This document discusses renal disease associated with viral hepatitis. It covers the basic virology of hepatitis B and C, describes different testing methods used to diagnose active infection, and reviews the epidemiology of both viruses globally and in the UK. It then examines associations between viral hepatitis, chronic kidney disease, and end-stage renal disease, describing different types of renal pathology that can occur. Treatment approaches for hepatitis-related renal conditions are outlined.

1. Renal Disease and Viral Hepatitis
Richard McCrory

2. Basic Virology
Hepatitis B
Hepadnavirus
• 4 serotypes, 8 genotypes (impact
virulence)
Circular DNA Genome
• DNA →RNA →DNA
Hepatitis C
Flavivirus
• 7 genotypes but high rate of
mutation
Single Strand positive RNA genome

3. Testing for HBV
Test Result Typical interpretation
HBsAg
anti-HBc
anti-HBs
negative
negative
negative
Susceptible (needs vaccination)
HBsAg
anti-HBc
anti-HBs
negative
positive
positive
Resolved HBV infection
HBsAg
anti-HBc
anti-HBs
negative
negative
positive
Vaccinated
HBsAg
anti-HBc
anti-HBs
positive
positive
negative
Active HBV infection
(usually chronic)
HBsAg
anti-HBc
anti-HBs
negative
positive
negative
Various possibilities, including:
- distant resolved infection
(most common)
- recovering from acute infection
- false positive
- 'occult' HBV ( +ve HBV DNA viral load)

4. Testing for HCV
HCV antibody (4-6 weeks to become +ve)
● May be negative in the first 6 weeks after exposure
● Does not distinguish between acute and chronic infection
● Low signal-to-cutoff ratio may be present during acute HCV infection
or represent a false-positive result
HCV RNA (10-14 days to become +ve)
● Viral fluctuations >log10 IU/mL may indicate acute HCV infection
● Alone does not distinguish between acute and chronic infection

5. Epidemiology
Hepatitis B
• Worldwide
– 240-350 million HbSAg +ve
• 1:350 UK Population
Transmission
– Blood or Contaminated
Equipment
– Sexual
– Vertically
Hepatitis C
• Worldwide
– 135-200 million HCV Ab +ve
• 1 in 250 UK Population
Transmission
– Blood or Contaminated
Equipment
– Sexual (less common)

7. The Many faces of Chronic HBV
Infection

9. Associations of Viral Hepatitis with
CKD / ESRD in Taiwan
HBV
HBV +ve prevalence >15% 1985
Incidence of ESRD in untreated
chronic HBV cohort 2% (HR 3.85)
HCV
High HCV Prevalence
• Incidence of ESRD in chronic
HCV patients 2.14 fold
higher than age matched
cohort
• Patients aged 50-59 had
highest incidence
BUT
Taiwan has high prevalence of Type 2 Diabetes
Associations between T2DM and both Hepatitis Viruses

10. Spectrum of Renal Disease Associated
with Hepatitis Viruses
Membranous
Nephropathy
MPGN
Polyarteritis
Nodosa

11. Sample Questions
A 41-year-old woman with a recent diagnosis of hepatitis C infection was
found to have a serum creatinine of 167 umol/L. Urine dipstick was
positive for 3+ protein and + blood
Other results are as follows:
24hr Urinary protein - 2.7 g/24 h
C4 - <0.14 g/L C3 - 0.23 g/L
Rheumatoid factor – Positive
ANCA / ANA / Anti-GBM - Negative

12. Light Immuno
against IgG
EM

13. What is the most likely diagnosis?
A. IgA Nephropathy
B. Cryoglobulinemic Glomerulonephritis
C. Membranous Nephropathy
D. Thrombotic Microangiopathy
E. Crescentic Glomerulonephritis

14. Membranoproliferative GN
● Large glomeruli with accentuation
of lobules
● Irregular thickening of glomerular
basement membrane by
interposition of mesangial cells
between endothelium and
basement membrane
● Causes tram track / double contour
appearance (PAS or silver stain),
crescents in 20%

16. Cryoglobulins in HCV
Type II cryoglobulins
● IgM directed against Fc of IgG
● Rheumatoid Factor behaviour
40-90% of patients with Chronic HCV have
evidence of cryoglobulins
● <10% of these will manifest with vasculitis

17. Cryoglobulinaemic Vasculitis

18. The patient was commenced on treatment for cyroglobulinaemic
vasculitis and is discharged 10 days after admission. She
presents at outpatient clinic 3 weeks later with increasing
shortness of breath.
Blood Tests at date of admission and at 6 weeks are shown
below:
Admission Week 5
Haemoglobin
(g/L)
115 78
MCV 86 102
WCC 11.8 7.2
Platelets 242 196

19. What agent started at treatment is most likely to
explain the patient’s shortness of breath?
A. Cyclophosphamide
B. Interferon-Alpha
C. Ribavirin
D. Losartan

20. HCV Related Glomerular Disease
● Membranoproliferative GN
● IgA Nephropathy
● Post-infectious GN
● Thrombotic Microangiopathy
● FSGS
● Fibrillary GN

21. Treatment of HCV-related renal
disease
Patients with nephrotic-range proteinuria and/or progressive renal
failure:
● Immunosuppressive plus antiviral treatment
o Rituximab: 375 mg/m2 weekly for 4 wk
o Cyclophosphamide: 2 mg/kg per d for 2 to 4 months
o Methylprednisolone pulses: 0.5 to 1 g/d for three consecutive
days
● RBV daily: initial dose according to GFR
● Some newer agents do not require dose adjustment for GFR
● Plasma exchange in case of high cryoglobulin levels
o 3 l of plasma three times per week for 2 or 3 wk

22. Antivirals for Hepatitis C
Virologic cure = Sustained Virological Response
● Absence of detectable HCV RNA >12 weeks after
completion of therapy
Response depends heavily on Genotype
● Genotype 1 - 40% response at 48 weeks
● Genotype 2/3 - 80% response rate within 12 weeks

24. HBV Associated Membranous (HBV-MN)
Children
● Strong (>80%) Male Preponderance
● Commonly presents with nephrotic
syndrome or microscopic
haematuria
● Often don’t have overt liver disease
● Remission correlates with viral
clearance
Adults
● Less favourable prognosis
● Proteinuria + Hypertension
In high titre HBsAg Patients
● Nephrotic Syndrome + Abnormal
LFTs = >50% RRT at 3yrs
HBeAg / Anti-HBe immune complexes likely culprit for sub-
epithelial deposit substrate
HBV DNA can be detected in glomerular & interstitial tissues

25. Treatment of HBV-MN
Don’t forget measures utilised for other proteinuric
disease!
Immunosuppression monotherapy
● Causes more harm than good
● Increases viral replication, accelerates
progression
Antivirals
● Suppresses viral load, facilitates clearance of
antigen
Interferon
● Helps accelerate seroconversion

26. Antivirals in Hepatitis B
• Aim of therapy – to promote seroconversion
• No new drugs in Phase 3 trials presently
• Nucleoside Analogues
– Lamivudine
• Cheaper
• Mutation Resistance increases with treatment duration
– Entecavir
• More Expensive
• <1% resistance rate at three years treatment
• Interferon
– Finite duration of treatment
– No mutation resistance
– Side effects can be difficult to manage

27. A 45 year old man presents with a 10 week history of intermittent abdominal
pain after eating and weakness in his legs. Blood Pressure is elevated at
190/110 mmHg and examination confirms a right foot drop. You have been
asked to consult due to elevated serum creatinine.
Urine dipstick notes 1+ protein and 2+blood
Hb 110g/L WCC 7.5 CRP 25 mg/L
Coagulation Screen - Normal Thrombophilia Screen - Negative
Creatinine 220 umol/L Urine ACR - 30 mg/mmol
HIV Antibodies - Negative HBsAg - Positive HBeAg - Positive
ANA / ANCA / Anti-GBM - Negative C3 - 0.39 g/L C4 - 0.15 g/L
CT Brain - Normal
Ultrasound Renal Tracts - No obstruction, Left Kidney 10cm, Right Kidney 10.5cm

28. Which of the following would be the best investigation
to perform next?
A. Renal Biopsy
B. Mesenteric Angiography
C. CT Abdomen with Contrast
D. Sural Nerve Biopsy
E. Gastroscopy

29. “Testing is Cheap,
Treatment is not”

30. Viral Hepatitis & Dialysis
DOPPS (2004)
● HCV prevalence ranged from 3-23% HD units
over 3 continents
● HBV from 0-5%
● Prevalences in Developing World
– 18-80%

32. Vaccinating CKD Patients against HBV
Why not?
– Reduced efficacy of the vaccine
– The low rate of hepatitis B infection
CDC Position (2012)
“The cost of vaccinating patients is mitigated by
the reduced need for monthly surveillance of
antigen and antibody status”

33. Use of HBV Vaccines as treatment for
HBV?
“Third generation” vaccines show increased
immunogenic response in CKD patients

34. Chronic HBV and Pre-RT evaluation
Involve a Hepatologist!
HBeAg status and HBV DNA copy load can help
determine risk of reactivation post-Tx
HBsAg +ve patients routinely need liver biopsy
Are they a candidate for combined liver-kidney
transplant?

35. Hepatitis B & Renal Transplantation
The HBsAg Positive Donor Kidney
● Should not be transplanted into HBV-naive
recipients except in urgent scenario
● Risk of de novo infection reduced if donor
anti-HBc positive

36. General Rules for Recipients with HBV
HBsAg +ve Recipients
● Lifelong anti-viral therapy
Anti-HBc +ve(or -ve) / anti-HBs +ve Recipients
● No prophylaxis immediately needed, may
need vaccine booster if titre <10IU/ml,
need antiviral until anti-HBs >10IU/ml
● HBV DNA monitoring (NICE guidance)

37. Hepatitis C & Renal Transplantation
The HCV +ve donor kidney
Good experience of transplanting into HCV+ve
recipients
Transplantation confers survival advantage over
staying on waiting list
BUT Higher rates of Graft Loss, Rejection
Episodes, NODAT, CMV Disease

38. Potential KT Recipients with HCV
Sustained virological response preferable to be
achieved pre-transplant
Immunosuppression encourages HCV
reactivation even if SVR initially achieved

40. Recommendations on Treatment of Hepatitis C
(2014)
● Suggest IFN-free regime pre-Tx Regimens of anti-HCV
therapy post transplant similar to non-transplanted
patients (without IFN)
● Newer agents not yet extensively investigated
“New Drugs; New Interactions”

41. Don’t Forget...
● HCC Screening (USS & AFP) (HBV/HCV)
● Monitoring blood glucose for development of
NODAT (HCV)

42. Take Home Points
Testing & Prevention is Cheap
Burden of Disease & Treatment is Costly
Hepatitis B
● Preventing Transmission & Vaccination Works
Hepatitis C
o “On the Cusp of Change” with new antivirals