Antoni Mas

Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome.

BACKGROUND/AIM Ornipressin, a vasopressin analog with potent splanchnic vasoconstrictor action, has been shown to reverse hepatorenal syndrome. However, its usefulness in clinical practice is limited by frequent ischemic complications. The aim of this study was to assess the efficacy of terlipressin, an analog of vasopressin with a low profile of side effects, plus albumin in this condition. METHODS Nine consecutive patients with cirrhosis and hepatorenal syndrome were included in a pilot study of terlipressin (0.5-2 mg/4 h i.v.) therapy associated with iv albumin. RESULTS Treatment (9 days, range 5-15) was associated with a marked reduction of serum creatinine (3.9+/-0.7 to 1.3+/-0.1 mg/dl, p<0.001, mean+/-SE). Reversal of hepatorenal syndrome (reduction of creatinine below 1.5 mg/dl) was observed in seven of the nine patients. There was a remarkable improvement in circulatory function, with an increase in mean arterial pressure (68+/-2 to 80+/-4 mmHg, p<0.05) and suppression of vasoconstrictor systems activity (plasma renin activity and plasma norepinephrine decreased from 23+/-12 ng/ml x h and 1549+/-373 pg/ml to 3.5+/-2 ng/ml x h and 373+/-98 pg/ml, respectively, p<0.01 for both). No patient developed signs of intestinal, myocardial or distal ischemia. CONCLUSIONS Terlipressin associated with albumin appears to be a safe and effective treatment of hepatorenal syndrome.

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

Relative adrenal insufficiency is frequent in patients with severe sepsis and is associated with hemodynamic instability, renal failure, and increased mortality. This study prospectively evaluated the effects of steroids on shock resolution and hospital survival in a series of 25 consecutive patients with cirrhosis and septic shock (group 1). Adrenal function was evaluated by the short corticotropin test within the first 24 hours of admission. Patients with adrenal insufficiency were treated with stress doses of intravenous hydrocortisone (50 mg/6 h). Data were compared to those obtained from the last 50 consecutive patients with cirrhosis and septic shock admitted to the same intensive care unit in whom adrenal function was not investigated and who did not receive treatment with steroids (group 2). Incidence of adrenal insufficiency in group 1 was 68% (17 patients). Adrenal dysfunction was frequent in patients with advanced cirrhosis (Child C: 76% vs. Child B: 25%, P = .08). Resolution of septic shock (96% vs. 58%, P = .001), survival in the intensive care unit (68% vs. 38%, P = .03), and hospital survival (64% vs. 32%, P = .003) were significantly higher in group 1. The main causes of death in group 1 were hepatorenal syndrome or liver failure (7 of 9 patients). In contrast, refractory shock caused most of the deaths in group 2 (20 of 34 patients). In conclusion, relative adrenal insufficiency is very frequent in patients with advanced cirrhosis and septic shock. Hydrocortisone administration in these patients is associated with a high frequency of shock resolution and high survival rate. (HEPATOLOGY 2006;44:1288–1295.)

A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation.

BACKGROUND/AIMS To compare the efficacy in preventing hepatitis B virus (HBV) recurrence of lamivudine vs. lamivudine plus hepatitis B immune globulin (HBIg) after a short course of HBIg and lamivudine in liver transplanted chronic hepatitis B patients. METHODS Forty-six patients with HBV cirrhosis received lamivudine before liver transplantation and were then randomized to receive lamivudine plus HBIg for 1 month followed by lamivudine or both drugs for 17 months. RESULTS Thirty-two patients were transplanted and 29 were randomized to receive combination therapy (15 cases) or lamivudine monotherapy (14 cases). HBV DNA was undetectable in all cases (17 induced by lamivudine therapy) at the time of liver transplantation. After 18 months of follow-up, all patients survived without HBV recurrence: hepatitis Bs antigen and HBV DNA were negative; however, HBV DNA was detected by polymerase chain reaction in four cases (three with HBIg plus lamivudine and one with lamivudine). Alanine aminotransferase levels were normal except in six cases (one HCV and two HDV coinfections). There were no drug-related adverse events. CONCLUSIONS Lamivudine monotherapy after a short course of lamivudine and HBIg is equally as efficacious in preventing HBV recurrence as HBIg plus lamivudine during the first 18 months after liver transplantation. This strategy is more economic and convenient to administer than long-term HBIg plus lamivudine.

Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial

BACKGROUND/AIMS The efficacy and safety of rifaximin in comparison with lactitol in the treatment of acute hepatic encephalopathy was assessed in a prospective randomized, double-blind, double-dummy, controlled trial. METHODS A total of 103 patients with grade I-III acute hepatic encephalopathy were randomized to receive rifaximin (50 patients, 1200 mg/day) or lactitol (53 patients, 60 g/day) for 5-10 days. Changes in the portal-systemic encephalopathy (PSE) index on entry and at the end of the study were used to evaluate the efficacy of the two therapies. RESULTS Both groups were comparable before treatment with regard to demographic data and characteristics of the hepatic encephalopathy episode. The global efficacy of both therapies was similar: 81.6% in the rifaximin group and 80.4% in the lactitol group showed improvement or total regression of the episode. A significantly better evolution of the PSE index was observed in the rifaximin group, due to a greater effect of rifaximin in two components of the index: EEG abnormalities and ammonia levels. No serious adverse events related to either treatment were found during the study. CONCLUSIONS Rifaximin may be considered a useful and safe alternative therapy to lactitol in the treatment of acute hepatic encephalopathy in cirrhosis.

Ecstasy: A common cause of severe acute hepatotoxicity

BACKGROUND/AIMS Ecstasy is a synthetic amphetamine recently identified as a possible cause of acute liver injury. This drug is consumed by young people and has a marked effect on improving sociability. The extent of ecstasy-associated severe hepatic damage is unknown to date. METHODS The clinical histories of 62 patients with acute liver failure admitted to the Intensive Care Liver Unit between January 1994 and December 1996 were reviewed to assess the frequency, the epidemiological, clinical and histological characteristics and the outcome of ecstasy-induced severe hepatitis. RESULTS Over this period of time, five patients (8%) were admitted because of ecstasy-induced acute liver failure, representing 31% of the cases with drug hepatotoxicity. Ecstasy was the second most common cause of liver injury in patients under the age of 25 years, being 20% in this subset of patients and 36% after ruling out the cases of viral etiology. All the patients had severe liver disease of acute onset, with jaundice, high peak of serum transaminases activity, hypoglycemia and low prothrombin activity, but no hepatic encephalopathy. Full recovery was observed in all cases from 3 to 12 months. CONCLUSIONS Ecstasy is responsible for a relatively high number of cases of acute liver failure in young people. Therefore, the use of this drug should be investigated in all patients with severe hepatitis of unclear origin. Efforts must be made to advise young people of the risks of ecstasy consumption.

Acute liver failure in Spain: Analysis of 267 cases

The cause of acute liver failure (ALF) is a major determinant of its outcome. Acetaminophen (paracetamol) overdose is a leading cause of ALF in some developed countries, whereas in others, such as Spain, it is extremely rare. To analyze the etiology, characteristics, and outcome of ALF in Spain, we performed a retrospective analysis of 267 patients whom we observed from 1992 to 2000. Seventeen tertiary‐care hospitals with active liver transplantation (LT) programs contributed data. Causes of ALF were viral hepatitis in 98 (37%; hepatitis B virus in 75 patients), unknown in 86 (32%), drug or toxic reactions in 52 (19.5%; acetaminophen overdose in 6), and miscellaneous in 31 (11.6%). Overall survival was 58%. LT was performed in 150 patients, with a survival of 69%. Despite fulfilling criteria, 51 patients were not transplanted because of contraindications; their survival was only 7.8%. Forty‐seven (85.5%) of 55 patients without transplant criteria survived. Hepatitis B virus is the most common cause of ALF in Spain, although the origin of 30% of cases remains undetermined. Acetaminophen overdose represents a very rare cause of ALF. LT was performed in >50% of cases. Patients without transplant criteria had a very good prognosis; those who fulfilled these criteria but who had contraindications for transplantation had a high mortality rate. Liver Transpl, 2007.

Use of primary human liver cells originating from discarded grafts in a bioreactor for liver support therapy and the prospects of culturing adult liver stem cells in bioreactors: a morphologic study.

Introduction. The development of a bioreactor providing a three-dimensional network of interwoven capillary membranes with integrated oxygenation and decentralized mass exchange enables the culture of primary human liver cells from discarded donor organs for extracorporeal liver support. Methods. Primary liver cells were isolated from 54 discarded organs (donor age 56.7±13.2 years). Between 2.8×1010 and 6.4×1010 parenchymal cells (PC) were cocultured with nonparenchymal cells (NPC) of the same organ in bioreactors (n=36). The metabolic activity of the cells was regularly determined during culture. The cell morphology and ultrastructure were investigated after culture periods of 1 to 5 weeks. Results. Cell metabolism was maintained over at least 3 weeks after a phase of adaptation lasting 2 to 3 days. Through the use of transmission electron microscopy and immunohistochemistry, it was demonstrated that PC and NPC spontaneously formed tissue-like structures. Vascular cavities (CD 31 immunoreactivity [IR]) and bile duct-like channels (CK 19 IR), both exhibiting proliferation activity (Ki-67 IR), were regularly distributed. Some of the bile duct-like channels showed similarities to the Canals of Hering found in the natural liver. Cells expressing morphologic and antigenic characteristics of adult liver stem cells (CD 34 IR and c-kit IR) and areas with cells that showed both hepatocyte and biliary characteristics were detected. Conclusion. The results show that primary human liver cells obtained from discarded donor organs recover and can be maintained in bioreactors for clinical liver support therapy. In addition, initial observations on adult liver stem-cell culture in bioreactors are presented.

Hepatitis C Virus Infection in Patients with Nonalcoholic Chronic Liver Disease

STUDY OBJECTIVE To determine the prevalence and meaning of antibodies to the hepatitis C virus (HCV) in patients with nonalcoholic chronic liver diseases. DESIGN Cross-sectional study. SETTING The liver unit of a referral-based university hospital. PATIENTS Three hundred and forty-six consecutive patients, including 137 with cryptogenic chronic liver disease, 156 with chronic hepatitis B, 47 with primary biliary cirrhosis, and 8 with persistently abnormal aminotransferase serum levels and normal liver histology. Among patients with cryptogenic liver disease, 41 received blood transfusions before discovery of liver disease and 18 had circulating nonorgan-specific autoantibodies. For comparison, 1495 apparently healthy volunteer blood donors were included in the study. LABORATORY INVESTIGATIONS: The presence of anti-HCV antibodies (anti-HCV) was determined by a recently developed enzyme-linked immunoassay. MEASUREMENTS AND MAIN RESULTS In patients with cryptogenic liver disease, the prevalence of anti-HCV was 82% (95% CI, 76% to 89%), being higher (P = 0.02) in patients with histories of blood transfusion than in those with unknown sources of exposure. Antibodies to HCV were not detected in patients with antinuclear antibodies at high titer. Among patients with chronic hepatitis B, anti-HCV were found in 11% (CI, 5% to 18%) of those with hepatitis B virus (HBV)-associated DNA in serum and in 29% (CI, 17% to 43%) of those with undetectable HBV replication (P less than 0.05). The prevalence of anti-HCV in blood donors was 1.2% (CI, 1.1% to 1.3%). CONCLUSIONS Our results indicate that HCV infection probably plays an important etiologic role in cryptogenic liver disease and, in some patients, in chronic hepatitis B. Determining whether anti-HCV are present appears to be useful for differentiating viral from autoimmune chronic liver diseases.

Renin, aldosterone and renal haemodynamics in cirrhosis with ascites.

Abstract. The interrelationships between the reninangiotensin‐aldosterone system, renal haemodynamics and urinary sodium excretion were investigated in fifty‐six non‐azotaemic cirrhotics with ascites. In twelve additional patients the renal renin secretion rate was also studied. Plasma renin activity and concentration and plasma aldosterone ranged from normal to very high values. There was a significant inverse relationship between plasma aldosterone and the urinary sodium excretion. Plasma aldosterone showed a highly significant direct correlation with plasma renin activity, and plasma renin concentration was closely and directly related to the estimated renin secretion rate. Neither plasma renin activity, plasma renin concentration nor the estimated renin secretion rate correlated with the renal plasma flow or the glomerular filtration rate. These results suggest that in non‐azotaemic cirrhosis with ascites the renin‐angiotensin‐aldosterone system is an important factor influencing sodium excretion, increased plasma renin and aldosterone concentrations are mainly due to an increased secretion rate, and total renal perfusion is not a major factor influencing renin secretion.

Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis.

BACKGROUND AND AIMS:Pruritus is a distressing symptom in patients with primary biliary cirrhosis, and when uncontrollable it is an indication for liver transplantation. Since pruritus can result from unknown substances that accumulate systemically as a consequence of impaired biliary secretion, we have assessed whether a new extracorporeal albumin dialysis (ECAD) procedure, the molecular-adsorbing recirculating system—MARS™, has any effect on pruritus of cholestasis.METHODS:Four patients with primary biliary cirrhosis and resistant pruritus were treated with two 7-h ECAD sessions 1 day apart. Pruritus was recorded from 15 days before the first session, before and after each session, and during the follow-up using a visual analogue scale (VAS). Standard liver tests as well as serum bile acid levels were also measured.RESULTS:There was a clear association between ECAD treatment and relief of itching, which promptly disappeared in two patients, or decreased markedly in the other two. One patient was free of pruritus for 18 months except for short periods with mild pruritus. The second patient experienced amelioration of itching, which almost disappeared completely and recurred mildly 4 months later. In the other two patients pruritus was alleviated markedly after ECAD but gradually recurred. These two patients were treated again 9 and 7 months later with favorable effects on pruritus. The scratching skin lesions improved or disappeared in parallel with the alleviation of itching. The albumin dialysis procedure did not result in liver test changes, except for circulating bile acids, which decreased in all the patients. No significant adverse effects were observed.CONCLUSIONS:The ECAD procedure seems to be an effective alternative for the treatment of patients with pruritus of cholestasis who do not respond to other therapeutic methods.