sustained virological and biochemical response was 12.5%. This rate was slightly higher (18%) if only the 17 patients who finished the whole course of therapy were analysed. Histological improvement was achieved in 31.5% of treated patients. Conclusions Combination therapy has a very limited efficacy in the liver transplant setting, although some benefit may be achieved, even in those with advanced graft fibrosis. Tolerance, however, remains a matter of concern.

Hepatocellular carcinoma (HCC) is still considered a controversial indication for liver transplantation (LT), mainly because of long waiting times and underlying viral cirrhosis. The goal was to evaluate the outcome of LT in 104 patients with HCC and cirrhosis, mainly hepatitis C virus (HCV)-related, in a center with a short waiting time (median, 105 days). Four groups were formed according to the HCC and HCV status: HCV positive with HCC (group 1, n = 81), HCV negative with HCC (group 2, n = 23), HCV positive without HCC (group 3, n = 200), and HCV negative without HCC (group 4, n = 207). Predictive factors of tumor recurrence were demographics, tumor related (size or number of nodules, capsule, bilobar involvement, vascular or lymphatic invasion, clinical and pathologic TNM staging, pre-LT percutaneous ultrasound-guided ethanol injection or transarterial chemoembolization, alpha-fetoprotein levels), donor and surgery related, and year of transplantation. The same variables and "tumor recurrence (yes/no)" were applied to evaluate the effect on survival. The median follow up was 29 months (range, 0 to 104 months). Patient survival was 70% at 1 year and 59% at 5 years for group 1, 87% at 1 year and 77% at 5 years for group 2, 81% at 1 year and 64% at 5 years for group 3, and 88% at 1 year and 77% at 5 years for group 4 (P =.013). Survival was significantly lower in patients with HCC than in those without (74% and 63% versus 85% and 70%, at 1 and 5 years, respectively; P =.05). The causes of death in those with and without HCC were tumor recurrence (24%) and recurrent HCV (8%) versus sepsis (34%) and recurrent HCV (14%). HCC recurrence occurred in 12 patients (11.5%) at a median of 14 months (range, 3 to 60 months) with a probability increasing from 8% at 1 year to 16% at 5 years. In patients with HCC, tumor recurrence was associated with vascular invasion (P =.0004) by multivariate analysis; variables predictive of survival were donor old age (P =.01), viral-related etiology (P =.02), and tumor recurrence (P =.001). Although LT still remains an adequate indication for HCC in centers with high prevalence of HCV infection and short waiting times, both tumor and HCV-related recurrent diseases hamper significantly the outcomes of these patients.

Long-term administration of hepatitis B immune globulin is effective as prophylaxis for hepatitis B virus (HBV) reinfection but is limited by cost, side effects, availability and a failure rate of 20%. Famciclovir has been shown to be effective in the treatment of hepatitis B in the immunocompetent patient. Fewer data exist in the liver transplant setting, particularly regarding its efficacy in de novo HBV infection. The aims of this pilot study were to determine the effectiveness and safety of long-term administration of famciclovir in recurrent (n = 3) and de novo (n = 3) HBV infection after liver transplantation.Six patients with postransplant HBV infection (positivity of serum HBsAg and HBV DNA), four of whom were HBeAg positive, were treated with famciclovir (500 mg, 3 times a day) with a minimum follow-up period of 12 months. Biochemical, serological, virological (HBV DNA by hybridization assays and polymerase chain reaction), and histological (including HBV immunostaining) endpoints were evaluated.None of the patients had a complete biochemical response, with a near complete normalization of ALT levels being observed in 3/6 patients. There was a lack of correlation between virological and biochemical responses. None of the patients seroconverted to anti-HBs or anti-HBe. A virological clearance was observed in only two patients, whereas a moderate reduction in HBV DNA levels was present in one. HBV DNA levels were higher than levels during pretreatment in the three remaining patients. Histological improvement was only observed in one patient.Famciclovir alone appears of limited efficacy in the treatment of HBV infection after liver transplantation.

To determine whether the presence of hepatitis C virus (HCV) viremia correlates with the severity of liver disease in anti-HCV-positive apparently healthy blood donors, we studied 98 blood donors found positive for anti-HCV using enzyme-linked immunosorbent assay (ELISA). Each subject underwent a liver biopsy, a test for HCV RNA in the serum by polymerase chain reaction (PCR), and a panel of liver injury tests. As a result, 97% of the anti-HCV-positive blood donors had some type of histological abnormality:22 (22%) had minimal changes, 1 (1%) had chronic lobular hepatitis, 40 (41%) had chronic persistent hepatitis (CPH), and 32 (33%) had chronic active hepatitis (CAH). Only 3 subjects had a normal liver histology. HCV RNA was detectable in the serum in 65% of the anti-HCV-positive donors. HCV RNA in serum was detectable in none of the donors with a normal liver histology, in 36% (confidence interval [CI], 17% to 59%) of those with minimal changes, in 70% (CI, 53% to 83%) of those with CPH, and in 87% (CI, 71% to 96%) of those with CAH (P = .00001). HCV RNA was detectable in 75% of the donors with elevated (> 45 U/L) alanine transaminase (ALT) values and in 59% of those with normal ALT levels (P = not significant). The incidence of chronic hepatitis was higher in HCV RNA-positive than in HCV RNA-negative donors (88% vs. 50%; P = .00005).(ABSTRACT TRUNCATED AT 250 WORDS)

Liver transplantation rapidly evolved throughout the 1980s into an effective treatment for end-stage liver disease. Most adult patients undergoing liver transplantation have cirrhosis and portal hypertension; however, the etiology of cirrhosis varies (1). Chronic hepatitis C virus (HCV) infection is a common cause of end-stage cirrhosis leading to the consideration of OLT (2). Many cirrhotic patients experience repeated bouts of encephalopathy despite therapy with lactulose/lactitol and/or neomycin. In fact, encephalopathy is the second most common quality-of-life indication of OLT in these patients (3). In our series, 29% of the cirrhotic patients undergoing OLT had had at least one episode of encephalopathy before transplantation.

A morphometric study of the distal esophageal mucosa (within 5 cm above the gastroesophageal junction) has been carried out in a group of 11 cirrhotic patients undergoing esophageal transection with SPTU gun for variceal bleeding. The relative thickness of the papillae (62.2 +/- 3.9%) and basal zone (11.8 +/- 1.9%) were within normal limits. Polymorphonuclear infiltrates were not found either in the lamina propria or in the epithelium. The absence of histopathologic changes in the esophageal mucosa from patients with liver cirrhosis and bleeding esophageal varices confirms the hypothesis that gastroesophageal reflux does not play a pathogenic role in the development of variceal bleeding.