Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website https://www.gastrores.org

Review

Volume 14, Number 3, June 2021, pages 139-156

A Focused Review on Recent Advances in the Diagnosis and Treatment of Viral Hepatitis

**Table 1.** High-Risk Groups for Hepatitis Viruses
At-risk group	Virus
HAV: hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HDV: hepatitis D virus; HEV: hepatitis E virus; HBsAg: HBV surface antigen.
Individuals who have ever injected drugs	HAV, HBV, HCV, HEV
Individuals suffering from homelessness	HAV, HBV, HCV
Men who have sex with men	HAV, HBV, HCV
Patients with end-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis and home dialysis	HBV, HCV, HEV
Sexually active individuals (more than one partner in the past 6 months)	HBV, HCV
Individuals living in close household contact with or have sexual contacts with active infected patients	HBV, HCV
Health care providers and public safety workers at risk for occupational exposure to blood or blood-contaminated body fluid	HBV, HCV
Inmates and staff of correctional facilities	HBV, HCV
All pregnant women	HBV, HEV
Exposure to undercooked meat, fish, or shellfish	HAV, HEV
Individuals born in or adopted from countries where hepatitis B is common (Asia, Africa, South America, Pacific Islands, Eastern Europe, and the Middle East)	HBV
Individual born or adopted in areas where hepatitis C is common (Central Asia, East Asia, North Africa, and West Africa)	HCV
Individuals with chronic HBV infection	HDV, HEV
Those with blood transfusion or organ donation prior to 1992	HCV
Individuals who have ever injected drugs who are HBsAg+	HDV
Men who have sex with men who are HBsAg+	HDV
Individuals who are HBsAg+ and have elevated liver function tests	HDV
Individuals who are HBsAg+ and have immigrated from areas of high HDV endemicity	HDV

Table 1. High-Risk Groups for Hepatitis Viruses

At-risk group

Virus

HAV: hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HDV: hepatitis D virus; HEV: hepatitis E virus; HBsAg: HBV surface antigen.

Individuals who have ever injected drugs

HAV, HBV, HCV, HEV

Individuals suffering from homelessness

HAV, HBV, HCV

Men who have sex with men

HAV, HBV, HCV

Patients with end-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis and home dialysis

HBV, HCV, HEV

Sexually active individuals (more than one partner in the past 6 months)

HBV, HCV

Individuals living in close household contact with or have sexual contacts with active infected patients

HBV, HCV

Health care providers and public safety workers at risk for occupational exposure to blood or blood-contaminated body fluid

HBV, HCV

Inmates and staff of correctional facilities

HBV, HCV

All pregnant women

HBV, HEV

Exposure to undercooked meat, fish, or shellfish

HAV, HEV

Individuals born in or adopted from countries where hepatitis B is common (Asia, Africa, South America, Pacific Islands, Eastern Europe, and the Middle East)

HBV

Individual born or adopted in areas where hepatitis C is common (Central Asia, East Asia, North Africa, and West Africa)

HCV

Individuals with chronic HBV infection

HDV, HEV

Those with blood transfusion or organ donation prior to 1992

HCV

Individuals who have ever injected drugs who are HBsAg+

HDV

Men who have sex with men who are HBsAg+

HDV

Individuals who are HBsAg+ and have elevated liver function tests

HDV

Individuals who are HBsAg+ and have immigrated from areas of high HDV endemicity

HDV

**Table 2.** Guidelines for Chronic Hepatitis B Treatment
	HBV cirrhosis	HBV non-cirrhotic HBeAg+	HBV non-cirrhotic HBeAg-	Other indications to initiate treatment
HBV: hepatitis B virus; HBeAg: hepatitis B E antigen; ALT: alanine aminotransferase; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases.
EASL	Treat	HBV DNA cutoff of 2,000 IU/mL	HBV DNA cutoff of 2,000 IU/mL	ALT > 40 U/L with histologic evidence of moderate necroinflammation and/or moderate fibrosis ALT > 40 U/L with histologic evidence of moderate necroinflammation and/or liver stiffness > 9 kPa ALT > 80 U/L and HBV DNA > 20,000 IU/mL, if histology is not available.
AASLD	Treat	HBV DNA cutoff of 20,000 IU/mL	HBV DNA cutoff of 2,000 IU/mL	ALT > 70 U/L (for male) and ALT > 50 U/L (for female) or histologic evidence of moderate or severe necroinflammation or significant fibrosis for initiating treatment
AASLD	Treat	HBV DNA cutoff of 20,000 IU/mL	HBV DNA cutoff of 2,000 IU/mL	ALT > 70 U/L (for male) and ALT > 50 U/L (for female) or histologic evidence of moderate or severe necroinflammation or significant fibrosis for initiating treatment

Table 2. Guidelines for Chronic Hepatitis B Treatment

HBV cirrhosis

HBV non-cirrhotic HBeAg+

HBV non-cirrhotic HBeAg-

Other indications to initiate treatment

HBV: hepatitis B virus; HBeAg: hepatitis B E antigen; ALT: alanine aminotransferase; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases.

EASL

Treat

HBV DNA cutoff of 2,000 IU/mL

ALT > 40 U/L with histologic evidence of moderate necroinflammation and/or moderate fibrosis
ALT > 40 U/L with histologic evidence of moderate necroinflammation and/or liver stiffness > 9 kPa
ALT > 80 U/L and HBV DNA > 20,000 IU/mL, if histology is not available.

AASLD

Treat

HBV DNA cutoff of 20,000 IU/mL

HBV DNA cutoff of 2,000 IU/mL

ALT > 70 U/L (for male) and ALT > 50 U/L (for female) or histologic evidence of moderate or severe necroinflammation or significant fibrosis for initiating treatment

AASLD

Treat

HBV DNA cutoff of 20,000 IU/mL

HBV DNA cutoff of 2,000 IU/mL

ALT > 70 U/L (for male) and ALT > 50 U/L (for female) or histologic evidence of moderate or severe necroinflammation or significant fibrosis for initiating treatment

**Table 3.** Class I Evidence (Beneficial, Effective, and Useful Treatment) With Data From Multiple Randomized Clinical Trials, Meta-Analysis or Equivalent
Patient population	First line treatment regimens
^aPatients without baseline NS5A RAS Y93H for velpatasvir. ^bPatients both with and without cirrhosis.
Genotype 1a without cirrhosis	Elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir
Genotype 1a + compensated cirrhosis	Elbasvir/grazoprevir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, glecaprevir /pibrentasvir
Genotype 1b without cirrhosis	Elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir
Genotype 1b + compensated cirrhosis	Elbasvir/grazoprevir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir
Genotype 2 without cirrhosis	Glecaprevir/pibrentasvir, sofosbuvir/velpatasvir
Genotype 2 + compensated cirrhosis	Sofosbuvir/velpatasvir
Genotype 3 without cirrhosis	Glecaprevir/pibrentasvir, sofosbuvir/velpatasvir
Genotype 3 + compensated cirrhosis	Sofosbuvir/velpatasvir^a
Genotype 4 without cirrhosis	Elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir
Genotype 4 + compensated cirrhosis	Sofosbuvir/velpatasvir
Genotypes 5 + 6^b	Glecaprevir/pibrentasvir

Table 3. Class I Evidence (Beneficial, Effective, and Useful Treatment) With Data From Multiple Randomized Clinical Trials, Meta-Analysis or Equivalent

Patient population

First line treatment regimens

^aPatients without baseline NS5A RAS Y93H for velpatasvir. ^bPatients both with and without cirrhosis.

Genotype 1a without cirrhosis

Elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir

Genotype 1a + compensated cirrhosis

Elbasvir/grazoprevir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, glecaprevir /pibrentasvir

Genotype 1b without cirrhosis

Elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir

Genotype 1b + compensated cirrhosis

Elbasvir/grazoprevir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir

Genotype 2 without cirrhosis

Glecaprevir/pibrentasvir, sofosbuvir/velpatasvir

Genotype 2 + compensated cirrhosis

Sofosbuvir/velpatasvir

Genotype 3 without cirrhosis

Glecaprevir/pibrentasvir, sofosbuvir/velpatasvir

Genotype 3 + compensated cirrhosis

Sofosbuvir/velpatasvir^a

Genotype 4 without cirrhosis

Elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir

Genotype 4 + compensated cirrhosis

Sofosbuvir/velpatasvir

Genotypes 5 + 6^b

Glecaprevir/pibrentasvir

**Table 4.** Summary of the Diagnostic and Therpaeutic Strategies for Hepatitis Viruses
Virus	Diagnostic testing modalities	Treatment strategies
HAV: hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HDV: hepatitis D virus; HEV: hepatitis E virus; EIA: enzyme immunoassay; IgM: immunoglobulin M; HBsAg: HBV surface antigen; HBeAg: hepatitis B E antigen; HBcrAg: Hepatitis B core-related antigen; NAAT: nucleic acid amplification technology; POC: point of care.
HAV	IgM anti-HAV antibodies via EIA Rapid immunochromatographic test IgG anti-HAV rapid salivary test	Supportive care
HBV	HBsAg, HBeAg, and IgM/IgG anti-HBc antibodies via EIA Quantitative HBV DNA level via NAAT Quantitative HBsAg HBcrAg POC HBsAg	Interferon formulations Nucles(t)ide analogs
HCV	IgG anti-HCV antibodies via EIA Quantitative HCV RNA level via NAAT POC anti-HCV	DAAT Interferon formulations
HDV	Total anti-HDV antibody Quantitative HDV RNA level via NAAT	No FDA approved formulations Bulevirtide (myrcludex): viral entry inhibitor approved in Europe
HEV	Anti-HEV IgG/IgM antibodies via EIA Quantitative HEV RNA via NAAT POC anti-HEV1 and anti-HEV3 IgM	Ribavirin ± pegylated interferon HEV vaccine in China

Table 4. Summary of the Diagnostic and Therpaeutic Strategies for Hepatitis Viruses

Virus

Diagnostic testing modalities

Treatment strategies

HAV: hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HDV: hepatitis D virus; HEV: hepatitis E virus; EIA: enzyme immunoassay; IgM: immunoglobulin M; HBsAg: HBV surface antigen; HBeAg: hepatitis B E antigen; HBcrAg: Hepatitis B core-related antigen; NAAT: nucleic acid amplification technology; POC: point of care.

HAV

IgM anti-HAV antibodies via EIA
Rapid immunochromatographic test
IgG anti-HAV rapid salivary test

Supportive care

HBV

HBsAg, HBeAg, and IgM/IgG anti-HBc antibodies via EIA
Quantitative HBV DNA level via NAAT
Quantitative HBsAg
HBcrAg
POC HBsAg

Interferon formulations
Nucles(t)ide analogs

HCV

IgG anti-HCV antibodies via EIA
Quantitative HCV RNA level via NAAT
POC anti-HCV

DAAT
Interferon formulations

HDV

Total anti-HDV antibody
Quantitative HDV RNA level via NAAT

No FDA approved formulations
Bulevirtide (myrcludex): viral entry inhibitor approved in Europe

HEV

Anti-HEV IgG/IgM antibodies via EIA
Quantitative HEV RNA via NAAT
POC anti-HEV1 and anti-HEV3 IgM

Ribavirin ± pegylated interferon
HEV vaccine in China