Medical education Lessons from practice
Digestive system diseases Urology
Volume 205 - Issue 5

Reversal of end-stage renal failure using direct-acting antiviral agents for chronic hepatitis C

Authors:  Tim Mitchell, Aron Chakera, Gary P Jeffrey, Leon A Adams, George Garas, Tamara Jones and Gerry MacQuillan

Med J Aust 2016; 205 (5): 205-206. || doi: 10.5694/mja16.00207
Published online: 5 September 2016
A case of significant recovery of renal function in a patient treated with direct-acting antiviral medications for chronic hepatitis C virus infection
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Clinical record

A 58-year-old Eritrean woman presented to hospital in December 2014 with a vasculitic rash, peripheral oedema, acute renal impairment and microscopic haematuria with proteinuria. She had a history of genotype 4 hepatitis C virus (HCV) infection, which was unsuccessfully treated with pegylated interferon and ribavirin in 2010. Results of laboratory investigations showed a pattern consistent with mixed cryoglobulinaemia (Box 1). After a renal biopsy to assess progressive renal impairment, a diagnosis of membranoproliferative glomerulonephritis (MPGN) was made. The patient began taking an angiotensin-converting enzyme inhibitor and diuretic therapy.

The patient’s creatinine level continued to worsen, from 202 μmol/L (reference interval [RI], 45–90 μmol/L) (estimated glomerular filtration rate [eGFR], 27 mL/min/1.73 m2 [RI, > 60 mL/min/1.73 m2]) in January 2015 to 412 μmol/L (eGFR, 10 mL/min/1.73 m2) in July 2015. The renal impairment was associated with increasing serum cryoglobulin levels, worsening proteinuria and increased requirement for ascitic drainage. The ascitic fluid was a transudate, and a transjugular liver biopsy excluded cirrhosis. Infection and malignancy were also excluded. As the eGFR was below 15 mL/min/1.73 m2 and fluid overload had become refractory to medical management, preparations for dialysis were made and a Tenckhoff (peritoneal dialysis) catheter was inserted. At this stage, direct-acting antiviral medication was obtained through a compassionate access program to treat the HCV infection.

The patient began a 12-week course of HCV treatment with paritaprevir–ritonavir (150 mg/100 mg) and ombitasvir (25 mg) plus ribavirin (200 mg) daily on 2 July 2015. Ribavirin was discontinued at Week 5, as her haemoglobin level had fallen from a baseline of 102 g/L (RI, 115–160 g/L) to 76 g/L. Overall, the treatment was well tolerated. HCV viral load was undetectable at Week 2, and sustained viral response (SVR) 12 weeks after completion of treatment was achieved, indicating the HCV was cured. Creatinine levels improved markedly with treatment, associated with a rapid decline in serum cryoglobulin level and improvement in the urine albumin:creatinine ratio (Box 2). The ascites was last drained on 24 August 2015, and the Tenckhoff catheter was subsequently removed.

Mixed cryoglobulinaemia is a frequently encountered extrahepatic complication of chronic HCV infection and can be associated with considerable morbidity and mortality.1 The most common renal manifestation of mixed cryoglobulinaemia is MPGN, which is associated with a mixed cryoprecipitate, hypocomplementaemia, positive rheumatoid factor, microscopic haematuria and proteinuria.1 The clinical presentation ranges from asymptomatic proteinuria to nephritic or nephrotic syndrome.1 Progression to end-stage renal failure occurs in 10–33% of patients.1

Treatment of mixed cryoglobulinaemia due to HCV is reserved for symptomatic patients and centres on viral eradication.2 In a series of 86 patients with HCV infection and cryoglobulinaemic vasculitis treated with pegylated interferon and ribavirin, remission of symptoms occurred in 88% of patients who achieved SVR.2 However, management of patients with concurrent renal disease is complicated by the difficulties associated with using pegylated interferon and ribavirin in the setting of severe renal failure, and a lower response rate is reported in this cohort.2 In clinical practice, interferon and ribavirin therapy is therefore rarely pursued in patients receiving dialysis. In addition, the reversibility of renal impairment in the setting of HCV-induced cryoglobulinaemia has traditionally been thought to be poor, particularly once end-stage renal disease has been reached.

There are limited data available on the outcomes of interferon-free HCV treatment regimens in patients with mixed cryoglobulinaemia.3 The efficacy of sofosbuvir-based regimens has been studied in a series of 12 patients with HCV-associated mixed cryoglobulinaemia, with seven patients also having renal impairment related to MPGN.3 In this study, patients who achieved SVR had decreased proteinuria and improved renal function; however, the degree of baseline renal impairment was mild (eGFR, 30–60 mL/min/1.73 m2).3 Sofosbuvir is not currently recommended for use in patients with an eGFR < 30 mL/min/1.73 m2.3

The combination of ombitasvir and ritonavir-boosted paritaprevir is an interferon-free antiviral regimen for the treatment of genotype 4 HCV infection, with the addition of dasabuvir required for genotype 1 HCV infection.4 The efficacy and safety of this combination in patients with end-stage renal disease have been demonstrated in a pilot trial of 20 patients with genotype 1 HCV infection,5 although the impact of viral clearance on renal function has not been reported.

A literature review of the PubMed database on this topic did not identify other cases, so we believe this to be the first reported case of significant recovery of renal function in this clinical setting.

Lessons from practice

  • In patients with chronic hepatitis C virus (HCV) infection and renal failure from cryoglobulin-related glomerulonephritis, direct-acting antiviral medications may be safe and effective, and successful treatment may significantly improve renal function.

  • Chronic HCV infection can have numerous extrahepatic manifestations that may abate considerably after virus eradication.

  • Patients with chronic HCV infection who were previously considered difficult to treat due to medical comorbidities should be reassessed for HCV treatment with direct-acting antiviral medications.

Box 1 – Results of diagnostic investigations

Laboratory test

Result

Reference interval

Urinary protein

+++

nd

Urinary blood

+++

nd

Albumin:creatinine ratio (mg/mmol)

121.1

< 3.5

Creatinine (μmol/L)

179

45–90

Cryoglobulins (g/L)

0.44

< 0.08

C3 (g/L)

0.80

0.88–1.98

C4 (g/L)

0.04

0.16–0.52

Rheumatoid factor (kU/L)

117

< 14

Hepatic venous pressure gradient (mmHg)

10

1–5

nd = not detectable.

Box 2 – Results of investigations showing response to treatment with direct-acting antiviral medications

Laboratory test

Reference interval

Result

Before treatment (July 2015)

End of treatment (Sept 2015)

12 weeks after treatment (Dec 2015)

Haemoglobin (g/L)

115–160

102

125

113

Albumin (g/L)

35–50

33

35

40

Creatinine (μmol/L)

45–90

412

186

196

eGFR (mL/min/1.73 m2)

> 60

10

25

24

HCV viral load (IU/mL)

nd

2.00 × 106

nd

nd

Cryoglobulins (g/L)

< 0.08

3.46

0.84

0.56

Albumin:creatinine ratio (mg/mmol)

< 3.5

394

nr

67.7

C3 (g/L)

0.88–1.98

0.67

0.94

0.87

C4 (g/L)

0.16–0.52

< 0.03

0.06

0.06

eGFR = estimated glomerular filtration rate. HCV = hepatitis C virus. nd = not detectable. nr = no result available.

Authors

  • Tim Mitchell1
  • Aron Chakera1
  • Gary P Jeffrey1,2
  • Leon A Adams1,2
  • George Garas1,2
  • Tamara Jones1
  • Gerry MacQuillan1,2
  • 1. Sir Charles Gairdner Hospital, Perth, WA
  • 2. University of Western Australia, Perth, WA

Correspondence: Tim.Mitchell2@health.wa.gov.au

Competing interests

No relevant disclosures.

References

Provenance: Not commissioned, externally peer reviewed.

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