Hepatitis-related Renal Disease

Kar Neng Lai

Future Virology. 2011;6(11):1361-1376.

Future Perspective

Chronic HBV and HCV infection remains a major health burden in endemic areas, resulting in hepatic and extrahepatic complications such as glomerulopathy.

For treating HBV-related complications including GN, the future treatment strategy should target: universal vaccination program for endemic areas and populations at risk (such as intravenous drug users); the use of newer antiviral agents, including entecavir, with appropriate dose adjustment according to renal function; stratification of treatment response according to HBV genotype; and downregulation of HBeAg production or enhancement of HBeAg seroconversion through viral mutation as exemplified by precore stop codon mutation and the basal core promoter mutation. For treating HCV-related complications, including GN, the future treatment strategy should target: vaccine development; exploration of the role of the CD4⁺ T-cell response in the control of early HCV infection, which will increase the opportunity for the identification of protective epitopes that could be used in future vaccine development; stratification of treatment response according to HCV genotype; and clinical trials of newer antiviral agents.

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Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Table 1. Clinical presentation of HBV-related membranous nephropathy.
Characteristic	Children	Adult
Route of HBV infection: Vertical or horizontal within family members Intravenous drug abuse Blood transfusion Sexually	+ - - -	+ (in endemic areas) + (in nonendemic areas) + (in nonendemic areas) + (in nonendemic areas)
Male:female ratio	4:1	2–3:1
History of liver disease	Absent	Absent in endemic areas
Abnormal liver functions	Uncommon	Mild rise in ALT
Presenting symptoms	Nephrotic syndrome	Nephrotic syndrome/proteinuria
Hypertension	<25%	25–40%
Renal insufficiency	Rare	Occasional
Serum positivity for HBeAg and anti-HBc	+ (88.2%)	+ (87.5%)

ALT: Alanine aminotransferase; HBeAg: Hepatitis B e antigen.

Table 2. Characteristics and outcome of published studies on HBV-related glomerulonephritis treated with lamivudine.
Study	Study design	Country	Patient number	Age or mean age (yr)	MN	Proteinuria (g/day)	Serum creatinine (mg/dl)	HBeAg	Follow-up (mon)	LAM (mg/day)	LAM duration (mon)	Proteinuria (sustained remission)	HBsAg clearance	HBeAg clearance	Ref.
Connor et al.	CR	Australia	1	6	Yes	>300^†	Normal	Positive	21	100	12	Yes	No	Yes	[33]
Filler et al.	CR	Canada (Vietnamese)	1	5	Yes	>3	NA	Positive	6	50	6	Relapse after stopping LAM	No	NA	[34]
Tang et al.	CCT	Hong Kong	10	48 ± 13	100%	4.9 ± 2.4	0.98 ± 0.18	70%	49	100	12	70%	No	50%	[24]
Gan et al.	CR	Canada (Chinese)	2	44 and 46	Yes	7.1 and 8.1	NA	Positive	36	100	12	50%	No	50%	[35]
Izzedine et al.	CR	Canada (Chinese)	1	48	Yes	3.9	0.76	Negative	36	100	36	Yes	No	NA	[36]
Okuse et al.	CR	Japan	1	37	Yes	4.8	GFR 25 ml/min	Positive	108	100	48	Yes	No	Yes	[37]
Kanaan et al.	CR	Belgium	1	57	Yes	4.0	Normal	Positive	25	100	17	Yes	Yes	Yes	[38]
Wen et al.	CR	Taiwan (Chinese)	1	39	MCGN	4.5	1.4	Positive	9	100	6	Yes	No	Yes	[39]
Chuang et al.	CR	Taiwan (Chinese)	1	22	Yes	6.0	0.9	Yes	13	100	6	Yes	No	Yes	[40]
Mesquita et al.	CR	Belgium	1	28	Yes^‡	14.5	Normal	Negative	84	100	84	Yes	NA	NA	[41]

^†Urine albumin to creatinine ratio (normal 0–3 mg/mmol).
^‡Precore HBV mutant.
CCT: Clinical controlled study; CR: Case report; GFR: Glomerular filtration rate; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; LAM: Lamivudine; MCGN: Mesangiocapillary glomerulonephritis; MN: Membrous nephropathy; mon: Month; NA: Not available; yr: Year.

Table 3. Classification of cryoglobulins.
Type	Immunoglobulin composition	RF activity	Most common disease association	Other disease associations
I	Single monoclonal IgG, IgA or IgM	No	Multiple myeloma	Waldenström's macroglobulinemia Idiopathic monoclonal gammopathy Chronic lymphocytic leukemia
II^†	Polyclonal IgG and monoclonal IgM	Yes	HCV infection	Chronic lymphocytic leukemia Lymphoproliferative disease Essential^‡
III^†	Polyclonal IgG and polyclonal IgM	Yes	Connective tissue disease, particularly RA	Lymphoproliferative disease Chronic liver disease Essential^‡

^†Also known as mixed cryoglobulinemia due to the presence of more than one immunoglobulin type.
^‡When no definite disease association is found, these are known as essential mixed cryoglobulinemia.
RA: Rheumatoid arthritis; RF: Rheumatoid factor.

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