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.

Clinical characteristics of hepatocellular carcinoma in patients with cirrhosis: a comparative cohort study.

Background and study aims: The epidemiology of cirrhosis has changed over the last two decades. We aimed to assess whether the epidemiology and clinical presentation of hepatocellular carcinoma (HCC) occurring in cirrhosis has changed. Patients and methods: The patients were recruited from the Cirrhosis Registry. This database included patients with cirrhosis who had attended the outpatient' liver clinic at the Centre Hospitalier Jolimont in La Louvière, Belgium, since January 1995. We extracted data on two cohorts of patients with cirrhosis collected over an identical time period and followed up for the same duration. Results: Cohort 1 included 504 patients enrolled from 1995 to 2005; among them, 89 patients developed HCC during the defined follow-up period (group 1). Cohort 2 included 566 patients enrolled from 2006 to 2016, among whom 73 patients developed HCC during the defined follow-up period (group 2). When patients with HCC in both groups were compared, no differences were found in the age at HCC diagnosis, the test that alerted on the presence of HCC, the extension, and the stage of the lesion at diagnosis. In the group 1, hepatitis C virus-related HCC occurred in 53% of the cases compared with 18% in the group 2 (P<0.001). Alcohol-related HCC occurred in 27% in the group 1 compared with 60% in the group 2 (P<0.001). The prevalence of metabolic dysfunction-associated steatotic liver disease-related HCC accounted for 10% in all groups. Conclusion: The general epidemiology of HCC has not changed; however the etiology of underlying cirrhosis has changed.

Epidemiological and prognostic factors involved in upper gastrointestinal bleeding: results of a French prospective multicenter study.

BACKGROUND AND STUDY AIMS: The mortality rate from upper gastrointestinal bleeding (UGIB) remains high, at 5 % - 10 %. The aim of the current study was to describe the epidemiological characteristics, prognostic factors, and actual practice in a cohort of patients with UGIB admitted to French general hospitals. METHODS: From March 2005 to February 2006, a prospective multicenter study was conducted at 53 French hospitals. A total of 3298 patients admitted for UGIB were enrolled consecutively. Patient data were collected up to the date of discharge from hospital. RESULTS: Data were available for 2130 men and 1073 women (mean age 63 ± 18 years), one-third of whom were taking drugs that would increase the risk of UGIB. The two main causes of bleeding were peptic ulcers (38 %) and esophagogastric varices (EGV) or portal hypertensive gastropathy (24.5 %). Mean Rockall score was 5.0 ± 2.3. Endoscopy was performed on 96 % of patients (within 24 hours in 79 %), and 66 % of those with ulcers and 62.5 % of the EGV patients underwent hemostatic therapy when indicated. Rebleeding occurred in 9.9 % of the patients, and 8.3 % died. Independent predictors of rebleeding were: need for transfusion (odds ratio [OR] 19.1; 95 % confidence interval [95 %CI] 10.1 - 35.9); hemoglobin < 10 g/dL (OR: 1.7; 95 %CI 1.1 - 3.3); Rockall score (OR: 1.4 for each 1 point score increase; 95 %CI 1.0 - 1.9), systolic blood pressure < 100 mmHg (OR: 1.9; 95 %CI 1.4 - 2.5), and signs of recent bleeding (OR: 2.4; 95 %CI 1.7 - 3.5). Independent predictors of mortality were: Rockall score (OR: 2.8; 95 %CI 2.0 - 4.0), co-morbidities (OR: 3.6 for each additional co-morbidity; 95 %CI 2.0 - 6.3), and systolic blood pressure < 100 mmHg (OR: 2.1; 95 %CI 1.8 - 2.8). Rockall score, blood pressure and co-morbidities were taken as continuous variables meaning that the OR was 1.4 for every point increase, it was the same for blood pressure. CONCLUSION: UGIB still occurs mainly as a result of peptic ulcers and portal hypertension in France, and causes significant rates of mortality. There is scope for improvement via better prevention (better use of UGIB-facilitating drugs), endoscopic therapy, and management of co-morbidities.

5-year mortality of alcohol-related cirrhosis: patients die just as much but not in the same manner.

Background and study aim: Patients with alcohol-related cirrhosis have a poor short-term prognosis. We aimed to determine whether the 5-year mortality of alcohol-related cirrhosis has changed over the past two decades in our institution. Patients and methods: From January 1995 to December 2014, 932 cirrhotic patients who attended the hepatology outpatient's clinics of our institution were consecutively listed in a registry. From this registry, 565 patients had alcohol-related cirrhosis and were the subject of this study. 16 patients were excluded because they were loss to follow-up and 114 patients were excluded because the diagnosis of cirrhosis was made more than 2 years before the inclusion in the registry. We separated the 435 remaining patients into two cohorts collected during two similar period of 10-year duration, but 10 years apart: the cohort 1, patients included in the registry from 1995 to 2004 (n = 206) and the cohort 2, patients included from 2005 to 2014 (n = 229). The 5-year mortality was assessed in both cohorts and the precipitating events leading to death were compared. Results: From the 206 patients in the cohort 1, 80 died within 5 years after the diagnosis of cirrhosis (Group A) compared to 83 patients from the 229 patients in the cohort 2 (Group B) (Cohort 1: 39 % vs Cohort 2: 36 %, p = 0.6). Patients in Group A died more often from gastrointestinal bleeding than patients in Group B (Group A: 30 % vs Group B: 9 %, p = 0.003). Patients in Group A died less by sepsis than patients in Group B (Group A: 1.5 % vs Group B: 14 %, p = 0.009). Conclusions: The 5-year mortality rate in patients with alcoholrelated cirrhosis has not changed however, the circumstances of death have changed.

Validation of Baveno VI and Expanded-Baveno VI Criteria for predicting gastroesophageal varices in patients with alcoholic and non-alcoholic fatty liver disease.

Background and aims: Baveno VI and Expanded-Baveno VI Criteria were validated to rule out high-risk esophageal varices (HRV) and to prevent unneeded endoscopies in compensated advanced chronic liver disease (cACLD) mainly related to viral hepatitis. We aim to assess these criteria to rule out low- and high- risk varices in patients with cACLD secondary to alcoholic liver disease (ALD) and non- alcoholic fatty liver disease (NAFLD). Methods: Data were collected retrospectively from 2016 to 2020. Inclusion criteria were: NAFLD and /or ALD related cACLD, a liver stiffness measurement (LSM) ≥ 10 kPa and an esophagogastroduodenoscopy (EGD) within 12 months. Exclusion criteria were: use of non cardioselective ß-blockers, hepatic decompensation, previous variceal bleeding, portal thrombosis, liver cancer, or liver transplant. Results: One hundred and ninety-four patients were included in this study. Eighty-one patients (42%) met Baveno VI criteria and 103 (53%) met Expanded-Baveno VI criteria. Baveno VI criteria yielded a high negative predictive value (NPV ≥ 95%) for detecting HRV and varices of any size. Expanded-Baveno VI criteria yielded a high NPV ≥ 95% only for detecting HRV: the miss rate for varices of any size was 8%. Expanded-Baveno VI criteria could avoid more endoscopies than the original Baveno VI criteria to rule out HRV (53% versus 42%). Conclusion: In this study, both criteria showed high NPV to rule out HRV but only original Baveno VI criteria yielded a satisfactory high NPV to rule out varices of any size. Expanded-Baveno VI criteria could avoid more endoscopies to exclude HRV.

The changing pattern of cirrhosis in Belgium: a study based on two cohorts prospectively collected 15 years apart.

BACKGROUND AND STUDY AIM: The epidemiology of cirrhosis is evolving over the past decades in Western countries. The aim of this study was to assess the changes in the epidemiology of cirrhosis in our region by comparing two cohorts of patients diagnosed 15 years apart. PATIENTS AND METHODS: From the outpatient's liver clinics of our hospital and from January 1995 to December 2017, we consecutively recorded all patients with cirrhosis. From this registry, the current study compared two cohorts of patients diagnosed 15 years apart. Epidemiologic data and liver-related mortality were compared between both cohorts with a 3 to 8-year follow-up. RESULTS: During a 23-year period, 1151 patients consented to be included in the cirrhosis registry. The current study compared 197 patients with cirrhosis diagnosed from 1995 to 1999 (cohort C1) with 237 patients with cirrhosis diagnosed from 2010 to 2014 (cohort C2). Our results showed that in the cohort C2, compared with the cohort C1, the prevalence of NAFLD-related cirrhosis increased (C1 : 3% vs C2 : 16%, p< 0.0001) while the prevalence of HCV-related cirrhosis decreased (C1 : 22% vs C2 : 10%, p< 0.0001). In the more recent cohort, liver biopsy was less frequently performed (C1 : 65% vs C2 : 20%, p<0.0001). An intriguing finding was the increasing age at cirrhosis diagnosis for patients with alcohol-related cirrhosis (C1 : 52±11 years vs C2 : 57±10 years, p<0.0001). CONCLUSIONS: The epidemiology of cirrhosis has changed over time. Effective prevention strategies are needed to reduce the burden of liver disease.

A 2-log drop in viral load at 1 month is the best predictor of sustained response in HCV patients with normal ALT: a kinetic prospective study.

The most reliable predictor of a sustained virological response in patients with persistently normal ALT has not been identified. We analysed 17 patients with genotype 1 chronic HCV who underwent therapy with pegylated interferon alfa 2b and ribavirin for 48 weeks. Two patients discontinued therapy within 28 days because of side effects and the remaining 15 patients were analysed in detail. An analysis of on treatment virological response using area under the receiver operating characteristic analyses showed that a 2 log drop in HCV RNA at day 28 was the best predictor of a sustained virological response and a failure to reduce viral load by 2 logs correctly identified patients with a low (<15%) probability of achieving a sustained virological response. Introduction of this early discontinuation rule in patients with normal ALT would allow nearly half of the patients to discontinue futile therapy at an early stage.

Upper gastrointestinal bleeding: what has changed during the last 20 years?

AIM OF THE STUDY: The purpose of this study was to assess the clinical, epidemiological, therapeutic and prognostic changes observed in patients with upper gastrointestinal bleeding (UGIB) during the last two decades. METHODS: Two cohorts of 200 patients with UGIB consecutively recruited during the period 1984-1987 (cohort A) then during the period 2004-2006 (cohort B) were compared. RESULTS: Median age was 61.5 years in the cohort A and 67 years in the cohort B. The main etiologies remained variceal bleeding and peptic ulcer, but esophagitis and Mallory-Weiss syndrome were more frequently observed recently. The intake of gastrotoxic drugs did not decreased despite the widely acknowledged harmful effects of these drugs. Regarding management practices, a therapeutic intervention during the first endoscopy was performed in 36% of the cases in the cohort B but only in 2% of the cases 20 years ago. The frequency and the volume of blood transfusion dramatically decreased during the last two decades. Regarding the outcome, the requirement for surgery and the rate of recurrent bleeding decreased by half, but mortality remained unchanged. CONCLUSION: The main changes observed in patients admitted for UGIB 20 years apart concerned epidemiological features, treatment and prognosis.

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.

Epidemiology of chronic hepatitis B infection in France: risk factors for significant fibrosis--results of a nationwide survey.

BACKGROUND: Epidemiological data concerning hepatitis B are scarce in France. AIM: To describe epidemiological, clinical, virological and histological features of HBsAg-positive patients followed at non-academic hospitals in France. METHODS: Clinical, biological, virological and histological data of all HBsAg-positive consecutive patients observed from April 1, 2001 to May 31, 2002 in participating centres were recorded prospectively. Multivariate analyses of factors associated with significant fibrosis and cirrhosis were performed. RESULTS: Nearly 1166 HBsAg-positive patients were seen in the 58 centres: 671 males and 495 females from metropolitan France (32%) and from outside metropolitan France (68%); mean age 41 +/- 15 years. Twenty-nine percent of patients were probable HBsAg inactive carriers, while 50% had chronic hepatitis; 43% of these were HBeAg-positive and 57% HBeAg-negative. Liver biopsy had been performed in 558 (51%) patients; 205 (17.6%) patients had cirrhosis. By multivariate analysis, factors associated with significant fibrosis were: age >40 years (P < 0.05), HBeAg-negative status (P < 0.02) and histological activity (P < 0.0001). Factors associated with cirrhosis: age (P < 0.0001), platelet count <150 000/mm(3) (P < 0.0001) and viral co-infection (P < 0.03). CONCLUSION: HBV infection represents a significant workload for hepatogastroenterologists at non-academic hospitals in France.

Review article: the treatment of non-alcoholic steatohepatitis with thiazolidinediones.

It is generally accepted that non-alcoholic fatty liver disease will be the most frequent liver disease in the near future and that the management of patients with non-alcoholic fatty liver disease will be a challenge for hepatologists in the next decades. Non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome, in which insulin resistance plays a crucial role. Although steatosis will often not progress to severe liver disease, in some patients, it results in cirrhosis and even hepatocellular carcinoma. Therefore, it is important to identify those patients at risk for developing fibrosis. Age, diabetes, obesity and hypertriglyceridaemia are independent risk factors for fibrosis in patients with elevated serum alanine aminotransferase levels and steatosis on ultrasound. The presence of multiple metabolic disorders increases the risk. Apart from diet, exercise and correction of underlying metabolic abnormalities, no specific treatment is available at the moment. Theoretically, thiazolidinediones are an attractive way to treat non-alcoholic fatty liver disease, because they improve insulin resistance. Some preliminary studies with thiazolidinediones were encouraging, as steatosis, inflammation and fibrosis improved in a substantial number of patients. Although no serious side effects occurred in the pilot studies, we should look vigilantly for hepatotoxicity, as the first generation thiazolidinediones proved to be toxic for the liver.

[Primary linitis plastica of the rectum and colon. Report of a case and review of the literature]. / Linite plastique primitive du rectum et du côlon. Rapport d'un cas et revue de la littérature.

We report a new case of primary linitis plastica of the rectum in a 32-year-old man. The diagnosis was made two months after the onset of clinical symptoms. Computerized tomography was helpful in the evaluation of the locoregional extension of the tumour. Despite intensive therapy (i. e. surgery, radiotherapy and chemotherapy) peritoneal carcinomatosis developed and death occurred fifteen months after diagnosis. As it has been emphasized in the literature which was reviewed extensively (less than eighty cases), this report confirms the very poor outcome of this disease.

[Hypoxic hepatitis. Prospective, clinical and hemodynamic study of 45 cases]. / Hépatite hypoxique. Etude prospective, clinique et hémodynamique de 45 épisodes.

The authors report 45 episodes of centrilobular liver cell necrosis, called ischemic hepatitis, in 43 cardiac patients. In 75 percent of the episodes, centrilobular liver cell necrosis was preceded by a period of progressive deterioration of myocardiac function. In 100 percent of the episodes, liver cell necrosis occurred after an acute clinical event inducing a transient fall of cardiac output. Shock was observed in only 47 percent of the episodes. The biological hallmarks of this centrilobular liver cell necrosis were a massive increase in serum aminotransferase levels and in 85 percent of the episodes, a decrease in the prothrombine time below 50 percent of control level. The mortality rate, 15 days after admission, was 42 percent. Prognosis was mainly related to cardiac function. The hemodynamic comparison between the 45 episodes of centrilobular liver cell necrosis and 22 cases of cardiogenic shock without liver cell necrosis showed that, besides hepatic ischemia, passive venous congestion of the liver and arterial hypoxemia were also involved in the onset of liver cell necrosis in these cardiac patients. Among these 45 episodes of liver cell necrosis of cardiac origin, a unique case of hepatic necrosis secondary to major hypoxemia and passive venous congestion, despite an high cardiac output was observed and is reported in detail. Accordingly, the appellation "hypoxic hepatitis" seems to be more appropriate than "ischemic hepatitis".

[Fulminant or sub-fulminant hepatocellular failure caused by metastatic invasiveness of the liver: an other cause of hypoxic hepatitis?]. / Insuffisance hépatocellulaire fulminante ou subfulminante secondaire à une infiltration métastatique du foie: une autre cause d'hépatite hypoxique?

OBJECTIVES: The purpose of this retrospective study was to report a series of 9 new cases of fulminant hepatic failure due to metastatic liver disease and to identify signs to support a theory of hypoxia. METHODS: In these 9 cases and in 38 previously published cases of fulminant or subfulminant liver failure, we looked for clinical (shock, sepsis, and cutaneous signs of circulatory failure), laboratory (marked increase in serum aminotransferases levels) and histological (cell necrosis) parameters compatible with liver hypoxia. RESULTS: Cutaneous signs of circulatory failure or shock were observed in 3 of the 9 cases in this study, and were not due to cardiogenic or septic shock. A marked increase in serum aminotransferases levels, 10 times above the upper limit of normal, was observed in 8 of the 9 cases in the present study and in 23 of 37 cases of the literature. Liver cell necrosis was observed in 6 of the 7 autopsied patients in this series and in 20 of 34 cases in the literature. Generally, liver cell necrosis was more severe than tumor cell necrosis and was related to the degree of sinusoidal involvement by tumoral cells. In one case, hepatic blood flow was decreased despite a high level of cardiac blood flow suggesting impairment of circulation in the liver. CONCLUSIONS: These 9 cases and a review of the literature support the hypothesis of hypoxic liver cell necrosis leading to acute liver failure in cases of metastatic liver disease. However, liver hypoxia cannot explain all the reported cases and was never due to circulatory failure from cardiac or septic causes, but to the sinusoidal involvement by tumor cells.

[lymphocytic colitis associated with lansoprazole treatment]. / Colite lymphocytaire associée à la prise de lansoprazole.

We report two cases of lymphocytic colitis with severe diarrhea in patients treated by lansoprazole for six weeks. Complete remission occurred rapidly after lansoprazole withdrawal.

Hepatocellular carcinoma associated with precocious puberty and oral contraceptives. A case report.

A 36-year-old woman presented with sudden abdominal pain and vomiting. Computed tomography showed a tumour of the right hepatic lobe with possible signs of acute haemorrhage. Her medical history revealed precocious puberty when she was a 5-year-old and the use of oral contraceptives for 18 years. Bisegmentectomy was performed and histological examination revealed hepatocellular carcinoma. The role of male and female sex hormones in the development of hepatic tumours has been well documented but, to our knowledge, association with precocious puberty has not yet been described.

[Unexplained fever or inflammatory syndrome. Diagnostic value of liver puncture-biopsy]. / Fièvre ou syndrome inflammatoire inexpliqués. Intérêt diagnostique de la ponction-biopsie hépatique.

The value of transcutaneous biopsy of the liver was assessed in a series of 110 cases of fever of unknown origin or of unexplained inflammatory syndrome. Liver histology was useful to the ultimate etiological diagnosis in 12 cases (11 per cent). The result of a transcutaneous biopsy of the liver was considered an essential aid to the ultimate diagnosis in 7 of these 12 cases. A hepatic lesion regarded as useless for the ultimate diagnosis was present in 16 cases (14.5 per cent). In the other cases, hepatic histology was normal or showed a non-specific reactive hepatitis. Unicteric cholestasis was present in 73 per cent of the cases but was of no predictive value for the detection of a useful hepatic lesion. On the other hand, serum transaminase levels were significantly higher when a useful lesion of the liver was observed.

[Lipoprotein (a) in liver diseases. Correlation between low levels and liver function]. / La lipoprotéine(a) dans les hépatopathies. Corrélation entre sa diminution et l'état fonctionnel du foie.

OBJECTIVES: To analyze the role of the liver function on the serum levels of lipoprotein(a) (Lp(a)), a lipoprotein considered to be a risk factor for atherosclerosis. METHODS: To measure the Lp(a) levels in patients with liver disease (n = 68) due to various causes and in patients with no liver disease and of similar age and sex-ratio (n = 62) and to analyze the relationship between Lp(a) levels on one hand and liver function and lipid and apoprotein levels on the other hand. RESULTS: Patients with liver disease had significantly lower levels of Lp(a). Lp(a) levels were significantly lower in patients with more severe liver disease (Child Turcotte classification) and significantly correlated with liver function tests, in particular those related to the microsomal function and the synthetic capacity of the liver (albumin, coagulation tests, apoprotein A-II). In patients with liver disease, mean Lp(a) levels were not significantly different between those with and those without chronic alcohol intake. CONCLUSIONS: Patients with liver disease have low levels of Lp(a) that are related to reduced synthetic capacity of this organ and are not linked to a specific cause of liver disease, in particular excess alcohol intake.

[The problem of abortion. Viewpoint of the general practitioner]. / Le problème de l'avortement. Le point de vue d'un omnipraticien

PIP: The author, a general practitioner, describes the development of practices and attitudes toward abortion in Belgium. The laws prohibiting abortion are ineffective and counterproductive: formerly, they prompted the use of dangerous methods, with serious or fatal complications; presently, they are circumvented by having abortions performed abroad, where they are legal. It is concluded that physicians should be permitted to follow their own conscience, without being forced to perform abortions whenever requested by patients, but authorized to perform them when it is obvious that there is a high risk of malformation or congenital disease, or that the child would be unwanted, abandoned, or psychologically refused by the parents.^ieng