Studies in portal hypertension

Our work focussed on one of the most frequent and serious complications of portal hypertension i.e. variceal bleeding. In particular, studies were initiated aimed at developing a more effective therapeutic strategy for the primary and secondary prevention of variceal bleeding. Aspects of primary prevention of variceal bleeding are discussed in Chapters 2, 3 and 4. Primary prevention implies the need to identify patients at risk. Chapter 2 discusses the feasibility of a simple radiological method to detect oesphageal varices and addresses the reliability of this approach in comparison with the more usual endoscopic diagnostic method. The majority of patients with oesphageal varices will remain free of bleeding. On the other hand, in a proportion of patients variceal haemorrhage will be a fatal event. Therefore, identification of risk factors for variceal bleeding is of paramount importance, in particular with respect to selecting patients for prophylactic therapy. In chapter 3 we report a study assessing the reliability of the NIEC risk score system and report on attempts to further improve its prognostic reliability. Chapter 4 reports the results of a multicentre randomized controlled trial assessing sclerotherapy as prophylaxis for first variceal bleeding. Variceal bleeding is a medical emergency associated with significant morbidity and mortality. In patients with active bleeding one of the medical priorities and challenges is to arrest bleeding. The results of a study on the use of thrombin as an endoscopic haemostatic agent are reported in chapter 5. A number of treatments have been proposed for the secondary prevention of variceal bleeding. Relative new therapeutic options are TIPS and endoscopic band ligation. In chapter 6 we report the results of a randomized controlled clinical trial comparing these treatment modalities, and discuss our results in the context of the cumulative results of comparable studies

Anthranoid self-medication causing rapid development of melanosis coli

It is widely known that long-term use of anthranoid-containing laxatives is the cause of melanosis coli. We describe a case of melanosis coli, which occurred in a 39-year-old liver transplant patient who took an over-the-counter product containing aloe, rheum and frangula. The typical brownish pigmentation of the colonic mucosa developed in a period of ten months. The anthranoid medication was stopped and follow-up colonoscopy one year later showed normal looking mucosa once more. However, in contrast to previous examinations, a sessile polypoid lesion was found in the transverse colon. Histology showed tubulovillous adenoma with extensive low-grade dysplasia. Since there have been preliminary reports suggesting a possible role of anthranoid-containing laxatives in the development of colorectal adenomas and cancer, their use should be discouraged

A randomised study on the efficacy and safety of an automated Tru-Cut needle for percutaneous liver biopsy

BACKGROUND: We studied whether the theoretical advantages of a spring-loaded liver biopsy needle exist in clinical practice and if so if they are dependent upon the experience of the physician performing the biopsy. METHODS: In a stratified randomised study we enrolled 215 consecutive patients to compare the safety and efficacy of a new automatic biopsy gun (Acecut) with that of a standard Tru-Cut needle. RESULTS: A total of 464 biopsies were performed. The endpoints of the study were number of needle passes needed per patient, tissue yield of each needle pass and post-biopsy complications. The performance of the automatic needle was superior and more consistent with respect to tissue yield compared with the Tru-Cut needle (median yield 100% and 80%, respectively; p < 0.001). The difference was most marked for inexperienced physicians. There was no difference between the two needles in the number of passes needed. More post-biopsy pain and post-biopsy use of analgesics were observed in the automatic needle group (p = 0.04). CONCLUSION: The automatic Tru-Cut needle offers an advantage, particularly for physicians with no or limited experience in liver biopsies. However more post-biopsy pain and post-biopsy use of analgesics were observed in the automatic needle group

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt (TIPS)

We reported the case of a patient in whom severe, and ultimately fatal, pulmonary hypertension developed 1.5 yrs after transjugular intrahepatic portosystemic shunt (TIPS). Pulmonary artery pressures were not affected by 100% oxygen, prostacyclin or nifedipine. Postmortem examinations showed pulmonary and vascular abnormalities typical of pulmonary hypertension. Pulmonary artery pressures should be measured in each patient with otherwise not readily explained dyspnoea following transjugular intrahepatic portosystemic shunt

A pilot study exploring the role of glucocorticoid receptor variants in primary biliary cirrhosis and primary sclerosing cholangitis

BACKGROUND: In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) significant therapeutic effects of glucocorticoids have not been documented. The most important clinical problem in patients with these diseases is fatigue, which is occasionally invalidating. Abnormalities in the hypothalamo-pituitary-adrenal axis have been suggested as a cause of fatigue. Most effects of glucocorticoids are mediated by the glucocorticoid receptor (hGR alpha). Recently a causative role for a splicing variant of the glucocorticoid receptor (hGR beta) has been proposed in glucocorticoid resistance in asthma and ulcerative colitis, whereas another splicing variant (hGR P) might be associated with glucocorticoid-resistant haematological malignancies. The aims of the present pilot study were to assess abnormalities in glucocorticoid receptor expression and to relate these abnormalities to the development of fatigue and to disease activity and severity in autoimmune cholestatic liver disease. METHODS: Five fatigued and five nonfatigued patients with PBC or PSC were included, and the results were compared with healthy controls. RESULTS: The expression of hGR P was not different from controls, but hGR beta mRNA was significantly increased (p=0.02) and hGR alpha mRNA decreased (p=0.015). There were no significant differences between fatigued and nonfatigued patients. A significant negative correlation between the serum activity of alkaline phosphatase and hGR alpha and hGR P mRNA was found. CONCLUSION: Although there was no relation with fatigue, abnormalities in hGR expression appear to occur in patients with these diseases, and may play a role in its pathophysiology and the poor response to glucocorticoid treatment

Oral naltrexone treatment for cholestatic pruritus: A double-blind, placebo-controlled study

Background and Aims: The efficacy of currently available therapeutic agents for cholestatic pruritus is often disappointing. The aim of this study was to assess the antipruritic effect of naltrexone, an oral opiate receptor antagonist. Methods: Sixteen patients with pruritus of chronic cholestasis were randomized to receive naltrexone (4-week course of 50 mg naltrexone daily) or placebo. Pruritus, quality of sleep, fatigue (using visual analogue scales), side effects, and liver function were assessed every 2 weeks. Serum naltrexone and 6β-naltrexol concentrations in all patients and 5 healthy controls were measured during the first day of naltrexone treatment. Results: Mean changes with respect to baseline were significantly different, in favor of the naltrexone group, for daytime itching (-54% vs. 8%; P = 0.001) and nighttime itching (-44% vs. 7%, P = 0.003). In 4 naltrexone-treated patients, side effects (transient in 3 cases) consistent with an opiate withdrawal syndrome were noted. No deterioration of the underlying disease was observed. Naltrexone and 6β-naltrexol levels did not differ between patients and controls, and there was no significant association with treatment response. Conclusions: For patients with cholestatic liver disease and itching, refractory to regular antipruritic therapy, oral naltrexone may be an effective and well-tolerated alternative

Microbiology and antibiotic susceptibility patterns in spontaneous bacterial peritonitis: A study of two Dutch cohorts at a 10-year interval

Background: Recent investigations suggest an increasing prevalence of Gram-positive and antibiotic-resistant bacteria causing spontaneous bacterial peritonitis (SBP), probably related to changes in antibiotic prescription patterns, in particular more widespread and long-term use of antibiotic prophylaxis with quinolones. Objective: The primary objective of this study was to assess potential changes in the microbiology of SBP in two patient cohorts studied at a 10-year interval. Further aims were to study prognostic factors and outcome of SBP. Methods: A retrospective double-cohort study, including all ascitic cultures from patients with cirrhosis obtained 2003–2005 and 2013–2014, was conducted. Results: In total 312 patients were included, 125 patients in the first and 187 patients in the second cohort. SBP was diagnosed in 132 of 840 analyzed ascitic fluid samples; 62 samples were culture positive. An increase of Gram-positive bacterial isolates was noted from 26% to 46% between cohorts (p = 0.122). The prevalence of multidrug-antibiotic–resistant pathogens increased from 25% to 32% (p = 0.350). Survival after SBP among the two cohorts was comparable. Conclusion: This single-center study in the Netherlands found a modest but nonsignificant increase in the proportion of patients with SBP caused by Gram-positive bacteria and multidrug-antibiotic–resistant bacteria over a 10-year period. Our findings differ from reported data in other countries and suggest empiric antibiotic prophylaxis and treatment of SBP should be based on national and regional microbiological findings and resistance patterns

The efficacy and safety of rifaximin-α: a 2-year observational study of overt hepatic encephalopathy

Background: After 5 years since the registration of rifaximin-α as a secondary prophylaxis for overt hepatic encephalopathy (HE) in the Netherlands, we aimed to evaluate the use of hospital resources and safety of rifaximin-α treatment in a real-world setting. Methods: We carried out prospective identification of all patients using rifaximin-α for overt HE. We assessed hospital resource use, bacterial infections, and adverse events during 6-month episodes before and after rifaximin-α initiation. Results: During 26 months we included 127 patients [71.7% male; median age 60.8 years (interquartile range: 56.2–66.1); median model for end-stage liver disease (MELD) score 15.0 (interq