Hepatic dysfunction is a common problem in HSCT
recipients. Diagnosis can be accomplished by interpretation of the clinical setting
in which liver dysfunction occurs in order to institute appropriate therapy.
In the current study, the prevalence of pre-transplant
liver function abnormalities in both allogeneic and autologus patients before
conditioning is 11.1% (7.4% had grade I hepatic dysfunction and 3.7% had grade
II hepatic dysfunction) that increased to 48.8% after conditioning regimens of
which 27.9% had grade I, 7.9% had grade II and 6.3% had grade III and similarly
grade IV hepatic dysfunction).
The prevalence is similar to a previous report by
kamel et al from Egypt who found that 10% of patients had mild hepatic
dysfunction pretransplant that increased
after conditioning to 47%.8 By contrast, previous report by wang et al. showed
a higher percentage of liver function abnormalities pre-transplant (19.8%) that
increased to 81% during conditioning regimen.
When we correlated between pre-transplant abnormal
transaminase levels and the rise in liver transaminases during
transplantation (from D0 to D+30), we
found highly statistically significant difference (P-value 0.000).
Conversely, we found that the incidence of long-term
hepatic complications was independent of abnormal transaminases pre-transplant.
Various observations suggest that patients with
dysfunction before transplantation may be at risk of hepatic disease
post-transplant. Others reported that hepatic disease at the time of
transplantation did not appear to increase the risk.
In our study, the major cause of hepatic injury in
allogeneic patients is conditioning regimen (38.8%) followed by acute GVHD
(14.7%) of which 6.4% of patients had grade I, 19.3% had grade II, 32.2% had
grade III and 41.9% had grade IV) respectively. Then similarly, 2% of patients
had flare of viral hepatitis, sepsis, SOS or CMV hepatitis.
These figures are dramatically changed after day +100
as chronic hepatic GVHD is the primary cause of liver injury which occurred in
about 40% of allogeneic patients of which (7.1% had grade I, 23.2% had grade
II, 32% had grade III and 37.5% had grade IV) followed by significant decrease
of drug-induced hepatotoxicity (39%), iron overload in 2.9%.
In autologus patients, the first cause of
hepatotoxicity is also conditioning regimen involving 27.9% of patients
followed by flare of viral hepatitis in 7.9% and sepsis in 6.3% of cases.
Long-term, drug-induced hepatotoxicity
involved 11.4% of patients and is the major cause of hepatotoxicity.
In a similar study, barba et al found that acute
hepatic GVHD was found in 17% of patients who underwent allo-HSCT while chronic
hepatic GVHD was found in 50% of their cohort.3 Another multicenter
retrospective study by Battipaglia et al. that included 146 adults with AML and
receiving allo-HSCT, the main cause of liver function abnormalities among
patients were acute GVHD (31%), chronic GVHD at 2 years was 25%.
Regarding the type of conditioning regimen and
hepatotoxicity, busulfan-based conditioning regimens had statistically
significant hepatotoxic effect compared to non-busulfan conditioning regimens .
The population of Egypt has a very burden of liver
disease. The overall prevalence of positive antibody testing to hepatitis C in
the general population is around 15-20%.11 The prevalence of HCV in our
patients is 19% while the prevalence of HBV was 16% and CMV is 8%. Similarly,
previous report by kamel et al from Egypt with similar environmental factors
revealed that the prevalence of pre-transplant HBV, HCV in their patients was
27%, 31% respectively.
Flare of viral hepatitis in both autologus and
allogeneic patients represented 3% from all patients.
In a recent retrospective study by Torres et al. at MD
Anderson who included 59 patients (14 autologus and 13 allogeneic HSCT), all of
his patients were HCV infected recipients, HCV reactivation was seen in 11% of
patients infected with genotype 1; median time to HCV reactivation was 41 days
In our study, viral hepatitis reactivation had
statistically insignificant effect on liver injury neither during or
post-transplant in both allogeneic and
autologus patients. For patients with HBV, the usage of lamivudine prophylaxis
starting before conditioning regimen might be responsible for the reduced risk
of reactivation as previously reported by Lau et al.13 similarly, In a study by
Firpi and Nelson they found that prophylactic lamivudine dramatically reduced
the chance of reactivation (from 24-53% to 0-5%) and also led to improvement in
survival-free from hepatitis.
46.6% of acute hepatic GVHD patients were HCV
positive. While, 16.6% of patients with chronic hepatic GVHD were HCV +ve and
similarly, 16.6% had HBV infection.
Prevalence of CMV infection in our center in
allogeneic patients was 57% with reactivation occurred in about 65% of those
who had primary infection, while the prevalence of CMV infection in autologus
patients was about 18%. CMV hepatitis reactivation had statistically
insignificant effect on hepatic injury neither during nor post-transplant in
both autologus and allogeneic patients.
In a retrospective study done by piukovisc et al. the
prevalence of CMV in autologus patients was 24% 15 while panagou et al. studied
the prevalence of CMV in allogeneic
patients. 48% of his patients at least developed 1 episode of CMV viremia
during the first 90 days post-transplant.
The risk of infection in the post-engratment period is
a function of the dynamics of immune reconstitution. Factors that delay immune
reconstitution following HSCT are related to the increased risk of infection.
The most important factors influencing the speed of immune reconstitution are
the immune status before HSCT and the need for additional immunosuppressive
treatment. Likewise, additional chemotherapy after HSCT greatly increases the
risk of infection.
When we correlated between septicemia and hepatic
injury between autologus and allogeneic patients, we found that septicemia had
no statistically significant effect on liver injury during transplant. On the
other hand, a statistically significant effect of septicemia on liver injury
post-transplant was observed. Sepsis was higher in allogeneic patients due to
prolonged use of immunosuppressive therapy and chronic GVHD.