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Direct-acting antivirals reduce cryoglobulinemia in hepatitis C
Keith Alcorn, 2016-02-19 08:20:00
Treatment with direct-acting antivirals not only cures
people of hepatitis C, but can also rapidly reduce the severity of one of the
most troublesome extrahepatic manifestations of the disease, a study published
this month shows.
Although studies of direct-acting antivirals show that
newly-licensed combinations can cure hepatitis C in 90 to 95% of people, there
is less information about the extent to which curing hepatitis C leads to
improvements in the health of the liver or resolution of symptoms such as cryoglobulinemia.
Cryoglobulinemia is the presence of complexes of abnormal
antibodies and proteins, which cluster in the blood vessels, in the kidneys or
joints (vasculitis) causing skin lesions (purpura), pain in the joints of the hands
and legs and damage to peripheral nerves (peripheral neuropathy). The presence of
mixed cryoglobulins in the kidneys can lead to inflammation and kidney damage
(glomerular nephritis) and the loss of kidney function over time.
Mixed cryoglobulinemia may be detected in up to half of
people with hepatitis C, but in most people the condition does not cause
symptoms. About one in twenty people with hepatitis C develop symptoms. There
is some evidence that cryoglobulinemia increases the risk of developing cirrhosis.
Symptomatic disease as a result of cryoglobulinemia –
especially kidney disease – is considered a reason to take hepatitis C
treatment, regardless of the extent of liver damage. In the past, responses to treatment
with pegylated interferon and ribavirin have been poor with a high rate of
adverse events. Researchers from Massachusetts General Hospital and Brigham and
Women’s Hospital, Boston, have now reported the first case series of 12 people
with symptomatic cryoglobulinemia treated with direct-acting antivirals.
Half had cirrhosis and half had experienced failure of at
least one previous course of interferon-based hepatitis C treatment. The
duration of cryoglobulinemia ranged from six months to 17 years and eight of
the twelve had multiple symptoms associated with cryoglobulinemia. Fifty-eight
per cent had glomerulonephritis, 50% had purpura and 50% had arthralgia. One
third had peripheral neuropathy. Of those with kidney damage, all had hypertension
and five had active glomerulonephritis (two were in remission). All of those
with active glomerulonephritis had an EGFR (creatinine clearance) < 60,
indicating moderate impairment of kidney function. Three patients had severe
proteinuria, although none were diabetic. Six of the seven had received some
form of immunosuppressive therapy prior to direct-acting antiviral therapy in
order to manage the glomerulonephritis.
The twelve patients received sofosbuvir-based therapy
without interferon. Eight received sofosbuvir and simeprevir; four received
sofosbuvir and ribavirin, in almost all cases for 12 weeks. Ten of the twelve achieved
a sustained virologic response (SVR12). The remaining two patients experienced
virologic relapse after completing treatment. Post-treatment cryoglobulin
levels were available for nine patients; median levels fell from 1.5% to 0.5%,
with cryoglobulin disappearing altogether in four patients. In most cases
cryoglobulin levels had declined to their greatest extent within a median of
4.6 months of treatment initiation, although in one case levels continued to
decline for up to one year. Cryoglobulin levels rebounded in one of the
patients who experienced virologic relapse, and also became detectable at a low
level once more in a patient who achieved a sustained virologic response.
Kidney function improved in all patients after treatment,
although eGFR remained below 60 in three people. Proteinuria improved in all
patients for whom before and after measurements were available, including one
who did not achieve SVR 12, and in this case eGFR remained low at 33mL/min
after completing treatment. This patient also needed to continue immunosuppressive
treatment for glomerulonephritis after direct-acting antiviral treatment.
Four patients experienced a complete resolution of symptoms
after treatment. In a further three patients at least one symptom resolved,
with joint pain and neuropathy more likely to persist after treatment. There
was no correlation between changes in cryoglobulin level or cryoglobulin
detectability and resolution of symptoms.
Direct-acting antiviral treatment was well tolerated; one
patient was hospitalised for hyperkalemia and one patient discontinued
treatment at week 10 due to anxiety and insomnia, but both achieved SVR12.
Comparing their findings to a historic cohort of patients
with cryoglobulinemia who had been treated with pegylated interferon and
ribavirin, the researchers found a very low rate of sustained virologic
response (10%), a high rate of treatment discontinuation (50%), lack of
improvement in symptoms and lack of change in cryoglobulin levels.