the spectrum of chronic hbv infection ranges from asymptomatic infection to chronic hepatitis with progression to cirrhosis , end - stage liver disease and hepatocellular carcinoma .
a 30-year - old man presented with recent hypertension , severe headache and lethargy on a background of recently diagnosed hbv infection .
urine microalbumin / creatinine ratio was 31.6 mg / mmol of creatinine ( < 2.5 mg / mmol ) with a urine protein excretion of 350 mg / day .
other abnormal investigations included alanine transaminase 108 u / l ( 5 - 55 ) , aspartate transaminase 76 u / l ( 5 - 55 ) and erythrocyte sedimentation rate 46 mm / h ( 030 mm / h ) . hbsag and hepatitis b e antigen ( hbeag ) were positive , while igm hepatitis b core antibody was negative .
hepatitis b viral dna was quantitated at 364 million iu / ml . electrophoresis of serum and urine were negative for paraprotein .
antinuclear antibody , antineutrophil cytoplasmic antibody , extractable nuclear antigen , complements and anti - double - stranded dna were negative .
three months after diagnosis , he continued to have high viral load suggesting a chronic hbv infection .
mol / l with an estimated glomerular filtration rate ( egfr ) of 57 ml / mt .
glomeruli were normal on light microscopy with evidence of tubulointerstitial nephritis ( figure 1a ) .
there was interstitial oedema and dense mononuclear cell infiltrate comprising lymphocytes , plasma cells and occasional eosinophils .
trace deposits of granular iga ( < 1 + ) were seen on immunofluorescence microscopy .
nuclear abnormalities in the form of condensed chromatin and round structures with a dense core surrounded by a clear halo were observed in some of the tubules ( figure 1b and c ) .
( a ) light microscopy view from the first renal biopsy showing degeneration of tubular epithelium ( arrows ) and associated interstitial nephritis ( lhs of image ) 20 ; ( b ) electron microscopy showing necrosis of tubular epithelium cells ( asterisk ) , ( c ) virus - like particles in the nucleus of a tubular epithelial cell .
tubulo interstitial nephritis ( tin ) was attributed to chronic hbv infection , and he was initiated on entecavir 0.5 mg twice a day .
although the viral dna load decreased significantly over the next 4 weeks ( 429 copies / ml , 58 iu / ml ) , renal function deteriorated ( serum creatinine rose 210 mol / l egfr 35 ml / mt ) . on a repeat renal biopsy ,
nine months after initiation of entecavir , egfr improved to 45 ml / mt ( serum creatinine 165
extra hepatic manifestations associated with chronic hbv infection can be varied with renal , skin , joint and nervous system manifestations .
the renal manifestations of chronic hbv infection usually include glomerulonephritis , essential mixed cryoglobulinaemia and polyarteritis nodosa ( pan ) .
the most characteristic presentation is nephrotic syndrome , with membranous nephropathy being the most common pathological finding .
children have a good prognosis with up to 95% achieving clinical resolution within 7 years .
adults , in contrast , may have a relentless course with 30% progressing to renal failure and 10% eventually requiring haemodialysis .
pan is a rare complication of chronic hbv infection , occurring in 1% to 5% of patients .
human immunodeficiency virus , cytomegalovirus , epstein  barr virus , hanta virus , polyoma and adenovirus are some of the viruses associated with tin .
we are not aware of any published report of hbv associated tin in the english literature .
the renal biopsy findings of tin in our patient were quite unexpected as the usual renal manifestation of hbv nephritis is glomerular .
however , the electron microscopic findings of viral structures akin to hbv along with positive immunohistochemical staining for hbv antigen in the tubules , and a progressively worsening renal function with increasing viral load further strengthened our belief of hbv infection as the cause of tin .
although the majority of patients spontaneously clear the viraemia , active treatment was initiated considering progressive renal impairment .
entecavir , a potent nucleoside analogue with low risk of antiviral resistance , was chosen , as lamivudine and interferon were considered to be less effective in the presence of very high viral load .
improvement of egfr with prolonged entecavir treatment further supports our view that hbv infection is the cause of tin in this patient .
an interplay of host , virus and other environmental factors is necessary for nephropathy to develop .
this is supported by the observation that only few patients with chronic hbv infection have renal disease .
much of the available evidence points to a direct cytopathic effect by virus , immune complex deposition , viral induced cytokine injury or a specific immunological effector mechanism induced by hbv as probable explanations for renal injury . in summary , we conclude that , in our patient , tin was associated with chronic hbv infection .
we suggest that tin should be considered as a possible cause of renal impairment in hbv - infected patients .
our case exemplifies that aggressive antiviral treatment in such patients would stabilize and improve renal function .
the exact pathogenesis of tin in association with hbv infection needs to be elucidated by future experimental work and further clinical observations .
 hepatitis b viral infection is usually a self - limiting disease in immunocompetent individuals . 
 chronic infection can be seen in up to 5% of infected patients . 
 renal manifestations of chronic hbv infection are usually glomerular . 
 we describe here an uncommon presentation of a patient with chronic hbv infection with very high viral load and rapidly progressive renal failure . 
 renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of hbv infection . 
 entecavir treatment slowed down the progression of his renal disease . 
 tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with hbv infection . 
 early antiviral treatment may halt the progression of renal disease . 
Introduction
Case report
Discussion