Liver Transplant And Hepatitis C
The liver is one of the most important organs in the human body. It is
intimately Involved in almost every part of the body’s processes, and it has
four crucial functions: Fuel Management, Nitrogen Excretion, Water
Balance, and Detoxification. Being the central role of the body systems,
when liver diseases or viruses like Hepatitis C strikeat the core, it can be
You cannot survive without your liver. Over 80-90% of Hepatitis C (HCV)
infections become chronic and lead to liver disease, including cirrhosis
and liver failure.HCV infection is typically mild in its early stages, and it is
rarely recognized until it has caused significant damage to the liver. The
cycle of the disease from infection to significant liver damage can take
twenty years or more. This was the case for my best friend’s father, J.N., at
Kaiser Oakland. J.N. is a fifty-three year old man who has lived with HCV for
over fifteen years. His liver could no longer withstand the virus and began
to shut down. J.N. was on a liver transplant list since December of 2000,
and on December 31, 2006 his prayers were answered. He got the phone
call transplant seekers dream of. The hospital had found a donor.
J.N.’s life as a young adult was composed mostly of partying, drugs,
and alcohol. He began using drugs at the age of thirteen, and didn’t stop
until his early thirties. His love for getting “high” and seeking different levels
of euphoria led him to the use of needles. His heroine use led to his crack
use. He said, “I couldn’t afford heroine anymore, so I started buying crack. It
was a good high, not as clean, didn’t last long, but it was good enough”
(J.N., personal communication, January 31, 2007).
J.N. didn’t find out he had contracted HCV through the use of sharing
dirty syringes until six years later. As J.N. began to clean up his act, he got
remarried, and was becoming closer to his daughter, but J.N. felt tired all
the time and was constantly getting sick. He had a good job at this point,
with full medical coverage, so he went for routine blood tests and HCV was
detected by his doctor. “I felt like I hit a brick wall. All my fun days of partying
where over, but now they were going to follow me for the rest of my life,
which wouldn’t be much longer according to my doctor” (J.N., personal
communication, January 31, 2007).
J.N. didn’t anticipate that the severe damage HCV was causing his
liver and it was a shock when the rest of his body started to shut down. By
the time he was put on the waiting list for a liver transplant in December of
2000, his liver disease was forbidding him from working, exercising, or
carrying out any of his other daily activities. Being that the liver was
responsible for critical portions of his metabolism, it had become
overwhelmed with the HCV, and a number of essential metabolic
processes were compromised. J.N.’s body was losing the ability to store
and synthesize glucose. This was affecting his CNS function and mental
process. His body wasn’t able to manage amino acid metabolism and the
removeal nitrogen, which decreased his ability to synthesize glucose
leading to CNS dysfunction and cause accumulation of nitrogen waste,
resulting in toxicity to many surrounding tissues (Huether, S.E. & McCance
The overall ability of his body to manage and use fuels diminished
drastically leading to fatigue and general sense of “not feeling well”. HCV
was causing disturbances in water distribution, which made J.N. feel
“swollen all over”. The edema and generalized alteration of cell function
was causing muscle and joint pain, and malaise (epidemic.org/HepatitisC).
J.N. felt like he was going to die very soon. He tried numerous drug
therapies to try to slow down the progression of the disease. However, J.N.
admits to not being very active in his health care. After the diagnoses of
HCV, he felt doomed, and did not do any extra research on the disease that
could eventually take his life. J.N.’s doctor started his treatment with peg
interferon alfa-2a in summer 2005. Research has shown over the last
ten years that peg interferon alfa-2a alone produces significantly higher
sustained virology responses than treatment with interferon alfa-2a alone
in patients with chronic hepatitis C virus (HCV) infection
J.N. received his new liver on January 01, 2007. Walking into J.N.’s
private room at Kaiser Oakland was shocking at first. He looked extremely
sick. It had barely been a month since his transplant. He looked lifeless in
his bed. His face was sunk in and his skin was jaundice. He was receiving
supplemental oxygen via a nasal cannula at all times, and he looked like
he was going to die. He said he didn’t feel much better since the
transplant, but he knew it was the result of all the drugs he was getting to
lower his immune system.
In the long-term, HCV RNA levels are related to level of
immunosuppression and correlate with severity of liver injury. However,
despite immunosuppression, some liver transplant recipients show
HCV-specific major histocompatibility complex class II-restricted CD4.
T-cell responses and experience minimal or no histological recurrence.
Conversely, transplant recipients who lack appropriate immunologic
responses to HCV antigens may experience severe recurrence. These
processes are highly dynamic. It has been estimated that the balance
between HCV cytotoxicity, immunologic destruction of infected hepatocytes,
and hepatic regeneration may lead to complete allograft replacement
within 2 weeks. Immunosuppression tips the balance to favor accelerated
loss of the allograft. Strategies to reduce the impact of
immunosuppression on recurrent HCV have included global reduction in
total immunosuppression, discontinuation of individual agents, and use of
immunosuppressive agents with possible antiviral properties.
Immunosuppressive drugs may be classified into five groups: calcineurin
inhibitors (cyclosporine [CSA] or tacrolimus [TAC], steroids (prednisone or
methylprednisolone), inhibitors of purine biosynthesis (azathioprine [AZA]
or mycophenolate mofetil [MMF]), inhibitors of mammalian target of
rapamycin (sirolimus [rapamycin (RAPA)]), and monoclonal or polyclonal
antibodies (OKT3, antithymocyte globulin, antilymphocyte globulin [ALG],
and interleukin-2 (IL-2) receptor antibody (www.cdc.gov/hepatitis/c/faq.htm).
Steroids often are prescribed in the early post transplantation period,
but are now commonly withdrawn after 3 months. Doses and duration of
steroid therapy vary considerably. AZA and MMF inhibit purine synthesis
and are used to enhance immunosuppression or allow dose reductions in
CSA, TAC, or steroids. Antibodies and high-dose steroids are used for
induction and to treat acute cellular rejection. The overriding goal of
maintenance immunosuppression is prevention of allograft rejection.
Current immunosuppressive agents, when administered in high dosage
or multi-drug Combinations induce global immunosuppression and
markedly reduce the risk for allograft rejection. However, excessive
immunosuppression to prevent rejection favors viral replication and
facilitates viral-mediated graft injury. Research found that the
survival of HCV-positive a transplant has decreased in recent years, and at
least one factor was the use of stronger immunosuppressive treatments.
Specific immunosuppressive calcineurin inhibitors, TAC and CSA, are
the mainstays of current immunosuppressive regimens. Their
immunosuppressive effect is through inhibition of early T-cell signal
pathways and IL-2 production and release. TAC is more potent then CSA,
and as a result, doses of TAC are typically 25 to 60 fold less than doses of
CSA. Each of the three centers used different induction
immunosuppression: CSA plus Prednisone plus AZA, CSA plus
Prednisone, and ALG followed by CSA Prednisone plus AZA. All centers
participated in the TAC primary immunosuppression trial and had a
subgroup of patients treated with TAC-based immunosuppression. They
observed no difference in either patient or reducing immunosuppression is
a balancing act between the attempt to control recurrence of HCV
and maintenance of adequate immunosuppression to prevent rejection
(Liver Transplantation, Vol. 8, No 10, Suppl.1. October, 2002: pp S19-S).
Even though my best friend’s father looked and felt like he was dying,
his chances for survival are 100 folds with his new liver. The
immunosuppressants are causing him to have very little appetite and
therefore to lose excessive amounts of weight, feel nauseous and fatigue
all the time. His body isn’t rejecting the new liver and he will continue the
immunosuppressant therapy for another three months. J.N. expresses
his deepest gratitude, and he feels anxious towards going home, “HCV
was my disease. I brought in upon myself, and now my wife and daughter
suffers from my carelessness. I wish I could take care of them the way they
have taken care of me” (J.N., personal communication, January 31, 2007).
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Liver Transplantation, Journal Vol. 8, No 10, Suppl.1. October, 2002: pp S19-S.