La cirrosi epatica da HBV, una lunga storia di uomini, Virus, cofattori e farmaci Prof. E. Sagnelli Dipartimento di Medi

2. 1761 De sedibus, et causis morborum per anatomen indagatis (Libro III, Delle malattie del ventre, Lettera XXXVIII, Dell’Idropisia ascite, della Timpanite, dell’Idropisia del peritoneo e di altre idropisie dette saccate)

3. Termine “cirrosi” volgarizzando i termini greci Skirròs che significa duro, fibroso e Kirrhós', che significa giallo, dal colore che il fegato assume nella cirrosi detta oggi di Morgagni-Laennec.

5. In 1963, in his most famous discovery, he identified the virus that causes Hepatitis B, a frequently fatal disease often transmitted through blood transfusions. He found an antigen for the disease in the blood of Australian aborigines, which led to the development of a safe and effective vaccine. The association of the Australian antigen with acute hepatitis B was subsequently demonstrated and led to the development of specific tests for the identification of HBV infection. 1976 Nobel Prize in Medicine

6. Histologic: Bridging fibrosis Ishak 3/6 - 4/6 Metavir 3/4 Cirrhosis Ishak 5/6 - 6/6 Metavir 4/4 How do we define advanced liver disease? Classically, this has been defined histologically by the presence of advanced fibrosis. Fibrosis, after all, is the precursor to the development of limitations in hepatic reserve and portal hypertension and, ultimately, the lack of synthetic function necessary to sustain the body. Histologically speaking, we define bridging fibrosis as stage 3 or 4 on the 6-point Ishak scale or stage 3 on the 4-point Metavir index. Cirrhosis is the endpoint of the fibrosis spectrum, otherwise known as “irreversible fibrosis,” and is histologically defined by dense bands of fibrosis surrounding regenerative nodules. On the Ishak scale, cirrhosis is classified as stage 5 or 6, and on the Metavir index, it is defined as stage 4. Interestingly, current reports have suggested that cirrhosis may not be as fully irreversible as once thought. These data have suggested that there may be an element of reversibility, at least in early cirrhosis—an important concept when we think about the therapeutic goals in chronic viral hepatitis.How do we define advanced liver disease? Classically, this has been defined histologically by the presence of advanced fibrosis. Fibrosis, after all, is the precursor to the development of limitations in hepatic reserve and portal hypertension and, ultimately, the lack of synthetic function necessary to sustain the body. Histologically speaking, we define bridging fibrosis as stage 3 or 4 on the 6-point Ishak scale or stage 3 on the 4-point Metavir index. Cirrhosis is the endpoint of the fibrosis spectrum, otherwise known as “irreversible fibrosis,” and is histologically defined by dense bands of fibrosis surrounding regenerative nodules. On the Ishak scale, cirrhosis is classified as stage 5 or 6, and on the Metavir index, it is defined as stage 4. Interestingly, current reports have suggested that cirrhosis may not be as fully irreversible as once thought. These data have suggested that there may be an element of reversibility, at least in early cirrhosis—an important concept when we think about the therapeutic goals in chronic viral hepatitis.

7.  Ampio spettro morfologico Cirrosi iniziale: “early cirrhosis”. Cirrosi settale incompleta. Cirrosi completa attiva/inattiva. Cirrosi micro/macronodulare.

8. In 1997, Rizzetto Mario detected a new antigen in serum samples of patients with severe chronic liver disease

11. Temporal trend of HBsAg prevalence among chronic hepatitis cases in Italy

12. HBeAg/anti-HBe

20.  Possibile rimodellamento e regressione della fibrosi con persistenza della nodulazione e delle anomalie vascolari. Desmet VJ, et all. “Cirrhosis reversal : a duel between dogma and myth” J Hep 40:860-67; 2004 Panta rhei, ouden menei! (Eraclito di Efeso) may perhaps became accelerated iatrogencally in the future

21. HBeAg positivi o negativi PEG-INF o IFN nei pazienti senza storia di scompenso , senza imminente rischio di scompenso e senza segni di ipertensione portale, in particolare se giovani, HBeAg positivi e con predittori di risposta favorevole (HBV-DNA <2.000.000UI/mL, ALT elevate, genotipo HBV non D) (BII). INF può indurre esacerbazioni epatitiche (CIII). NA possono essere presi in considerazione in tutti i pazienti. Le opzioni sono (BIII): monoterapia con ETV, monoterapia con TDF monoterapia con LdT se HBV-DNA<2.000.000IU/mL (BIII).

23. Dieta iposodica (sale= 88 mmol/die, 2000mg/die). Una maggior sodio restrizione non è indicata. Diuretici: -antialdosteronici -diuretici dell’ansa Paracentesi.

24. Prima scelta: antialdosteronico (spironolattone 100-400 mg/die), si può associare furosemide (40-160 mg/die). Importante monitoraggio del calo ponderale per prevenire l’insufficienza renale: non > 0.5 Kg/die (no edemi periferici) e non > 1 Kg/die (se edemi). Monitoraggio dell’escrezione urinaria di sodio: importante nei pazienti in cui non vi è calo ponderale per valutare la risposta al diuretico.

25. Ascite che limita in modo significativo le attività della vita quotidiana (ascite massiva o tesa). Marcata ritenzione sodica (sodiuria <10 mmol/l), con rapida formazione di ascite anche con apporto sodico limitato. Strategie terapeutiche: paracentesi totali (Ginès ‘87 , Salerno ‘87) incremento dei diuretici. Non differenze sulla mortalità, ma minor effetti collaterali con la paracentesi. Diuretici come mantenimento.