Questionnaire PLD-complaint-specific assessment identifies need for therapy in polycystic liver disease: A multi-centric prospective study.

BACKGROUND AND AIMS: Polycystic liver disease (PLD) can lead to extensive hepatomegaly. Symptom relief is the primary goal of the treatment. The role of the recently developed disease-specific questionnaires for identification of the thresholds and the assessment of therapy needs further investigation. METHODS: A five-year prospective multi-centric observational study in 21 hospitals in Belgium gathered a study population of 198 symptomatic PLD-patients of whom the disease-specific symptom questionnaire PLD-complaint-specific assessment (POLCA) scores were calculated. The thresholds of the POLCA score for the need for volume reduction therapy were analyzed. RESULTS: The study group consisted of mostly (82.8%) women with baseline mean age of 54.4 years ±11.2, median liver volume expressed as height-adjusted total liver volume(htLV) of 1994 mL (interquartile range [IQR] 1275; 3150) and median growth of the liver of +74 mL/year (IQR +3; +230). Volume reduction therapy was needed in 71 patients (35.9%). A POLCA severity score (SPI) ≥ 14 predicted the need for therapy both in the derivation (n = 63) and the validation cohort (n = 126). The thresholds to start somatostatin analogues (n = 55) or to consider liver transplantation (n = 18) were SPI scores of ≥14 and ≥ 18 and the corresponding mean htLVs were 2902 mL (IQR 1908; 3964) and 3607 mL (IQR 2901; 4337), respectively. Somatostatin analogues treatment resulted in a decrease in the SPI score -6.0 versus + 4.5 in patients without somatostatin analogues (p < 0.01). Changes in the SPI score were significantly different between the liver transplantation group and no liver transplantation group, +4.3 ± 7.1 versus -1.6 ± 4.9, respectively, (p < 0.01). CONCLUSION: A polycystic liver disease-specific questionnaire can be used as a guide on when to start a volume reduction therapy and to assess the effect of treatment.

Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018.

BACKGROUND & AIMS: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes. METHODS: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using standardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies. RESULTS: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected individuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hospitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). CONCLUSIONS: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors. CLINICAL TRIAL REGISTRATION: The protocol was submitted to clinicaltrials.gov (NCT04670419). IMPACT AND IMPLICATIONS: HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.

Acute upper gastrointestinal bleeding in cirrhosis: changes and advances over the past two decades.

BACKGROUND AND AIMS: Few studies have compared two or more cohorts of cirrhotic patients admitted for upper gastrointestinal bleeding (UGIB) several decades apart. Our aim was to compare epidemiological, clinical, therapeutic and prognostic characteristics of UGIB (whatever the source) in two cohorts of cirrhotic patients admitted to the emergency room of the same general hospital 2 decades apart. METHODS: One-hundred cases of UGIB in cirrhotic patients consecutively admitted between 1984 and 1990 (cohort A) were compared with 100 similar cases admitted between 2004 and 2009 (cohort B). RESULTS: The sex ratio (M/F: 2/1), mean age (approximately 55Y) and the proportion of patients with alcoholic cirrhosis (approximately 80%) did not change. Mean Child-Pugh score and the proportion of patients in Child-Pugh stage C increased from 7.6 and 19% in cohort A to 8.8 and 35% in cohort B (p < 0.001). Therapeutic intervention was performed during initial endoscopy in 13 cases from cohort A and 50 from cohort B (p < 0.001), respectively. The number of transfused patients (85 in cohort A, 58 in cohort B) and the number of red blood cell units administered on the first day (median: 4 in cohort A, 2 in cohort B) were significantly decreased in cohort B (p < 0.001). The rate of rebleeding (45 in cohort A, 11 in cohort B), the need for rescue surgery (8 in cohort A, 0 in cohort B) and the in-hospital mortality (24 in cohort A, 9 in cohort B) significantly decreased in the more recent cohort (p < 0.005). CONCLUSION: This study demonstrated that several characteristics of cirrhotic patients admitted with UGIB have changed over the past 2 decades. Above all, outcome has improved despite an increase in the severity of cirrhosis.

IL28B polymorphism and the control of hepatitis C virus infection: ready for clinical use?

Polymorphisms in the region of the interleukin-28B (IL28B) gene have recently been associated with spontaneous and treatment induced clearance of hepatitis C virus infection. The specific mechanisms of how IL28B polymorphisms affect HCV suppression remain unknown. It is a matter of ongoing debate how to incorporate the IL28B data into the current treatment algorithms with pegylated interferon-alpha and ribavirin. The eventual role of the IL28B genotype in new therapeutic regimes with direct antiviral agents needs to be explored in the ongoing and future clinical studies with these agents.

Acute lower limb ischemia as a triggering condition in hypoxic hepatitis: a study of five cases.

BACKGROUND/AIM: Acute centrilobular liver cell necrosis in hypoxic hepatitis (HH) occurs mainly in the setting of hemodynamic failure owing to cardiac failure, respiratory failure, and septic-toxic shock. Cases of HH were also reported under specific conditions such as heat stroke, grand mal seizure, obstructive sleep apnea, and complicated aortic aneurysm. In this study, we report 5 cases of HH occurring in the course of acute lower limb ischemia (ALLI). To the best of our knowledge, the association between HH and ALLI has not yet been reported. METHODS: In a prospective and consecutive series of 142 cases of HH, we identified 5 cases (3.5%) in which ALLI was the triggering condition. The clinical, hemodynamic, and liver laboratory data of these 5 cases are reported. A review of the literature on liver injury observed in the case of ALLI is also made. RESULTS: The 5 patients were 4 males and 1 female of mean age 63 years. All 5 had typical HH after ALLI. Four of them were in shock on admission. Arterial blood pH lower than 7.15 was observed upon admission in the 3 patients who died. Other potential causes of liver hypoxia were present in all patients. Urgent and efficient revascularization of the ischemic limb was a necessary condition for survival. CONCLUSIONS: Acute lower limb ischemia should be added to the list of conditions able to trigger HH. In this particular setting, urgent revascularization of the ischemic limb seems to be a prerequisite for survival.

Large spectrum of liver vascular lesions including high prevalence of focal nodular hyperplasia in patients with hereditary haemorrhagic telangiectasia: the Belgian Registry based on 30 patients.

OBJECTIVES: We report the Belgian Registry of 30 patients (19 women and 11 men) with hereditary haemorrhagic telangiectasia (HHT) and liver involvement. RESULTS: Twenty-three patients (77%) were asymptomatic. Within the seven symptomatic patients (23%), four suffered from high output cardiac failure, two died before liver transplantation and one was transplanted. Three patients developed symptomatic biliary disease, two were transplanted and one was listed. Intrahepatic shunts and a large hepatic artery (6-14 mm, mean: 9.3 mm) were found in all patients and are characteristic of liver involvement. We observed a high prevalence (47%) of asymptomatic hepatic tumours with radiological and histological characteristics of focal nodular hyperplasia (FNH) for the majority of these tumours. The histological examination of the three explanted livers revealed the coexistence of a large spectrum of hepatic vascular lesions including intrahepatic shunts, FNH, nodular regenerative hyperplasia, sinusoidal dilatation and ischaemic cholangiopathy. All these lesions should be diagnosed early to avoid invasive procedures even if a liver biopsy was performed in six of our patients without complications. The liver biopsy led to the diagnosis of HHT in one patient and to FNH in another one. CONCLUSION: Liver involvement in HHT is characterized by a high prevalence of FNH and a large spectrum of vascular lesions such as intrahepatic shunts, nodular regenerative hyperplasia, sinusoidal dilatation and ischaemic cholangiopathy that may coexist simultaneously in the same patient.

Evaluation of amantadine in chronic hepatitis C: a meta-analysis.

BACKGROUND/AIMS: The benefit of amantadine combination therapy, either with interferon (IFN) alone (double therapy) or with ribavirin and IFN (triple therapy) is unknown. METHODS: We analyzed the effect of amantadine on the end-of-treatment virological response and the sustained response using meta-analysis of 31 randomized controlled trials. RESULTS: Overall analysis revealed a significant effect of amantadine. Triple therapy was the best regimen for improving the sustained response (mean difference: 8.4%, 95% CI: 2.4-13.8%, P=0.002). In subgroup analysis, amantadine did not have a significant effect upon naive patients or relapsers. In non-responders, combination therapy with amantadine was associated with a significant effect on the sustained response (mean difference: 8.3%, 95% CI: 1.9-14.6%, P=0.01). In sensitivity analysis, double therapy did not improve virological responses. Conversely, triple therapy tended to improve the end-of-treatment virological response and was associated with a significant effect upon the sustained response (mean difference: 12.7%, 95% CI: 3.8-21.6%, P=0.005). CONCLUSIONS: Combination therapy with amantadine is of no effect upon naive patients or relapsers. In non-responders, triple therapy with amantadine improved the sustained response. New randomized controlled trials are required to confirm this meta-analysis.

[Screening for hepatocarcinoma in a cohort with cirrhosis mainly of alcoholic origin]. / Dépistage du carcinome hépatocellulaire dans une cohorte de malades porteurs d'une cirrhose d'origine principalement alcoolique.

OBJECTIVES: To assess the feasibility and efficiency of the screening for hepatocarcinoma in a cohort of cirrhoseis mainly of alcoholic origin. PATIENTS AND METHODS: 293 patients with cirrhosis, among them 186 (63.5%) from alcoholic origin, were included in a surveillance programme for hepatocarcinoma by carrying out liver ultrasonography and alpha-foetoprotein dosage every 6 months. Results were analyzed with a mean follow-up of 60 months. Seventeen hepatocarcinoma discovered through the surveillance programme ("screened HCC") were compared with 40 hepatocarcinoma discovered outside the surveillance programme during the same period ("incidental HCC"). RESULTS: The alcoholic origin of the cirrhosis was a predictive factor of poor compliance to the surveillance programme. Among the 186 patients with alcoholic cirrhosis, 129 (69%) were lost during the surveillance programme due to lack of compliance (97 cases) or death (32 cases). By comparison, among the 65 patients with hepatitis C-related cirrhosis, 18 were lost by lack of compliance (11 cases) or death (7 cases) (P<0.001). Moreover, sustained or relapsing alcohol abuse after inclusion in the surveillance programme were also related to the quality of the compliance. Seventeen hepatocarcinoma were discovered through the surveillance giving an annual incidence of 2% for the emergence of hepatocarcinoma. The comparison between screened (n=17) and incidental (n=40) hepatocarcinoma showed that screened HCC were more often asymptomatic (P<0.01), were more often a solitary nodule less than 5 cms (P<0.001) and underwent more often curative treatment (P=0.02). However, the survival between screened and incidental hepatocarcinoma was not different. CONCLUSIONS: Screening for hepatocarcinoma in patients with alcoholic cirrhosis is a difficult task due to poor compliance and early death. According to our results, a surveillance every 6 months is sufficient to detect early lesions accessible to curative treatment by surgical resection or transcutaneous ablation.