title: The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study.
abstract: OBJECTIVE
  Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known.
  
  
  METHODS
  A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months.
  
  
  RESULTS
  Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52-92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5-20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24-42%) and 76% (95% CI: 67-83%), respectively.
  
  
  CONCLUSIONS
  Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV.
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.affiliation: Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Viganò
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Loglio
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Mangia
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Facchetti
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Primignani
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Manol
authors.initials: M
authors.lastname: Jovani
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Iavarone
authors.affiliation: Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Fraquelli
authors.affiliation: Department of Biomedical and Clinical Sciences, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casazza
authors.affiliation: Division of Gastroenterology, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: de Franchis
authors.affiliation: "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. Electronic address: massimo.colombo@unimi.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D054459:Elasticity Imaging Techniques / Q000379:methods; D016099:Endoscopy, Gastrointestinal; D004932:Esophageal and Gastric Varices / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents; D007558:Italy / Q000453:epidemiology; D019259:Lamivudine / Q000008:administration & dosage*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use*; D063065:Organophosphonates / Q000008:administration & dosage*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D015996:Survival Rate / Q000639:trends; D000068698:Tenofovir / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D007166:Immunosuppressive Agents; D009705:Nucleosides; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine
keywords: Cirrhosis; Esophageal varices; Gastrointestinal bleeding; HBsAg clearance; Hepatitis B virus; Hepatocellular carcinoma; Nucleos(t)ide analogs; Transient elastography