RESUMO
To date, few reports have evaluated the pneumococcal vaccination status in cirrhotic patients. No data are available for European countries. We have explored this topic and the potential independent predictors motivating lack of vaccination in Italy. Between January 1st and June 30th 2022, 1419 cirrhotic patients of any etiology were consecutively enrolled in an observational, prospective study at 8 referral centers in Italy. Adjusted odds ratios (ORs) for the association with lack of vaccination were evaluated by multiple logistic regression analysis. Overall vaccine coverage was 17.9% (8.9% in patients < 65 years of age and 27.1% in those aged ≥ 65 years; p < 0.001). Among the 1165 unvaccinated patients, 1068 (91.7%) reported lack of information regarding vaccination as the reason for not having undergone vaccination. Independent predictors associated with lack of vaccination were age < 65 years (OR 3.39, CI 95% 2.41-4.76) and a higher number of schooling years (OR 2.14, CI 95% 1.58-2.91); alcoholic etiology resulted only marginally associated (OR 1.91, CI 95% 1.03-3.52). These findings establish evidence on how pneumococcal vaccination status in Italy is largely suboptimal among cirrhotic patients. These results raise concern, considering the severe outcomes of pneumococcal infection in patients with chronic liver diseases.
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Infecções Pneumocócicas , Vacinas Pneumocócicas , Idoso , Humanos , Itália/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Estudos Prospectivos , Vacinação , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.
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Cirrose Hepática Biliar , Albuminas/uso terapêutico , Ascite/tratamento farmacológico , Ascite/etiologia , Bilirrubina , Ácido Quenodesoxicólico/análogos & derivados , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/tratamento farmacológico , MasculinoRESUMO
BACKGROUND & AIMS: Gamma-glutamyltransferase (GGT) is a serum marker of cholestasis. We investigated whether serum level of GGT is a prognostic marker for patients with primary biliary cholangitis (PBC). METHODS: We analyzed data from patients with PBC from the Global PBC Study Group, comprising 14 centers in Europe and North America. We obtained measurements of serum GGT at baseline and time points after treatment. We used Cox model hazard ratios to evaluate the association between GGT and clinical outcomes, including liver transplantation and liver-related death. RESULTS: Of the 2129 patients included in our analysis, 281 (13%) had a liver-related clinical endpoint. Mean age at diagnosis was 53 years and 91% of patients were female patients. We found a correlation between serum levels of GGT and alkaline phosphatase (ALP) (r = 0.71). Based on data collected at baseline and yearly for up to 5 years, higher serum levels of GGT were associated with lower hazard for transplant-free survival. Serum level of GGT at 12 months after treatment higher than 3.2-fold the upper limit of normal (ULN) identified patients who required liver transplantation or with liver-related death at 10 years with an area under the receiver operating characteristic curve of 0.70. The risk of liver transplantation or liver-related death in patients with serum level of GGT above 3.2-fold the ULN, despite level of ALP lower than 1.5-fold the ULN, was higher compared to patients with level of GGT lower than 3.2-fold the ULN and level of ALP lower than 1.5-fold the ULN (P < .05). Including information on level of GGT increased the prognostic value of the Globe score. CONCLUSIONS: Serum level of GGT can be used to identify patients with PBC at risk for liver transplantation or death, and increase the prognostic value of ALP measurement. Our findings support the use of GGT as primary clinical endpoint in clinical trials. In patients with low serum level of ALP, a high level of GGT identifies those who might require treatment of metabolic disorders or PBC treatment escalation.
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Colestase , Cirrose Hepática Biliar , Transplante de Fígado , Feminino , Humanos , Prognóstico , gama-GlutamiltransferaseRESUMO
The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9 units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5 years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25-5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02-2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9-4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.
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Hepatite B Crônica/epidemiologia , Adulto , Idoso , Antivirais/uso terapêutico , Portador Sadio/epidemiologia , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , MigrantesRESUMO
The rapid evolution of molecular biology techniques has a significant impact on laboratory medicine. Nowadays a large number of diagnostic tools are available to diagnose and to characterize the different phases of hepatitis B virus (HBV) infection. The advent of the assay for nucleic acid amplification and detection enables clinicians to initiate and monitor antiviral therapy whilst allowing basic scientists to carry out studies on HBV biology. This review will focus on the evolution of the diagnostic tools to detect and monitor HBV infection.
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Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/virologia , DNA Viral/sangue , Anticorpos Anti-Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Humanos , Replicação ViralRESUMO
BACKGROUND AND AIMS: Few reports, all retrospective, have evaluated vaccine coverage against COVID-19 infection in cirrhotic subjects. No data are available for European Countries. We aimed to explore this topic and potential independent predictors of lack of vaccination. METHODS: Between January 1st and June 30th 2022, 1512 cirrhotic subjects of any etiology were consecutively enrolled in an observational - prospective study in 8 referral centers in Italy. Adjusted Odds Ratios (O.R.) for the association with lack of vaccination and with occurrence of breakthrough infection were evaluated by multiple logistic regression analysis. RESULTS: Overall vaccine coverage was 89.7% (80% among people born abroad). Among the 1358 vaccinated people, 178 (13.1%) had a breakthrough infection; of them 12 (6.7%) were hospitalized, but none died. Independent predictors associated with lack of vaccination were birth abroad, age <65 years and lower years of schooling. Child stage B/C was the only independent predictor of breakthrough infection. Occurrence of breakthrough infection was more likely reported in subjects who received 2 doses of vaccine than in those who received 3 doses (33.9% versus 9.0%; P<0.001). CONCLUSION: High vaccine coverage against COVID-19 infection is observed among cirrhotic subjects in Italy. Vaccine is effective in preventing severe outcomes. Three doses are more effective than two, even in cirrhotic subjects. LAY SUMMARY: This large cohort study evidenced high vaccine coverage against COVID-19 infection among cirrhotic subjects in a European country and the effectiveness of vaccine in preventing severe outcomes. Three doses of vaccine are more effective than two in preventing breakthrough infection and hospitalization. Informative campaigns targeting people younger than 65 years of age and those with lower years of schooling may increase these excellent results.
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Vacinas contra COVID-19 , COVID-19 , Idoso , Criança , Humanos , Infecções Irruptivas , Estudos de Coortes , Hospitalização , Itália , Cirrose Hepática , Estudos Prospectivos , Estudos Retrospectivos , VacinaçãoRESUMO
Hepatitis D is caused by infection with hepatitis D virus (HDV), a defective RNA virus that requires the obligatory helper function of hepatitis B virus (HBV) for its in vivo transmission. Thus, HDV is acquired only by coinfection with HBV or by superinfection of an HBV carrier. The clinical outcome of hepatitis D differs according to the modality of infection. Whereas coinfection evolves to chronicity in only 2% of the cases, superinfection results in chronic infection in over 90% of the cases. HDV is a highly pathogenic virus that causes acute, often fulminant hepatitis, as well as a rapidly progressive form of chronic viral hepatitis, leading to cirrhosis in 70 to 80% of the cases. The clinical picture of HDV disease is evolving as a consequence of a significant change in the epidemiology of HDV infection, which has led to a significant decline in incidence in Western countries, mainly as a result of universal HBV vaccination programs. However, in the face of a declining prevalence in areas of old endemicity like Europe, immigration poses a threat of HDV resurgence. The interaction of HDV with other hepatitis viruses or human immunodeficiency virus is complex and may lead to different patterns in terms of virologic expression and immunologic responses. Multiple viral infections are associated with rapid progression of liver fibrosis and eventually with the development of hepatocellular carcinoma. Hepatitis D is not a vanishing disease, and continuous efforts should be made to improve its prevention and treatment.
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Carcinoma Hepatocelular/etiologia , Coinfecção , Hepatite D/complicações , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Superinfecção/complicações , Genótipo , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite B/patologia , Hepatite C/complicações , Hepatite C/patologia , Hepatite D/epidemiologia , Hepatite D/patologia , Hepatite D Crônica/etiologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/patogenicidade , Humanos , Fígado/patologia , Fígado/virologiaRESUMO
BACKGROUND & AIMS: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. METHODS: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. RESULTS: One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. CONCLUSIONS: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.
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Antivirais/uso terapêutico , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Adulto , Idoso , Feminino , Hepatite B Crônica/virologia , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Fatores de TempoRESUMO
Hepatitis delta virus (HDV) is a unique human virus, showing similarities with plant viroids. Although impressive knowledge on virus structure and replication has been achieved, several questions like HBV/HDV interaction and post translational modifications of HD antigens remain to be answered. Potential targets for therapeutic strategies are now emerging. To date, eight major genotypes of the HDV have been identified. The HDV-1 is the prevailing genotype in Europe, but migration phenomena may change this profile. Immune response is likely to play an important role in the pathogenesis of HDV-induced liver disease; few data are available on T cells response either during infection and therapy. HDV usually suppresses HBV replication; recent studies show as viral dominances may change over time. Delta infection leads to severe liver disease, with different patterns of progression to liver fibrosis and decompensation. Beside the association between HDV/HBV and HCC is demonstrated a risk specifically related to HDV remains controversial.
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Hepatite D Crônica , Lipopeptídeos , Antivirais , Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Hepatite D , Vírus Delta da Hepatite , HumanosRESUMO
BACKGROUND & AIMS: We evaluated the long-term outcomes after antiviral therapy of patients with decompensated cirrhosis and hepatitis C virus (HCV) infection. METHODS: Seventy-five patients with HCV infection and decompensated cirrhosis received therapy with peginterferon alfa-2b and ribavirin. We compared adverse-event profiles and mortality rates between patients with or without sustained virologic responses (SVRs). The mean follow-up time off therapy was 51 ± 18 months (range, 3-78 months). RESULTS: Seven patients with HCV genotypes 1 or 4 (16%) and 17 patients with genotypes 2 or 3 (55%) achieved SVRs. The mean survival times were 53 months among patients who did not achieve SVRs (95% confidence interval [CI], 48-59 months) and 73 months among those who did achieve SVRs (95% CI, 67-80 months) (P = .004). During the study, 25 patients died (2 with and 23 without SVRs). During the follow-up period, 8 of 24 patients with SVRs (33.3%) and 49 of 51 without SVRs (96.1%) experienced further events of decompensation (P < .0001). The hospital readmission rates for patients with and without SVRs were 7.4 and 56 per 1000 person-months, respectively (ratio of 7.5 without/with SVR; 95% CI, 4.0-16.0; P < .0001). At the end of the follow-up period, the incidence of hepatocellular carcinoma was not associated with clearance of HCV. CONCLUSIONS: Among patients with cirrhosis that is a result of HCV infection and who have progressed to a stage of liver decompensation, an SVR after antiviral therapy is a positive prognostic factor.
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Antivirais/administração & dosagem , Insuficiência Hepática/diagnóstico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/patologia , Idoso , Antivirais/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Insuficiência Hepática/mortalidade , Hepatite C Crônica/mortalidade , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Resultado do TratamentoRESUMO
Hepatitis D virus (HDV) is a small, defective RNA virus that depends on hepatitis B virus (HBV) for virion assembly and transmission. It replicates within the nucleus of hepatocytes and interacts with several cellular proteins. Chronic hepatitis D is a severe and progressive disease, leading to cirrhosis in up to 80% of cases. A high proportion of patients die of liver decompensation or hepatocellular carcinoma (HCC), but the lack of large prospective studies has made it difficult to precisely define the rate of these long-term complications. In particular, the question of whether HDV is an oncogenic virus has been a matter of debate. Studies conducted over the past decade provided evidence that HDV is associated with a significantly higher risk of developing HCC compared to HBV monoinfection. However, the mechanisms whereby HDV promotes liver cancer remain elusive. Recent data have demonstrated that the molecular profile of HCC-HDV is unique and distinct from that of HBV-HCC, with an enrichment of upregulated genes involved in cell-cycle/DNA replication, and DNA damage and repair, which point to genome instability as an important mechanism of HDV hepatocarcinogenesis. These data suggest that HBV and HDV promote carcinogenesis by distinct molecular mechanisms despite the obligatory dependence of HDV on HBV.
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Carcinoma Hepatocelular/virologia , Hepatite D/virologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/patogenicidade , Neoplasias Hepáticas/virologia , Carcinogênese , Genoma Viral , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Hepatite D Crônica/virologia , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Cirrose Hepática , RNA Viral/genética , Montagem de VírusRESUMO
INTRODUCTION: Hepatitis D Virus (HDV) infection is vanishing in Italy. It is therefore believed that hepatitis D is no longer a medical problem in the domestic population of the country but remains of concern only in migrants from HDV-endemic areas. OBJECTIVES: To report the clinical features and the medical impact of the residual domestic HDV infections in Italy. METHODS: From 2010 to 2019, one hundred ninety-three first-time patients with chronic HDV liver disease attended gastroenterology units in Torino and San Giovanni Rotondo (Apulia); 121 were native Italians and 72 were immigrants born abroad. For this study, we considered the 121 native Italians in order to determine their clinical features and the impact of HDV disease in liver transplant programs. RESULTS: At the last observation the median age of the 121 native Italians was 58 years. At the end of the follow-up, the median liver stiffness was 12.0 kPa (95% CI 11.2-17.4), 86 patients (71.1%) had a diagnosis of cirrhosis; 80 patients (66.1%) remained HDV viremic. The ratio of HDV to total HBsAg transplants varied from 38.5% (139/361) in 2000-2009 to 50.2% (130/259) in 2010-2019, indicating a disproportionate role of hepatitis D in liver transplants compared to the minor prevalence of HDV infections in the current scenario of HBsAg-positive liver disorders in Italy. CONCLUSION: Though HDV is vanishing in Italy, a legacy of ageing native-Italian patients with advanced HDV liver disease still represents an important medical issue and maintains an impact on liver transplantation.
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Hepatite D , Transplante de Fígado , Antígenos de Superfície da Hepatite B , Hepatite D/diagnóstico , Hepatite D/epidemiologia , Vírus Delta da Hepatite/genética , Humanos , Cirrose Hepática , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. METHODS: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. RESULTS: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). CONCLUSIONS: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. LAY SUMMARY: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.
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BACKGROUND & AIMS: To investigate the impact of HDV infection on morbidity and mortality of patients. PATIENTS AND METHODS: This was a retrospective study on 188 patients that underwent a program of periodic surveillance until 2008. The demographic data, stage of liver disease, treatment efficacy, development of liver complications (ascites, oesophageal bleeding, encephalopathy), and survival were registered. A Cox regression analysis was carried out to determine the impact of viral and patient features on survival. RESULTS: At baseline, 126 patients (67%) tested positive for serum IgM anti-HDV antibodies, 171 (91%) for anti-HBe, 175 (93%) for serum HDV-RNA, and 61 (33%) for serum HBV-DNA. Eighty-two patients (43%) had chronic hepatitis at histology; the remaining 106 individuals had a clinical/histological diagnosis of cirrhosis. Ninety-six patients received interferon (n = 90) or lamivudine (n = 6) therapy, and 27 of them (30%) attained a sustained response. During follow up, 21 patients with chronic hepatitis progressed to cirrhosis. Of the 127 cirrhotic patients, hepatic decompensation occurred in 42 patients (33%) and hepatocellular carcinoma in 17 (13%). The 5- and 10-year survival free of events were 96.8% and 81.9%, respectively, for patients with chronic hepatitis, and 83.9% and 59.4% for cirrhotics (p<0.01). At multivariate analysis, lack of antiviral therapy (p = 0.01), cirrhosis at presentation (p<0.01), and male sex (p = 0.03) independently predicted a worse outcome. CONCLUSION: HDV liver disease lasts several decades. Half of all patients who develop cirrhosis later will advance to liver failure. At present, interferon therapy is recommended as soon as possible to slow or alter the natural course of liver disease.
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Hepatite D Crônica/complicações , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Estudos de Coortes , Feminino , Seguimentos , Hepatite D Crônica/tratamento farmacológico , Hepatite D Crônica/mortalidade , Humanos , Itália , Fígado/patologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy. PARTICIPANTS: Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis). MEASUREMENTS: We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child-Pugh-Turcotte class, Model for End-Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow-up were registered. RESULTS: Ninety-five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow-up of 14 ± 4 months (range 5-23 months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5 mg/dL or less, and 3 or more comorbidities were the most at risk. CONCLUSION: In a real-world setting, DAAs are safe and effective in older adults with HCV-related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long-term DAA therapy.
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Antivirais/uso terapêutico , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Idoso de 80 Anos ou mais , Doença Hepática Terminal , Feminino , Humanos , Itália , Cirrose Hepática/tratamento farmacológico , Masculino , Resposta Viral SustentadaRESUMO
AIM: To investigate the feasibility of pegylated interferon plus ribavirin treatment in cirrhotic patients who presented with, or developed while on-treatment, platelet counts ≤ 80,000/µL and/or neutrophil counts ≤ 1,500/µL. METHODS: A retrospective analysis of prospectively gathered data on 123 cirrhotic patients treated with pegylated interferon and ribavirin. Adverse effects and haematological changes were monitored: bleeding and infectious events were registered and related to platelet and absolute neutrophil counts. RESULTS: Among the 58 patients (47.2%) with nadir platelets ≤ 50,000/µL during therapy, 6 (10.3%) experienced a bleeding episode; of the remaining 65 patients with platelets constantly >50,000/µL, 3 (4.6%) bled. Of the 11 bleedings, 3 manifested during an infection, while patients had platelets >50,000/µL. Nadir neutrophils ≤ 750/µL occurred in 45 patients (38.2%) during treatment, and 14 of them (29.8%) had an infectious event. Infections were also documented in 18 of the 76 patients (23.7%) with neutrophils constantly >750/µL. CONCLUSIONS: The study reveals the feasibility of treating cirrhotic patients with cytopenia with pegylated interferon and ribavirin, as bleeding or infectious events under therapy were unrelated to platelet and neutrophil counts. Withdrawal of therapy or variations in the pre-assigned dosages of either pegylated interferon or ribavirin owing to abnormally low haematological parameters seems to no longer be tenable.
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Antivirais/efeitos adversos , Varizes Esofágicas e Gástricas/sangue , Hemorragia Gastrointestinal/sangue , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Cirrose Hepática/sangue , Neutropenia/sangue , Neutrófilos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Trombocitopenia/sangue , Idoso , Quimioterapia Combinada/efeitos adversos , Epistaxe/sangue , Epistaxe/etiologia , Varizes Esofágicas e Gástricas/etiologia , Estudos de Viabilidade , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gengival/sangue , Hemorragia Gengival/etiologia , Hepatite C Crônica/complicações , Humanos , Infecções/sangue , Infecções/etiologia , Contagem de Leucócitos , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Contagem de Plaquetas , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Trombocitopenia/virologiaRESUMO
Hepatitis delta virus (HDV) is a small, defective RNA virus that can infect only individuals carrying hepatitis B virus. HBV/HDV co-infection results in more severe liver disease than HBV single infection and more rapid progression to cirrhosis and hepatocellular carcinoma (HCC). The epigenetic events involved in hepatocyte transformation towards malignancy in this context are poorly known. Here we report that, in Huh-7 cells, HDV induces DNMT3b expression and is associated to E2F1 transcription factor hypermethylation. Moreover our cell cycle analysis showed that HDV induces G2/M arrest. These findings suggest that HDV could play a role in HCC development at least in part by altering DNA methylation events. A better understanding of the molecular mechanisms involved in HDV-related carcinogenesis could help to identify new therapeutic targets.
Assuntos
Metilação de DNA , Vírus Delta da Hepatite/fisiologia , Neoplasias Hepáticas/patologia , Ácidos Aminossalicílicos/farmacologia , Antígenos Virais/genética , Azacitidina/farmacologia , Benzenossulfonatos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/efeitos dos fármacos , Fator de Transcrição E2F1/genética , Epigênese Genética/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Vírus Delta da Hepatite/imunologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Fator de Transcrição STAT3/antagonistas & inibidores , DNA Metiltransferase 3BRESUMO
Hepatitis delta virus (HDV) consists of a circular single-stranded RNA genome which assembles two viral proteins and acquires a lipid envelope in which the hepatitis B surface antigens (HBsAg) are embedded. HDV does not encode its own polymerase, but exploits a cellular enzyme for its replication. A better understanding of the mechanisms of HDV replication mechanism would provide new insights for antiviral strategies. Based on genomic variability, eight major genotypes of HDV have been identified, which differ as much as 40% in the nucleotide sequence. The cloning of HDV-RNA has provided genetic probes for the measurement of HDV-RNA in serum and liver; the sensitivity of HDV-RNA detection improved significantly when the reverse transcriptase-polymerase chain reaction (PCR) technique was introduced. As no commercial test is standardized for viral load detection, home-made assays have been developed in the different referral centers, which may not be comparable. Quantification of HDV in serum by real-time PCR has been recently proposed in the management of chronically infected patients. No specific inhibitors of HDV are available at present and, in spite of the crucial relationship between HDV and HBV, drugs that block HBV have only a theoretical but no sound effect on HDV replication.
Assuntos
Hepatite D/genética , Vírus Delta da Hepatite/genética , RNA Viral/sangue , Hepatite B/complicações , Hepatite D/sangue , Hepatite D/tratamento farmacológico , Hepatite D/virologia , Vírus Delta da Hepatite/crescimento & desenvolvimento , Vírus Delta da Hepatite/patogenicidade , HumanosRESUMO
Specific HLA alleles and immunoregulatory genes have been evaluated in primary biliary cirrhosis (PBC), but data are discordant. We determined whether TNF-alpha promoter polymorphisms (G-308A and G-238A) and alleles of HLA class II (HLA-DRB1) might be associated either with PBC occurrence and severity in Italian populations from two distinct areas. The distribution of TNF1 (G/G) genotype did not differ either between patients and controls or between patients from Northern and Southern Italy. Contrariwise, the HLA-DRB1*08 appeared positively linked to the occurrence of disease (8.4% in patients vs. 2.5% in controls, P = 0.003), whereas the HLA-DRB1*13 appeared to be protective, being more frequent in controls (12.8%) than in patients (7%) (P = 0.038). Neither positively nor negatively associated alleles of the two genomic loci had an effect on disease progression. We report a distinct genetic risk of developing PBC in the Italian population, with no interaction between the HLA and TNF alleles.