Viral hepatitis: Milestones, unresolved issues, and future goals

Table 1 Direct-acting antiviral agents currently available in Italy and clinical indications (from Italian Association for the Study of the Liver[253])

DAAs	Clinical indications
Glecaprevir/Pibrentasvir	Pangenotypic regimen
	8 wk treatment in naïve/experienced (except GT3) non-cirrhotic pts and naïve CPT A5 cirrhotic pts
	12 wk treatment in experienced (except GT3) CPT A5 cirrhotic pts
	16 wk treatment in experienced GT3 non-cirrhotic or CPT A5 cirrhotic pts
	ESRD and/or hemodialysis (same treatment duration of pts without CKD)
	Contraindicated in decompensated cirrhosis
Grazoprevir/Elbasvir	GT1b, GT4
	12 wk treatment in GT1b or GT4 with HCV-RNA < 800000 IU/mL, naïve/experienced, CPT A5 cirrhotic or non-cirrhotic pts
	ESRD and/or hemodialysis (same treatment duration of pts without CKD)
	Contraindicated in decompensated cirrhosis
Sofosbuvir/Velpatasvir	Pangenotypic regimen
	12 wk treatment in naïve/experienced, cirrhotic or non-cirrhotic pts
	Indicated in decompensated cirrhosis
	Add RBV (if tolerated) in GT3 cirrhotic pts or in decompensated cirrhosis
	Optimal profile for drug interactions
	Contraindicated in pts with eGFR < 30 mL/min
Sofosbuvir/Velpatasvir/Voxilaprevir1	Pangenotypic regimen
	8 wk treatment in naïve/experienced non cirrhotic pts or GT3 naïve/experienced CPT A5 cirrhotic pts
	12 wk treatment in GT1, 2, 4, 5, 6 naïve/experienced CPT A5 cirrhotic pts
	First line therapy for retreatment after DAAs failure
	Contraindicated in pts with eGFR < 30 mL/min
	Contraindicated in decompensated cirrhosis

¹In Italy, this regimen is currently refundable only for retreatment after direct-acting antiviral agent failure. DAAs: Direct-acting antiviral agents; GT: Genotype; pts: Patients; CPT: Child Pugh Turcotte Score; ESRD: End stage renal disease; CKD: Chronic kidney disease; RBV: Ribavirin; eGFR: Estimated glomerular filtration rate; HCV: Hepatitis C virus.

Table 2 New classification of chronic hepatitis B phases

HBsAg+ ≥ 6 mo
HBeAg-positive chronic infection (1)
HBe: HBeAg+; HBV DNA: very high; ALT: persistently normal; Liver disease: minimal or absent	Ex “immune-tolerant;” Typical of children and young adults infected at birth; HBV DNA: > 1 million IU/mL; highly contagious people; Low rate of spontaneous HBeAg loss.
HBeAg-positive chronic hepatitis (2)
HBe: HBeAg+; HBV DNA: high; ALT: elevated; Liver disease: moderate or severe	Ex “immune reactive HBeAg-positive;” People infected in adulthood are likely to enter this phase; HBV DNA > 20000 IU/mL; rapid progression to fibrosis; Frequent HBe seroconversion.
HBeAg-negative chronic infection (3)
HBe: HBeAg-, anti-HBe+; HBV DNA: low or undetectable; ALT: normal; Liver disease: low	Ex “inactive HBV carrier;” HBV DNA: < 2000 IU/mL; it can also be > 2000 IU/mL but usually < 20000 IU/mL; Low risk of progression to cirrhosis or HCC; HBsAg loss in 1%–3%/yr.
HBeAg-negative chronic hepatitis (4)
HBe: HBeAg-, anti-HBe+; HBV DNA: moderate or high; ALT: elevated (variable); Liver disease: moderate or severe	HBV DNA: 2000-20000 IU/mL; Older people, frequent mutant precore HBV; Fluctuating levels of HBV DNA and ALT; Rare spontaneous remission and rapid progression to cirrhosis.

HBV: Hepatitis B virus; HBeAg: Hepatitis B E antigen; HBsAg: Hepatitis B surface antigen; ALT: Alanine aminotransferase; HCC: Hepatocellular carcinoma.