Hepatitis B and chronic kidney disease: Bench to bedside

Table 1 Common renal diseases/conditions associated with hepatitis B virus infection

Renal involvement	Features
Chronic hepatitis B in absence of cirrhosis	Membranous nephropathy
	Membranoproliferative glomerulonephritis
	Mesangial proliferative glomerulonephritis
	Polyarteritis nodosa
	IgA nephropathy
	Amyloidosis
Use of antiviral drugs for hepatitis B	Reduction in GFR
	Proteinuria
	Proximal tubular damage
	Fanconi syndrome
	Osteomalacia
Cirrhosis due to hepatitis B	Acute kidney injury
	Hepatorenal syndrome
	Urinary tract infections

IgA: Immunoglobulin A; GFR: Glomerular filtration rate.

Table 2 Seroprevalence of markers of occult hepatitis B infection in people on maintenance hemodialysis as reported in a few of the major studies (%)

Ref.	Country	Number of participants	Proportion with seropositive status in unvaccinated HBsAg negative population
			HBV DNA	IgG anti-HBc	Anti-HBs	IgG anti-HBc + anti-HBs
Siagris et al[22], 2006	Greece	49	20.4	-	-	-
Yakaryilmaz et al[23], 2006	Turkey	188	2.7	6.4	-	-
Aghakhani et al[24], 2010	Iran	289	50% of IgG anti-HBc reactive	6.2	-	-
Mina et al[25], 2010	Greece	346	0.9	-	-	-
Helaly et al[26], 2015	Egypt	100	45.8% of IgG anti-HBc positive group	48	-	-
Sowole et al[27], 2015	United Kingdom	778	-	3	-	17
Kalantari et al[28], 2016	Iran	400	-	2.5	-	5.5
Tang et al[29], 2020	China	330	-	10.8	-	48
Farshadpour et al[30], 2023	Iran	274	11.7	24.1	-	-

HBV: Hepatitis B virus; DNA: Deoxyribonucleic acid; IgG: Immunoglobulin G; Anti-HBc: Anti hepatitis B core antibody; Anti-HBs: Hepatitis B surface antibody.

Table 3 Non-invasive methods used to assess liver fibrosis and their potential limitations in patients with chronic kidney disease

Method for liver disease severity	Interpretation about liver disease	Limitation(s) in patients with CKD
Pedal edema and/or ascites	It is a feature of decompensation and its presence indicate liver cirrhosis with significant portal hypertension	Pedal edema may be present due to fluid overload and hypoalbuminemia which is common in CKD patients
Low serum albumin level	Indicates poor synthetic function of the liver	Serum albumin may be low due to albuminuria or poor nutritional status
Liver biopsy	Gold standard for assessing liver fibrosis	High risk of bleeding in patients with CKD
APRI which require serum AST and Platelet counts	A widely-validated index whose value correlates well with significant liver fibrosis, and values > 2.0 strongly suggest the presence of cirrhosis	May underestimates liver fibrosis, because serum AST elevation is commonly attenuated in those with renal failure, particularly those on MHD
FIB-4 which is based on age, ALT, AST, and Platelet counts	A widely-validated index whose value correlates well with significant liver fibrosis, and values > 3.25 strongly suggest the presence of cirrhosis	May underestimates liver fibrosis, because serum elevation of ALT as well as AST is attenuated in those with renal failure, particularly those on MHD
Transient elastography	Measures liver stiffness, which correlates well with the stage of liver fibrosis, particularly in patients with HCV infection	Fluid overload adds to liver stiffness, leading to overestimation of the stage of liver fibrosis

APRI: Aspartate aminotransferase to platelet ratio index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; FIB-4: Fibrosis-4 index; MHD: Maintenance hemodialysis; CKD: Chronic kidney disease.

Table 4 Dose modifications of antiviral drugs recommended according to estimated glomerular filtration rate

Antiviral drug	Creatinine clearance (mL per minute)
	> 50	30-49	10-29	< 10 or dialysis
Tenofovir disoproxil fumarate	300 mg tablet once a day	300 mg tablet every 48 hours	300 mg tablet every 72-96 hours	300 mg tablet every seven days or following completion of dialysis
Entecavir	0.5 mg tablet daily	0.5 mg tablet every 48 hours	0.5 mg tablet every 72 hours	0.5 mg tablet every week
Tenofovir alafenamide	25 mg tablet once a day	25 mg tablet once a day	25 mg tablet once a day up to creatinine clearance of 15 mL/minute	25 mg tablet after completion of dialysis

GFR: Glomerular filtration rate.

Table 5 Three generations of hepatitis B vaccines

Vaccine generation	Hepatitis B antigen	Examples	Remarks
First	SHBs protein	Heptavax-B (Merck & Co., United States); Hevac B (Pasteur, France); KGC (Korea Green Cross, Korea)	Not in use
Second	SHBs, MHBs protein	Recombivax (Merck & Co., United States); Engerix-B (GSK, Belgium); TGP 943 [P31] (Takeda, Japan); Fendrix (GSK, Belgium); HBVaxPro (Sanofi-Pasteur, MSD)	Most commonly used and easily available
Third	SHBs, MHBs, Large hepatitis B surface protein	GenHevac B (Pasteur, France); Bio-Hep-B (Bio Technology General, Israel)	Limited availability and higher costs

SHBs: Small hepatitis B surface; MHBs: Medium hepatitis B surface.