Extrahepatic Manifestations of Hepatitis C
Extrahepatic Manifestations of Hepatitis C
Glomerulonephritis is defined as an inflammatory process which, in the case of hepatitis C, is due to immune dysregulation and an ineffective response by the body to deal with the HCV. The most common glomerulonephritis associated with HCV-related cryoglobulinaemia is membranoproliferative glomerulonephritis. The pathophysiology of HCV-related glomerulonephritis is believed to involve deposition of immune complexes, anti-HCV immunoglobulin and an IgM subtype rheumatoid factor.
Presentation ranges from hypertension, which is present in 80% of patients with an associated moderate renal insufficiency. 20%–35% of patients may present as a nephrotic syndrome and up to a quarter of patients will be nephritic. However, 10% of patients will present with rapidly deteriorating renal function and warrant urgent referral to specialist nephrology services (Table 4).
Treatment is underpinned by aggressive hypertensive therapy with associated renin-angiotensin system blockade. This is achieved using ACE inhibitors, angiotensin receptor blockers and diuretics. Patients tend to have high lipid and triglyceride levels and managing coronary risk factors have been proven to be beneficial. Treating the underlying HCV infection has not only been shown to clear the virus successfully but also in preventing or limiting renal damage. Dual therapy with interferon and ribavirin has been shown to reduce viral load, as well as reduce proteinuria but has mixed success in improving glomerular filtration and creatinine levels, but studies have consistently shown that commencing antiviral therapy stabilises renal function. Data also support prolonged therapy for at least 48–52 weeks, irrespective of early reductions in HCV loads at 12 weeks, but therapy can be considered for as long as 72 weeks in patients with non-responding viral load, but with biochemical and clinical improvements. Caution has to be taken in using ribavirin at full dose as clearance is related to renal function.
In patients who present with rapidly progressive glomerulonephritis and nephritic syndrome, early aggressive therapy is crucial. Plasma exchange is used in order to remove circulating cryoglobulins and hence reducing the insult on organs and tissues. This is normally carried out by exchanging 3 litres, three times a week over 2–3 weeks. Pulsed steroid therapy in conjunction with plasma exchange has also been shown to be beneficial in correcting glomerular filtration dysfunction. Cyclophosphamide has been used to suppress B cell function during the acute phase of the illness by reducing cryoglobulin production. However, as discussed previously, more recent studies have not provided evidence to support its recommendation and is not currently recommended as first-line therapy. More recent studies have looked at the potential role of rituximab in treating nephritic syndrome and glomerulonephritis. The rationale behind this research is the impact that the CD20 targeted antibody has on selectively targeting B cells, the driving force in cryoglobulinaemias. Small studies have shown mixed benefits in reducing proteinuria and stabilising renal function, but no large randomised control studies have yet shown clear benefit and concerns remain over the potential to predispose patients to overwhelming sepsis. There also remains concern that suppressing immune function leads, while improving renal disease, paradoxically increases circulating viral load, which has been shown in cyclophosphamide, but not yet shown in rituximab.
Unlike the HCV, prognosis with glomerulonephritis is relatively poor and up to 50% of patients will progress to end stage renal disease (figure 2).
(Enlarge Image)
Figure 2.
The treatment algorithm for patients presenting with glomerulonephritis.
Glomerulonephritis
Glomerulonephritis is defined as an inflammatory process which, in the case of hepatitis C, is due to immune dysregulation and an ineffective response by the body to deal with the HCV. The most common glomerulonephritis associated with HCV-related cryoglobulinaemia is membranoproliferative glomerulonephritis. The pathophysiology of HCV-related glomerulonephritis is believed to involve deposition of immune complexes, anti-HCV immunoglobulin and an IgM subtype rheumatoid factor.
Presentation ranges from hypertension, which is present in 80% of patients with an associated moderate renal insufficiency. 20%–35% of patients may present as a nephrotic syndrome and up to a quarter of patients will be nephritic. However, 10% of patients will present with rapidly deteriorating renal function and warrant urgent referral to specialist nephrology services (Table 4).
Treatment is underpinned by aggressive hypertensive therapy with associated renin-angiotensin system blockade. This is achieved using ACE inhibitors, angiotensin receptor blockers and diuretics. Patients tend to have high lipid and triglyceride levels and managing coronary risk factors have been proven to be beneficial. Treating the underlying HCV infection has not only been shown to clear the virus successfully but also in preventing or limiting renal damage. Dual therapy with interferon and ribavirin has been shown to reduce viral load, as well as reduce proteinuria but has mixed success in improving glomerular filtration and creatinine levels, but studies have consistently shown that commencing antiviral therapy stabilises renal function. Data also support prolonged therapy for at least 48–52 weeks, irrespective of early reductions in HCV loads at 12 weeks, but therapy can be considered for as long as 72 weeks in patients with non-responding viral load, but with biochemical and clinical improvements. Caution has to be taken in using ribavirin at full dose as clearance is related to renal function.
In patients who present with rapidly progressive glomerulonephritis and nephritic syndrome, early aggressive therapy is crucial. Plasma exchange is used in order to remove circulating cryoglobulins and hence reducing the insult on organs and tissues. This is normally carried out by exchanging 3 litres, three times a week over 2–3 weeks. Pulsed steroid therapy in conjunction with plasma exchange has also been shown to be beneficial in correcting glomerular filtration dysfunction. Cyclophosphamide has been used to suppress B cell function during the acute phase of the illness by reducing cryoglobulin production. However, as discussed previously, more recent studies have not provided evidence to support its recommendation and is not currently recommended as first-line therapy. More recent studies have looked at the potential role of rituximab in treating nephritic syndrome and glomerulonephritis. The rationale behind this research is the impact that the CD20 targeted antibody has on selectively targeting B cells, the driving force in cryoglobulinaemias. Small studies have shown mixed benefits in reducing proteinuria and stabilising renal function, but no large randomised control studies have yet shown clear benefit and concerns remain over the potential to predispose patients to overwhelming sepsis. There also remains concern that suppressing immune function leads, while improving renal disease, paradoxically increases circulating viral load, which has been shown in cyclophosphamide, but not yet shown in rituximab.
Unlike the HCV, prognosis with glomerulonephritis is relatively poor and up to 50% of patients will progress to end stage renal disease (figure 2).
(Enlarge Image)
Figure 2.
The treatment algorithm for patients presenting with glomerulonephritis.
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