Patients should have serum transaminases (ALT and AST) levels
monitored at one month, and then every 3 months, following
initiation of therapy. Mild to moderate fluctuations in liver
enzyme levels are common in persons with chronic HCV
infection, and in the absence of signs and/or symptoms of liver
disease they do not require interruption of antiviral therapy.
Significant elevation in liver enzymes levels – more than 5 times
the upper limit of normal – should prompt careful evaluation for
liver insufficiency and for alternative causes of liver injury.
Eventually, withdrawal of antiviral treatment may be required.
A high baseline VL correlates with higher fibrosis and necrosisinflammation
scores (Mallet 2008). In patients with histologically
proven cirrhosis without esophageal varices, successful
treatment, as defined by a SVR, is associated with a reduction in
decompensation, occurrence of HCC and mortality (Bruno 2007).
The Child-Pugh (CP) classification of patients with HCV-induced
cirrhosis is used in predicting the likelihood of SVR rate after
antiviral therapy (AISF 2009):
– Patients with “histologically proven” cirrhosis without
esophageal varices (Child class A5 to 6), identified by stages
5 and 6 of Ishak’s score and stage 4 of the Metavir and
Knodell scores. Presumed SVR rate is 25% in HCV G1 and
75% in non-G1 infected patients.
– Patients with “compensated” cirrhosis with or without
esophageal varices (including Child class B7). Recognized
SVR rate is <15% in HCV G1 and <60% in non-G1 infected
patients.
– Patients with “decompensated” cirrhosis (Child class B8 or
more) defined by any evidence of previous decompensation
(ascites, esophageal bleeding, portal encephalopathy,
Patients’ monitoring during and after treatment | 41
jaundice). Assumed SVR rate is <7% in HCV G1 and <40% in
non-G1 infected patients.
The progression of fibrosis and other HCV-associated
histopathologic changes may also be related to coagulationcascade
activity and hepatic accumulation of iron, which have
been associated with mutations in factor V and
hemochromatosis genes, respectively.
The HIV-HCV coinfection is a particularly challenging situation.
The severity of liver disease must be routinely assessed in these
patients in order to initiate treatment before progression of liver
disease. An important number of coinfected patients are referred
to hepatology clinics only when they have hepatic
decompensation, at which time the HCV treatment options are
limited.
Drug-induced liver injuries (DILI) following antiretroviral
therapy pose significant problems in HIV/HCV co-infection,
especially in persons with advanced liver disease and cirrhosis.
Dose modifications or even avoidance of liver-metabolized
antiretroviral drugs may be required in patients with CP class B
and C disease. Overall, in the absence of clinically significant
fibrosis, it seems worthwhile to defer treatment. However, it is
equally important to apply the results of the clinical studies on a
case by case basis, weighing the treatment response rate and the
long-term outcomes.
Outlook
Nucleic acid testing, genotyping and assessment of the level of
hepatic fibrosis are invaluable tools in the diagnosis of HCV
infection, treatment guidance and monitoring.
Although LB is still considered the gold standard for the
progression of hepatic fibrosis in chronic hepatitis C, a series of
non-invasive radiological and serum-based markers are being
investigated for their diagnostic accuracy. New real-time PCR
tests are faster and more cost-effective methods for the
42 | Hepatitis C Treatment
assessment viral kinetics. Virological end points are surrogate
references for assessing the efficiency of HCV treatments, but
many randomized trials on similar drug classes have established
their value in correctly evaluating the clinical outcome.
However, biochemical and histological improvements can be
attained even in patients who fail to eradicate HCV infection.
Obtaining data on the long-term clinical outcomes in patients
included in previous treatment trials is logistically difficult, due
to relatively high dropout rates and to interferences of retreatment
regimens. Cumulative meta-analysis may be relevant
for the planning of future clinical trials.
monitored at one month, and then every 3 months, following
initiation of therapy. Mild to moderate fluctuations in liver
enzyme levels are common in persons with chronic HCV
infection, and in the absence of signs and/or symptoms of liver
disease they do not require interruption of antiviral therapy.
Significant elevation in liver enzymes levels – more than 5 times
the upper limit of normal – should prompt careful evaluation for
liver insufficiency and for alternative causes of liver injury.
Eventually, withdrawal of antiviral treatment may be required.
A high baseline VL correlates with higher fibrosis and necrosisinflammation
scores (Mallet 2008). In patients with histologically
proven cirrhosis without esophageal varices, successful
treatment, as defined by a SVR, is associated with a reduction in
decompensation, occurrence of HCC and mortality (Bruno 2007).
The Child-Pugh (CP) classification of patients with HCV-induced
cirrhosis is used in predicting the likelihood of SVR rate after
antiviral therapy (AISF 2009):
– Patients with “histologically proven” cirrhosis without
esophageal varices (Child class A5 to 6), identified by stages
5 and 6 of Ishak’s score and stage 4 of the Metavir and
Knodell scores. Presumed SVR rate is 25% in HCV G1 and
75% in non-G1 infected patients.
– Patients with “compensated” cirrhosis with or without
esophageal varices (including Child class B7). Recognized
SVR rate is <15% in HCV G1 and <60% in non-G1 infected
patients.
– Patients with “decompensated” cirrhosis (Child class B8 or
more) defined by any evidence of previous decompensation
(ascites, esophageal bleeding, portal encephalopathy,
Patients’ monitoring during and after treatment | 41
jaundice). Assumed SVR rate is <7% in HCV G1 and <40% in
non-G1 infected patients.
The progression of fibrosis and other HCV-associated
histopathologic changes may also be related to coagulationcascade
activity and hepatic accumulation of iron, which have
been associated with mutations in factor V and
hemochromatosis genes, respectively.
The HIV-HCV coinfection is a particularly challenging situation.
The severity of liver disease must be routinely assessed in these
patients in order to initiate treatment before progression of liver
disease. An important number of coinfected patients are referred
to hepatology clinics only when they have hepatic
decompensation, at which time the HCV treatment options are
limited.
Drug-induced liver injuries (DILI) following antiretroviral
therapy pose significant problems in HIV/HCV co-infection,
especially in persons with advanced liver disease and cirrhosis.
Dose modifications or even avoidance of liver-metabolized
antiretroviral drugs may be required in patients with CP class B
and C disease. Overall, in the absence of clinically significant
fibrosis, it seems worthwhile to defer treatment. However, it is
equally important to apply the results of the clinical studies on a
case by case basis, weighing the treatment response rate and the
long-term outcomes.
Outlook
Nucleic acid testing, genotyping and assessment of the level of
hepatic fibrosis are invaluable tools in the diagnosis of HCV
infection, treatment guidance and monitoring.
Although LB is still considered the gold standard for the
progression of hepatic fibrosis in chronic hepatitis C, a series of
non-invasive radiological and serum-based markers are being
investigated for their diagnostic accuracy. New real-time PCR
tests are faster and more cost-effective methods for the
42 | Hepatitis C Treatment
assessment viral kinetics. Virological end points are surrogate
references for assessing the efficiency of HCV treatments, but
many randomized trials on similar drug classes have established
their value in correctly evaluating the clinical outcome.
However, biochemical and histological improvements can be
attained even in patients who fail to eradicate HCV infection.
Obtaining data on the long-term clinical outcomes in patients
included in previous treatment trials is logistically difficult, due
to relatively high dropout rates and to interferences of retreatment
regimens. Cumulative meta-analysis may be relevant
for the planning of future clinical trials.
No comments:
Post a Comment