An unusual cause of extrahepatic cholestasis associated with solid liver lesions: a case report.

IgG4-related sclerosing cholangitis is a special type of cholangiopathy often associated with autoimmune pancreatitis. In this article, we report an unusual case of IgG4-SC limited to the common hepatic duct and associated with pseudo tumoral liver lesions, but without evidence of pancreatic involvement. Corticosteroid therapy was rapidly effective and allowed normalization of liver tests.

Percutaneous portal vein recanalization using self-expandable nitinol stents in patients with non-cirrhotic non-tumoral portal vein occlusion.

PURPOSE: The purpose of this study was to evaluate the feasibility, safety, and efficacy of portal vein recanalization (PVR) and propose a new classification for better selecting candidates with portal vein occlusion (PVO) in whom PVR could be feasible. MATERIALS AND METHODS: The charts of 15 non-cirrhotic patients in whom stent placement using a trans-hepatic approach was attempted for the treatment of PVO with cavernous transformation were reviewed. There were 12 men and 3 women with a mean age of 47 ± 12 years (range: 22­60 years) [corrected]. Intrahepatic involvement was classified into 3 groups according to the intrahepatic extent of PVO: type 1 included occlusions limited to the origin of the main portal vein and/or the right or left portal branches, type 2 included type 1 plus extension to the origin of segmental branches, type 3 included type 2 plus extension to distal branches. RESULTS: There were 6 patients with PVO type 1, 7 patients with PVO type 2, and 2 patients with PVO type 3. Indications for PVR were gastrointestinal bleeding (n=6), portal biliopathy (n=2), reduce portal pressure before surgery (n=4), or other (n=3). PVR was successful in 13 patients (87%) with no severe side effects. Failure of PVR or early stent thrombosis occurred in 100% of type 3 vs. 8% of type 1 and 2 patients (P=0.03). During a mean follow-up of 42±28 months (range: 6-112 months), patients with a permeable stent had resolution of portal hypertension-related manifestations. In 13 patients in whom PVR was feasible, stent permeability was 77% at 2 years (87% vs. 60% in patients who received anticoagulation or not, respectively; P=0.3). CONCLUSION: PVR is feasible in most patients with non-cirrhotic, non-tumoral portal vein occlusion when there is no extension of the occlusion to distal branches.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies.

[Factors influencing development and progression of alcoholic liver disease]. / Facteurs impliqués dans le développement et la progression de la maladie aLcoolique du foie.

Only a minority ot excessive drinkers develop cirrhosis. The main cofactors implicated in the pathophysiology of alcoholic liver disease are obesity, diabetes or the metabolic syndrome. Several genetic polymorphisms have been associated with a higher risk of alcoholic cirrhosis. Recent data indicate that gut microbiota could play a role in the pathogenesis of alcoholic liver disease. The aim of this review is to summarize the factors that influence development and progression of alcoholic liver disease.

Systematic review with meta-analysis: self-expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.

BACKGROUND: The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard-of-care fails to control bleeding. New treatment modalities are needed in these patients. AIM: To synthesise the available evidence on the efficacy of self-expanding metal stents (SEMS) in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. METHODS: Meta-analysis of trials evaluating SEMS in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. RESULTS: Thirteen studies were included. The pooled estimate rates were 0.40 (95% confidence interval, CI = 0.31-0.49) for death, 0.41 (95% CI = 0.29-0.53) for liver-related death and 0.36 (95% CI = 0.26-0.47) for death at day 30, with low heterogeneity between studies. The pooled estimate rates were 0.12 (95% CI = 0.07-0.21) for mortality related to variceal bleeding, and 0.18 (95% CI = 0.11-0.29) for failure to control bleeding with SEMS, with no or low heterogeneity between studies. The pooled estimate rate were 0.16 (95% CI = 0.04-0.48) for rebleeding after stent removal and 0.28 (95% CI = 0.17-0.43) for stent migration, with high heterogeneity. A significant proportion of patients had access to liver transplantation or to TIPSS [pooled estimate rate 0.10 (95% CI = 0.04-0.21) and 0.26 (95% CI = 0.18-0.36), respectively]. CONCLUSIONS: Fewer than 40% of patients treated with SEMS were dead at 1 month. SEMS can be used as a bridge to TIPSS or to liver transplantation in a significant proportion of patients. Additional studies are required to identify potential risk factors leading to a poor prognosis in patients with acute variceal bleeding in whom the use of SEMS could be considered.

MMN and P300 are both modulated by the featured/featureless nature of deviant stimuli.

OBJECTIVE: This study was designed to test the effect of the featured/featureless nature of deviant stimuli on mismatch negativity (MMN), P300 (P3a and P3b) and on behavioral discrimination performances. METHODS: Ten healthy adults were submitted to stimuli contrasted by the presence or absence of a frequency sweep. Discrimination performances were collected during the neurophysiological sessions. RESULTS: MMN, P3a and P3b were much larger for featured deviants than for featureless ones. Behavioral data (d', at ceiling level, and reaction times) were not affected by the featured/featureless nature of the deviant stimulus. CONCLUSION: Behavioral results and MMN amplitudes are in accordance with our previous study, using the same design albeit in an ignore condition and with collection of the behavioral data deferred until after the neurophysiological sessions. The present study strengthens previous evidence suggesting that two mechanisms contribute to the MMN evoked by featured deviants: the memory comparison process and the adaptation/fresh-afferent phenomenons. SIGNIFICANCE: We here demonstrate that the neurophysiological processes underlying P300 generation are also impacted by the featured/featureless nature of the deviant stimulus and that the dissociation from behavioral data, which are not impacted, is also observed when both types of data are recorded simultaneously.

Hearing loss is part of the clinical picture of ENPP1 loss of function mutation.

BACKGROUND: Ecto/nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) loss-of-function mutations have been described in patients with autosomal recessive hypophosphatemic rickets (HR), in patients with generalized arterial calcification of infancy (GACI) and in several patients with both conditions. Out of more than 50 cases of homozygous or compound heterozygous ENPP1 loss-of-function mutations published so far, 1 case with labyrinthine deafness probably due to occlusion of inner ear supplying arteries and 2 cases of conductive hearing loss due to stapedovestibular calcification diagnosed in childhood have been reported. AIMS: To report a case of ENPP1 loss-of-function novel mutation presenting with HR and very early onset and severe hearing loss. METHODS: Case report and review of the literature. RESULTS: We report on a patient homozygous for a novel 1-bp deletion in ENPP1 that presented with GACI evolving towards HR associated with a mixed hearing loss (both labyrinthine and conductive) diagnosed at 9 days of life that evolved towards profound labyrinthine deafness. CONCLUSION: Hearing loss is a rare finding in patients with ENPP1 loss-of-function mutations. Interestingly, it has already been described in other affected patients, in ENPP1 knock-out mice and in other diseases of pyrophosphate metabolism. Conversely it seems to be absent in children with the X-linked form of HR.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

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.

[Management of chronic hepatitis C in 2012 in Belgium]. / Prise en charge de l'hépatite C chronique en 2012 en Belgique.

Chronic hepatitis C virus infection is a major public health problem. It is estimated that 15 to 35% of infected patients will develop cirrhosis after a period of 30 years. Fibrosis stage must be evaluated in all hepatitis-C-infected patients. Noninvasive methods for the evaluation of liver fibrosis have been developed, mainly serum markers and transient elastography or Fibroscan. The goal of therapy is to achieve a sustained virological response, defined by hepatitis C RNA undetectable in serum 6 months after the end of therapy. This indicates viral eradication. Treatment of chronic hepatitis C has considerably improved. The association of pegylated interferon with ribavirin remains the standard of care for non-genotype-1-infected patients. Genotype-1-infected patients (who represent the majority of cases) are preferentially treated by triple therapy pegylated interferon plus ribavirin plus a first generation protease inhibitor (telaprevir or boceprevir). While triple therapy represents a major advance, by increasing the possibility of viral eradication, such therapy also presents new challenges, including the need for strict compliance, risk of additional side effects and development of resistant variants, drug-drug interactions, etc., which call for first-rate expertise in management of chronic hepatitis C therapy. Several new antiviral compounds are currently in clinical development and might lead to viral eradication in the vast majority of infected patients in the near future.

Meta-analysis: the impact of IL28B polymorphisms on rapid and sustained virological response in HCV-2 and -3 patients.

BACKGROUND: Recent studies suggested that IL28B polymorphisms may affect rapid and sustained virological response rates in HCV patients infected with genotype 2 or 3. AIM: To assess the role of IL28B polymorphisms on the virological response in HCV-2 and -3 patients. METHODS: We performed meta-analysis of studies evaluating the impact of rs12979860 and rs8099917 polymorphisms on rapid and sustained virological response in HCV-2 or -3 patients. RESULTS: Twenty-three studies involving 3042 patients were included. The first meta-analysis evaluated the impact of rs12979860 polymorphism and included 1963 patients. When compared with rs12979860 CT/TT patients, CC patients had a higher rapid virological response rate (mean difference: 12.9%, 95% CI: 6.5-19.4%, P < 0.001) and a higher sustained virological response rate (mean difference: 4.9%, 95% CI: 0.1-9.8%, P = 0.046). The second meta-analysis evaluated the impact of rs8099917 polymorphism and included 2246 patients. When compared with rs8099917 TG/GG patients, TT patients had a higher rapid virological response rate (mean difference: 14.8%, 95% CI: 7.2-22.4%, P < 0.001) and a higher sustained virological response rate (mean difference: 5.5%, 95% CI: 0.4-10.6%, P = 0.033). When considering only patients treated for 24 weeks, results were unchanged. No potential sources of between-study heterogeneity were identified. CONCLUSIONS: Favourable IL28B polymorphisms are associated with higher rapid and sustained virological response rates in HCV-2 and -3 patients. However, as the impact on a sustained response is very limited, it is unlikely that IL28B polymorphisms provide additional predictive value when considering other predictors of a sustained response.

Effect of phonological training in French children with SLI: perspectives on voicing identification, discrimination and categorical perception.

The aim of the present study was to investigate the effect of auditory training on voicing perception in French children with specific language impairment (SLI). We used an adaptive discrimination training that was centred across the French phonological boundary (0 ms voice onset time--VOT). One group of nine children with SLI attended eighteen twenty-minute training sessions with feedback, and a control group of nine children with SLI did not receive any training. Identification, discrimination and categorical perception were evaluated before, during and after training as well as one month following the final session. Phonological awareness and vocabulary were also assessed for both groups. The results showed that children with SLI experienced strong difficulties in the identification, discrimination and categorical perception of the voicing continuum prior to training. However, as early as after the first nine training sessions, their performance in the identification and discrimination tasks increased significantly. Moreover, phonological awareness scores improved during training, whereas vocabulary scores remained stable across sessions.

Hepatic venous pressure gradient in the assessment of portal hypertension before liver resection in patients with cirrhosis.

BACKGROUND: Preoperative measurement of hepatic venous pressure gradient (HVPG) is not performed routinely before hepatectomy in patients with cirrhosis, although it has been suggested to be useful. This study investigated whether preoperative HVPG values and indirect criteria of portal hypertension (PHT) predict the postoperative course in these patients. METHODS: Between January 2007 and December 2009, consecutive patients with resectable hepatocellular carcinoma (HCC) in a cirrhotic liver were included in this prospective study. PHT was assessed by transjugular HVPG measurement and by classical indirect criteria (oesophageal varices, splenomegaly and thrombocytopenia). The main endpoints were postoperative liver dysfunction and 90-day mortality. RESULTS: Forty patients were enrolled. A raised HVPG was associated with postoperative liver dysfunction (median 11 and 7 mmHg in those with and without dysfunction respectively; P = 0·017) and 90-day mortality (12 and 8 mmHg in those who died and survivors respectively; P = 0·026). Oesophageal varices, splenomegaly and thrombocytopenia were not associated with any of the endpoints. In multivariable analysis, body mass index, remnant liver volume ratio and preoperative HVPG were the only independent predictors of postoperative liver dysfunction. CONCLUSION: An increased HVPG was associated with postoperative liver dysfunction and mortality after liver resection in patients with HCC and liver cirrhosis, whereas indirect criteria of PHT were not. This study suggests that preoperative HVPG measurement should be measured routinely in these patients.

Evidence for a dual versus single origin of the MMNs evoked by cued versus cueless deviants.

OBJECTIVE: This study was designed to separately test the effect of the cued/cueless nature of deviant stimuli and that of temporal distance between sound and deviance onsets on the mismatch negativity (MMN) as well as to look for discrepancies between behavioural discrimination performances and MMN amplitude when deviants are cueless. METHODS: Ten healthy adults passively listened to stimuli that were contrasted by the presence or absence of a frequency sweep starting early or late within the sound. Discrimination performances were collected after the electrophysiological sessions. RESULTS: MMNs were much larger for cued than for cueless deviants. The temporal distance between sound and deviance onsets affected MMNs evoked by both cued and cueless deviants, even to the point of abolishing the MMN when cueless deviance occurred late in the stimulus. Behavioural data were at ceiling levels for all conditions, contrasting with the absence of MMN evoked by cueless deviants with late onset. CONCLUSIONS: Two mechanisms contribute to the MMN evoked by cued deviants: the memory comparison process and the adaptation/fresh-afferent one. Within the temporal window of integration, the delay at which each component disappears is different. SIGNIFICANCE: Comparing waveforms evoked by cued versus cueless deviants provides a fairly simple way of isolating the MMN memory-based component.

Anti-viral therapy in haemodialysed HCV patients: efficacy, tolerance and treatment strategy.

BACKGROUND: In end-stage renal disease (ESRD) patients, hepatitis C virus (HCV) eradication improves patient and graft survival. AIM: To determine optimal use of erythropoietin (EPO) and ribavirin, to compare ribavirin concentrations with those of HCV patients having normal renal function and to evaluate sustained virological response (SVR) in a prospective observatory of ESRD candidates for renal transplantation. METHODS: Thirty-two naïve patients were treated with Peg-IFN-α2a and ribavirin. Two different schedules of ribavirin and EPO administration were used: starting ribavirin at 600mg per week and adapting EPO when haemoglobin (Hb) fell below 10g/dL (adaptive strategy) or starting ribavirin at 1000mg per week while increasing EPO from the start of treatment (preventive strategy). RESULTS: Patients treated with the adaptive strategy had lower median Hb levels (9.6 vs. 10.9g/dL, P=0.02) and more frequent median Hb levels below 10g/dL (58 vs. 5%, P=0.0007) despite lower median ribavirin doses (105 vs. 142mg/day, P<0.0001) than patients treated with the preventive strategy. There was a trend for more frequent transfusion in patients treated with the adaptive strategy than in patients treated with preventive strategy (50 vs. 20%, P=0.08). Compared to patients with normal renal function, ESRD patients had lower ribavirin concentrations during the first month (0.81 vs. 1.7mg/L, P=0.007) and similar concentrations thereafter. SVR was reached in 50%. CONCLUSIONS: Pegylated interferon (Peg-IFN) and an adapted schedule of ribavirin are effective in ESRD patients. Increasing EPO from the start of treatment provides better haematological tolerance. The optimal dosage of ribavirin remains unresolved, in light of frequent side effects.

High prevalence of advanced fibrosis in association with the metabolic syndrome in a Belgian prospective cohort of NAFLD patients with elevated ALT. Results of the Belgian NAFLD registry.

INTRODUCTION: Non-alcoholic Fatty Liver Disease (NAFLD) is increasingly recognised as a source of liver related morbidity and mortality. Hard data on epidemiology and natural history are scarce. AIM: To study demographic and metabolic characteristics of the NAFLD patients seen by Belgian hepatologists. METHODS: Belgian hepatologists filled in a questionnaire for every newly diagnosed NAFLD patient between January 1st and December 31st 2004. Liver biopsy was advised if ALT > 1.5 x ULN and if 3/5 of the criteria for the metabolic syndrome (MS) (ATPI-II) were present, but was not mandatory. Biopsy was scored using the Brunt classification. RESULTS: 230 patients were prospectively included in 9 centres; 54% were males; mean age was 49.4 +/- 13.9 y; mean BMI was 30.6 +/- 4.6 kg/m2. The MS was present in 53%. In 16% formerly undiagnosed diabetes was discovered. 51% had a liver biopsy: 25% met the criteria, 26% did not. Grading did not differ between patients with or without MS. Staging was significantly more severe in patients with MS (2.43 +/- 1.25 vs. 1.73 +/- 1.18, p < 0.001). A subgroup of patients with GGT > 5 x ULN were significantly older (55.9 vs. 47.64 y, p = 0.02), more frequently diabetic (53% vs. 23%, p = 0.01) and had more advanced fibrosis (3.42 vs. 1.08, p = 0.008). ALT levels were variable. CONCLUSIONS: The MS is highly prevalent in Belgian NAFLD patients and is associated with more severe disease. Mild to moderate fibrosis is frequent, and the proposed criteria for liver biopsy are not accurate in selecting these patients. Patients with elevated GGT constitute a subgroup with more advanced disease.

Fatal hypoxic hepatitis in a patient with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease).

Hypoxic (ischemic) hepatitis generally requires the concurrence of an underlying condition which chronically exposes the liver to some degree of hypoxia (for example, congestive heart failure) combined with a triggering event (for example, arrhythmia) which further decreases the oxygen supply. We report a case of hypoxic hepatitis in which hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease) constituted this underlying condition and gastrointestinal hemorrhage was the triggering event. To our knowledge, this is the first reported case of hypoxic hepatitis in hereditary hemorrhagic telangiectasia with the exception of therapeutic ligation or embolization of the hepatic artery so as to decrease shunting of liver blood. Hemodynamic mechanisms are proposed to explain this particular outcome.

The H reflex as a diagnostic tool for Miller Fisher syndrome in pediatric patients.

Miller Fisher syndrome (MFS) is characterized by gait ataxia, external ophthalmoplegia and areflexia. Immunohistochemical studies suggest a pathophysiological role for anti-GQ1b antibodies at the paranodal regions of the oculomotor nerves, at some neurons of the dorsal root ganglia (DRG) and at motor nerve terminals. The variability of abnormal electrophysiological findings reported is significant. Nerve conduction studies, H reflex and F waves were performed in three pediatric patients with MFS. The H reflex was absent in all three patients. It was the sole abnormality in two patients whereas the third patient also had extended motor and sensory nerve conduction impairments. The transient character of this isolated absence has been confirmed in one patient. These data point to a proximal demyelinating process near the DRG. This may involve selective demyelination of Ia spinocerebellar afferent fibers originating in muscle spindles. In a pediatric practice, the H reflex seems to be a useful tool in the diagnostic approach to MFS.