Evangelista Sagnelli | Università della Campania Luigi Vanvitelli (original) (raw)
Papers by Evangelista Sagnelli
Journal of Medical Virology, 2015
It has been shown that sexual hormones have an opposite effect on hepatic fibrosis progression an... more It has been shown that sexual hormones have an opposite effect on hepatic fibrosis progression and hepatocellular carcinoma development. Sex differences among 2,762 chronic HBsAg carriers consecutively referring Italian hospitals in 2001 and in 2007 have been evaluated, particularly focusing on the role of gender on severity of liver disease. The overall sex ratio (males/females) was 2.6. Females were more likely born abroad and new diagnosis cases; but less likely HIV coinfected. No sex difference was observed regarding coinfection with other hepatitis viruses. The sex ratio linearly increased with increasing severity of liver disease, being 1.3 in normal ALT, 2.8 in chronic hepatitis, 3.6 in liver cirrhosis, and 6.8 in hepatocellular carcinoma. Adjustment by multiple logistic regression analysis for the confounding effect of age, alcohol intake, HDV infection, HCV infection, and BMI shows that male gender is an independent predictor of the likelihood of more severe liver disease (O.R. 1.7; C.I. 95% = 1.3-2.1). HBV-DNA levels resulted not associated with the outcome of chronic HBV infection. Despite some potential risk factors associated with liver disease, such as HBV genotype or mutations, not having been controlled for due to lack of availability, the observed sex disparity in the outcome of chronic HBV infection may support biological obervation that HBV infection could be considered a sex hormone-responsive virus. J. Med. Virol. © 2015 Wiley Periodicals, Inc.
Journal of medical …, 2001
The sustained response to interferon-a treatment was evaluated in 147 anti-HCV/HCV-RNA-posi - tiv... more The sustained response to interferon-a treatment was evaluated in 147 anti-HCV/HCV-RNA-posi - tive, HBsAg-negative, chronic hepatitis patients, according to HCV genotypes and the presence or absence of anti-HBs and anti-HBc. These patients had been included in a controlled ...
Autoimmunity Reviews, 2011
Objective: The objective of this review was to define a core set of recommendations for the treat... more Objective: The objective of this review was to define a core set of recommendations for the treatment of HCVassociated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigencontent diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Conclusion: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.
Journal of Hepatology, 1991
Digestive and Liver Disease, 2014
The statements produced by the consensus conference on infection in end-stage liver disease promo... more The statements produced by the consensus conference on infection in end-stage liver disease promoted by the Italian Association for the Study of the Liver, are here reported.
World journal of clinical cases, Jan 16, 2015
To analyze the host genetics factors influencing the clinical course and the response to antivira... more To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC). We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article. Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC ...
Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2015
The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been assoc... more The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been associated to protection of anemia and sustained virological response, respectively, in patients with chronic hepatitis C (CHC) during antiviral therapy. Aim of this study was to evaluate the single and combined role of both polymorphisms in the management of peg-interferon-ribavirin treatment in CHC patients. We studied 79 Italian patients with histology proven CHC treated with pegylated interferon plus ribavirin for 6-12 months on the base of HCV genotype. Patients were carefully followed-up for anemia development which was classified as mild, moderate or severe in relation to levels of haemoglobin decreasing; ribavirin dosage reduction and/or epoietin administration were carried out, where needed. Sustained virological response (SVR) was considered for HCV-RNA clearance after 6 months of treatment stop. Decay of haemoglobin at month 1 of treatment significantly correlated with ITPA activit...
Digestive Diseases and Sciences, 2015
The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been associated with liver s... more The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been associated with liver steatosis and disease progression in nonalcoholic steatohepatitis and chronic hepatitis C. The aim of the present study was to evaluate the influence of the PNPLA3 I148M polymorphisms on the clinical, histological, viral, and host parameters in Italian patients with chronic hepatitis B (CHB). Ninety-nine patients with CHB entered the study and underwent a clinical, histological, virological, and biochemical evaluation. PNPLA3 (p.I148M) variants were genotyped. PNPLA3 rare variant (148M) was significantly associated with liver steatosis (p = 0.0019) and cholesterol (p = 0.04) levels, but not with fibrosis or histological activity index. The 13 patients with severe liver steatosis (score > 3) (38 %) were more frequently homozygous for PNPLA3 148M variant than the 86 without (6 %, p = 0.003). At logistic regression analysis, severe steatosis was independently associated with the rare allele (p = 0.001) and waist circumference, but not with body mass index (BMI). In our CHB patients, the PNPLA3 polymorphisms influenced the development of liver steatosis, but not fibrosis status. The association of PNPLA3 p.I148M with liver steatosis increased with the greater amount of abdominal fat, irrespective of BMI.
Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2003
This case-control study evaluated the real need for liver biopsy in subjects with persistently no... more This case-control study evaluated the real need for liver biopsy in subjects with persistently normal aminotransferase values over a long period by comparing the histological features of these subjects with those of patients with abnormal aminotransferase values. We considered as "Cases" all 32 consecutive anti-HCV/HCV-RNA positive subjects with at least eight normal serum ALT values during the last twelve months; for each "Case", we selected as a "Control" one anti-HCV/HCV-RNA positive patient with at least two abnormal serum ALT values during the last twelve months. The Cases and Controls were matched for age ( 5 years) and sex. In the Case group, 1 subject showed normal liver tissue, 18 minimal chronic hepatitis (CH) and 13 mild CH. In the Control group, 7 subjects showed minimal CH, 19 mild CH, 3 moderate CH, 1 severe CH and 2 cirrhosis. The subjects in the Control group showed a significantly higher HAI score (5.39+2.81) than those in the Case grou...
Liver, 1989
In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg p... more In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg positive chronic hepatitis (CH), we evaluated numerous clinical, biochemical and histological aspects in 203 consecutive HBsAg positive CH patients. The presence of hepatitis delta antigen (HD-Ag) in the liver tissue was the criterion used to identify HDV infection. HD-Ag was observed in none of the 7 patients with non-specific reactive hepatitis, in 14.6% of the 48 with chronic persistent hepatitis (CPH), in 36.4% of the 44 with chronic lobular hepatitis (CLH), in 36% of the 25 with mild chronic active hepatitis (CAH), in 52% of the 36 with severe CAH and in 30.2% of the 43 with inactive or moderately active cirrhosis. Compared with the 139 HD-Ag negative patients in this study, the 64 HD-Ag positive patients more frequently had severe CAH (29.7 vs. 12.2%, p less than 0.01) and less frequently CPH (10.9 vs. 29.5%, p less than 0.01). Of the 139 HD-Ag negative patients, 80 were anti-HD positive and 59 anti-HD negative. The 59 patients with no HD-Ag or anti-HD showed severe CAH less frequently than the 64 HD-Ag positive patients (6.8 vs. 29.7, p less than 0.01) and CPH more frequently (44.1 vs. 10.9, p less than 0.001). Both in CPH and CLH the presence of HD-Ag in the hepatocytes identified subgroups of patients who frequently showed high serum levels of aminotransferases and gammaglobulins and more extended areas of circumscribed lobular necrosis. HD-Ag positive CAH was characterized by a more frequent occurrence of eosinophilic degeneration of hepatocytes without peripolesis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Research in Virology, 1998
ABSTRACT The aims of the study were to evaluate the long-term efficacy and tolerability of differ... more ABSTRACT The aims of the study were to evaluate the long-term efficacy and tolerability of different doses of interferon-alpha (IFN alpha) and different durations of treatment in chronic hepatitis C by comparing 3 or 6 mega units (MUs) three times weekly given for either 12 or 24 months, and the possibility of obtaining a response in non-responder patients by increasing the dose or by administering IFN daily. A total of 504 patients with non-cirrhotic chronic hepatitis C enrolled in a multicentre study were consecutively assigned to receive either 3 (255 patients) or 6 MU (249 patients) of lymphoblastoid IFN alpha 3 times a week (tiw). At the 12th month of therapy, patients with normal aminotransferase (AMT) in both groups were either given IFN for an additional 12 months with an unmodified or halved dose, or else discontinued therapy. For patients with unmodified AMT levels after 6 months of therapy, the IFN dose was doubled in the 3-MU group, while it was administered at 3 MU daily in the 6-MU group. When no improvement was achieved, therapy was discontinued; otherwise it was prolonged until the 18th month. Patients were followed up for 12 months after discontinuing IFN. Of the 255 patients enrolled at 3 MU, therapy was stopped during the first 6 months in 36 patients (14.1%) because of side effects, and in 24 (9.4%) because of lack of cooperation. Of the remaining 195 patients at the 6th month of therapy, 119 (61%) had normal and 76 (39%) unmodified AMT levels; 14 of the 76 normalized AMT after doubling the dose of IFN, but only 5 (6.6%) had a sustained response. Of the 119 patients with normal AMT, 40 discontinued IFN at the 12th month (schedule A), 39 remained at 3 MU tiw (schedule B) and 40 were given a dose of 1.5 MU tiw (schedule C) for an additional 12 months. At the end of follow-up, 23/40 (57.5%) patients in schedule A, 31/39 (79.5%) on schedule B and 29/40 (72.5%) on schedule C still had normal AMT (A vs. B p = 0.04). In an intention-to-treat analysis, the sustained response rate for patients enrolled at 3 MUs, including the 5 initial non-responders, was 34.5%. Of the 249 patients enrolled at 6 MU, therapy was discontinued during the first 6 months for 39 (15.7%) because of side effects, and for 27 (10.8%) because of lack of cooperation. Of the remaining 183 patients at the 6th month of therapy, 110 (60%) had normal and 73 (40%) unmodified AMT levels. Of the 73 patients, 55 accepted the daily regimen and 8 of them (14.5%) showed a sustained response. Of the 110 patients with normal AMT, 32 (29.1%), despite normalization of AMT, spontaneously discontinued IFN or reduced the dose because of a poor quality of life, while 78 continued with 6 MU until the 12th month, when therapy was discontinued for 28 (schedule A1); 24 patients were given an unmodified dose (schedule B1) and 26 a halved dose (schedule C1) for an additional 12 months. At the end of follow-up, 18/28 (64.3%) patients on schedule A1, 19/24 (79.2%) on schedule B1 and 19/26 (73.1%) on C1 still had normal AMT (p = NS). In an intention-to-treat evaluation, the sustained response rate for patients enrolled at 6 MU, including the 8 from the daily treatment, was 25.7% (64/249). HCV viraemia was undetectable 1 year after discontinuation of IFN in 72.6% of patients with a sustained response. Sustained response was observed in 36.4% of patients with minimal, 46.6% of those with mild, and 33.3% with moderate or severe histological activity (p = NS). The rate of sustained response was lower in patients with genotype 1b (23.6%) than in those with genotype 2a (67.8%, p = 0.002) or genotype 3 (50%, p = 0.03), irrespective of the histological activity. In conclusion, 6 MU IFN alpha are no more effective than 3 MU in inducing a sustained response in treatments of both 12 and 24 months. A 24-month treatment is more effective than a 12-month treatment in maintaining a biochemical response after discontinuation of IFN. In terms of efficacy, compliance and cost, 3 MU for 24 months app
Journal of Viral Hepatitis, 2006
We carried out a multicentre study on 2830 patients with chronic liver disease from 79 liver unit... more We carried out a multicentre study on 2830 patients with chronic liver disease from 79 liver units (25 in northern, 24 in central and 30 in southern Italy) to evaluate naturally acquired immunity against hepatitis A virus (HAV) in relation to age, sex, geographical area of origin and entity of liver disease, and to define the strategy for specific vaccination. Antibody to HAV (anti-HAV) was detected in 1514 (53.5%) of the 2830 patients tested; the prevalence was 50.4% in males and 59.1% in females. Both in central and southern Italy the prevalence of anti-HAV positive subjects increased with increasing age from 43.3 and 44.7%, respectively, in the 0-30-year-old subjects to 80.1 and 68.3%, respectively, in those aged over 60 years. The overall prevalence was much lower in northern Italy, as were the variations from one age group to another, from 28.4% in the 0-30-year-old subjects to 38% in those aged over 60 years. 40.6% of patients with cirrhosis lacked naturally acquired protection against HAV; this percentage was higher in northern (60.5%) than in central (34.9%, P < 0.0001) and southern Italy (27.6%, P < 0.0001). The high prevalence of patients in Italy with chronic hepatitis or cirrhosis who lack naturally acquired immunity to HAV warrants the implementation of vaccination programmes against hepatitis A in such patients.
Journal of Medical Virology, 2008
17 with genotype non-1 showed severe fibrosis (P ¼ 0.003); patients with occult HBV infection did... more 17 with genotype non-1 showed severe fibrosis (P ¼ 0.003); patients with occult HBV infection did not show such difference. Instead of seeking occult HBV infection in patients with chronic hepatitis C, both anti-HBs negative/anti-HBc positive and anti-HBs positive/anti-HBc positive, in plasma alone, more reliable information can also be obtained from the liver tissue and PBMCs.
![Research paper thumbnail of [639] ANTIVIRAL TREATMENT IN CHRONIC HBV/HCV COINFECTION: VIROLOGICAL CHANGES IN THREE COMPARTMENTS (PLASMA, PBMC AND LIVER TISSUE) AND CLINICAL OUTCOME](https://attachments.academia-assets.com/42290114/thumbnails/1.jpg)
](Journal of Hepatology, 2007
suggest HCV virus as critical in the pathogenesis of steatosis. The lack of resolution of steatos... more suggest HCV virus as critical in the pathogenesis of steatosis. The lack of resolution of steatosis in other genotypes suggest the potential for further liver damage in non G3 coinfected patients that achieved SVR. Further research to explore these complex relationships is needed.
![Research paper thumbnail of [502] ADEFOVIR AND LAMIVUDINE COMBINATION THERAPY IS SUPERIOR TO ADEFOVIR MONOTHERAPY FOR LAMIVUDINE-RESISTANT PATIENTS WITH HBeAg-NEGATIVE CHRONIC HEPATITIS B](https://attachments.academia-assets.com/42290123/thumbnails/1.jpg)
](Journal of Hepatology, 2007
![Research paper thumbnail of 98 EXTENDED (2 YEARS) TREATMENT WITH PEGINTERFERON ALFA-2A [40KD] IMPROVES SUSTAINED RESPONSE RATES IN GENOTYPE D PATIENTS WITH HBEAG NEGATIVE CHRONIC HEPATITIS B](https://attachments.academia-assets.com/42290124/thumbnails/1.jpg)
](Journal of Hepatology, 2010
the candesartan group (P < 0.05). Child-Pugh score and MELD score were not changed between 6 mont... more the candesartan group (P < 0.05). Child-Pugh score and MELD score were not changed between 6 months. No significant complication and side effect was observed during the present study. Conclusions: Administration of ARB in alcoholic liver disease was associated with decreased fibrosis both in histology and quantitative measurements. These results provide strong evidence for a beneficial role of ARB in alcohol-related fibrosis.
Journal of Hepatology, 2010
Journal of Hepatology, 2010
POSTERS virological with or without biochemical breakthroughs and received add-on adefovir therap... more POSTERS virological with or without biochemical breakthroughs and received add-on adefovir therapy for ≥12 months. Sera drawn at baseline, at 6 and 12 months of initial therapy as well as at the diagnosis of breakthroughs and at 6 and 12 months after adefovir addition were tested blindly using the M30-Apoptosense ELISA Kit (PEVIVA) that measures the apoptosis-associated neoepitope in the C-terminal domain of K-18 (aa 387-396). Results: During initial therapy, K-18 fragments (U/L) levels significantly reduced from baseline [mean±SD (range): 446±459 (149-2461)] to 6 months [180±74 (110-454) U/L, P < 0.001] and from 6 to 12 months [162±47 (113-280), P = 0.031]. K-18 fragments levels increased at breakthroughs [250±198 (124-1063)] compared to last previous visits [197±146 (118-809), P = 0.042] but remained lower than baseline (P = 0.016). Changes of K-18 fragments levels correlated positively with changes of ALT and HBV-DNA from baseline to 6 (r = 0.869, P < 0.001 and r = 0.396, P = 0.014) or 12 months of initial therapy (r = 0.873, P < 0.001 and r = 0.544, P < 0.001). In contrast to initial therapy, in patients with breakthroughs, K-18 fragments levels had only a trend for decline from adefovir addition [303±290 (124-1219)] to 6 [274±377 (122-1576), P = 0.109] and mainly to 12 months [223±201 (122-878), P = 0.055]. In the latter subgroup, changes of K-18 fragments levels correlated positively with changes of ALT at 6 (r = 0.624, P = 0.017) or 12 months (r = 0.765, P < 0.001) and with changes of HBV-DNA only at 12 months (r = 0.535, P = 0.010) after adefovir addition. Conclusions: Apoptotic caspase activity decreases significantly during oral antiviral therapy in HBeAg-negative CHB in parallel with the improvements in ALT and HBV-DNA levels. It increases again during breakthroughs and may improve after an effective rescue treatment but at a slower rate compared to the initial therapy.
Journal of Hepatology, 2011
Journal of Medical Virology, 2015
It has been shown that sexual hormones have an opposite effect on hepatic fibrosis progression an... more It has been shown that sexual hormones have an opposite effect on hepatic fibrosis progression and hepatocellular carcinoma development. Sex differences among 2,762 chronic HBsAg carriers consecutively referring Italian hospitals in 2001 and in 2007 have been evaluated, particularly focusing on the role of gender on severity of liver disease. The overall sex ratio (males/females) was 2.6. Females were more likely born abroad and new diagnosis cases; but less likely HIV coinfected. No sex difference was observed regarding coinfection with other hepatitis viruses. The sex ratio linearly increased with increasing severity of liver disease, being 1.3 in normal ALT, 2.8 in chronic hepatitis, 3.6 in liver cirrhosis, and 6.8 in hepatocellular carcinoma. Adjustment by multiple logistic regression analysis for the confounding effect of age, alcohol intake, HDV infection, HCV infection, and BMI shows that male gender is an independent predictor of the likelihood of more severe liver disease (O.R. 1.7; C.I. 95% = 1.3-2.1). HBV-DNA levels resulted not associated with the outcome of chronic HBV infection. Despite some potential risk factors associated with liver disease, such as HBV genotype or mutations, not having been controlled for due to lack of availability, the observed sex disparity in the outcome of chronic HBV infection may support biological obervation that HBV infection could be considered a sex hormone-responsive virus. J. Med. Virol. © 2015 Wiley Periodicals, Inc.
Journal of medical …, 2001
The sustained response to interferon-a treatment was evaluated in 147 anti-HCV/HCV-RNA-posi - tiv... more The sustained response to interferon-a treatment was evaluated in 147 anti-HCV/HCV-RNA-posi - tive, HBsAg-negative, chronic hepatitis patients, according to HCV genotypes and the presence or absence of anti-HBs and anti-HBc. These patients had been included in a controlled ...
Autoimmunity Reviews, 2011
Objective: The objective of this review was to define a core set of recommendations for the treat... more Objective: The objective of this review was to define a core set of recommendations for the treatment of HCVassociated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigencontent diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Conclusion: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.
Journal of Hepatology, 1991
Digestive and Liver Disease, 2014
The statements produced by the consensus conference on infection in end-stage liver disease promo... more The statements produced by the consensus conference on infection in end-stage liver disease promoted by the Italian Association for the Study of the Liver, are here reported.
World journal of clinical cases, Jan 16, 2015
To analyze the host genetics factors influencing the clinical course and the response to antivira... more To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC). We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article. Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC ...
Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2015
The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been assoc... more The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been associated to protection of anemia and sustained virological response, respectively, in patients with chronic hepatitis C (CHC) during antiviral therapy. Aim of this study was to evaluate the single and combined role of both polymorphisms in the management of peg-interferon-ribavirin treatment in CHC patients. We studied 79 Italian patients with histology proven CHC treated with pegylated interferon plus ribavirin for 6-12 months on the base of HCV genotype. Patients were carefully followed-up for anemia development which was classified as mild, moderate or severe in relation to levels of haemoglobin decreasing; ribavirin dosage reduction and/or epoietin administration were carried out, where needed. Sustained virological response (SVR) was considered for HCV-RNA clearance after 6 months of treatment stop. Decay of haemoglobin at month 1 of treatment significantly correlated with ITPA activit...
Digestive Diseases and Sciences, 2015
The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been associated with liver s... more The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been associated with liver steatosis and disease progression in nonalcoholic steatohepatitis and chronic hepatitis C. The aim of the present study was to evaluate the influence of the PNPLA3 I148M polymorphisms on the clinical, histological, viral, and host parameters in Italian patients with chronic hepatitis B (CHB). Ninety-nine patients with CHB entered the study and underwent a clinical, histological, virological, and biochemical evaluation. PNPLA3 (p.I148M) variants were genotyped. PNPLA3 rare variant (148M) was significantly associated with liver steatosis (p = 0.0019) and cholesterol (p = 0.04) levels, but not with fibrosis or histological activity index. The 13 patients with severe liver steatosis (score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 3) (38 %) were more frequently homozygous for PNPLA3 148M variant than the 86 without (6 %, p = 0.003). At logistic regression analysis, severe steatosis was independently associated with the rare allele (p = 0.001) and waist circumference, but not with body mass index (BMI). In our CHB patients, the PNPLA3 polymorphisms influenced the development of liver steatosis, but not fibrosis status. The association of PNPLA3 p.I148M with liver steatosis increased with the greater amount of abdominal fat, irrespective of BMI.
Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2003
This case-control study evaluated the real need for liver biopsy in subjects with persistently no... more This case-control study evaluated the real need for liver biopsy in subjects with persistently normal aminotransferase values over a long period by comparing the histological features of these subjects with those of patients with abnormal aminotransferase values. We considered as "Cases" all 32 consecutive anti-HCV/HCV-RNA positive subjects with at least eight normal serum ALT values during the last twelve months; for each "Case", we selected as a "Control" one anti-HCV/HCV-RNA positive patient with at least two abnormal serum ALT values during the last twelve months. The Cases and Controls were matched for age ( 5 years) and sex. In the Case group, 1 subject showed normal liver tissue, 18 minimal chronic hepatitis (CH) and 13 mild CH. In the Control group, 7 subjects showed minimal CH, 19 mild CH, 3 moderate CH, 1 severe CH and 2 cirrhosis. The subjects in the Control group showed a significantly higher HAI score (5.39+2.81) than those in the Case grou...
Liver, 1989
In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg p... more In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg positive chronic hepatitis (CH), we evaluated numerous clinical, biochemical and histological aspects in 203 consecutive HBsAg positive CH patients. The presence of hepatitis delta antigen (HD-Ag) in the liver tissue was the criterion used to identify HDV infection. HD-Ag was observed in none of the 7 patients with non-specific reactive hepatitis, in 14.6% of the 48 with chronic persistent hepatitis (CPH), in 36.4% of the 44 with chronic lobular hepatitis (CLH), in 36% of the 25 with mild chronic active hepatitis (CAH), in 52% of the 36 with severe CAH and in 30.2% of the 43 with inactive or moderately active cirrhosis. Compared with the 139 HD-Ag negative patients in this study, the 64 HD-Ag positive patients more frequently had severe CAH (29.7 vs. 12.2%, p less than 0.01) and less frequently CPH (10.9 vs. 29.5%, p less than 0.01). Of the 139 HD-Ag negative patients, 80 were anti-HD positive and 59 anti-HD negative. The 59 patients with no HD-Ag or anti-HD showed severe CAH less frequently than the 64 HD-Ag positive patients (6.8 vs. 29.7, p less than 0.01) and CPH more frequently (44.1 vs. 10.9, p less than 0.001). Both in CPH and CLH the presence of HD-Ag in the hepatocytes identified subgroups of patients who frequently showed high serum levels of aminotransferases and gammaglobulins and more extended areas of circumscribed lobular necrosis. HD-Ag positive CAH was characterized by a more frequent occurrence of eosinophilic degeneration of hepatocytes without peripolesis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Research in Virology, 1998
ABSTRACT The aims of the study were to evaluate the long-term efficacy and tolerability of differ... more ABSTRACT The aims of the study were to evaluate the long-term efficacy and tolerability of different doses of interferon-alpha (IFN alpha) and different durations of treatment in chronic hepatitis C by comparing 3 or 6 mega units (MUs) three times weekly given for either 12 or 24 months, and the possibility of obtaining a response in non-responder patients by increasing the dose or by administering IFN daily. A total of 504 patients with non-cirrhotic chronic hepatitis C enrolled in a multicentre study were consecutively assigned to receive either 3 (255 patients) or 6 MU (249 patients) of lymphoblastoid IFN alpha 3 times a week (tiw). At the 12th month of therapy, patients with normal aminotransferase (AMT) in both groups were either given IFN for an additional 12 months with an unmodified or halved dose, or else discontinued therapy. For patients with unmodified AMT levels after 6 months of therapy, the IFN dose was doubled in the 3-MU group, while it was administered at 3 MU daily in the 6-MU group. When no improvement was achieved, therapy was discontinued; otherwise it was prolonged until the 18th month. Patients were followed up for 12 months after discontinuing IFN. Of the 255 patients enrolled at 3 MU, therapy was stopped during the first 6 months in 36 patients (14.1%) because of side effects, and in 24 (9.4%) because of lack of cooperation. Of the remaining 195 patients at the 6th month of therapy, 119 (61%) had normal and 76 (39%) unmodified AMT levels; 14 of the 76 normalized AMT after doubling the dose of IFN, but only 5 (6.6%) had a sustained response. Of the 119 patients with normal AMT, 40 discontinued IFN at the 12th month (schedule A), 39 remained at 3 MU tiw (schedule B) and 40 were given a dose of 1.5 MU tiw (schedule C) for an additional 12 months. At the end of follow-up, 23/40 (57.5%) patients in schedule A, 31/39 (79.5%) on schedule B and 29/40 (72.5%) on schedule C still had normal AMT (A vs. B p = 0.04). In an intention-to-treat analysis, the sustained response rate for patients enrolled at 3 MUs, including the 5 initial non-responders, was 34.5%. Of the 249 patients enrolled at 6 MU, therapy was discontinued during the first 6 months for 39 (15.7%) because of side effects, and for 27 (10.8%) because of lack of cooperation. Of the remaining 183 patients at the 6th month of therapy, 110 (60%) had normal and 73 (40%) unmodified AMT levels. Of the 73 patients, 55 accepted the daily regimen and 8 of them (14.5%) showed a sustained response. Of the 110 patients with normal AMT, 32 (29.1%), despite normalization of AMT, spontaneously discontinued IFN or reduced the dose because of a poor quality of life, while 78 continued with 6 MU until the 12th month, when therapy was discontinued for 28 (schedule A1); 24 patients were given an unmodified dose (schedule B1) and 26 a halved dose (schedule C1) for an additional 12 months. At the end of follow-up, 18/28 (64.3%) patients on schedule A1, 19/24 (79.2%) on schedule B1 and 19/26 (73.1%) on C1 still had normal AMT (p = NS). In an intention-to-treat evaluation, the sustained response rate for patients enrolled at 6 MU, including the 8 from the daily treatment, was 25.7% (64/249). HCV viraemia was undetectable 1 year after discontinuation of IFN in 72.6% of patients with a sustained response. Sustained response was observed in 36.4% of patients with minimal, 46.6% of those with mild, and 33.3% with moderate or severe histological activity (p = NS). The rate of sustained response was lower in patients with genotype 1b (23.6%) than in those with genotype 2a (67.8%, p = 0.002) or genotype 3 (50%, p = 0.03), irrespective of the histological activity. In conclusion, 6 MU IFN alpha are no more effective than 3 MU in inducing a sustained response in treatments of both 12 and 24 months. A 24-month treatment is more effective than a 12-month treatment in maintaining a biochemical response after discontinuation of IFN. In terms of efficacy, compliance and cost, 3 MU for 24 months app
Journal of Viral Hepatitis, 2006
We carried out a multicentre study on 2830 patients with chronic liver disease from 79 liver unit... more We carried out a multicentre study on 2830 patients with chronic liver disease from 79 liver units (25 in northern, 24 in central and 30 in southern Italy) to evaluate naturally acquired immunity against hepatitis A virus (HAV) in relation to age, sex, geographical area of origin and entity of liver disease, and to define the strategy for specific vaccination. Antibody to HAV (anti-HAV) was detected in 1514 (53.5%) of the 2830 patients tested; the prevalence was 50.4% in males and 59.1% in females. Both in central and southern Italy the prevalence of anti-HAV positive subjects increased with increasing age from 43.3 and 44.7%, respectively, in the 0-30-year-old subjects to 80.1 and 68.3%, respectively, in those aged over 60 years. The overall prevalence was much lower in northern Italy, as were the variations from one age group to another, from 28.4% in the 0-30-year-old subjects to 38% in those aged over 60 years. 40.6% of patients with cirrhosis lacked naturally acquired protection against HAV; this percentage was higher in northern (60.5%) than in central (34.9%, P < 0.0001) and southern Italy (27.6%, P < 0.0001). The high prevalence of patients in Italy with chronic hepatitis or cirrhosis who lack naturally acquired immunity to HAV warrants the implementation of vaccination programmes against hepatitis A in such patients.
Journal of Medical Virology, 2008
17 with genotype non-1 showed severe fibrosis (P ¼ 0.003); patients with occult HBV infection did... more 17 with genotype non-1 showed severe fibrosis (P ¼ 0.003); patients with occult HBV infection did not show such difference. Instead of seeking occult HBV infection in patients with chronic hepatitis C, both anti-HBs negative/anti-HBc positive and anti-HBs positive/anti-HBc positive, in plasma alone, more reliable information can also be obtained from the liver tissue and PBMCs.
Journal of Hepatology, 2007
suggest HCV virus as critical in the pathogenesis of steatosis. The lack of resolution of steatos... more suggest HCV virus as critical in the pathogenesis of steatosis. The lack of resolution of steatosis in other genotypes suggest the potential for further liver damage in non G3 coinfected patients that achieved SVR. Further research to explore these complex relationships is needed.
Journal of Hepatology, 2007
Journal of Hepatology, 2010
the candesartan group (P < 0.05). Child-Pugh score and MELD score were not changed between 6 mont... more the candesartan group (P < 0.05). Child-Pugh score and MELD score were not changed between 6 months. No significant complication and side effect was observed during the present study. Conclusions: Administration of ARB in alcoholic liver disease was associated with decreased fibrosis both in histology and quantitative measurements. These results provide strong evidence for a beneficial role of ARB in alcohol-related fibrosis.
Journal of Hepatology, 2010
Journal of Hepatology, 2010
POSTERS virological with or without biochemical breakthroughs and received add-on adefovir therap... more POSTERS virological with or without biochemical breakthroughs and received add-on adefovir therapy for ≥12 months. Sera drawn at baseline, at 6 and 12 months of initial therapy as well as at the diagnosis of breakthroughs and at 6 and 12 months after adefovir addition were tested blindly using the M30-Apoptosense ELISA Kit (PEVIVA) that measures the apoptosis-associated neoepitope in the C-terminal domain of K-18 (aa 387-396). Results: During initial therapy, K-18 fragments (U/L) levels significantly reduced from baseline [mean±SD (range): 446±459 (149-2461)] to 6 months [180±74 (110-454) U/L, P < 0.001] and from 6 to 12 months [162±47 (113-280), P = 0.031]. K-18 fragments levels increased at breakthroughs [250±198 (124-1063)] compared to last previous visits [197±146 (118-809), P = 0.042] but remained lower than baseline (P = 0.016). Changes of K-18 fragments levels correlated positively with changes of ALT and HBV-DNA from baseline to 6 (r = 0.869, P < 0.001 and r = 0.396, P = 0.014) or 12 months of initial therapy (r = 0.873, P < 0.001 and r = 0.544, P < 0.001). In contrast to initial therapy, in patients with breakthroughs, K-18 fragments levels had only a trend for decline from adefovir addition [303±290 (124-1219)] to 6 [274±377 (122-1576), P = 0.109] and mainly to 12 months [223±201 (122-878), P = 0.055]. In the latter subgroup, changes of K-18 fragments levels correlated positively with changes of ALT at 6 (r = 0.624, P = 0.017) or 12 months (r = 0.765, P < 0.001) and with changes of HBV-DNA only at 12 months (r = 0.535, P = 0.010) after adefovir addition. Conclusions: Apoptotic caspase activity decreases significantly during oral antiviral therapy in HBeAg-negative CHB in parallel with the improvements in ALT and HBV-DNA levels. It increases again during breakthroughs and may improve after an effective rescue treatment but at a slower rate compared to the initial therapy.
Journal of Hepatology, 2011