Midodrine in the prevention of hepatorenal syndrome type 2 recurrence: a case-control study.

BACKGROUND: Hepatorenal syndrome is a severe complication of cirrhosis. Treatment with terlipressin has currently the best efficacy pedigree, inducing hepatorenal syndrome reversal in a high proportion of patients. However, hepatorenal syndrome recurrence after terlipressin withdrawal is very common, especially in type 2 hepatorenal syndrome. Midodrine, an oral adrenergic vasoconstrictor, has been suggested to be an effective therapy in hepatorenal syndrome. AIMS: To analyse the impact of treatment with midodrine after hepatorenal syndrome type 2 reversal induced by terlipressin on the prevention of hepatorenal syndrome recurrence. PATIENTS AND METHODS: A case-control design was used. The outcome of 10 patients with hepatorenal syndrome type 2 treated successfully with terlipressin and then with midodrine (7.5-12.5mg/tid) was compared with that of an historical control group of hepatorenal syndrome type 2 patients responders to treatment with terlipressin. Patients and controls were matched by age, plasma renin activity (PRA) levels and severity of renal and liver failure. RESULTS: Cases and controls were similar with respect to pre-treatment with terlipressin. The hepatorenal syndrome recurrence probability was the same in the two groups (cases and control: 9/10, 90%, p=ns). No significant differences were found between cases and controls with respect to serum creatinine (1.9+/-0.1mg/dl vs. 2+/-0.2mg/dl), blood creatinine clearance (28+/-5ml/min vs. 24+/-5ml/min), urinary sodium excretion (12+/-6mequiv./d vs. 19+/-4mequiv./d) and PRA levels (17+/-3ng/ml/h) vs. 20+/-3ng/ml/h) after terlipressin withdrawal (p=ns). CONCLUSIONS: These results show that in patients responders to terlipressin hepatorenal syndrome recurrence is not different between patients treated with midodrine and subjects who did not receive vasoconstrictor treatment after terlipressin withdrawal. These data suggest that midodrine is not effective in preventing hepatorenal syndrome type 2 recurrence.

Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study.

BACKGROUND/AIMS: Treatment of hepatorenal syndrome (HRS) is based on vasoconstrictors. Terlipressin is the one with the soundest evidence. Noradrenalin has been suggested as an effective alternative. The current study was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in patients with HRS. METHODS: Twenty-two consecutive cirrhotic patients with HRS (9 with HRS type 1; 13 with HRS type 2) were included. Patients were randomly assigned to be treated with noradrenalin (0.1-0.7 microg/kg/min) and albumin (10 patients) or with terlipressin (1-2 mg/4h) and albumin (12 patients). Treatment was administered until HRS reversal or for a maximum of two weeks. Patients were followed-up until liver transplantation or death. RESULTS: Reversal of HRS was observed in 7 of the 10 patients (70%) treated with noradrenalin and in 10 of the 12 patients (83%) treated with terlipressin, p=ns. Treatment led in both groups to a significant improvement in renal and circulatory function. No patient developed signs of myocardial ischemia. CONCLUSIONS: Data from this unblinded, pilot study suggest that noradrenalin is as effective and safe as terlipressin in patients with HRS. These results would support the use of noradrenalin, a cheap and widely available drug, in the management of these patients.

[Gastroenterology outpatient clinic of the Molinette Hospital (Turin, Italy): the 2003-2006 report]. / Poliambulatori specialistici di gastroenterologia: l'esperienza 2003-2006 dell'Ospedale Molinette di Torino.

AIM: Given the demographic shifts and needs of cost rationalization, it is of high priority to organize health care on the basis of ambulatory outpatients models. The aim of this study was to examine activity at the gastro-hepatology outpatients clinic of the Molinette Hospital. In this facility, the management is based on a work team organization that follows cohorts of patients with specific pathologies. METHODS: All services, consultations and urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, carried out from January 2003 to December 2006, were extrapolated from the computerized system. Consultations were divided into first examination and controls. Furthermore, the destination of the patients after each consultation was considered. RESULTS: During the year 2003, 8 842 consultations and 4 071 UBT were carried out, in the year 2004, 11 342 consultations and 2 409 UBT, in the year 2005, 12 474 consultations and 2 510 UBT, in the year 2006, 12 249 consultations and 2 357 UBT. No further specialistic management was required for 25% of patients, while 2% had been hospitalized in the bed unit, 3% in the short hospitalization unit or the day-hospital. The remaining 70% were included in work teams or monitored thereafter. The comparison with consultations from 1994 shows an increase due to both first examination (+300%) and controls (+83%). CONCLUSIONS: The burden of the requests from the population and primary care structures addressed to the outpatients clinic of gastro-hepatology is relevant. The activity of this facility leads to a low rate of hospitalization as well as of cost reduction.

Adrenaline plus cyanoacrylate injection for treatment of bleeding peptic ulcers after failure of conventional endoscopic haemostasis.

BACKGROUND: Endoscopic therapy is a safe and effective method for treating non-variceal upper gastrointestinal bleeding. However failure of therapy, in terms of continuing bleeding or rebleeding, is seen in up to 20%. Cyanoacrylate is a tissue glue used for variceal bleeding that has occasionally been reported as an alternative haemostatic technique in non-variceal haemorrhage. AIM: To retrospectively describe personal experience using cyanoacrylate injection in the management of bleeding ulcers after failure of first-line endoscopic modalities. PATIENTS AND METHODS: Between January 1995 and March 1998, 18 [12 M/6 F, mean age 68.1 years) out of 176 patients, referred to our Unit for non-variceal upper gastrointestinal bleeding, were treated with intralesional injection of adrenaline plus undiluted cyanoacrylate. Persistent bleeding after endoscopic haemostasis or early rebleeding were the indications for cyanoacrylate treatment. RESULTS: Definitive haemostasis was achieved in 17 out of 18 patients treated with cyanoacrylate. One patient needed surgery. No early or late rebleeding occurred during the follow-up. No complications or instrument lesions related to cyanoacrylate were recorded. CONCLUSIONS: In our retrospective series, cyanoacrylate plus adrenaline injection was found to be a potentially safe and effective alternative to endoscopic haemostasis when conventional treatment modalities fail in controlling bleeding from gastroduodenal ulcers.

Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis.

BACKGROUND/AIMS: Treatment with hepatitis B virus immune globulins (HBIG) or lamivudine has reduced the rate of hepatitis B recurrence after liver transplantation to approximately 50%. METHODS: To further decrease hepatitis B recurrence, 33 hepatitis B virus (HBV)-related cirrhotic patients were treated with lamivudine before liver transplantation and with lamivudine together with low-dose HBIG (46 500 IU the first month followed by 5,000 lU/monthly) after surgery. RESULTS: While on lamivudine, serum HBV DNA level decreased significantly in all patients and in 11 (33%) the Child-Pugh score improved. Twenty-six patients were transplanted. Among the 25 who survived for longer than 12 months, only one (4%) experienced a hepatitis B recurrence over an average follow-up of 31 months, a rate significantly lower (P = 0.0002) than the 50% recurrence rate among a historical control group of 12 patients. However, low-level HBV replication was detected sporadically throughout the follow-up in 64% of patients. CONCLUSIONS: Over the medium-term, combined prophylaxis with lamivudine and HBIG significantly decreases the risk of hepatitis B recurrence after liver transplantation. Though low-level HBV infection recurred in two thirds of patients, the pathogenic expression of HBV was prevented.

CO(2) wedged hepatic venography in the evaluation of portal hypertension.

BACKGROUND/AIMS/METHODS: During hepatic vein catheterisation, in addition to measurement of hepatic venous pressure gradient (HVPG), iodine wedged retrograde portography can be easily obtained. However, it rarely allows correct visualisation of the portal vein. Recently, CO(2) has been suggested to allow better angiographic demonstration of the portal vein than iodine. In this study we investigated the efficacy of CO(2) compared with iodinated contrast medium for portal vein imaging and its role in the evaluation of portal hypertension in a series of 100 patients undergoing hepatic vein catheterisation, 71 of whom had liver cirrhosis. RESULTS: In the overall series, CO(2) venography was markedly superior to iodine, allowing correct visualisation of the different segments of the portal venous system. In addition, CO(2), but not iodine, visualised portal-systemic collaterals in 34 patients. In cirrhosis, non-visualisation of the portal vein on CO(2) venography occurred in 11 cases; four had portal vein thrombosis and five had communications between different hepatic veins. Among non-cirrhotics, lack of portal vein visualisation had a 90% sensitivity, 88% specificity, 94% negative predictive value, and 83% positive predictive value in the diagnosis of pre-sinusoidal portal hypertension. CONCLUSIONS: Visualisation of the venous portal system by CO(2) venography is markedly superior to iodine. The use of CO(2) wedged portography is a useful and safe complementary procedure during hepatic vein catheterisation which may help to detect portal thrombosis. Also, lack of demonstration of the portal vein in non-cirrhotic patients strongly suggests the presence of pre-sinusoidal portal hypertension.

The role of portal pressure in the severity of bleeding in portal hypertensive rats.

The aim of this study was to investigate the role of portal hypertension determining the severity of bleeding in portal hypertensive rats. The effects of section of branches of the ileocolic vein were studied in sham-operated (SO), partial portal vein-ligated (PPVL), and common bile duct-ligated (CBDL) rats. The ensuing hemorrhage was compared with that caused by section of femoral vein, where the portal hypertensive factor is excluded. In PPVL rats, section of branches of increasing size (divided into fourth, third, second, and first order) resulted in increasingly severe bleeding (arterial pressure: / +/- 4%, / 6 +/- 12%, / /15 +/- 8%, and / 28 +/- 13%; P <.005; hematocrit / 4 +/- 2%, / 6 +/- 1%, / 7 +/- 2%, and / 10 +/- 4%; P <.005). Bleeding from first-order branches was mild in SO, moderate in PPVL, and severe in CBDL rats, as shown by increasing changes in arterial pressure (/ 3 +/- 3%, / 12 +/- 16% and, / 43 +/- 23%; P <.01), hematocrit (/ 4 +/- 1%, / 12 +/- 2%, and / 32 +/- 19%; P <.01), and mortality (0%, 0%, and 56%; P <.001). Greater blood loss in CBDL rats was associated with higher portal pressure (16.6 +/- 2.7 vs. 13. 1 +/- 1.1 mm Hg in PPVL; P <.01) and more prolonged bleeding time (70 +/- 4 vs. 35 +/- 3 seconds in PPVL; P <.001). Vessels were similarly dilated in CBDL and PPVL (0.7 +/- 0.2 and 0.7 +/- 0.1 vs. 0.4 +/- 0.1 mm in SO; P <.05). Section of femoral vein caused equal blood loss in SO, PPVL, and CBDL rats, assessed by falls in hematocrit (/ 8 +/- 2%, / 7 +/- 1%, / 8 +/- 1%, respectively; NS) and by the blood loss (3.6 +/- 0.7, 3.5 +/- 0.9, and 3.8 +/- 0.7 g; NS). The study shows that the degree of portal pressure elevation is a major determinant of the severity of portal hypertension-related bleeding in PPVL and CBDL rats.

Hypercalcaemia secondary to hepatocellular carcinoma.

Many syndromes reflecting impaired metabolism have been described in association with primary neoplastic diseases. Hypercalcaemia secondary to malignancy without bone metastases and with normal parathyroid glands has been described as "pseudohyperparathyroidism". Differentiation from primary hyperparathyroidism is difficult and care should be taken to exclude an occult malignancy prior to surgical exploration for a parathyroid adenoma. Hypercalcaemia associated with hepatocellular carcinoma is not uncommon. Nevertheless, we describe a rare case of coma with persistent hypercalcaemia in a cirrhotic patient not previously known to have hepatocellular carcinoma.

Recurrence of hepatitis B in liver transplants treated with antiviral therapy.

BACKGROUND AND AIMS: In patients with terminal Hepatitis B Virus-related liver diseases, liver transplantation carries a consistent risk of Hepatitis B Virus recrudescence in the graft. In the attempt to reduce the reinfection rate with antiviral therapy, we studied a total of 16 viraemic patients. PATIENTS AND METHODS: Twelve patients received Ganciclovir, starting 4-67 days (mean 25 days) before transplantation and prolonged for 10 days after transplantation; four patients were treated with Lactosaminated Arabinoside-Monophosphate 6 hours before surgery and prolonged for 28 days after surgery. All received hepatitis B immunoglobulins. RESULTS: At transplantation, HBV-DNA had decreased to about 10(4) virus/ml (as assessed by the polymerase chain reaction assay) in 10 of the 12 patients treated with Ganciclovir. Of these patients, 4 died perioperatively from causes unrelated to Hepatitis B Virus reinfection. Of the eight survivors, only the patient who maintained a titre of 10(6) virus/ml at the time of transplantation developed viral recurrence 4 months after surgery. Before transplantation, 2 of the patients treated with Lactosaminated Arabinoside-Monophosphate had a viraemic load of 10(6) and 2 of 10(4) virus/ml. In all cases, viraemia became undetectable at the end of therapy. None died and Hepatitis B Virus recurred 2 months after transplantation in one. The overall rate of Hepatitis B Virus recurrence was 16.6%. The recurrence rate decreased to 9% in patients in whom the viraemic load decreased to around 10(4) virus/ml following treatment, compared to an overall recurrence rate of 50% in our historical series of patients transplanted for Hepatitis B Virus-related cirrhosis. CONCLUSION: Antiviral therapy was effective in decreasing the risk of Hepatitis B Virus reinfection of the liver graft by decreasing the viral load before surgery.

Efficacy of lamivudine re-treatment in a patient with hepatitis B virus (HBV) recurrence after liver transplantation and HBV-DNA breakthrough during the first treatment.

BACKGROUND: Transplantation for terminal hepatitis B virus (HBV) disease is aggravated by a high rate of reinfection and disease recurrence. Lamivudine, a new nucleoside analog, is a potent inhibitor of HBV synthesis, but its use may lead to the emergence of HBV-DNA polymerase mutants resistant to the drug. METHODS AND RESULTS: We describe the case of a patient who developed an HBV recurrence after liver transplantation and was treated with lamivudine. An HBV-DNA breakthrough occurred 7 months after the start of therapy, and the drug was stopped after 9 months. The molecular state of HBV-DNA was analyzed, and a mutation in the YMDD (tyrosine, methionine, aspartate, aspartate) locus of HBV-DNA polymerase was identified. Nine months after the suspension of lamivudine the patient experienced a new hepatic attack accompanied by high HBV-DNA levels. Lamivudine was given again. Serum HBV-DNA levels normalized after 45 days of re-treatment, but lamivudine-resistant mutants were again the prevalent viral population after 3 months. CONCLUSIONS: The case described suggests that retherapy with lamivudine after a first emergence of YMDD mutants is temporarily effective in recontrolling HBV synthesis but ultimately induces the accelerated reemergence of a prevalently mutant population of HBV. This emphasizes the need for combined antiviral therapy.

[Lipohyperplasia or intestinal lipomatosis]. / Lipoiperplasia o lipomatosi intestinale.

Lipohyperplasia or intestinal lipomatosis is an infrequent disease characterised by anomalous infiltration of adipose tissue in the intestinal submucosa. Localised forms are generally asymptomatic, whereas diffuse forms may lead to intestinal subocclusion, digestive hemorrhage or diarrhoea. Although benign, the differential diagnosis of intestinal lipomatosis with malignant pathologies of the colon or appendix often prompts the need for surgical exploration and the histological analysis of biopsy material. Surgical exeresis of the lesion is generally associated with the normalisation of clinical symptoms. The authors report the onset and clinical evolution of two cases of intestinal lipomatosis referred to their attention.

Epithelioid haemangioendothelioma of the liver: report of a case submitted to orthotopic liver transplantation.

A case of hepatic epithelioid haemangio-endothelioma is described in a 42-year-old female who presented with abdominal pain and hepatomegaly. The radiographic finding showed multiple hepatic lesions in both lobes. Diagnosis was based on the liver biopsy. The tumour cells were immunoreactive with factor VIII related antigen and vimentine. A liver transplantation was performed. Although at the time of diagnosis there was no clinical evidence of metastasis, the intra-operatorive examination revealed multiple mesenteric and pulmonary neoplastic nodules. The patient is alive and well seven months after liver transplantation.

Hepatotoxicity of intravenous cyclosporin A in patients with acute ulcerative colitis on total parenteral nutrition.

A group of 24 patients underwent a 7-14-day course of continuously infused Cyclosporin A (2 mg.kg-1.day-1) to treat a severe attack of ulcerative colitis. In 19 of them, including eight treated with total parenteral nutrition, we retrospectively analyzed the serum aminotransferase (AST/ALT) levels at the beginning and at the end of Cyclosporin infusion. The baseline levels of AST/ALT in the group were 19.9 +/- 3.2 and 31.4 +/- 6.4; on stopping Cyclosporin infusion, they were 43 +/- 15.8 and 119 +/- 56, respectively. Six patients showed an ALT change above 1.5 times the upper limit of reference. They included five of the eight patients treated with total parenteral nutrition (62.5%). In one of six, ALT rose to 1000 U/l and was accompanied by full-blown febrile cholangitis (proven by liver biopsy). This episode was preceded by excessive accumulation of Cyclosporin in blood. The development of liver toxicity was independent of the length of Cyclosporin treatment, nor did it impair drug efficacy. Thus, in these patients total parenteral nutrition and Cyclosporin were synergistic, causing twice the frequency of liver damage (62.5%) reported for ulcerative colitis patients on total parenteral nutrition alone (37%). Total parenteral nutrition should not be used to support patients needing Cyclosporin for autoimmune disease. However, too high a dose of Cyclosporin may cause liver disease per se.

[Hepatic Wilson's disease: clinical presentation and prognosis. Indications for liver transplantation]. / Malattia di Wilson epatica: presentazione clinica e prognosi. Indicazioni al trapianto di fegato.

Wilson's disease is a hereditary disorder of biliary copper excretion. Most often the disease presents with hepatic and neurological involvement. In the hepatic forms, hypocerulo-plasminemia, the determination of eye copper and the dosage of copper in serum, urine and liver tissue are all leads to diagnosis. The presentation and the biochemistry may direct the diagnosis of the acute forms. Treatment differs according to the clinical patterns. Early diagnosis in the asymptomatic patient leads to chelating therapy to prevent copper overload. Chronic disease may benefit from chelation and liver transplant. Transplantation is the cure for fulminant forms. We report three young women with Wilson's disease; one had a fulminant form and was transplanted and the other two responded to chelation therapy. Family screening allowed the identification of an asymptomatic sibling.