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CO-MORBID CONDITIONS ASSOCIATED WITH
CHRONIC HEPATITIS C
Abdel-Rahman El-Zayadi, MD
Prof. of Hepato-Gastroenterology,
Ain Shams University and Cairo Liver
Center, Cairo – Giza, Egypt.
Once the diagnosis of chronic hepatitis
C (CHC) has been established, selection
of the proper patients for antiviral
therapy is initiated. During the process
of selection, some patients prove to be
suffering from associated disorders
which would aggravate the progression of
liver disease and may reduce the
response rate to interferon therapy. The
following represent the common
comorbidities with chronic hepatitis C:
Fatty liver disease (FLD) is one of the
common causes of elevated serum transaminases especially in obese
patients. Core protein may induce
steatosis by interfering with fatty acid
oxidation in mitochondria and induction
of insulin resistance. Steatosis
progress to steatohepatitis which
develop to cirrhosis. Gradual weight
loss and antioxidants can return ALT to
normal level and slow progression of the
disease in most of the patients.
Type II diabetes mellitus is frequently
associated with hyperinsulinemia and
fatty liver disease. Hyperinsulinemia
downregulate mitochondrial -oxidation
and block secretion of triglycerides
from the liver leading to accumulation
of the latter in the hepatocytes. Type
II diabetes mellitus should be
adequately controlled by weight
reduction, Metformin and insulin
sensitizers.
Intestinal Schistosomiasis is an
immunological disease as manifested by
depressed cell mediated immunity and
downregulation of Th1 cytokines that
paves the way for chronicity and may
prevent response to IFN. Infestation
should be ruled out by rectal snips and
active cases (living ova) should be
treated with specific oral
antibilharzial therapy.
Drug hepatotoxicity may occur either
directly or through an immune-mediated
mechanism. The most common drugs that
cause hepatotoxicity are paracetamol,
phenytoin, -methyl dopa, nitrofurantoin,
sex hormones, NSAIDs, tricyclic
antidepressants, anabolic steroids
…….etc. Cessation or substitution of the
offending agents is a crucial step
before start of antiviral therapy.
Hepatocellular iron overload: Sometimes
patients with chronic hepatitis C have
difficulty in excreting iron from body
leading to increase of hepatic iron.
Iron induces hepatocellular injury and
increases collagen synthesis either
directly or indirectly by lipid
peroxidation. To control these
disorders, avoid iron-rich foods and
repeated venesection is recommended.
Intestinal bacterial overgrowth: In
chronic liver disease, there is
increased gut permeability to bacteria
and bacteria-derived toxins associated
with impaired reticulo-endotheial system
of liver. In the mean time, gut flora
acts on cabohydrates in the gut
producing endogenous ethanol. Both
endotoxins and endogenous ethanol
provoke a generalized proinflammatory
response that cause liver cell injury
with elevated ALT. Probiotics and
intestinal decontamination improves the
necroinflamation and the ALT level.
Alcohol related liver disease: This
include fatty liver “steatoisis”,
alcoholic steatohepatitis and alcoholic
cirrhosis (micronodular) with serious
complications such as HCC. Alcohol
inhibits the immune response necessary
to control or eliminate HCV infection.
HCV infection is 8 times more common in
alcoholics than in general population.
Abstinence of alcohol consumption is
necessarily before starting antiviral
therapy.
Heavy Smoking and liver: Heavy smoking
yields chemical substances with cytotoxicc potentials and increases iron
levels in serum and hepatocytes. Liver
cell injury is caused either by direct
toxic effects of smoke constituents or
secondary to smoker’s polycythemia. In
CHC patients, smoking increased the
severity of hepatic lesions (fibrosis
and activity scores, and HCC) and reduce
the response rate to interferon.
Psychological distress: this is a
mixture of both anxiety and depression
often encountered among some CHC
Egyptian patients. Reciprocal
relationship has been currently
documented between the psychological
status and the immune status of the
patient. Immune suppression may be
mediated by release of stress hormones
including corticosteroids and other
neuropeptides in response to
psychological stress. Alleviation of
patient’s anxiety and reassurance of the
family may be a very helpful step in the
management of CHC patients.
In conclusion, control of the co-morbid
disorders before embarking on interferon
therapy would downregulate progression
of the disease, normalize ALT levels and
augments the response rate to interferon
therapy.
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