Hepatitis E: a largely underestimated, emerging threat.

Hepatitis E virus has two distinct clinical and epidemiological patterns based on the varying genotypes. Genotypes 3 and 4 cause widespread, sporadic infection in high-income countries and are emerging as the most common type of viral hepatitis in much of Europe. These infections carry significant morbidity and mortality in the growing numbers of immunosuppressed patients or in patients with established liver disease. Furthermore the growing extra-hepatic associations of the virus, including neurological and kidney injury, suggest that it may have been misnamed as a 'hepatitis' virus. This review explores current understanding of the epidemiology, virology and clinical presentations of hepatitis E infection and identifies vulnerable patient groups, who are at serious risk from infection. Guidance is offered regarding the diagnosis, treatment and prevention of this growing public health hazard.

Case report: Thromboembolic and septic complications of migrated cyanoacrylate injected for bleeding gastric varices.

Endoscopic injection of N-butyl-2-cyanoacrylate combined with radio-opaque lipiodol is widely used to achieve haemostasis in bleeding gastric varices. We present a case of migration of injected cyanoacrylate, thrombus formation and subsequent septic embolisation.

The role of hepatitis E virus testing in drug-induced liver injury.

BACKGROUND: Locally acquired hepatitis E is an emerging infection in developed countries and can be misdiagnosed as drug-induced liver injury. AIM: To study the role of hepatitis E virus (HEV) testing in drug-induced liver injury. METHODS: Retrospective review of a cohort of patients with suspected drug-induced liver injury (n = 69) and hepatitis E (n = 45). The standard criteria for drug-induced liver injury were applied. Patients with suspected drug-induced liver injury who met these criteria were retrospectively tested for HEV on stored sera taken at the time of presentation. The two cohorts were compared to determine variables that predicted either of the diagnoses. RESULTS: Forty-seven out of 69 patients had criterion-referenced drug-induced liver injury. 22/47 were HEV negative and thus had confirmed drug-induced liver injury. 19/47 were not tested for HEV, as there was no sera available from the time of presentation. 6/47 were HEV positive and thus did not have drug-induced liver injury, but had hepatitis E infection. Compared to patients with confirmed drug-induced liver injury, patients with hepatitis E were significantly more likely to be male (OR 3.09, CI 1.05-9.08); less likely to present in November and December (0.03, CI 0.01-0.52); have lower serum bilirubin (P = 0.015); and higher serum alanine aminotransferase (P < 0.001) and alanine aminotransferase/alkaline phosphatase ratio (P < 0.001). CONCLUSION: The diagnosis of drug-induced liver injury is not secure without testing for HEV.

Jaundice as a presentation of heart failure.

On rare occasions the first manifestation of heart disease is jaundice, caused by passive congestion of the liver or acute ischaemic hepatitis. We looked for this presentation retrospectively in 661 patients referred over fifty-six months to a 'jaundice hotline' (rapid access) service. The protocol included a full clinical history, examination and abdominal ultrasound. Those with no evidence of biliary obstruction had a non-invasive liver screen for parenchymal liver disease and those with suspected heart disease had an electrocardiogram, chest X-ray and echocardiogram. 8 patients (1.2%), bilirubin 31-79 micromol/L, mean 46 micromol/L, had a primary cardiac cause for their jaundice. All had dyspnoea, an increased cardiothoracic ratio on chest X-ray and an abnormal electrocardiogram. The jugular venous pressure was raised in the 3 in whom it was recorded. In 6 patients the jaundice was attributed to hepatic congestion and in 2 to ischaemic hepatitis. All patients had severe cardiac dysfunction. Jaundice due to heart disease tends to be mild, and a key feature is breathlessness. The most common mechanism is hepatic venous congestion; ischaemic hepatitis is suggested by a high aminotransferase.

Octreotide increases the proportions of arachidonic acid-rich phospholipids in gall-bladder bile.

BACKGROUND AND AIMS: Octreotide treatment of acromegalic patients induces cholesterol gallstone formation, in part by impairing cholecystokinin release and gall-bladder contraction. However, there are few data on the effect of octreotide on biliary arachidonic acid-rich phospholipids or mucin glycoprotein, factors which also influence cholesterol gallstone formation. METHODS: In acromegalic patients studied before and during 3 months of octreotide treatment, we measured mucin glycoprotein concentrations and the molecular species of phosphatidylcholine, and related the results to the cholesterol saturation and percentage of deoxycholic acid in gall-bladder bile. RESULTS: The relative proportions of the major arachidonic acid-rich phosphatidylcholine species, PC 16:0-20:4 and PC 18:0-20:4, increased significantly during octreotide treatment. These changes were associated with a rise in the cholesterol saturation index and a non-significant twofold increase in mucin glycoprotein concentration. There were significant correlations between PC 16:0-20:4 and the cholesterol saturation index, percentage of vesicular cholesterol and percentage of deoxycholic acid in gall-bladder bile. CONCLUSIONS: In acromegalic patients, octreotide increases the proportions of arachidonic acid-rich phospholipids, with associated rises in: (a) the cholesterol saturation index and percentage of vesicular cholesterol, and (b) the percentage of deoxycholic acid in gall-bladder bile-changes similar to those found in patients with cholesterol-rich gall-bladder stones.

Clearance of barium from the oesophagus with diet cola and metoclopramide: a one stop approach to patients with dysphagia.

AIM: To establish a "one-stop" dysphagia service in which a consultation, barium swallow and endoscopy can all be performed in the same hospital visit. MATERIALS AND METHODS: In order to allow both barium swallow examination and endoscopy to be performed on the same day, a novel technique for clearing barium from the upper gastrointestinal tract was established. Following the barium swallow examination, patients were given diet cola and metoclopramide syrup. If appropriate, an upper gastrointestinal endoscopy was then performed shortly afterwards. The service was piloted for 6 months in which time 25 patients were investigated in this way. RESULTS: All patients were seen within 2 weeks of referral. The mean time between barium swallow and endoscopy was 3 h 38 min (range, 1 h 50 min to 5 h 20 min). In all 24 patients in whom an endoscopy was performed, barium had been satisfactorily cleared from the oesophagus and stomach. CONCLUSION: This technique allows both barium swallow and upper gastrointestinal endoscopy to be performed on the same day, providing a rapid, safe and accurate diagnosis with minimum patient inconvenience. Mitchell, J., (2001). Clinical Radiology56, 64-66

The predictive value of transabdominal ultrasonography in the diagnosis of biliary tract complications after orthotopic liver transplantation.

BACKGROUND: In transplant recipients with choledococholedocostomy (CDCD), endoscopic retrograde cholangiopancreatography (ERCP) remains the gold standard for the diagnosis of biliary leak or strictures. Transabdominal ultrasonography (TAUS) has been used to screen patients with suspected biliary tract complications, prior to ERCP, although the clinical effectiveness remains unclear. AIMS: To assess the predictive value of TAUS in the diagnosis of biliary tract complications after liver transplantation. METHODS: 144 consecutive ERCP and corresponding ultrasonogram reports performed over a 67 month period in 79 patients after liver transplantation were analysed retrospectively. RESULTS: 77 ERCP patients had both a TAUS and a successful ERCP. Biliary tract abnormalities were found at TAUS in 49 (64%) of the 77 patients. TAUS had an overall sensitivity of 77%, and specificity of 67%, with positive and negative predictive values of 26% and 95% respectively, when adjusted for the prevalence rate of biliary complications after liver transplantation of 12.8% in our population. The use of bile duct calibre as sole criterion for an abnormal scan improved the specificity (76%) and with a corresponding reduction in sensitivity (66%). The risk of false negative TAUS was similar in both the early and late post-transplant periods. CONCLUSIONS: A normal TAUS after liver transplantation with CDCD makes the presence of biliary complications unlikely.

Regional bone mineral density after orthotopic liver transplantation.

OBJECTIVES: Although there is a fall in lumbar spine bone mineral density (BMD) after liver transplantation, little is known about femoral neck or total body BMD. Therefore we determined: (a) the proportion of patients with preexisting hepatic osteopenia before transplantation and (b) the effects of transplantation on global and regional BMD. DESIGN: Retrospective analysis of BMD measurements of patients before and up to 2 years after liver transplantation. METHODS: BMD was assessed by dual energy X-ray absorptiometry in 56 patients, before and at regular intervals after liver transplantation, for up to 24 months, to measure total body, lumbar spine (L2-L4) and femoral neck BMDs. RESULTS: Pre-transplant, 23% of patients had osteoporosis (a negative Z score > 2). Paired data before and after transplantation revealed no change in total body BMD. However, there was a fall in lumbar spine BMD (1.04+/-0.03 to 1.02+/-0.03 g/cm2; P < 0.04) at 1 month after transplantation. The reduction in lumbar spine BMD was seen up to 12 months, BMD at 18-24 months being similar to pre-transplant values. Femoral neck BMD also fell (0.96+/-0.06 to 0.83+/-0.04 g/cm2; P < 0.03), but only after 6-9 months, thereafter remaining below pre-transplant values until the end of the follow-up period. CONCLUSIONS: Although osteopenia is common in patients with liver disease, total bone density does not fall after transplantation. Nonetheless regional lumbar spine and femoral neck bone density does fall after transplantation with a risk period for femoral neck fracture which may extend for up to 2 years.

Dark adaptation in early primary biliary cirrhosis.

BACKGROUND: The role of vitamin A in early primary biliary cirrhosis (PBC) remains uncertain. METHODS: We assessed dark adaptation and assayed vitamin-A-related compounds in 10 patients with early PBC and a group of age- and sex-matched controls. RESULTS: In patients compared with controls: (i) mean final light threshold value was 11.8% greater (p < 0.004), (ii) time taken to see the first light stimulus was longer (2.8 +/- 0.6 vs 1.4 +/- 0.2 min, mean +/- SEM; p < 0.03) and (iii) sensitivity to light stimuli was impaired after 6 min in the dark (p < 0.03). Three patients had an abnormal final light threshold despite receiving regular vitamin A; two had a low serum vitamin A. Raised serum bilirubin and increased age were the most important determinants of impaired dark adaptation. CONCLUSIONS: Patients with early PBC have modestly impaired dark adaptation, despite standard vitamin A supplementation, although these changes may not have a significant effect on visual function. Vitamin A supplementation should be recommended for older patients with jaundice, but its effect should be carefully monitored.

Effects of orthotopic liver transplantation on body composition.

AIMS/BACKGROUND: The effects of orthotopic liver transplantation on body composition are unclear. We aimed to assess changes in body composition after transplantation using dual energy x-ray absorptiometry and total body potassium. METHODS: Dual energy x-ray absorptiometry and total body potassium counting to assess muscle mass were performed in 55 patients before and up to 24 months after liver transplantation and the results expressed as paired data before and at time intervals after transplantation. RESULTS: The results showed that total body weight fell by 3.6 +/- 1.3 kg (p < 0.02) at 1 month, with a maximal fall in lean tissue mass at 2-5 months of 4.8 +/- 1.2 kg (p < 0.003). Thereafter, no change in lean tissue mass was recorded, although there were increases at 12 and 24 months of total body weight (11.5 +/- 2.4 kg, 7.8 +/- 3.1 kg; p < 0.03, respectively) and fat mass (12.9 +/- 2.2 and 10.5 +/- 2.7 kg; p < 0.003). A fall in total body potassium was seen at 1 month (118 +/- 12 mmol; p < 0.003) and 2-5 months (176 +/- 9.9 mmol; p < 0.03), which mirrored the fall in lean mass. CONCLUSIONS: After liver transplantation there is an initial fall in body weight due to a loss of lean mass. Lean mass does not recover after transplantation, although there is an increase in fat mass that leads to the observed increase in total body weight.

Risk factors for loss of lean body mass after liver transplantation.

BACKGROUND: After liver transplantation there is a fall in lean body mass. AIMS: To determine the risk factors for this fall in lean body mass using univariate and subgroup analyses. PATIENTS AND METHODS: Dual energy X-ray absorptiometry was performed in 36 patients (12 with Child-Pugh Class A, 20 with Class B and 4 with Class C disease) before and up to 24 months after liver transplantation. Univariate and sub-group comparative analyses were performed to assess possible risk factors for the fall in lean body mass post-transplantation. RESULTS: The pre-transplantation serum albumin inversely correlated with the fall lean body mass at 1 month (r = 0.55; p < 0.009) and at 6-9 months (r = 0.51; p < 0.05) post-transplantation. A positive correlation between the fall in lean body mass and: (i) cumulative dose of steroids administered at 2-5 months (r = 0.57; p < 0.05) and (ii) length of hospital stay after transplantation (r = 0.52; p < 0.05) were also observed. Neither the severity or presence of cholestatic liver disease pre-transplant, nor acute cellular rejection post-transplant were risk factors for a fall in lean mass. DISCUSSION: A hypercatabolic state post-transplant (represented by low albumin pre-transplantation), immobility, lack of exercise and steroid induced catabolism of muscle may cause the observed fall in lean mass after liver transplantation. Earlier transplantation of patients with better nutritional status and the use of low dose steroid immunosuppressive regimens may prevent the observed fall in lean body mass after transplantation.

Gallstone dissolution with oral bile acid therapy. Importance of pretreatment CT scanning and reasons for nonresponse.

In patients with cholesterol-rich gallbladder stones and a patent cystic duct, complete stone clearance rates of 65-90% have been reported with oral bile acids (OBAs) alone or with adjuvant lithotripsy (extracorporeal shock-wave lithotripsy; ESWL). The aims of the present study were to analyze pretreatment gallstone characteristics that predict the speed and completeness of dissolution with OBAs +/- ESWL, and to assess, in patients with incomplete dissolution, the reasons for the poor response. We compared pretreatment gallstone characteristics in 43 patients who became stone-free after a median of 9 months OBAs +/- ESWL with those in 43 age- and sex-matched patients whose stones failed to dissolve after two years of treatment. In those with incomplete gallstone dissolution, we repeated the oral cholecystogram and computed tomogram (CT) and, in selected patients, obtained gallbladder bile by percutaneous fine-needle puncture. In patients who became stone-free, those with stones that were isodense with bile and/or had CT scores of < 75 Hounsfield units had the fastest dissolution rates. In the 43 nonresponders, the main causes for treatment failure were impaired gallbladder contractility and acquired stone calcification. CT-lucent, noncholesterol stones, or failure of desaturation of bile with the prescribed bile acids, occurred in a minority. We conclude that the pretreatment CT attenuation score predicts both the speed and completeness of gallstone dissolution. In patients with incomplete stone dissolution, the combination of oral cholecystography, CT, and analysis of gallbladder bile will determine the underlying reasons for treatment failure in most, but not all, cases.

Severe hepatitis E infection during pregnancy.

In areas with endemic hepatitis E virus (HEV), acute liver failure secondary to hepatitis E infection is common in pregnancy and associated with a mortality rate of up to 20%. However, there is little information on the clinical course of severe hepatitis E infection during pregnancy in non-endemic areas such as the UK. Here we describe two cases of severe hepatitis E in pregnancy in patients returning from the Indian subcontinent. These cases were diagnosed by the detection of IgM anti-HEV antibody using an enzyme immunoassay with recombinant hepatitis E viral antigens. The first case describes acute hepatic failure, with coagulopathy and encephalopathy, warranting intensive therapy and elective ventilation. In the other case, the patient had severe hepatitis with coagulopathy. Both cases spontaneously resolved with no foetal loss. These cases highlight the need for suspicion of HEV infection in patients returning from endemic areas and presenting with acute non-A non-B hepatitis, especially when pregnant. Furthermore, the intensive treatment of acute liver failure caused by HEV may reduce the high mortality reported in Asia.

Role of intestinal transit in the pathogenesis of gallbladder stones.

Increasing evidence implicates prolonged intestinal transit (slow transit constipation) in the pathogenesis of conventional gallbladder stones (GBS), and that of gallstones induced by long term octreotide (OT) treatment. Both groups of GBS patients have multiple abnormalities in the lipid composition and physical chemistry of their gallbladder bile-associated with, and possibly due to, an increased proportion of deoxycholic acid (DCA) (percentage of total bile acids). In turn, this increase in the percentage of DCA seems to be a consequence of prolonged colonic transit. Thus, in acromegalic patients OT treatment significantly prolongs large bowel transit time (LBTT) and leads to an associated increase of the percentage of DCA in fasting serum (and, by implication, in gallbladder bile). LBTT is linearly related to the percentage of DCA in fasting serum and correlates significantly with DCA input (into the enterohepatic circulation) and DCA pool size. However, these adverse effects of OT can be overcome by the concomitant use of the prokinetic drug cisapride, which normalizes LBTT and prevents the rise in the percentage of serum DCA. Therefore, in OT-treated patients and other groups at high risk of developing stones, it may be possible to prevent GBS formation with the use of intestinal prokinetic drugs.

Clinical economics review: the management of gallstone disease.

Surgical techniques have an inherent advantage over oral bile therapy and extracorporeal shock-wave lithotripsy because they remove both gallstones and the gallbladder, thus preventing stone recurrence. Moreover, surgical techniques are more effective for patients with symptomatic gallstones compared with non-surgical techniques. Laparoscopic surgery is the best therapy from the clinical economic viewpoint being cost-minimal, effective and beneficial compared with other surgical and medical techniques. However, non-surgical techniques may be preferable in selected patients at high risk from general anaesthesia such as the elderly and those with significant cardiopulmonary disease.

Roles of gall bladder emptying and intestinal transit in the pathogenesis of octreotide induced gall bladder stones.

BACKGROUND: Octreotide treatment of acromegalic patients increases the % deoxycholic acid conjugates and the cholesterol saturation of gall bladder bile, and induces gall stone formation. AIMS: To study the roles of gall bladder emptying and intestinal transit in these phenomena. METHODS AND PATIENTS: Gall bladder emptying and mouth to caecum transit was measured in (a) control subjects and acromegalic patients given saline or 50 micrograms of octreotide, and (b) acromegalic patients taking long term octreotide. In the second group, large bowel transit was also measured. RESULTS: A single dose of octreotide inhibited meal stimulated gall bladder emptying, the ejection fraction falling from mean (SEM) 66.0 (2.3)% to 7.0 (5.3)% in controls (p < 0.001); from 72.5 (2.1) to 16.6 (5.1)% in untreated acromegalic patients (p < 0.001), and to 30.4 (9.5)% in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic group). Octreotide prolonged mouth to caecum transit time, from 112 (15) min to 237 (13) min in controls (p < 0.001), from 170 (13) min to 282 (11) min in untreated acromegalic patients (p < 0.001), and to 247 (10) min in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic patients). The mean large bowel transit in octreotide untreated compared with treated acromegalic patients remained unchanged (40 (6) h v 47 (6) h). CONCLUSIONS: Prolongation of intestinal transit and impaired gall bladder emptying may contribute to lithogenic changes in bile composition and gall stone formation in patients receiving long term octreotide.