The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs ), which had decreased programmed death (PD)-1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage.

Position statement on how can we can implement the Greendeal in our gastrointestinal and gastrointestinal endoscopy department in Belgium.

The importance to reach the target to be carbon net zero by 2050, as presented by the European Commission in the European Green Deal, cannot be overestimated. In a current endoscopy world, where single use has found its place and techniques are constantly evolving, it will be a challenge to reach these goals. How can we reconcile this evolution to a carbon neutral status by 2050 without compromising patients care, clinical standards and training needs? The European Society of Gastrointestinal Endoscopy (ESGE) together with the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) recently published a position statement (1) whereas in the UK there is the work from the green endoscopy group (2) in line with the strategy of the British Society of Gastroenterology (BSG) on sustainability (3). In Flanders, a project called "greendeal in duurzame zorg" had its kick off in March 2023 (4) so it is about time that we in Belgium, as gastroenterologists, start with tangible actions to a more sustainable daily practice. We wrote this position statement in cooperation with the Vlaamse Vereniging voor Gastro-Enterologie (VVGE), the Société royale belge de Gastro-entérologie (SRBGE) and the Belgian Society of Gastrointestinal Endoscopy (BSGIE). We will also work together in the coming years to continue to motivate our members to work on these initiatives and to co-opt new projects within the framework of the greendeal.

Coinfection of hepatitis B and hepatitis delta virus in Belgium: a multicenter BASL study. Prospective epidemiology and comparison with HBV mono-infection.

Epidemiological data on hepatitis delta virus (HDV) infection in Belgium are lacking. A multicenter questionnaire-based registry on HDV infection was collated between March 1, 2008 and February 28, 2009. It consisted of patients coinfected with hepatitis B virus (HBV) and HDV. The data samples were compared to those of a concurrent registry on HBV infection. Prospective data of patients with HBV-HDV coinfection were collected. Active HBV replication is defined as HBeAg positivity or HBV DNA > 2,000 IU/ml. Forty-four patients from 15 centers were registered. A comparison of 29 patients infected with HDV (registered in the concurrent HBV registry) was made against 785 HBV mono-infected patients. The seroprevalence of patients coinfected with HBV and HDV in Belgium is reported to be 3.7% (29/785), consisting solely of the HBV-HDV coinfected patients in the HBV registry. This rises to 5.5% (44/800) if all patients infected with HDV from the two registries combined are included. The patients coinfected with HBV and HDV had higher (P < 0.05) ALT values and more advanced liver disease (Metavir score ≥F2), but had less active HBV replication and lower HBV DNA titers when compared with the patients infected only with HBV. Additionally, the majority of HBV-HDV coinfected patient was male, and 13.6% (6/44) of the patients that were coinfected HBV and HDV were also infected with HCV. In conclusion, this study provided much needed epidemiological data on the current state of HDV infection in Belgium.

Pathophysiology and management of post resection liver failure.

Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and nonparenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

The influence of laboratory-induced MELD score differences on liver allocation: more reality than myth.

BACKGROUND: Liver allocation in Eurotransplant (ET) is based on the MELD score. Interlaboratory MELD score differences in INR and creatinine determination have been reported. The clinical implication of this observation has not been demonstrated. METHODS: MELD scores were calculated in 66 patients with liver cirrhosis using bilirubin, creatinine, and INR analyzed in six liver transplant centers. Based on allocation results of ET, patients transplanted from December 2006 to June 2007 were divided according to MELD score in four groups. For each group, the influence of the match MELD on the probability of receiving a transplant was studied (Cox proportional hazards model). RESULTS: Laboratory-dependent significant differences in MELD score were demonstrated. Cox proportional hazards model showed a significant association between MELD score and the probability of organ allocation. The unadjusted hazard ratio for receiving a liver transplant was significantly different between group 2 and group 4 (group 2: MELD 19-24; group 4: MELD > 30). CONCLUSION: Laboratory-dependent significant differences in MELD score were observed between the six transplant centers. We demonstrated a significant association between the MELD score and the probability of organ allocation. The observed interlaboratory variation might yield a significant difference in organ allocation in patients with high MELD scores.

Recent advances in the approach to hepatopulmonary syndrome and portopulmonary hypertension.

Liver disease, cirrhosis and portal hypertension can be complicated by pulmonary vascular disease, which may affect prognosis and influence liver transplantation (LT) candidacy. Pulmonary vascular complications comprise hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). Although these two conditions develop on a same background and share a common trigger, pulmonary responses are distinct and occur at different anatomical sites of the pulmonary circulation. HPS affects 10-30% of patients referred for LT, and is characterized by gas exchange abnormalities due to pulmonary vasodilation and right-to-left shunting. POPH occurs in 5%, and is defined by pulmonary arterial hypertension due to increased pulmonary vascular resistance, which leads to hemodynamic failure. Even though HPS and POPH may have a substantial negative impact on survival, both entities are clinically underrecognized and frequently misdiagnosed. Without intervention, the 5-year survival rate is 23% in HPS and 14% in POPH. Their presence should be actively sought by organized screening in patients presenting with dyspnea and in all patients on the waitlist for LT, also because clinical symptoms are commonly non-specific or even absent. LT may lead to resolution, however, advanced stages of either HPS or POPH may jeopardize safe and successful LT. This implicates the need of proper identification of HPS and POPH cases, as well as the need to be able to successfully 'bridge' patients to LT by medical intervention. A review article on this topic has been published in this journal in 2007 (1). This updated review focuses on recent advances in the diagnosis and management of these 2 liver-induced pulmonary vascular disorders and incorporates results from our recent work.

Comorbidities and concomitant medications in patients with chronic hepatitis C virus infection receiving second-generation direct-acting antiviral regimens in Belgium: an observational study.

Objective: To describe comorbidities and concomitant medications in patients initiating treatment for hepatitis C virus (HCV) infection with direct-acting antiviral (DAA) regimens in Belgium. Methods: This was a noninterventional, observational, multicenter study of data from patient charts. Adult patients with HCV infection receiving second-generation DAA therapy were included. Comorbidities were assessed at the time of HCV treatment initiation. Concomitant medications were recorded at the time of diagnosis and at treatment initiation. Potential clinically relevant drug-drug interactions (DDIs) were assessed based on information available at www.hep-druginteractions.org. The primary objective was to describe concomitant medication use ; secondary objectives were to describe modifications in concomitant therapies and comorbidities. Results: 405 patients were included. A total of 956 comorbidities were reported by 362 patients (median, 2 ; range, 0-15). The most common comorbidities were hypertension (27.2%) ; HIV coinfection (22.5%), and type 2 diabetes mellitus (14.3%). Overall, 1455 concomitant medications were being taken by 365 patients (90.1% ; median, 3 ; range 0-16). The most common concomitant medications were psycholeptics (28.6%), antiviral agents (24.2%), and medications for acid-related disorders (21.0%) Overall, 74/365 (20.3%) patients receiving a concomitant medication required an adaptation to their concomitant medication. The medications that most frequently required change were drugs for acid-related disorders (n = 14) and antiviral drugs (n = 5) ; those that were most frequently stopped were lipid-modifying drugs (n = 25) and drugs for acid-related disorders (n = 13). Conclusion: Physicians are aware of the potential for DDIs with DAAs, but improved alignment between clinical practice and theoretical recommendations is required.

The HCV serum proteome: a search for fibrosis protein markers.

Liver fibrosis/cirrhosis is a serious health issue in hepatitis C virus (HCV-) infected patients and is currently diagnosed by the invasive liver biopsy. The aim of this study was to find useful fibrosis markers in HCV-patients' sera of different fibrosis degrees (METAVIR F0-F4) based on proteomics. Serum proteome profiles were created by two-dimensional gel electrophoresis. Profiles were analysed between different degrees of fibrosis (F0-F4) and between early (F0F1) and late (F2F3F4) fibrosis by univariate analyses (P

Previous intravenous substance use and outcome of liver transplantation in patients with chronic hepatitis C infection.

BACKGROUND: End-stage liver disease due to hepatitis C viral (HCV) infection is the most common reason for liver transplantation. One of the major risk factors for infection with HCV is intravenous drug use (IVDU). The pretransplantation characteristics and outcome of liver transplantation in patients with chronic hepatitis C (CHC) infected after IVDU are poorly known. METHODS: We performed a retrospective cohort study in patients with CHC who underwent liver transplantation between 1998 and 2002 in Belgium. Seven patients with and 60 patients without a history of IVDU were compared. RESULTS: Patients with CHC infected after IVDU were primarily men, significantly younger, and affected more by genotype 2 or 3. There was no relapse in substance use. No patients required a second transplantation or developed surgical complications. Progression to fibrosis in the posttransplantation period seemed to be slower. Graft and patient survival, and compliance were similar in both groups. CONCLUSIONS: Compared with patients in the non-IVDU group, patients with CHC infected after IVDU in complete remission have the same compliance, and patient and graft survival after liver transplantation. Therefore, patients with IVDU should not be excluded for liver transplantation because of HCV-induced cirrhosis.

Induction of tolerance in solid organ transplantation: the rationale to develop clinical protocols in liver transplantation.

Minimization or withdrawal of immunosuppressive treatments after organ transplantation represents a major objective for improving quality of life and long-term survival of grafted patients. Such a goal may be reached under some clinical conditions, particularly in liver transplantation, making these patients good candidates for tolerance trials. In this context in liver transplantation, the central questions are (1) how to promote the natural propensity of the liver graft to be accepted, (2) which type of immunosuppressive drug should be used for induction and maintenance, and (3) which biomarkers could be used to discriminate tolerant patients from those requiring long-term immunosuppression. Induction therapies using aggressive T-cell-depleting agents may favor graft acceptance. However, persistent and/or rapidly reemerging cell lines, such as memory-type cells or CD8(+) T cells, could represent a significant barrier for induction of tolerance. The type of maintenance drugs also remains questionable. Calcineurin inhibitors may be eventually deleterious in the context of tolerance protocols, through inhibitory effects on regulatory T cells, that are not observed with rapamycin. In conclusion, significant efforts must be made to achieve reliable strategies for immunosuppression minimization or withdrawal after organ transplantation into the clinics.

Hepatitis C virus (HCV) prevalence estimation in the adult general population in Belgium : a meta-analysis.

BACKGROUND AND STUDY AIMS: Although multiple HCV prevalence studies were recently performed in the general population from Belgium, they suffer from a lack of geographical representativeness, an insufficient number of participants or a lack of inclusion of high prevalence groups. The aim of this study is to provide robust information on the HCV burden. METHODS: Recently performed HCV prevalence studies in the general, adult population were included in this study, based on well-defined selection criteria. A meta-analysis was performed to estimate the seroprevalence, the prevalence of participants with viremia and the prevalence estimation for people with viremia which were unaware of their status. RESULTS: Eight studies fulfilled the criteria for inclusion of the quantitative prevalence estimation. Based on the meta-analysis on these 8 studies, we estimated an HCV seroprevalence of 1.01% [95% CI : 0.66-1.42%], representing a total of 90,722 adult, HCV seropositives of which 64,412 individuals (0.71%) were confirmed seropositive. Based on the RNA presence, an estimated viremic prevalence of 0.33% [95% CI : 0.21-0.47 %] was determined, corresponding with 29,642 individuals. This is 46,0% of the true HCV seropositive residents. Further, based on the availability of patient information in 5 out of the 8 studies, a prevalence of 0.18% [95% CI : 0.07-0.33] representing 16,168 individuals from the adult Belgian population are unaware of their HCV status. CONCLUSIONS: We believe that the quantitative measurement by the meta-analysis will be more reliable for their use in the design of a screening strategy or in the development of prevention campaigns as compared to the prevalence estimations performed at local level.

IgG4-related disease of the hepatobiliary tract : 2 case reports and review of the literature.

IgG4-related disease is a rare inflammatory disorder that may mimic many infectious, malignant, and autoimmune conditions. The biliary tract is frequently involved, but hepatic lesions are rarely seen. Diagnosis is often delayed due to the absence of specific clinical and radiological signs, and the lack of an accurate diagnostic marker. Differential diagnosis includes cholangiocarcinoma, primary sclerosing cholangitis and intrinsic or metastatic liver disease. Corticosteroids are the cornerstone of therapy but treatment has not been standardized and relapse is common. Based on two cases of IgG4-related hepatobiliary disease, we review the current literature on this pathological entity.

Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes.

BACKGROUND: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. AIM: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion. METHODS: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium. RESULTS: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. CONCLUSION: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss.

A rapid test of alloreactivity based on interleukin-2 mRNA expression might identify liver transplant recipients with donor-specific hyporesponsiveness.

BACKGROUND: Immunosuppression withdrawal is feasible in some liver transplant (OLT) recipients but may lead to severe rejection in others, underlying the need for reliable biomarkers to identify patients with tolerant profile in whose weaning/withdrawal could be safely proposed. We evaluated the value of real-time polymerase chain reaction (PCR)-based measurement of interleukin (IL)-2 mRNA in mixed lymphocyte reaction (MLR) to monitor in vitro anti-donor reactivity in OLT patients. METHODS: MLR were performed in three patients undergoing living donor OLT using a tolerogenic protocol including donor stem cells. IL-2 mRNA production in MLR was measured by PCR at several intervals after OLT. RESULTS: In the early posttransplant period, three patients presented with global immunodeficiency, as indicated by low IL-2 mRNA production against both donor and third-party antigens. In the two patients who has immunosuppression successfully withdrawn, donor-specific hyporesponsiveness was observed thereafter: IL-2 mRNA production against donor cells remained low, while IL-2 mRNA production against a third-party antigen-presenting cells progressively recovered. No such modulation of the anti-donor response was observed in the patient in whom withdrawal led to rapid rejection. CONCLUSION: Measurement of IL-2 mRNA production in MLR might prefer a tool to monitor anti-donor reactivity after OLT for decisions to minimize or withdraw immunosuppression in patients displaying donor-specific hyporesponsiveness.

The choice of recipient does not have a bearing on early outcome in liver transplant patients receiving grafts from non-heart-beating donors: a reappraisal?

INTRODUCTION: Donation after cardiac death has reemerged as a potential way of increasing the supply of organs for transplantation. We retrospectively reviewed the outcomes of non-heart-beating donor (NHBD) liver transplantation (OLT) experience and compared with standard heart-beating donation (HBD) at a single center. METHODS: From October 2003 to November 2006, 13/111 liver transplantations were performed in our institution with NHBD. Living donor liver transplantation, splitting procedures, combined, and pediatric liver transplantations were excluded from this analysis. RESULTS: Donor population was similar in both groups. The median warm ischemia time was 10 minutes (range 6 to 38). The median cold ischemia times 6 hours and 16 minutes (2.4 to 6.30 hours and 9 hours and 14 minutes (2.15 to 15.35 hours) for NHBD and HBD groups, respectively (P = .0002). In the NHBD groups, 4/13 (31%) grafts were retransplanted within 3 months, due to ischemic biliary lesions with severe cholestasis (n = 3) or due to the occurrence of primary nonfunction (n = 1). The retransplantation rate was significantly lower in the HBD group (11/98, 11%; P = .03). One-year patient and graft survivals were 62% and 54% versus 86% and 79%, respectively, for the NHBD and HBD groups (P = .107 and P = .003). CONCLUSION: Liver grafts procured from donors after cardiac death accounted for a significantly greater retransplantation rates, mainly due to nonanastomotic biliary strictures. This risk must be taken into account when transplanting such grafts. Based upon this experience, NHBD cannot rival HBD to be a comparable source of quality organs for liver transplantation.

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler Weber syndrome.

BACKGROUND AND STUDY AIMS: Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is usually asymptomatic and does not require treatment. However, when present, clinical manifestations can cause considerable morbidity and mortality. Current expertise in the variable clinical manifestations and recommendations for diagnostic approach and management of hepatic involvement in HHT are outlined. METHODS AND MATERIALS: A review of current literature was performed using the MEDLINE search string: "Hereditary hemorrhagic telangiectasia [ALL] OR Rendu-Osler-Weber [ALL] AND (liver OR hepatic [ALL])". RESULTS: Due to the lack of therapeutic consequence, systematic screening for hepatic involvement in asymptomatic patients with HHT is currently not recommended. In symptomatic patients, diagnostic tools include non-invasive techniques such as abdominal color Doppler ultrasound, CT and/or MRI. In any case, liver biopsy should be avoided in patients with suspected HHT because of the high bleeding risk. Liver transplantation is currently the only curative option for symptomatic hepatic involvement in HHT. Except for biliary or hepatocellular necrosis, which require urgent liver transplantation, consensus on the most appropriate timing of transplantation is lacking. Recent studies have shown a promising role for angiogenesis inhibitors as a causative treatment for hepatic involvement in HHT and its complications. CONCLUSIONS: Identification of specific risk factors for progression to the symptomatic phase is one of the main future challenges. This would subsequently allow for individualized and cost-effective screening of high-risk patients when they are still in the asymptomatic stage. However, until then screening in asymptomatic patients is not recommended. Additionally the effect of preventive measures in this high-risk population on the development of symptomatic liver involvement and on poor outcome should be established.

Hepatitis C infection-related liver disease: patterns of recurrence and outcome in cadaveric and living-donor liver transplantation in adults.

BACKGROUND: Preliminary data demonstrate that the recurrence of hepatitis C is more severe in patients undergoing adult-to-adult living liver (AAL) transplantation (Tx) in comparison with cadaveric liver (CL) Tx. The authors report on the 1-year follow-up of their cohort of hepatitis C virus (HCV) patients undergoing AALTx or CLTx. METHODS: Twenty-six patients with HCV end-stage liver cirrhosis underwent CLTx and 17 underwent AALTx. The diagnosis of recurrent HCV was made on the basis of increased transaminases, detectable HCV RNA levels, and histologic findings on liver biopsy. Liver biopsies were performed on the basis of clinical indications. Bilirubin concentration, partial thromboplastin time, and alanine aminotransferase activity were compared between the two groups at different time intervals. RESULTS: HCV recurrence was seen in 10 of 26 CLTx patients versus 6 of 17 AALTx patients (P=0.1). Time until recurrence was longer in AALTx patients (158+/-114 days vs. 227+/-154 days, P=0.4). Of the biochemical parameters, only bilirubin concentration at week 4 was significantly different between AALTx and CLTx patients (3.1+/-4.3 mg/dL vs. 1.26+/-0.83 mg/dL, P=0.04). Overall survival and the number of patients needing retransplantation were similar in both groups. CONCLUSIONS: At a follow-up period of 1 year, there is no difference in outcome between end-stage HCV patients undergoing AALTx or CLTx.

Non-transferrin-bound iron in untreated and ribavirin-treated chronic hepatitis C patients.

BACKGROUND: In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content and oxidative stress-related molecules have been reported. Treatment with ribavirin induces an increase in hepatic iron concentration. In situations of iron overload, non-transferrin-bound iron can appear. Therefore, we determined non-transferrin-bound iron levels in untreated chronic hepatitis C patients and in patients during interferon-ribavirin treatment. MATERIALS AND METHODS: In 10 untreated and 19 interferon-ribavirin-treated chronic hepatitis C patients, we examined non-transferrin-bound iron levels by a colorimetric method using nitrilotriacetic acid as a ligand and sodium triscarbonatecobalt (III) to block free iron binding sites on transferrin. RESULTS: Despite the presence of high serum iron saturation and ferritin levels, non-transferrin-bound iron was absent in the majority of hepatitis C virus patients (25/29, 86%). There was no difference in non-transferrin-bound iron levels between untreated and treated patients. Four patients with high non-transferrin-bound iron levels were distinguished by higher serum iron levels. In two of these patients, hepatocytic iron was present on liver biopsy. CONCLUSIONS: In the majority of chronic hepatitis C patients, non-transferrin-bound iron levels are normal. Treatment with ribavirin does not induce high non-transferrin-bound iron levels. Non-transferrin-bound iron levels are only higher than normal in hepatitis C patients with higher serum iron levels.

Multiple focal nodular hyperplasia.

Focal nodular hyperplasia (FNH) is a benign lesion of the liver which usually presents with one or two localizations. We report a patient with history of resection of a biliary cyst, and who had been taking oral contraceptives for the past 18 years, who had multiple localizations of FNH (more than 30 lesions). The largest lesion measured 10.5 x 11 x 12cm. The imaging characteristics of our patient were atypical. A central scar could be demonstrated only in the largest lesion, in an eccentric location. In the other lesions, no scar formations could be detected. Furthermore, imaging characteristics suggested that several of the lesions contained fat. This was confirmed by biopsy. The patient had an associated inflammatory syndrome which could not be otherwise explained. The patient was advised to stop taking the oral contraceptives. Follow-up after 2 years showed that the lesions were unchanged; the inflammatory syndrome persisted. Multiple localizations of FNH are very rare. Sometimes they are associated with malformations in other organs (vascular malformations and neoplasia, mostly of the brain). Often they occur as isolated cases, however. Usually their prognosis seems to be good.

Relationships between haemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis.

OBJECTIVE: In patients with cirrhosis, the relationships between haemodynamic alterations and the development of ascites or the occurrence of refractory ascites are unknown. The aim of the present study was to compare haemodynamic measurements obtained in patients with non-refractory ascites to haemodynamic measurements obtained in patients without ascites and in patients with refractory ascites. METHODS: A cohort of 121 patients was prospectively studied, of whom 29 patients did not have ascites, 45 had non-refractory ascites and 47 had refractory ascites. Splanchnic, renal and systemic haemodynamics were measured in all patients. RESULTS: The hepatic venous pressure gradient was significantly higher in patients with non-refractory ascites than in patients without ascites (18.5 +/- 0.8 mmHg versus 15.8 +/- 0.7 mmHg). Renal and systemic haemodynamics did not significantly differ between patients with non-refractory ascites and patients without ascites. The glomerular filtration rate and renal blood flow were significantly lower in patients with refractory ascites than in patients with non-refractory ascites (77 +/- 4 versus 107 +/- 5 ml/min and 867 +/- 62 versus 1,008 +/- 68 ml/min, respectively). Splanchnic and systemic haemodynamics did not significantly differ between patients with refractory ascites and patients with non-refractory ascites. CONCLUSIONS: In patients with cirrhosis, an increase in portal hypertension was the sole haemodynamic alteration related to the development of ascites. Renal vasoconstriction (and subsequent renal hypoperfusion and hypofiltration) was the only haemodynamic alteration related to the occurrence of refractory ascites. The development of ascites or refractory ascites was not associated with any alteration in systemic haemodynamics.