Ectopic Varices and Collaterals Development after Band Ligation Treatment in a Patient with Portal Hypertension

Esophageal and gastric varices may complicate the course of cirrhosis as a direct consequence of portal hypertension. Variceal hemorrhage has been reported to occur in 25–40% of patients with cirrhosis [Gastroenterol Clin North Am 1992;21:149–161]. Occasionally, varices develop at sites other than the esophagus and are detected either when they bleed or incidentally during upper or lower endoscopy [Eur J Gastroenterol Hepatol 2006;18:1155–1160; Digestion 2000;61:149–150]. Endoscopic treatment is often unsuccessful in these cases, and traditional treatment is usually surgical, while it has been suggested that bleeding can also be controlled by a transjugular intrahepatic portosystemic shunt (TIPS) [Endoscopy 1995;27:626–627]. Moreover, esophageal band ligation may interfere with the collateral web. We here report a case of an ectopic duodenal varix and the development of a large collaterals web that appeared after band ligation

Spontaneous Resolution of Brain Edema in Fulminant Hepatic Failure due to Hepatitis E

Fulminant hepatic failure is characterized by the presence of hepatic encephalopathy in the setting of acute liver injury that occurs in a noncirrhotic organ. Brain edema is the ultimate complication of advanced hepatic encephalopathy as it often leads to cerebral herniation and death. Thus, the presence of fulminant hepatic failure indicates the need for urgent liver transplantation to prevent death or irreversible brain damage. We report a very unusual evolution of fulminant hepatic failure complicated by brain edema and hepatic coma in a 45-year-old woman admitted with acute viral hepatitis E infection

Image-guided multipolar radiofrequency ablation of liver tumours: initial clinical results

The local effectiveness and clinical usefulness of multipolar radiofrequency (RF) ablation of liver tumours was evaluated. Sixty-eight image-guided RF sessions were performed using a multipolar device with bipolar electrodes in 53 patients. There were 45 hepatocellular carcinomas (HCC) and 42 metastases with a diameter ≤3cm (n = 55), 3.1-5cm (n = 29) and >5cm (n = 3); 26 nodules were within 5mm from large vessels. Local effectiveness and complications were evaluated after RF procedures. Mean follow-up was 17 ± 10months. Recurrence and survival rates were analysed by the Kaplan-Meier method. The primary and secondary technical effectiveness rate was 82% and 95%, respectively. The major and minor complication rate was 2.9%, respectively. The local tumour progression at 1- and 2-years was 5% and 9% for HCC nodules and 17% and 31% for metastases, respectively; four of 26 nodules (15%) close to vessels showed local progression. The survival at 1year and 2years was 97% and 90% for HCC and 84% and 68% for metastases, respectively. Multipolar RF technique creates ablation zones of adequate size and tailored shape and is effective to treat most liver tumours, including those close to major hepatic vessel

Role of manganese in the pathogenesis of portal-systemic encephalopathy

Amongst the potential neurotoxins implicated in the pathogenesis of hepatic encephalopathy, manganese emerges as a new candidate. In patients with chronic liver diseases, manganese accumulates in blood and brain leading to pallidal signal hyperintensity on T1-weighted Magnetic Resonance (MR) Imaging. Direct measurements in globus pallidus obtained at autopsy from cirrhotic patients who died in hepatic coma reveal 2 to 7-fold increases of manganese concentration. The intensity of pallidal MR images correlates with blood manganese and with the presence of extrapyramidal symptoms occurring in a majority of cirrhotic patients. Liver transplantation results in normalization of pallidal MR signals and disappearance of extrapyramidal symptoms whereas transjugular intrahepatic portosystemic shunting induces an increase in pallidal hyperintensity with a concomitant deterioration of neurological dysfunction. These findings suggest that the toxic effects of manganese contribute to extrapyramidal symptoms in patients with chronic liver disease. The mechanisms of manganese neurotoxicity are still speculative, but there is evidence to suggest that manganese deposition in the pallidum may lead to dopaminergic dysfunction. Future studies should be aimed at evaluating the effects of manganese chelation and/or of treatment of the dopaminergic deficit on neurological symptomatology in these patients

Anticoagulant therapy for nodular regenerative hyperplasia in a HIV-infected patient

<p>Abstract</p> <p>Background</p> <p>Nodular regenerative hyperplasia (NRH) has been recently recognized as an emergent cause of liver disease in HIV-infected patients. NRH may cause non-cirrhotic portal hypertension with potentially severe consequences such as refractory ascites, variceal bleeding and hypersplenism. Obliteration of the small intrahepatic portal veins in association with prothrombotic disorders linked to HIV infection itself or anti-retroviral therapy seem to be the causes of NRH and thus the term HIV-associated obliterative portopathy has been proposed.</p> <p>Case Presentation</p> <p>Here we describe a case of a HIV-infected patient with biopsy-proven NRH and listed for liver transplantation (LT) because of refractory ascites and repeated upper gastrointestinal bleedings. A transjugular intrahepatic portosystemic shunt was placed as a bridge to LT and did not improve liver function. However, anticoagulant therapy with low-molecular-weight heparin (LMWH) was associated with rapid improvement in the liver condition and allowed to avoid LT in this patient.</p> <p>Conclusions</p> <p>Thus, this case underscores the relation between thrombophilia and HIV-associated NRH and emphasizes anticoagulant therapy as possible treatment.</p

Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction

BACKGROUND & AIMS: Manganese (Mn) deposition could be responsible for the T(1)-weighted magnetic resonance signal hyperintensities observed in cirrhotic patients. These experiments were designed to assess the regional specificity of the Mn increases as well as their relationship to portal-systemic shunting or hepatobiliary dysfunction. METHODS: Mn concentrations were measured in (1) brain samples from basal ganglia structures (pallidum, putamen, caudate nucleus) and cerebral cortical structures (frontal, occipital cortex) obtained at autopsy from 12 cirrhotic patients who died in hepatic coma and from 12 matched controls; and from (2) brain samples (caudate/putamen, globus pallidus, frontal cortex) from groups (n = 8) of rats either with end-to-side portacaval anastomosis, with biliary cirrhosis, or with fulminant hepatic failure as well as from sham-operated and normal rats. RESULTS: Mn content was significantly increased in frontal cortex (by 38\%), occipital cortex (by 55\%), pallidum (by 186\%), putamen (by 66\%), and caudate (by 54\%) of cirrhotic patients compared with controls. Brain Mn content did not correlate with patient age, etiology of cirrhosis, or history of chronic hepatic encephalopathy. In cirrhotic and portacaval-shunted rats, Mn content was increased in pallidum (by 27\% and 57\%, respectively) and in caudate/putamen (by 57\% and 67\%, respectively) compared with control groups. Mn concentration in pallidum was significantly higher in portacaval-shunted rats than in cirrhotic rats. No significant changes in brain Mn concentrations were observed in rats with acute liver failure. CONCLUSIONS: These findings suggest that brain Mn deposition results both from portal-systemic shunting and from liver dysfunction

Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

<p>Abstract</p> <p>Background</p> <p>Alcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear.</p> <p>Methods</p> <p>We studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model.</p> <p>Results</p> <p>43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001).</p> <p>Conclusions</p> <p>In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.</p

Expression of the bile acid receptor FXR in Barrett's esophagus and enhancement of apoptosis by guggulsterone in vitro

BACKGROUND: Barrett's esophagus, a risk factor for esophageal adenocarcinoma, is associated with reflux disease. The aim of this study was to assess the expression of bile acid receptors in the esophagus (normal, esophagitis, Barrett's esophagus and adenocarcinoma) and to investigate their possible function. RESULTS: the expression of the bile acid receptors FXR and VDR in esophageal biopsies from patients with a normal mucosa, esophagitis, Barrett's esophagus or adenocarcinoma (n = 6 per group) and in cell lines derived from Barrett's esophagus and esophageal adenocarcinoma, was assessed by real time Q-PCR and immunohistochemistry. The effect of guggulsterone, an antagonist of bile acid receptors, on apoptosis of Barrett's esophagus-derived cells was assessed morphologically, by flow cytometry and by measuring caspase 3 activity. The expression of FXR was increased in esophagitis, Barrett's esophagus and adenocarcinoma compared to normal mucosa by a mean of 44, 84 and 16, respectively. Immunohistochemistry showed a weak expression in normal esophagus, a strong focal reactivity in Barrett's esophagus, and was negative in adenocarcinoma. VDR expression did not significantly differ between groups. In cell cultures, the expression of FXR was high in Barrett's esophagus-derived cells and almost undetectable in adenocarcinoma-derived cells, whereas VDR expression in these cell lines was not significantly different. In vitro treatment with guggulsterone was associated with a significant increase in the percentage of apoptotic cells and of the caspase 3 activity. CONCLUSION: the bile acid receptor FXR is significantly overexpressed in Barrett's esophagus compared to normal mucosa, esophagitis and esophageal adenocarcinoma. The induction of apoptosis by guggulsterone in a Barrett's esophagus-derived cell line suggests that FXR may contribute to the regulation of apoptosis

Phlegmonous colitis: another source of sepsis in cirrhotic patients?

<p>Abstract</p> <p>Background</p> <p>The clinical relevance of phlegmonous colitis (PC), a rare autopsy finding in cirrhotic patients, is poorly documented. We postulated that PC might be a source of sepsis in patients with portal hypertensive colopathy (PHC).</p> <p>Case presentation</p> <p>We report three cirrhotic patients who were admitted with abdominal sepsis and who illustrate, to various degrees, the clinico-pathological sequence of colonic alterations associated with portal hypertension. Two cirrhotic patients with PHC developed gram-negative bacteraemia and quickly responded to intravenous antibiotics. Another cirrhotic patient underwent emergency colectomy for PC, and subsequently died from multiple organ failure. Histological alterations in the operative specimen included: a) mucosal ulcerations; b) disseminated micro-abscesses in the submucosa; and c) a severe vasculopathy leading to complete obliteration of submucosal blood vessels.</p> <p>Conclusions</p> <p>These data suggest that cirrhotic patients with PHC may progress towards PC, which, in turn, may be the cause for life-threatening sepsis.</p

A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis

<p>Abstract</p> <p>Background</p> <p>Hepatic encephalopathy (HE) is a frequent and severe complication of cirrhosis. A single determination of ammonia in venous blood correlates poorly with neurological symptoms. Thus, a better biological marker is needed.</p> <p>Aim</p> <p>To make a diagnosis of HE, we explored the value of ammonia in capillary blood, an equivalent to arterial blood, measured at bedside following an oral glutamine challenge.</p> <p>Methods</p> <p>We included 57 patients (age 56 yrs; M/F: 37/20) with cirrhosis (alcoholic = 42; MELD score 13.8 [7-29], esophageal varices = 38) and previous episodes of HE (n = 19), but without neurological deficits at time of examination, and 13 healthy controls (age 54 yrs). After psychometric tests and capillary (ear lobe) blood ammonia measurements, 20 gr of glutamine was administered orally. Tests were repeated at 60 minutes (+ blood ammonia at 30'). Minimal HE was diagnosed if values were > 1.5 SD in at least 2 psychometric tests. Follow-up lasted 12 months.</p> <p>Results</p> <p>The test was well tolerated (nausea = 1; dizziness = 1). Patients showed higher values of capillary blood ammonia over time as compared to controls (0'-30'-60 minutes: 75, 117, 169 versus 52, 59, 78 umol/L, p < 0.05). At baseline, 25 patients (44%) had minimal HE, while 38 patients (67%) met the criteria for HE at 60 minutes (chi²: p < 0.01). For the diagnosis of minimal HE, using the ROC curve analysis, baseline capillary blood ammonia showed an AUC of 0.541 (CI: 0.38-0.7, p = 0.6), while at 60 minutes the AUC was 0.727 (CI: 0.58-0.87, p < 0.006). During follow-up, 18 patients (31%) developed clinical episodes of HE. At multivariate analysis, the MELD score (1.12 [1.018-1.236]), previous episodes of HE (3.2[1.069-9.58]), but not capillary blood ammonia, were independent predictors of event.</p> <p>Conclusions</p> <p>In patients with cirrhosis and normal neurological examination, bedside determination of ammonia in capillary blood following oral glutamine load is well tolerated and achieves a better diagnostic performance for minimal HE than basal capillary ammonia levels. However, capillary blood ammonia is a poor predictor of development of clinically overt HE.</p