Viral hepatitis: A brief introduction, review of management, advances and challenges

Table 1 Comparison of hepatotropic viruses hepatitis A-E

Hepatitis	A	B	C	D	E
Viral structure	Naked, ssRNA (Picornavirus)	Envelope, dsDNA (Hepadnavirus)	Envelope, ssRNA (Flavivirus)	Envelope, ssRNA (-ve) (Deltavirus)	Naked, ssRNA (Hepevirus)
Transmission	Faecal-oral	Parenteral, sexual	Parenteral, sexual	Parenteral, sexual	Faecal-oral
Incidence	1.4 million	> 250 million[88]	> 80 million	About 12 million (prevalence)[89]	20 million
Chronic infection	No	About 90% of infants infected; about 2%-6% adult infected	70% (55%-85%)	< 5% of those infected with HBV, > 80% of superinfection)[90]	No (very rarely in immunosuppressed adults)[91]
Other disease associations	None	HCC, cirrhosis	HCC, cirrhosis	Cirrhosis, fulminant hepatitis	None (cirrhosis in chronic HEV infection)
Treatment	Supportive	Viral suppressive therapy (see criteria for commencement of treatment below)	Eradication therapy DAA (gold standard)	PEG-IFN (sparse data)	Supportive

HBV: Hepatitis B virus; HEV: Hepatitis E virus; HCC: Hepatocellular carcinoma; DDA: Direct-acting antiviral.

Table 2 Diagnosing hepatitis A-E

Hepatitis	Serological testing	Molecular testing (via PCR), quantitative
A	Anti-HAV IgM (acute); Anti-HAV IgG (previous infection, vaccination); Note incubation period of 28 d[92]	HAV RNA
B	Anti-HBc (contact with HBV infection); HBsAg (current infection) appears 1-3 wk post exposure, duration > 24 wk denotes chronicity; Anti-HBS (vaccination, cleared HBV infection); HBeAg (high replication phase (> 10000 IU/mL); Anti-HBe (low replication phase (< 10000 IU/mL); Note incubation 90 d (ranges 45-160 d); Window period 1: first about 8 d of infection; Window period 2: clearance of HBsAg during this period Anti-HBc IgM is detectable[93]	HBV DNA
C	Anti-HCV: Note incubation 6-7 wk (ranges 2 wk to 6 mo)[93]	HCV RNA
D	Anti- HDV IgG	HDV RNA
E	Anti-HEV IgM and IgG and IgA	HEV RNA

HBV: Hepatitis B virus; HCV: Hepatitis C virus; HDV: Hepatitis D virus; HEV: Hepatitis E virus; PCR: Polymerase chain reaction; HBsAg: Hepatitis B surface antigen.

Table 3 European Association for the Study of the Liver 2017 clinical practice guidelines on the management of hepatitis B virus infection[12]

Clinical practice guidelines
All patients with HBeAg-positive or -negative chronic hepatitis B, defined by HBV DNA (2000 IU/mL, ALT) upper limit of normal (ULN) and/or at least moderate liver necroinflammation or fibrosis, should be treated (Evidence level I, grade of recommendation 1)
Patients with compensated or decompensated cirrhosis need treatment, with any detectable HBV DNA level and regardless of ALT levels (Evidence level I, grade of recommendation 1)
Patients with HBV DNA (20000 IU/mL, and ALT) 2 × ULN should start treatment regardless of fibrosis degree (Evidence level II-2, grade of recommendation 1)
Patients with HBeAg-positive chronic HBV infection, defined by persistently normal ALT and high HBV DNA levels, may be treated if they are older than 30 years regardless of the severity of liver histological lesions (Evidence level III, grade of recommendation 2)
Patients with HBeAg-positive or HBeAg-negative chronic HBV infection and family history of HCC or cirrhosis and extra-hepatic manifestations can be treated even if typical treatment indications are not fulfilled (Evidence level III, grade of recommendation 2)

HBV: Hepatitis B virus; HBeAg: Hepatitis B e-antigen; ALT: Alanine transaminase.

Table 4 Comparing pegylated-interferon therapy to nucelos(t)ide analogues therapy

	PEG-IFN	NA
Route of administration	Subcutaneous	Oral
Length of treatment	48 wk	Long-term in chronic HBV (stopping may be considered in some cases[13]); 8-16 wk in HCV
Contraindications	Many (i.e., decompensated disease, comorbidities)	None (dose adjustment according to eGFR)
Tolerance	Inferior tolerability	Excellent tolerance
Side effects	Significant adverse events (psychiatric, neurologic, endocrinological)	Renal impairment (some DAA)[12]
SVR in HCV	40%-75%[94,95]	> 90%[46]
Efficacy in chronic HBV	> 30% HBeAg loss; 3%-5% HBsAg loss[96]	> 11%-18% eAg loss (lower rate of HBeAg seroconversion); Very low HBsAg loss[97]
Cost	Expensive	Expensive when given long-term (i.e., chronic HBV infection)[98]
Resistance	No	Yes

PEG-IFN: Pegylated interferon; NA: Nucelos(t)ide analogues; HCV: Hepatitis C virus; HBeAg: Hepatitis B e-antigen; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; DDA: Direct-acting antiviral.

Table 5 First-line recommended direct-acting antiviral therapies for hepatitis C patients

Genotype	1	2	3	4	5/6
DAA schedule (non-cirrhotic)	Sofosbuvir/Ledipasvir; Or Glecaprevir/Pibrentasvir	Sofosbuvir/Velpatasvir	Sofosbuvir/Velpatasvir	Sofosbuvir/Ledipasvir	Sofosbuvir/Ledipasvir
Duration	8-12 wk	12 wk	12 wk	12 wk	12 wk
DAA schedule (cirrhotic)	Sofosbuvir/Ledipasvir	Sofosbuvir/Velpatasvir	Glecaprevir/Pibrentasvir	Sofosbuvir/Ledipasvir	Sofosbuvir/Ledipasvir
Duration	12 wk	12 wk	8-16 wk	12 wk	12 wk

DDA: Direct-acting antiviral.