Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

Pyogenic liver abscess caused by Gemella morbillorum.

Even though Gemella morbillorum infection (GMI) is rare in humans, it may nevertheless, cause endocarditis, meningitis, brain abscess, pleural empyema, nephritis, mediastinitis, and--occasionally--liver abscess. We are describing the case of a 64-years-old Caucasian male admitted with fever and abdominal pain. Laboratory parameters revealed inflammation signs, and instrumental examinations showed the presence of diverticula in the ascending colon. Abdominal ultrasound (US) and computer tomography (CT) showed two focal lesions in the right liver lobe. One had the characteristics of a simple cyst; the second was hypoechoic with a low density area, possibly containing necrotic material. US-guided needle biopsy was found negative for neoplastic cells, showing purulent infiltrate. Pus culture was found positive for GMI. Systemic antibiotic therapy coupled with repeated US-guided needle aspiration, induced the resolution of the hepatic abscess. Few cases have been reported of hepatic abscess caused by GMI in immunocompetent non-cirrhotic subjects.

A pesar de que la infección por Gemella morbillorum (GMI por el término en inglés) es poco común en seres humanos, puede causar endocarditis, meningitis, absceso cerebral, empiema pleural, nefritis, mediastinitis y en ocasiones, absceso hepático. Describimos el caso de un hombre caucásico de 64 años que ingresó con fiebre y dolor abdominal. Los parámetros de laboratorio revelaron signos de inflamación y los exámenes mostraron la presencia de divertículos en el colon ascendente. La ecografía abdominal (US) y la tomografía computarizada (CT) mostró dos lesiones focales en el lóbulo hepático derecho. Una presentó las características de un quiste simple; la segunda fue hipoecóica con una zona de baja densidad, que posiblemente contenía material necrótico. Biopsia con aguja guiada por US dio un resultado negativo para células neoplásicas, mostrando infiltrado purulento. Cultivo de pus fue encontrado positivo para GMI. Una terapia con antibióticos sistémicos, junto con aspiración repetida con aguja guiada por US indujo a la resolución del absceso hepático. Pocos casos se han reportado de absceso hepático causado por GMI en sujetos inmunocompetentes no cirróticos.

Altered oxidative stress/antioxidant status in blood of alcoholic subjects is associated with alcoholic liver disease.

BACKGROUND: Oxidative stress is implicated in pathogenesis of alcoholic liver disease (ALD). This study investigated the possible correlation among the erythrocyte indices of oxidative stress, the leukocyte panels of antioxidant proteins (metallothioneins), the serum biochemical parameters and the liver steatosis grade. METHODS: A total of 118 cases including 60 alcoholic subjects and 58 controls were enrolled. All the alcoholic subjects were screened for body mass index (BMI), liver steatosis, and blood chemistry and serology. The level of oxidative stress and oxidative stress-related parameters were measured in the blood and correlated with clinical findings. RESULTS: Alcoholic subjects showed higher BMI, moderate/severe hepatic steatosis, increase in the levels of triglycerides, cholesterol, glucose, γ-glutamyl-transpeptidase (GGT), alanine aminotransferase (ALT), bilirubin, alpha 1 and beta 2 globulins, iron and a decrease in the levels of aspartate aminotransferase (AST) and beta 1 globulin with respect to the reference values. Moreover, alcoholic subjects showed: (i) an increase in Thiobarbituric Acid Reactive Substance (TBARS) content representing a good estimation of global oxidative stress; (ii) a stimulation of the activities of the antioxidant enzymes catalase and SOD; (iii) a modulation of expression of metallothioneins, with a down-regulation of MT-1A and an up-regulation of MT-1E isoforms. CONCLUSIONS: Our data suggest that alcoholism is strongly associated with altered pattern of blood metallothioneins; this parameter combined with the score calculated by an ad hoc implemented algorithm (HePaTest) could offer a non-invasive alternative approach for evaluating alcohol-related damages and could be used in follow-up of alcoholic patients.

Pyogenic liver abscess caused by Gemella morbillorum / Absceso hepático piógeno causado por Gemella morbillorum

Even though Gemella morbillorum infection (GMI) is rare in humans, it may, nevertheless, cause endocarditis, meningitis, brain abscess, pleural empyema, nephritis, mediastinitis, and - occasionally - liver abscess. We are describing the case of a 64-year-old Caucasian male admitted with fever and abdominal pain. Laboratory parameters revealed inflammation signs, and instrumental examinations showed the presence of diverticula in the ascending colon. Abdominal ultrasound (US) and computer tomography (CT) showed two focal lesions in the right liver lobe. One had the characteristics of a simple cyst; the second was hypoechoic with a low density area, possibly containing necrotic material. US-guided needle biopsy was found negative for neoplastic cells, showing purulent infiltrate. Pus culture was found positive for GMI. Systemic antibiotic therapy, coupled with repeated US-guided needle aspiration, induced the resolution of the hepatic abscess. Few cases have been reported of hepatic abscess caused by GMI in immunocompetent non-cirrhotic subjects.

A pesar de que la infección por Gemella morbillorum (GMI, por el término en inglés) es poco común en seres humanos, puede causar endocarditis, meningitis, absceso cerebral, empiema pleural, nefritis, mediastinitis y en ocasiones, absceso hepático. Describimos el caso de un hombre caucásico de 64 años que ingresó con fiebre y dolor abdominal. Los parámetros de laboratorio revelaron signos de inflamación y los exámenes mostraron la presencia de divertículos en el colon ascendente. La ecografía abdominal (US) y la tomografía computarizada (CT) mostró dos lesiones focales en el lóbulo hepático derecho. Una presentó las características de un quiste simple; la segunda fue hipoecóica con una zona de baja densidad, que posiblemente contenía material necrótico. Biopsia con aguja guiada por US dio un resultado negativo para células neoplásicas, mostrando infiltrado purulento. Cultivo de pus fue encontrado positivo para GMI. Una terapia con antibióticos sistémicos, junto con aspiración repetida con aguja guiada por US indujo a la resolución del absceso hepático. Pocos casos se han reportado de absceso hepático causado por GMI en sujetos inmunocompetentes no cirróticos.

Involvement of the mu-opioid receptor gene polymorphism A118G in the efficacy of detoxification of alcohol dependent patients.

INTRODUCTION: The A118G (rs 1799971) polymorphism in the mu-opioid receptor gene (OPRM1) has been reported to be associated with alcohol addiction. METHODS: In this study 109 patients diagnosed with alcohol dependence in accordance with DMS-IV criteria and 95 healthy subjects were enrolled and everyone has been genotyped. RESULTS: The percentage of alcoholic patients with higher than normal gamma-glutamyl transferase (GGT) levels significantly decreased after six months of standard detoxification treatment, both in patients with A/A genotype and in the other ones with A/G genotype. However, the percentage of alcohol dependent patients with the A/A genotype recorded a slight decrease of the GGT and the mean corpuscolar volume of erythrocytes (MCV) combination marker after six months of therapy (30% vs 12%), while subjects with the A/G genotype showed no variation. CONCLUSION: This finding suggests that alcohol dependent patients with the A/A genotype could have a faster restoration of their liver function than those ones with the A/G genotype: it might be possible that the presence of G allele confers on these patients a reduced ability in abstaining from drinking alcohol.

Treatment of recurrent hepatitis C (genotype 1) with pegylated interferon alfa-2b and ribavirin combination and maintenance therapy.

BACKGROUND/AIMS: This study aims at evaluating the efficacy of treatment with pegylated interferon (PEG-IFN) alfa-2b and ribavirin in patients with recurrent hepatitis C (genotype 1) after orthotopic liver transplantation (OLT) and the impact of this therapy on hepatic fibrosis at the end of conventional therapy and at the end of a period of maintenance treatment in non-responder patients. METHODOLOGY: Thirty-two consecutive patients diagnosed with recurrent HCV were considered candidates for antiviral therapy. RESULTS: Ten patients (31.2%) interrupted therapy due to side effects; sustained virological response (SVR) was observed in 27.2%, sustained biochemical response (SBR) in 31.8% and NR in 40.9% of cases. Eighteen patients underwent a biopsy at the end of conventional treatment: improved fibrosis score in all patients with SVR, improved score in 1 patient with SBR and stable score in 6 patients with SBR, worse score in 1 NR patient and stable in 6 NR patients. Six NR patients with stable score submitted to a maintenance therapy: improved score in 1 patient and stable score in 5 patients. CONCLUSIONS: In recurrent hepatitis C, in spite of the type of response, treatment slows down hepatic fibrotic evolution.

[Omega-3 fatty acids and astaxanthin in health and disease. Recent knowledges]. / Promozione della salute attraverso l'uso di acidi grassi essenziali omega-3 e astaxantina: recenti evidenze.

At present, medicine is aimed to the treatment of lesions. Instead, it would be right to develop the maintenance of normal health. A number of authorities have recently recommended increases in intake of omega-3 fatty acids and astaxanthin for the health of general population. Omega-3 are necessary to provide the optimal function of cellular membrane in health and in disease states. It is well known how at least two servings of fish a week, or dietary supplementation of fatty acids omega-3, should be taken to obtain the health benefits of this essential nutrient. Astaxanthin is a powerful biological antioxidant. This property has been implicated in its various biological activities demonstrated in both experimental animals and clinical studies. For the recent evidence of the contemporary presence of omega-3 and astaxanthin in oil of Wild Pacific Salmon Sockeye, a review has been effected for the evaluation of a possible role of such association for the health promotion.

Influence of body mass index, cholesterol, triglycerides and steatosis on pegylated interferon alfa-2a and ribavirin treatment for recurrent hepatitis C in patients transplanted for HCV and alcoholic cirrhosis.

Up to today no work has evaluated yet the importance of parameters such Body Mass Index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis in the response to therapy with Pegylated Interferon Alfa-2a and Ribavirin in patients with recurrent hepatitis C (genotype 1). 30 consecutive prospectively followed patients diagnosed with recurrent HCV were considered candidates for antiviral therapy. Qualitative and quantitative detection of HCV-RNA was performed with the Cobas Amplicor Hepatitis C Virus Test, version 2.0 and the Cobas Amplicor HCV Monitor, version 2.0 (Roche Diagnostics, Branchburgh, NJ, U.S.A.). HCV genotyping was performed by sequencing of the 5 untraslated region (5' UTR) (Visible Genetics TruGene Hepatitis Assay, Toronto, Canada). The observed distribution of BMI, cholesterol, TGC and steatosis were confirmed to be normally distributed by the one-sample Kolmogorov-Smirnov Goodness of fit test procedure. Comparison of BMI, cholesterol, TGC and steatosis between non responders (NR), sustained virological responders (SVR) and sustained biochemical responders (SBR) groups were analyzed by ANOVA with a post hoc Bonferroni test and correlation between variables was tested by Pearson test. The multivariate analysis was performed to estimate the chance of response on basis of the above mentioned variables. In patients with abnormal results in at least two out of four considered variables the chance of no-response was 40 times higher than that of SBR and 96 times than that of SVR. We can conclude how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and, therefore, the response to PEG-IFN Alfa-2a and Ribavirin.

DNA damage in peripheral blood lymphocytes of patients with cirrhosis related to alcohol abuse or to hepatitis B and C viruses.

BACKGROUND: Both alcohol abuse and hepatitis B or C virus infections are implicated in the development of hepatocellular carcinoma, but it is still controversial whether the pathogenetic mechanism is epigenetic or genotoxic. AIM: Considering that alcohol promotes the generation of reactive oxygen species and both viruses infect peripheral lymphocytes, in this study we investigated the occurrence of DNA fragmentation in peripheral blood lymphocytes from patients with alcoholic cirrhosis and from patients with cirrhosis related to B and C viruses, and analyzed the correlation between the degree of DNA fragmentation and the Child-Pugh score used to assess the degree of hepatic insufficiency. METHODS: The study population consisted of two groups: group I involved 12 patients with alcoholic cirrhosis; group II involved 25 patients with hepatic B virus or hepatic C virus cirrhosis. The control group involved 20 healthy individuals. The degree of DNA fragmentation in peripheral blood lymphocytes was determined with the alkaline Comet assay that provides two indexes of the frequency of DNA single-strand breaks and alkali-labile sites, the tail length and the tail moment. RESULTS: Mean values of both tail length and tail moment were significantly increased (P<0.001) in lymphocytes from 12 patients with alcoholic cirrhosis and in lymphocytes from 25 patients with HBV or HCV cirrhosis, as compared with average tail length and tail moment values of lymphocytes from 20 healthy individuals. A significant positive correlation was found to exist between the degree of DNA fragmentation present in lymphocytes of each of the 37 patients with alcoholic or viral cirrhosis and the corresponding value of the Child-Pugh score. CONCLUSION: The occurrence of DNA fragmentation in peripheral blood lymphocytes reflects a direct genotoxic effect of either alcohol or HBV and HCV and suggests that the same genotoxic effect may operate in the liver and contribute to hepatocarcinogenesis.

Type-2 hepatorenal syndrome and refractory ascites: role of transjugular intrahepatic portosystemic stent-shunt in eighteen patients with advanced cirrhosis awaiting orthotopic liver transplantation.

BACKGROUND/AIMS: TIPS (transjugular intrahepatic portosystemic stent-shunt) has been used increasingly in the management of refractory variceal bleeding. Its role in the management of refractory ascites and hepatorenal syndrome still awaits further prospective studies. Type-2 hepatorenal syndrome is a moderate steady renal impairment. It arises spontaneously and it is the main mechanism of refractory ascites. Precipitating factors may lead to type-1 hepatorenal syndrome. Hepatorenal syndrome is a common complication of advanced cirrhosis with a 3-month mortality of more than 90% unless treated by orthotopic liver transplantation. However, because of the short survival of patients with hepatorenal syndrome and the limited availability of organs, only a small percentage of patients with hepatorenal syndrome can actually reach orthotopic liver transplantation. That is why awaiting orthotopic liver transplantation we have submitted some suitable patients to a TIPS setting. METHODOLOGY: We have considered eighteen consecutive patients affected by advanced cirrhosis (Child-Pugh 10-12) awaiting orthotopic liver transplantation and suitable for TIPS treatment for the presence of type-2 hepatorenal syndrome (10 males, average age 44.5). The criteria for the diagnosis of hepatorenal syndrome and refractory ascites have been effected according to a consensus recommendation. Organic kidney disease was excluded. After mild intravenous sedation and analgesia a puncture needle was advanced transjugular in a catheter through the inferior cava into one of the three hepatic veins. Subsequently, an intrahepatic branch of the portal vein was punctured and the shunt was established by the implantation of Wallstent (diameter 10 mm; Boston, Scientific, Natick, MA). In all patients, we compared serum creatinine, creatinine-clearance, sodium excretion and urine volume before the intervention and 12 weeks after TIPS. The differences among groups were analyzed using paired Student's t-test. RESULTS: The stent shunt was successfully established in all eighteen patients. Complications occurred in 4 patients (temperature above 38 degrees C or vomiting). No patients have developed hepatic encephalopathy resistant to medical treatment. As for the ascites a complete response with total remission of ascites was obtained in eight patients, while a partial response with the presence of sonographically detectable ascites--without the need of paracentesis--was obtained in ten patients. As regards renal functional parameters we have evidenced a significant improvement after TIPS. CONCLUSIONS: We can notice how the setting of TIPS, at least in the presented case, has allowed the treatment of ascites and, furthermore, has lead to improvement of the renal functional parameters. It all implies the enormous advantage of a better management of the patient waiting for orthotopic liver transplantation and, most of all, the advantage of preparing the patient for the surgical intervention with normal renal functional parameters: in fact, it is well known that the increase of serum creatinine influences the pre- and post-orthotopic liver transplantation course, and in particular can modify the mortality rate of the patient list. The lack of effective alternative treatment modalities and the almost universally fatal outcome of hepatorenal syndrome make TIPS an attractive option in the treatment of hepatorenal syndrome as a bridge to orthotopic liver transplantation.