Hepatitis: Pellicano R

Pellicano R. · Cattedra di Gastroenterologia Dipartimento di Medicina Interna Università degli Studi-Torino, Italy. · Minerva Gastroenterol Dietol. · Pubmed #19320084 No free full text.

This publication has no abstract.

Pellicano R, Ménard A, Rizzetto M, Mégraud F. · Department of Gastro-Hepatology, Molinette Hospital, Turin, Italy. · Lancet Infect Dis. · Pubmed #18353266 No free full text.

Abstract: The discovery of Helicobacter hepaticus as a causal agent of hepatitis and hepatocarcinoma in mice has stimulated interest in looking for Helicobacter spp in human liver samples. These bacteria could be a risk factor for the progression of liver disease to cirrhosis and hepatocellular carcinoma, especially among patients chronically infected with hepatitis C virus. We reviewed the studies done on this topic, and, with the exception of one, all studies reported an association between the presence of Helicobacter spp and liver disease. However, these data are weakened by the fact that Helicobacter spp DNA was detected but no bacteria could be grown, and by the difficulties in identifying the Helicobacter spp involved. More studies are therefore needed to confirm whether a causal association exits between the presence of Helicobacter spp in the liver and the development of cirrhosis and hepatocellular carcinoma.

Carrozzo M, Pellicano R. · Department of Oral Medicine, School of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. · Minerva Gastroenterol Dietol. · Pubmed #18299669 No free full text.

Abstract: An association between lichen planus (LP) and liver diseases has been reported. PubMed database has been used to extract information on hepatitis C virus (HCV) infection and LP. The results suggest that LP, mainly the oral type, is significantly associated with HCV infection in Southern Europe and Japan but not in Northern Europe. These differences may be related to genetic factors. Detection of HCV viral sequences and HCV-specific CD4+ and/or CD8+ T lymphocytes in oral samples of LP patients suggests that HCV might be involved in the development of oral lesions via an immunological pathway, characterized by an excessive production of Th1 cytokines following an uneffective antiviral immuno-response.

Pellicano R, Fagoonee S, Repici A, Rizzetto M. · Department of Gastro-Hepatology, Molinette Hospital, Turin, Italy. · Panminerva Med. · Pubmed #17625484 No free full text.

Abstract: It is estimated that, in the United States and Europe, 15-30% of people with human immunodeficiency virus (HIV) are coinfected with hepatitis C virus (HCV). Among these patients, approximately 80% are intravenous drug users (IVDU), 71% are hemophiliacs, and around 20% are homosexual/bi-sexual men. HIV infection accelerates the natural history of HCV infection. On the contrary, highly active antiretroviral therapy reduces the rate of mortality due to liver disease by immune restoration. Since having HIV implies being at risk also for HCV as both infections can be acquired in similar ways, all individuals with the former should be screened for the latter. Loss of antibodies against HCV in HIV-seropositive IVDU has been shown. Thus, quantitative tests determining HCV-RNA levels in blood are currently being employed for diagnosis confirmation in case of an obvious ''risk group''. Since HIV can progress more rapidly than HCV, it may be preferable to treat HIV first. The 2007 recommendations from HCV-HIV International Panel indicate current treatment of HCV in coinfected patients with pegylated formulation of interferon at standard doses plus weight based ribavirin. The treatment duration should be evaluated on the basis of HCV genotype. Liver transplantation is a most debated issue when dealing with HCV/HIV coinfected subjects. Mortality among HIV-infected liver transplant recipients is similar to that of age and race-matched HIV-negative controls. The present concise review attempts to highlight on the current clinical situation on HIV/HCV coinfection.

Pellicano R, Mladenova I, Dimitrova SM, Bruno CM, Sciacca C, Rizzetto M. · Unit of Gastro-Hepatology, Molinette Hospital, Turin, Italy. · Minerva Gastroenterol Dietol. · Pubmed #15719001 No free full text.

Abstract: Since the advent of sensitive diagnostic blood tests for the detection of antibody to hepatitis C virus (HCV) in donors, there has been a large decline in the incidence of transfusion-related hepatitis. Globally, the infection has an estimated prevalence of 3%, with a prevailing 1% in Europe while varying geographically within a North-South gradient, ranging from around 0.5% in Northern countries to 2% in Mediterranean area. The incidence is very difficult to estimate accurately as many patients with acute HCV infection are asymptomatic and, thus, do not present for diagnosis. Data from the US report a fall in the annual occurrence of new cases per year from 230,000 in the late 1980s to approximately 35,000 in the 1990s. Therefore, a reduction in incident cases might eventually lead to lower prevalence of HCV infection. Although the incidence of viral infection may be decreasing, the prevalence of liver disease caused by HCV is on the rise. This is due to the significant lag, often 20 years or longer, between the onset of infection and clinical manifestation of liver disease. HCV can be transmitted by a variety of routes. It is most efficiently passed on by large or repeated percutaneous exposures such as through transfusions, transplantation from an infected donor or intravenous drug use. Transmission may also occur from contacts with infected subjects in the household, through perinatal and parenteral exposures in the health care setting. The risk of sexual transmission of HCV is low. Despite this knowledge, nearly half of infected patients do not have a history suggesting a parenteral route of acquisition. Since a prophylactic vaccine is hitherto not available, prevention becomes extremely important: identification of infected persons and of risk factors associated with acquiring HCV allow to develop strategies for preventing the spread of infection as well as its complications, and for planning appropriate care and support services.

Durazzo M, Premoli A, Fagoonee S, Pellicano R. · Department of Internal Medicine, University of Turin, Italy. · Dig Dis Sci. · Pubmed #12757152 No free full text.

Abstract: The pattern of some autoimmune hepatitis can be difficult to classify, sometimes due to the overlap of these with primary biliary cirrhosis, primary sclerosing cholangitis and chronic viral hepatitis. The etiology of these variant forms remains unclear. The distinction among the overlap syndromes poses different problems both of prognosis and therapeutic approach. Presently, the utility of the scoring system devised and revised by the International Autoimmune Hepatitis Group regarding these cases is under discussion. Histological examination seems to be an important tool, but often the result does not help in defining a correct diagnosis. To date, the overlap syndromes can be classified at an intermediate level between cholestatic forms of autoimmune hepatitis or hepatic forms of cholestatic syndromes, but it cannot be excluded that the syndromes represent independent disorders.

Fagoonee S, Pellicano R, Rizzetto M, Ponzetto A. · Department of Biology Biochemistry and Genetics, University of Turin, Turin, Italy. · Panminerva Med. · Pubmed #11677423 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is a long-term consequence of chronic liver disease, whose aetiology could result from viral, environmental and hereditary causes. Viral infection, by itself, could only partially explain the pathogenesis of cirrhosis and HCC. A new aetiologic agent capable of inducing chronic active hepatitis and hepatocellular tumours was discovered: it is a bacterium belonging to the genus Helicobacter, and named H. hepaticus. Presence of sequences belonging to the 16S rRNA of Helicobacter species (spp.) has been demonstrated in liver of most patients with cirrhosis and HCC. H. pylori and related bacteria, such as H. hepaticus, produce toxins that kill hepatocyte by a granulating effect on liver cell lines. In vivo, such toxins might reach the liver through the portal tract, thereby causing hepatocellular damage. The recognition of Helicobacter spp. as a possible risk factor for cirrhosis and HCC might have a practical impact on the general population: the treatment of this infection is easy and far less expensive than liver transplantation or any long term treatment for the other risk factors of HCC. Any confirmation of the involvement of Helicobacter in liver disease would eventually come from the success of culturing the bacterium from liver tissues. Future research is needed to clarify the importance of Helicobacter spp. in respect to the other pathogens already known as causative agents of chronic inflammation of the liver and its long term sequelae, namely cirrhosis and HCC.

Leone N, Volpes R, Carrera M, Pellicano R, De Paolis P, Fiorentino M, Fronda GR, Rizzetto M. · Department of Gastroenterology, B Surgery, Molinette Hospital, Turin, Italy. · Panminerva Med. · Pubmed #10965777 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is closely associated with cirrhosis, but it also develops, although much less frequently, in a non-cirrhotic liver. It is suspected that hepatocellular carcinoma has a different etiology when associated and not associated with chronic liver disease. We report two cases of patients with hepatocellular carcinoma that developed in a non-cirrhotic liver. In the first case we describe an incidental liver nodular lesion containing multiple foci of HCC including pseudogland or trabecular formation and areas of sclerosis. The non-cancerous parenchyma of the liver was histologically unremarkable except for mild fatty changes of hepatocytes and minimal dysplasia. The second case describes a combined hepatocellular carcinoma and cholangiocellular carcinoma (CCC) (mixed carcinoma) in a patient who was serologically negative for both hepatitis B and C viruses. The adjacent liver parenchyma showed mild piecemeal necrosis and mild lobular activity compatible with chronic viral hepatitis, but cirrhosis was not established. This case appears to indicate that mixed type carcinoma can develop in a non-cirrhotic liver, with CCC being far more dominant than HCC; such a finding is extremely unusual, based on previously published reports.

Pellicano R, Craxi A, Almasio PL, Valenza M, Venezia G, Alberti A, Boccato S, Demelia L, Sorbello O, Picciotto A, Torre F, Ideo G, Cattaneo C, Berrutti M, Rizzetto M. · U.O.A.D.U. Gastro-Epatologia, Ospedale S. Giovanni Battista (Molinette), Corso Bramante 88-10126 Torino, Italy. · World J Gastroenterol. · Pubmed #16052676 links to  free full text

Abstract: AIM: To compare the efficacy and safety of recombinant human IFN beta-1a alone or in combination with ribavirin in treatment-naive subjects with chronic hepatitis C. METHODS: Open, randomized trial was performed in 6 Italian tertiary centers: 102 of the 108 patients screened were randomized to receive 6 MIU of recombinant human IFN beta-1a subcutaneously daily for 24 wk, alone (Group 1, n = 51) or in combination with ribavirin 1,000 to 1,200 mg/d (Group 2, n = 51). RESULTS: The end-of-treatment virologic response rate was 29.4% in Group 1 and 41.2% in Group 2 (non-significant). Twenty-four weeks after stopping therapy, sustained virologic response rate was 21.6% in Group 1 and 27.4% in Group 2 (non-significant). All subjects in Group 1 completed treatment, while two subjects in Group 2 stopped therapy due to treatment-related adverse events. CONCLUSION: Recombinant human IFN beta-1a, alone or in combination with ribavirin, has an excellent safety profile and, may represent an alternative for chronic hepatitis C patients who are unable to tolerate pegylated alpha-interferon.

Pellicano R, De Angelis C, De Luca L, Smedile A, Berrutti M, Astegiano M, Rizzetto M. · Department of Gastro-Hepatology, Molinette Hospital, Turin, Italy. · Minerva Gastroenterol Dietol. · Pubmed #19305375 No free full text.

Abstract: A precise understanding of the source of infection and modes of transmission of hepatitis C virus (HCV) is a worldwide priority in terms of public health. This is more evident where multi-ethnic customs cohabit. Despite the knowledge on risk factors for HCV transmission, nearly 50% of infected patients do not have a history suggesting a parenteral route of acquisition. In the present paper, the authors, focusing on ethnic and cultural aspects of HCV transmission, emphasize the need for health education in order to avoid the acquisition and the diffusion of the infection. With the current globalization and large-scale migrations, only by following a preventive strategy based on disseminate information risk behaviours may be modified.

De Luca L, De Angelis C, Fagoonee S, Di Bella S, Rizzetto M, Pellicano R. · Department of Gastroenterology and Digestive Endoscopy, Pellegrini Hospital, Naples, Italy. · Minerva Gastroenterol Dietol. · Pubmed #19305373 No free full text.

Abstract: The progression of chronic liver diseases is characterized by a common histopathological pathway comprising fibrosis formation and distortion of hepatic architecture which are the hallmark of evolution to cirrhosis. Several factors are responsible for the severity and progression of chronic hepatitis C. Here, we describe the most important data regarding the association between regular smoking and histological hepatic lesions. Some reports have shown that the proportion of patients with moderate or significant histological activity gradually increases with the daily consumption of tobacco. Moreover, fibrosis is associated with regular smoking in some studies. However, controversies result from other studies. Nicotine is mainly metabolised by the liver, and its administration in experimental animals showed development of steatosis and focal or confluent hepatic necrosis, probably linked to the oxidative stress associated with lipid peroxidation. In chronic hepatitis C patients, preliminary studies have suggested that hypoxia caused by smoking may induce expression of the cytokines vascular endothelial growth factor (VEGF) and VEGF-D and their corresponding soluble tyrosine kinase receptors fms-like tyrosine kinase receptor and kinase insert domain receptor. Since this issue is controversial and smoking is in any case unsafe, stopping is recommended for patients with liver diseases.

Fagoonee S, De Luca L, De Angelis C, Castelli A, Rizzetto M, Pellicano R. · Molecular Biotechnology Center, University of Turin, Turin, Italy. · Minerva Gastroenterol Dietol. · Pubmed #19212306 No free full text.

Abstract: Autoantibodies are disease markers of autoimmune hepatitis (AIH). Antinuclear antibodies, smooth muscle antibodies, antibodies to liver/kidney microsome type 1, and perinuclear antibodies to neutrophil cytoplasm constitute the ''conventional'' battery of autoantibodies, while an emerging interest to evaluate new autoantibodies as diagnostic or prognostic markers, such as the anti-Saccharomyces cerevisiae antibodies, is detectable (ASCA). This paper focuses mainly on the findings and the potential role of ASCA in AIH. These antibodies are present in 5-6.3% of blood donors and in the gastrointestinal setting, ASCA have been found most often in Crohn's disease and with lower frequency in the course of ulcerative colitis and celiac disease. Furthermore, they have been described, to a lesser extent, in patients with primary sclerosing cholangitis and primary biliary cirrhosis and in AIH. ASCA occur in 20-30% of patients suffering from AIH with a statistically significant increase observed only for IgG ASCA in type 1 AIH. This probably indicates collateral immune reactivities to the primary pathogenic process. The outcome of hepatitis is not influenced by the presence of ASCA. In conclusion, ASCA positivity does not imply that there exists a distinct subgroup of patients with AIH and these autoantibodies are not involved in the pathogenetic mechanism of AIH.

Giordanino C, Bugianesi E, Smedile A, Ciancio A, Abate ML, Olivero A, Pellicano R, Cassader M, Gambino R, Bo S, Ciccone G, Rizzetto M, Saracco G. · Gastroenterology, Molinette Hospital, Turin, Italy. · Am J Gastroenterol. · Pubmed #18702647 No free full text.

Abstract: BACKGROUND: Patients with chronic hepatitis C are at risk of developing type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG), and this risk may increase among hepatitis C virus (HCV) patients not responding to an antiviral therapy. AIM: To compare the incidence of glucose abnormalities (IFG or DM) after an antiviral therapy between HCV+ patients with a long-term virological response (LTR) and nonresponders (NR; persistently positive HCV-RNA). METHODS: All 202 HCV+ patients without the baseline glucose abnormalities enrolled by our center in investigational trials or routinely treated with interferon (IFN)/peginterferon (Peg-IFN) (+/- ribavirin) from 1988 to 2001, with the available baseline sera stored at -80 degrees C, were considered. The baseline data included age, sex, body mass index (BMI), viral load, genotype, liver histologic staging and steatosis, glucose, and cholesterol. The homeostatic assessment of insulin resistance (HOMA-IR) was calculated in the baseline serum. The incidence of IFG or DM at the end of follow-up was compared between patients with LTR and NR. RESULTS: After a median follow-up of 8.0 yr (range 5-16), the cumulative risk of DM (N = 7) or IFG (N = 33) among the 202 HCV+ included patients was 16.9% (95% confidence interval [CI] 11.3-22.5). The 8-yr risk was not significantly lower between LTRs (14.5%) compared to NRs (18.8%) (hazard ratio [HR] 0.60, CI 0.30-1.20, P= 0.16). The HR adjusted for the baseline risk factors for DM and the predictors of a poor response (age, sex, HOMA-IR, BMI, family history of diabetes, HCV genotype 1, high viral load, cirrhosis, and steatosis) was 0.88 (CI 0.38-2.02, P= 0.76). Among other factors, those more associated to IFG-DM were an increasing age (P= 0.017), a higher BMI (P= 0.054), and a family history of DM (P= 0.065). CONCLUSIONS: After adjustment for several baseline risk factors, the incidence of glucose abnormalities was not significantly different between LTRs and NRs. Our data suggest that HCV clearance does not significantly reduce the risk of glucose intolerance.

Actis GC, Fadda M, Pellicano R, David E, Rizzetto M, Sapino A. · Department of Digestive Disease and Nutrition, Ospedale Molinette, C.so Bramante 88, Torino, Italy. · Biomed Pharmacother. · Pubmed #18657949 No free full text.

Abstract: Despite the accumulation of positive data, the role of azathioprine (AZA) in the maintenance of remission of ulcerative colitis is still controversial. We looked at the follow-up of the ulcerative colitis patients who, after responding to either steroids or cyclosporin (CsA), received AZA at our referral center for over a decade. The 39 patients (29 m/10f) were treated between 1991 and 2007. Twenty-five of them had responded to CsA, the remaining 14 to corticosteroids. AZA was usually overlapped with either of the two agents at the initial dose of 2mg/kg/day. The definitions of remission, relapse, and AZA toxicity followed commonly agreed criteria. The median duration of the AZA treatment was 14 months (<1-201). Fifty-two percent and 14%, respectively, of the CsA and the steroid responders needed surgery (overall rate=38%). The figures were 32 and 15 at the first year. The majority of the patients had 1-2 relapses often in connection with withdrawal of AZA; only 3 of these relapsers needed hospitalization. AZA caused toxicity in 16/39 (41%) patients, requiring withdrawal in 23% of the cases; leukopenia (17%) and hepatitis/cholestasis (10%) ranked first and second for frequency. All of the patients in whom AZA was stopped (or reduced) relapsed. In conclusion, the 1-year colectomy rates compare favorably with the figures reported by the literature. By contrast, the toxicity rates were higher than expected. Failure to genotype or to use escalating AZA doses can only be hypothesized as causes.

Actis GC, Pellicano R, Bugianesi E, Lagget M, Rizzetto M. · Department of Gastro-Hepatology, Molinette Hospital, Turin, Italy. · Minerva Gastroenterol Dietol. · Pubmed #18614972 No free full text.

Abstract: AIM: Third-level Day-Hospital Services of Gastro-Hepatology are likely to recruit patients with an increased disease severity. The burden of request for immunomodulation drugs is presently unclear. METHODS: The charts of 1 012 consecutive patients who underwent day-hospital admission were reviewed. Among them, 975 were admitted for several reasons (percutaneous liver biopsies, abdominal fluid aspirations, infiltrations of hepatic nodules, gastrointestinal endoscopies with specific treatments). Data of the remaining 37 patients were elaborated. RESULTS: Of them, 31 (83%) suffered from ulcerative colitis (UC) or Crohn's disease (CD) (17 and 14, respectively) and 6 from autoimmune type 1 hepatitis (AIH). Of the 14 non-operated UC patients, 12 were taking azathioprine (AZA) and 2 infliximab (IFX). Among CD patients, the majority received AZA (N=6) or IFX (N=6). Of the AIH patients, 5 were treated with AZA and 2 had also cyclosporine. Overall, corticosteroids (32%) and IFX (21%) ranked first and second among the induction drugs, and AZA ranked first (62%) as maintenance option. Of the 4 CD patients under IFX treatment, 2 were switched to leukapheresis for incomplete response, the third one developed thrombotic complications, and the last one achieved disease remission after 12 months. Of the 2 cases of UC, one lost response soon and was colectomized, the other is maintaining moderately active disease, requiring scheduled injections every 8 weeks. CONCLUSION: Despite the caution imposed by the very small numbers, this analysis confirms that the potent available options are difficult to be correctly positioned in the therapeutic algorithm of inflammatory bowel disease.

Pellicano R, Puglisi G, Ciancio A, Balzola F, Saracco G, Ciccone G, Baldi I, Abate ML, Smedile A, Rizzetto M. · Department of Gastro-Hepatology, San Giovanni Battista (Molinette) Hospital, Torino, Italy. · J Med Virol. · Pubmed #18297716 No free full text.

Abstract: Several factors, including metabolic profile, are predictive of response to standard antiviral therapy in patients with chronic hepatitis C. In a retrospective study, it was investigated whether uric acid, involved in metabolic syndrome, could be included. A total of 153 patients (56.2% males; mean age 45.7 +/- 11.3 years) treated with pegylated-interferon and ribavirin were included. Eighty-five were infected with hepatitis C virus (HCV) genotype 1 or 4 and 68 with genotype 2 or 3. Viral load was >1,000,000 IU/ml in 101, < or =1,000,000 IU/ml in 35 and unknown in 17 patients. Ishak fibrosis score was < or =4 in 81, >4 in 15 and unknown in 57 patients. Mean serum uric acid was 5.05 +/- 1.3 mg/dl. Sustained virological response (negative serum HCV-RNA 6 months after treatment cessation) was achieved in 102 patients (67%). In the final logistic model, serum uric acid level > or =5.8 mg/dl (OR = 0.46; 95% CI: 0.30-0.62), viral load (OR = 0.29; 95% CI: 0.09-0.92) and HCV genotype (OR = 0.23; 95% CI: 0.09-0.60) were identified as the most important factors independently influencing clinical outcome. The prognostic role of serum uric acid was confirmed on the sub-sample reporting Ishak fibrosis score (OR = 0.49; 95% CI: 0.28-0.85). Serum uric acid level > or =5.8 mg/dl is predictive of poor response to HCV treatment. Prospective studies are needed to clarify the issue.

Actis GC, Olivero A, Lagget M, Pellicano R, Smedile A, Rizzetto M. · Department of Gastro-Hepatology and Clinical Nutrition, San Giovanni Battista (Molinette) Hospital, Torino, 10126, Italy. · Dig Dis Sci. · Pubmed #17436094 No free full text.

Abstract: The evolving role of liver biopsy has induced the formulation of several guidelines on its appropriateness. However, the great divergence among hepatologists is still unresolved. We report the 4-year activity of a day hospital of gastrohepatology in northern Italy. Between January 2001 and July 2004, 835 subjects (mean age, 43+/-12 years) underwent this procedure in our facility. Etiologically, in 465 (56%) and 157 (19%) patients, chronic hepatitis C and nonspecific elevated liver biochemical tests were the first and second indications, followed by chronic hepatitis B and suspected nonalcoholic steatohepatitis. On a purpose basis, procedures requested for staging (n = 578) and/or for diagnosis (n = 217) were identified. Among the former, 80% had the scope of staging chronic hepatitis C, and in 15% of these unsuspected superimposed cirrhosis was detected. Among diagnostic procedures, nonspecific raised liver enzyme level ranked first. Twenty-two percent of patients reported unwanted effects following the procedure. In conclusion, these data accord with indications expressed by international guidelines. The impact of liver biopsy on therapeutic decision-making needs to be studied further.

Pellicano R, Smedile A, Peyre S, Astegiano M, Saracco G, Bonardi R, Rizzetto M. · Department of Gastro-Hepatology, Molinette Hospital, Turin, Italy. · Minerva Gastroenterol Dietol. · Pubmed #15756146 No free full text.

Abstract: In face of numerous benefits induced by therapy based on interferon (IFN) associated with ribavirin for the treatment of chronic hepatitis C, there is an increasing concern regarding its tolerance, which can, in some cases, reduce the quality of life as well as compliance of patients. Among the less common side effects, there are the autoimmune ones which can be globally divided into appearance or increase in titres of auto-antibodies and/or manifestation of overt autoimmune pathologies. Whereas the former may concern more than 50% of treated subjects, the latter is reported in only 1-2% of patients under therapy. Thyroid dysfunction represents the well-studied autoimmune disorder. The presence of pre-existing anti-thyroid antibodies and being of female sex, constitute relevant risk factors for the development of a disease involving this gland. Often the treatment of thyropathy must be continuous in spite of IFN discontinuation because the disturbance usually does not abate with stopping antiviral therapy. Some observations have pointed out to the fact that IFN can lead to the development of insulin-dependent diabetes mellitus. Sometimes, during, as well as after IFN treatment, the appearance of anti-islet cell antibodies has been shown, but its interrelationship with the development of disease is uncertain. While being treated with IFN for chronic hepatitis C, the finding of non-organ specific antibodies at baseline can increase the likelihood of the development of autoimmune hepatitis. However, their presence does not constitute an absolute contraindication to the treatment, except in case of high titre. Other disorders, such as a lupus erythematosus-like syndrome, haemolytic anaemia, and immune-mediated thrombocytopenia have been reported. In conclusion, although the presence of auto-antibodies is considered to be an epiphenomenon without pathogenic significance in most patients suffering from chronic hepatitis C, it poses a problem when they need to be treated with IFN. This antiviral drug can induce or exacerbate a multitude of autoimmune-related disorders, however, clinically overt immune-mediated diseases are rare and affect a subset of subjects who have an underlying autoimmune diathesis.

Bruno CM, Neri S, Sciacca C, Bertino G, Di Prima P, Cilio D, Pellicano R, Caruso L, Cristaldi R. · Department of Internal Medicine and Sistemic Diseases, University of Catania, Italy. · World J Gastroenterol. · Pubmed #15112358 links to  free full text

Abstract: AIM: To investigate the serum erythropoietin (Epo) levels in patients with chronic liver diseases and to compare to subjects with iron-deficiency anaemia and healthy controls. METHODS: We examined 31 anaemic (ALC) and 22 non-anaemic (NALC) cirrhotic patients, 21 non- anaemic subjects with chronic active hepatitis (CAH), 24 patients with iron-deficiency anaemia (ID) and 15 healthy controls. Circulating Epo levels (ELISA; R and D Systems, Europe Ltd, Abingdon, UK) and haemoglobin (Hb) concentration were determined in all subjects. RESULTS: Mean+/-SD of Epo values was 26.9+/-10.8 mU/mL in ALC patients, 12.5+/-8.0 mU/mL in NALC subjects, 11.6+/-6.3 mU/mL in CAH patients, 56.4+/-12.7 mU/mL in the cases of ID and 9.3+/-2.6 mU/mL in controls. No significant difference (P>0.05) was found in Epo levels between controls, CAH and NALC patients. ALC individuals had higher Epo levels (P<0.01) than these groups whereas ID subjects had even higher levels (P<0.001) than patients suffering from ALC. CONCLUSION: Increased Epo values in cirrhotics, are only detectable when haemoglobin was lesser than 12 g/dL. Nevertheless, this rise in value is lower than that observed in anaemic patients with iron-deficiency and appears blunted and inadequate in comparison to the degree of anaemia.

Pellicano R, Mazzaferro V, Grigioni WF, Cutufia MA, Fagoonee S, Silengo L, Rizzetto M, Ponzetto A. · Ambulatorio di Gastroenterologia, Ospedale S Giovanni Battista, Via Chiabrera 34, III piano, 10126 Torino, Italy. · World J Gastroenterol. · Pubmed #14966925 links to  free full text

Abstract: AIM: Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultimately hepatocellular carcinoma (HCC), the mechanism underlying the worsening is still undefined. Experimental infection by Helicobacter hepaticus in mice causes chronic hepatitis and HCC and recently, more Helicobacter species (Helicobacter spp.) have been detected in the liver of patients suffering from cholestatic diseases and HCC arising from non-cirrhotic liver. We investigated whether Helicobacter spp. sequences could be detected in the liver of patients with cirrhosis and HCC compared to subjects with metastasis to liver from colon cancer. METHODS: Twenty-three liver samples from patients operated upon for HCC superimposed on hepatitis C virus (HCV)-related cirrhosis and 6 from patients with resected metastases from colorectal cancer, were tested by polymerase chain reaction for presence of genomic 16S rRNA of Helicobacter genus using specific primers. DNA sequencing and cag A gene analysis were also performed. RESULTS: Genomic sequences of Helicobacter spp. were found in 17 of 20 (85%) liver samples from patients with HCC and in 2 of 6 samples from patients with liver metastasis. In three samples of the first group the result was uncertain. H pylori was revealed in 16 out of 17 positive samples and Helicobacter pullorum in the other. CONCLUSION: Helicobacter spp., carcinogenic in mice, were found at a higher frequency in the liver of patients with HCV-related cirrhosis and HCC than those in patients without primary liver disease.

Leone N, Pellicano R, Brunello F, Cutufia MA, Berrutti M, Fagoonee S, Rizzetto M, Ponzetto A. · Department of Gastro-Hepatology, Molinette Hospital, Via Chiabrera 34, 10126 Turin, Italy. · Cancer Detect Prev. · Pubmed #14642558 No free full text.

Abstract: BACKGROUND: Infection by Helicobacter hepaticus causes chronic hepatitis and hepatocellular carcinoma (HCC) in mice, and Helicobacter pylori (H. pylori) genomic sequences have been demonstrated in the liver of patients with HCC. H. pylori infection reportedly occurs with high frequency in patients with cirrhosis but none of the studies has investigated it in subjects with cirrhosis and superimposed HCC. In this case-control study, we searched for the seroprevalence of H. pylori infection in patients with HCC. PATIENTS AND METHOD: Forty-six patients (30 males, 16 females, mean age 69 years) with HCC and hepatitis C virus (HCV)-related cirrhosis were compared to 46 sex and age (+/-1 year) matched patients presenting consecutively to the Emergency Department of Molinette Hospital of Torino. All subjects were tested for presence in serum of IgG antibodies against H. pylori and the result was analyzed using the chi-square test. RESULTS: H. pylori seropositivity was more prevalent among patients with HCC (36/46, 78.2%) than in controls (25/46, 54%) (P<0.05) (OR 3.02, 95% confidence interval ). Twenty-five out of 30 (83.3%) male patients showed seropositivity at a variance with 16/30 (53%) in the controls (P<0.05); 11 out of 16 (68.7%) female patients were seropositive versus 9 out of 16 (56.2%) control subjects (P=n.s.). CONCLUSION: Seroprevalence of antibodies to H. pylori was found to be higher in patients with HCC than in controls.

Ponzetto A, Pellicano R, Redaelli A, Rizzetto M, Roffi L. · Department of Internal Medicine, University of Turin. · New Microbiol. · Pubmed #14596342 No free full text.

Abstract: BACKGROUND AND GOALS: One-third of patients with liver cirrhosis suffers from acute peptic ulcer, a disease strongly correlated with Helicobacter pylori (H. pylori) infection. We report the seroprevalence of antibodies to H. pylori in 179 patients with Hepatitis C Virus (HCV)-related chronic active hepatitis and cirrhosis. MATERIALS AND METHODS: Among patients, 135 (86 males and 49 females, mean age 51.2 +/- 13.28, range 27-77 years) had chronic active hepatitis (CAH) and 44 cirrhosis (28 males and 16 females, mean age 62.4 +/- 9.2, range 37-77 years). Serum antibodies to H. pylori were tested using a commercial enzyme immunosorbent assay. The control population consisted of 619 consecutive blood donors (523 males, 96 females, mean age 47 +/- 5.3 years, range 18-65). RESULTS: The overall prevalence of antibodies to H. pylori was 73.1% (131/179) among patients and 47% (291/619) among blood donors (p<0.0001; OR 3.08 [95%CI, 2.10-4.51]). 70.5% (24/34) of patients aged less than 40 years were seropositive for H. pylori versus 34.2% (90/263) of controls (p<0.0001; OR 4.61[95%CI, 2.0-10.85]). Among cirrhosis patients, the prevalence of antibodies to H. pylori was 79.5% (35/44) versus 47% (291/619) of controls (p<0.0001; OR 4.38 [95%CI, 1.98-9.98]). Overall seroprevalence among CAH patients was 71.1% (96/135) versus 47% (291/619) of blood donors (p<0.0001; OR 2.77 [95%CI, 1.82-4.24]). CONCLUSIONS: The high seroprevalence of antibodies to H. pylori in patients with HCV-positive liver diseases explains the elevated incidence of peptic ulcer, and warrants studies on the pathogenic role in human liver diseases of Helicobacter spp which is known to cause chronic hepatitis and hepatocellular carcinoma in mice.

Pellicano R, Palmas F, Cariti G, Tappero G, Boero M, Tabone M, Suriani R, Pontisso P, Pitaro M, Rizzetto M. · U.O.A.D.U. Gastro-Hepatology, Hospital S Giovanni Battista (Molinette), Torino, Italy. · Eur J Gastroenterol Hepatol. · Pubmed #12468961 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of interferon-beta (IFN-beta) in the re-treatment of patients with chronic hepatitis C who did not respond to IFN-alpha monotherapy. PATIENTS AND METHODS: Thirty patients (24 men and six women; mean age, 41 +/- 13 (SD) years; range, 23-62 years), with chronic hepatitis C that was non-responsive to a standard course of IFN-alpha therapy, were re-treated with recombinant human IFN-beta-1a. All patients received IFN-beta, 12 MIU subcutaneously, three times weekly for 3 months, after which time patients' responses were evaluated. Responders (normal alanine aminotransferase, and negative for serum hepatitis C virus RNA) continued to receive IFN-beta, 12 MIU, for a further 3 months. Non-responders had their dose increased to 18 MIU for the remaining 3 months of treatment. After 6 months of treatment, therapy was stopped and patients were followed-up for a further 6 months. RESULTS: Overall, six (20%) of the 30 patients exhibited a response at the end of treatment. One patient (3.3%) maintained a sustained virological response at the end of post-treatment follow-up. CONCLUSIONS: Treatment with recombinant IFN-beta, at doses of up to 18 MIU for 6 months, is safe and well tolerated. However, the results of the trial do not support the use of IFN-beta monotherapy in patients with chronic hepatitis C that is resistant to IFN-alpha.

Leone N, Pellicano R, Brunello F, Rizzetto M, Ponzetto A. · Department of Gastroenterology, Hospital S Giovanni Battista, Turin, Italy. · Clin Exp Med. · Pubmed #12447608 No free full text.

Abstract: Chromogranin A is a cellular marker forneuroendocrine tumors. Elevated levels of chromogranin A are also found in patients with cancers of epithelial origin when neuroendocrine differentiation occurs, which is associated with a poor prognosis. We investigated the prevalence of serum levels of chromogranin A in patients with primary liver cancer. Seventy-nine patients (65 males, mean age 67.6 years, range 48-88 years) with liver cirrhosis and hepatocellular carcinoma were studied. The etiology of cirrhosis was identified as due to hepatitis C virus infection in 47 patients, to hepatitis C virus and alcohol in 7, to alcohol alone in 14, to hepatitis C and B virus in 2, and to hepatitis B virus alone in 4. Of the remaining patients, 2 suffered from hemochromatosis and 3 had cryptogenic cirrhosis. According to the Child-Pugh's score, 54 patients belonged to class A, 22 to class B, and 3 to class C. The concentration of chromogranin A was measured in serum with a commercial solid-phase two-site immunoradiometric assay. Elevated serum levels of chromogranin A were found in 32 of 79 patients (43%). Levels over 600 ng/ml were present in 7 of 76 patients (9.2%), all of whom had very high serum levels of alpha-fetoprotein. Hence, elevated serum levels of chromogranin A are present in over one third of patients with hepatocellular carcinoma. It is therefore possible that some hepatocellular carcinomas could acquire a neuroendocrine differentiation. We propose further studies to ascertain whether serum levels of chromogranin A are useful as a prognostic marker for hepatocellular carcinoma as in prostate cancer.

Durazzo M, Pellicano R, Premoli A, Berrutti M, Leone N, Ponzetto A, Rizzetto M. · Department of Internal Medicine, University of Turin, Italy. · Dig Dis Sci. · Pubmed #11855554 No free full text.

Abstract: Autoimmune hepatitis is characterized by a continuing hepatocyte necrosis that usually progresses to liver cirrhosis. Autoimmunity is also a feature of chronic infection by Helicobacter pylori, a gram-negative bacterium involved in the pathogenesis of peptic ulcer and upper gastrointestinal bleeding, with both events frequently occurring in patients with chronic liver disease. A newly described pathogenetic mechanism for chronic hepatitis and hepatocellular carcinoma in the mouse is linked to Helicobacter spp. infection. A high prevalence of H. pylori infection was demonstrated in patients with viral-related cirrhosis but never studied in cases of autoimmune hepatitis. In a case-control study, we examined 31 consecutive patients (25 women and 6 men, age range 20-66, mean age 46 +/- 4.3 years) suffering from autoimmune hepatitis and 62 sex- and age-matched blood donors (50 women, 12 men, age range 20-65, mean age 46 +/- 5.4 years) resident in the same area. Antibodies to H. pylori were present in 20 of 31 (64.5%) autoimmune patients compared to 33 of 62 (53.2%) controls (P = 0.3, odds ratio 1.60, 95% CI 0.60-4.28). The difference was not statistically significant either in female or male patients. In conclusion, the prevalence of H. pylori infection in patients and controls was similar in our study of patients with chronic autoimmune hepatitis.