Hepatitis C infection is the most common cause of cirrhosis worldwide. Management of chronic hepatitis C in peri-transplant period is challenging. Patients with compensated/Child's A cirrhosis due to hepatitis C virus (HCV) infection are treated like noncirrhotics, with peginterferon (PEG-IFN) and ribavirin, albeit with a higher incidence of complications. Treatment is not recommended for decompensated cirrhotics due to higher complication rate including the risk of death. After liver transplant, immunosuppression should be adjusted to prevent/delay recurrent HCV disease. Incidence and severity of recurrent HCV disease as well as patient and graft survival is similar between living donor and deceased donor liver transplants. It is currently recommended to treat established recurrent hepatitis C, that is raised alanine aminotransferase (ALT) with HAI >4 and/or F >1. Pre-emptive/prophylactic antiviral therapy is poorly tolerated and has low efficacy. Standard dose regimen (PEG-IFN 1.5 μg/Kg or 180 μg weekly + ribavirin 800–1200 mg/day) for 48 weeks irrespective of the genotype is the recommended treatment protocol. Therapy poses significant problems in the form of anemia, neutropenia, higher risk of rejection, and so on.

1. Management of chronic hepatitis C before and after liver transplant

2. Apollo Medicine 2012 March
Review Article
Volume 9, Number 1; pp. 24–31
© 2012, Indraprastha Medical Corporation Ltd
Management of chronic hepatitis C before and after liver transplant
Manav Wadhawan*, SunilTaneja*, Rajeev Shandil*, Neerav Goyal**, Subash Gupta**,
Ajay Kumar*
*Consultant, Department of Gastroenterology and Hepatology and Liver Transplantation, **Consultant, Department of Surgical
Gastroenterology and Liver Transplantation, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi – 110076, India.
ABSTRACT
Hepatitis C infection is the most common cause of cirrhosis worldwide. Management of chronic hepatitis C in peri-
transplant period is challenging. Patients with compensated/Child’s A cirrhosis due to hepatitis C virus (HCV) infec-
tion are treated like noncirrhotics, with peginterferon (PEG-IFN) and ribavirin, albeit with a higher incidence of
complications. Treatment is not recommended for decompensated cirrhotics due to higher complication rate includ-
ing the risk of death. After liver transplant, immunosuppression should be adjusted to prevent/delay recurrent HCV
disease. Incidence and severity of recurrent HCV disease as well as patient and graft survival is similar between
living donor and deceased donor liver transplants. It is currently recommended to treat established recurrent hepati-
tis C, that is raised alanine aminotransferase (ALT) with HAI >4 and/or F >1. Pre-emptive/prophylactic antiviral ther-
apy is poorly tolerated and has low efficacy. Standard dose regimen (PEG-IFN 1.5μg/Kg or 180μg weekly + ribavirin
800–1200mg/day) for 48 weeks irrespective of the genotype is the recommended treatment protocol.Therapy poses
significant problems in the form of anemia, neutropenia, higher risk of rejection, and so on.
Keywords: Decompensated cirrhosis, hepatitis C, interferon treatment, liver transplant
Correspondence: Dr. Manav Wadhawan, E-mail: manavwadhawan@rediffmail.com
doi: 10.1016/S0976-0016(12)60116-1
Hepatitis C accounts for almost one-third of cases of
chronic liver disease (CLD) and is a major cause of liver
disease deaths, and cases of hepatocellular carcinoma. It
represents the most common indication for liver transplan-
tation in India and abroad. Treatment of chronic hepatitis C
has well-documented and published guidelines. However,
peritransplant management of hepatitis C is a difficult
problem and ridden with controversies. In this article, we
have tried to summarize the Indian data on demography of
HCV infection, discuss the problems and results of treat-
ment of HCV infection in compensated and decompensated
cirrhosis and also reviewed the current management of
HCV recurrence post-liver transplant.
CHRONIC HEPATITIS C IN INDIA
The community prevalence of hepatitis C in India is 0.4–
1.5%.1–3
Chronic hepatitis C is responsible for 15–35% of
all CLD in India.4–6
The most common genotype in India is
3 (50–80%). Studies from some parts of southern India
have a higher prevalence of genotype 1 infection, whereas in
northern India genotype 3 is most common.7–9
Virological
response (VR) of hepatitis C in India varies according to
the type of interferon (IFN) used (peginterferon [PEG-IFN]
vs standard [Std] IFN), schedule of Std IFN (daily vs 3
times a week [TIW]), genotype (1/4 vs 2/3), extent of liver
disease (chronic hepatitis vs cirrhosis), and severity of cir-
rhosis (compensated vs decompensated cirrhosis). The syn-
opsis of the available published Indian data is as follows:
1. Sustained virological response (SVR) rates are better
with PEG-IFN (50–95%) compared with Std IFN
(33–90%).10,11
2. Sustained virological response is better with daily IFN
(60–90%) compared with TIW IFN (33–75%).12,13
3. Genotype 2/3 (50–100%) have a better SVR rates than
genotype 1/4 (33–78%).10–13
4. Noncirrhotics (50–95%) have a higher SVR than cir-
rhotics (25–90%).14–16
5. Higher SVR for compensated cirrhosis (53%) compared
with decompensated cirrhosis (32–46%).14–16

3. Management of chronic hepatitis C before and after liver transplant Review Article 25
© 2012, Indraprastha Medical Corporation Ltd
6. Studies from north India have shown a higher response
rate for both genotype 1/4 and genotype 2/3 in contrast
to studies published from southern India.
7. There are no published data on results of the treatment of
hepatitis C post-liver transplant from India.
CURRENT STATUS OF HEPATITIS C
TREATMENT IN CIRRHOSIS
In cirrhosis, the rationale for treatment is based on four
principles. Treatment may halt the progression of disease in
a proportion of cases, may prevent the development of
hepatocellular carcinoma (HCC) in HCV cirrhotics, may
decrease/delay the need for transplant in those who respond
to treatment, and finally it may prevent the recurrence of
HCV infection/disease post transplant. Treatment of HCV
in compensated (Child’s A and early Child’s B cirrhotics) is
based on the first three principles, whereas in decompen-
sated cirrhosis, the prevention of disease recurrence is
clearly the main target.
Treatment of hepatitis C in compensated cirrhosis/
Child’s A cirrhosis should be identical to that in non-
cirrhotic patients with chronic hepatitis C (PEG-IFN+
ribavirin). There is good evidence that lower dose of PEG-
IFN alfa-2b (1μg/Kg) may be as effective as the standard
dose (1.5μg/Kg).10,11,14,17
The incidence of complications
during treatment is higher in the cirrhotic patients com-
pared with noncirrhotic population, requiring higher rate
dose adjustments and discontinuation. Also, there is a risk
of decompensation while on treatment which has to be
explained to the patient before starting treatment. Dose adjust-
ments have also been quantified according to the level of
cytopenias (Table 1).18
The treatment in decompensated cirrhosis carries a lot
of risks. In addition to lower SVRs, treatment causes cyto-
penias (neutropenia and thrombocytopenia), hemolysis, and
increase in life-threatening infections especially when treat-
ing Child’s C cirrhotics. Some subjects may suffer from
severe depression and suicidal tendencies; others may have
worsening of Child-Turcotte-Pugh (CTP) score. Frequent
dose adjustments (60–100%) are required when treating these
patients; a significant proportion is not able to complete
treatment due to these problems. Currently International
Liver Transplantation Society (ILTS) recommends treatment
of hepatitis C in cirrhosis (Table 2).19
ROLE OF VIRAL LOAD REDUCTION
PRETRANSPLANT
Very few trials have studied the efficacy of treatment of
HCV with interferon-based regimens in patients awaiting
liver transplant.20–22,23,24
Five trials published as full papers
are summarized in Table 3. Of these studies, four have used
interferon with or without ribavirin, only one trial is on
PEG-IFN with ribavirin. The median duration of treatment
in these trials vary from 2 months to 14 months. The SVR
rate at 6 months after transplant in these trials varies between
20% and 26%. The factors associated with good response to
therapy were non-1 genotype, low pretreatment viral load
and >2 log reduction in viral load at 4 weeks.20,24
A short,
calibrated treatment course for patients awaiting transplant
may be specially relevant in a living donor liver transplant
(LDLT) program where the timing of transplant can be opti-
mally timed.
Thus, from these data, it can be inferred that treatment
of hepatitis C in patients listed for transplant may decrease
the recurrence of HCV post transplant in those who respond
to treatment. In nonresponders, treatment may actually worsen
the disease severity.22,24,25
Considering the poor tolerability
and low success rate of HCV treatment post transplant, treat-
ment for hepatitis C may be carefully considered before trans-
plant in a subset of patients listed for transplant.
If it is decided to treat patients with decompensated
cirrhosis, patient should be listed for transplant before
starting treatment. The treatment should be started as per
low accelerating dose regimen (LADR).20
Dose should be
Table 1 Dose adjustments of peginterferon and ribavirin in
relation to cytopenias.
Peginterferon dose 2/3 normal Ribavirin
ANC <1200/platelet <60 Hb <10,800mg
ANC <750/platelet <35½ normal Hb <8600mg
ANC <500/platelet <20 stop Hb <6 stop
ANC: absolute neutrophil count; Hb: hemoglobin.
Table 2Treatment of hepatitis C virus in cirrhosis—International
Liver Transplantation Society recommendations.
Consider CTP MELD
treatment score score
Strongly consider ≤7 <18
In select cases 8–11 18–25 Treat carefully
with transplant
(Tx) planned
Treatment not >11 >25 Consider Tx and
advised treat post-Tx
CTP: Child-Turcotte-Pugh; MELD: model for end-stage liver disease.

4. 26 Apollo Medicine 2012 March; Vol. 9, No. 1 Wadhawan et al
© 2012, Indraprastha Medical Corporation Ltd
slowly increased to maximum tolerated to achieve best
response.
IMMUNOSUPPRESSION PROTOCOLS IN
HEPATITIS C VIRUS-RELATEDTRANSPLANTS
Hepatitis C virus recurrence is accelerated in transplant
recipients due to immunosuppression. Serological recur-
rence is seen in all patients who are HCV-viremic at the
time of liver transplant. The type and intensity of immuno-
suppression is a predictor of severity of recurrence of hepa-
titis C post transplant. Immunosuppression protocols should
be different for HCV recipients as compared with nonHCV-
transplant recipients.
Corticosteroids and LiverTransplant
Corticosteroids enhance HCV replication and may be asso-
ciated with more severe recurrence of hepatitis C. Steroid
boluses cause a marked but transient increase in HCV
viremia.26
However, the role of pulse steroids for rejection
in increasing HCV recurrence is controversial (trials before
2000 showing higher incidence, most trials after 2000 show-
ing similar recurrence rates).
SteroidTaper,Withdrawal, and Avoidance
The role of steroids in HCV replication has prompted multi-
ple trials on steroid withdrawal. Many groups advocate early
steroid withdrawal.27,28
But a number of trials have shown
that early taper of steroids (before 6–12 months) should be
avoided as it increases the severity of HCV recurrence.29,30
The jury is still out on the role of complete steroid avoid-
ance in HCV-related liver transplants. First published trial
is an interim analysis of a study in 39 patients recruited out
of a planned total of 50 patients.31
All patients received
tacrolimus (TAC) and mycophenolate mofetil (MMF) and
were randomized to receive either daclizumab or cortico-
steroids. There was a trend toward less cellular rejection with
daclizumab. However, there was no difference in HCV recur-
rence other than that the small number of cases with advanced
fibrosis all occurred in the corticosteroid arm of the trial.
Another prospective trial published recently enrolled 28
patients, used steroid-free immunosuppression (calcineurin
inhibitor [CNI], MMF, and anti-CD25 antibody in 18 patients
vs steroid-based immunosuppression in 10 patients).32
Steroid-free immunosuppression was associated with lower
incidence of cytomegalovirus (CMV) infection (P=0.049).
Acute cellular rejection rates were similar in both groups.
Steroid-free group showed a rapid increase in HCV-RNA
(ribonucleic acid) (P<0.05), and a higher HCV recurrence
(46% vs 18.1% at 1 year, P=0.009).
Currently, most centers limit the use of steroids by
using initial small doses and withdrawing completely by
6–12 months post transplant.
Tacrolimus versus Cyclosporine
Cyclosporine has in vitro inhibitory activity on the replica-
tion of HCV. But in vivo effect has been questioned as most
studies show no difference in the severity of HCV recur-
rence with CysA orTAC.33–35
However, what is documented
is that if a patient needs treatment for HCV recurrence with
interferon, SVR is higher in those on cyclosporine as pri-
mary immunosuppressant compared with TAC.36
An on-
going multicenter trial is evaluating the use of CysA versus
TAC in HCV-positive transplant recipients.
Other Issues
OKT3 induction or its use for treatment of rejection is
associated with increased severity of HCV recurrence.30
Most centers all over the world have replaced azathioprine
with MMF in triple immunosuppression. However, in
Table 3 Trials evaluating treatment of hepatitis C virus cirrhosis patients awaiting liver transplant.
N Treatment Duration (mo) ETR SVR Transplanted SVR after LT
Crippin (2002)23
15 IFN±Riba 2 5 (33%) – 2 –
Thomas (2003)22
20 IFN 14 12 (60%) – 20 4 (20%)
Everson (2005)20
124 IFN+Riba 6–12 57 (46%) 30 (24%) 47 12 (26%)
Forns (2003)21
30 IFN+Riba 3 9 (30%) – 30 6 (20%)
Carrion (2009)24
51 PEG-IFN+Riba 4 15 (29%) – 43 10 (20%)
ETR: end of treatment response; IFN: interferon; LT: liver transplantation; PEG-IFN: peginterferon; SVR: sustained virological response.

5. Management of chronic hepatitis C before and after liver transplant Review Article 27
© 2012, Indraprastha Medical Corporation Ltd
liver transplant, the superiority of MMF over AZA is not
clearly demonstrated. A very recently published paper has
reviewed all trials regarding the use of azathioprine vis-à-vis
MMF in liver transplant patients.37
These authors report no
difference in graft or patient survival between liver transplant
recipients treated with MMF or azathioprine. Another
recently published trial comparing TAC monotherapy with
triple therapy with TAC, azathioprine, and steroids showed
a slower onset of histologically proven severe fibrosis and
portal hypertension in triple therapy compared with TAC
alone.38
Use of azathioprine has been associated with
decreased severity of recurrence of HCV post transplant in
other trials also39,37
and it may be considered along with
CNIs as a part of immunosuppression regimen. Rate and
severity of HCV recurrence is similar in interleukin (IL)-2
receptor antagonist immunosuppressive regimens compared
with conventional regimen.39
There is no available literature
on the use of sirolimus in liver transplant for HCV-related
disease.
NATURAL HISTORY OF CHRONIC
HEPATITIS C POST-LIVERTRANSPLANT
Cirrhosis due to HCV is a major indication for orthotopic
liver transplantation (OLT) in India and in the West account-
ing for almost 30% of total patients. Graft HCV re-infection
is early and universal in patients who are viremic at the time
of transplant. Five-year survival after HCV recurrence in
deceased donor liver transplant (DDLT) is lower than
nonHCV-related liver transplants. Histologic recurrence
is seen in 50% of these patients at 1 year post transplant.
Cumulative probability of graft cirrhosis is 30% at 5 years
post transplant, as compared with 5% in chronic HCV
infection in nontransplanted population. Actuarial risk
of decompensation once these transplant recipients
develop cirrhosis is 42% at 1 year, 62% at 5 years; whereas
in nontransplant HCV, it is 5% and 10% at 1 year and
3 years, respectively. Three-year survival after decompensa-
tion is <10% for recurrent HCV after liver transplantation.
Of the total number of patients transplanted for HCV-
related liver disease, 10–25% will need re-transplantation
within 5 years. All these data are from cadaveric liver
transplants.40–42
Initial comparative data of the severity of HCV recur-
rence following LDLT versus DDLT showed greater sever-
ity of recurrence and poorer 1 year graft survival.43,44
Subsequently, many trials have been published which show
no difference in the mean inflammation score or mean
fibrosis score, with similar occurrence of cirrhosis and
similar graft and patient survival at 4 years, in patients with
recurrent HCV in LDLT versus DDLT.42,45–47,48
DO ALL PATIENTS WITH HEPATITIS C VIRUS
NEEDTREATMENT POST-LIVER
TRANSPLANT?
Treatment protocols for HCV post-liver transplant can be
broadly divided in two main categories. Treatment for all
irrespective of alanine aminotransferase (ALT) and liver
biopsy findings (pre-emptive therapy) and treatment of
recurrent disease (ALT raised, liver biopsy HAI >4 and/or
Fibrosis >1). Multiple trials of pre-emptive therapy have
shown a pooled end of treatment response (ETR) of 13.6%
and a SVR of 9.1% (0–18%).49
The incidence of complica-
tions has been 60–90% (dose reduction—85%, discontinu-
ation—37%, and serious adverse events—27%). Only 15%
of total patients were able to receive complete and full-dose
treatment. However, one recent trial published from Japan has
shown a 45% ETR and 39% SVR after pre-emptive treatment
which continued for 1 year after first negative HCV-RNA
report.50
This study also showed similar survival between
patients transplanted for HCV and nonHCV cirrhosis.50
The minimum criteria for established disease needing
treatment are raised ALT levels, HAI >4 and/or fibrosis >1
on liver biopsy score according to modified Ishak’s system.19
The pooled SVR rate on IFN+ribavirin combination (27
published trials) has been reported to be 24% (13–53%).
Pooled discontinuation rate in these studies was 24%. On
the combination of PEG-IFN and ribavirin (21 studies),
pooled SVR rate was slightly higher (27% [26–50%]), and
so was the pooled discontinuation rate (26%).51
Acute cel-
lular rejection was reported in 2% (0–4%) receiving IFN
and 5% (2–25%) of those receiving PEG-IFN.
CURRENTTREATMENT PROTOCOL OF
TREATMENT OF HEPATITIS C VIRUS
POST-LIVERTRANSPLANT
Treatment is recommended for established HCV recurrence
post transplant only (HAI >4, F ≥1).19
Two treatment proto-
cols are followed: escalating dose regimen—PEG-IFN
(0.5–1.5μg/Kg or 90/135/180μg weekly) + ribavirin (400–
1200mg/day) or standard dose regimen (PEG-IFN 1.5μg/Kg
or 180μg weekly+ribavirin 800–1200mg/day). Most centers
prefer the standard dose over escalating regimen. Treat-
ment should be started at fibrosis score 1–2 as response

6. 28 Apollo Medicine 2012 March; Vol. 9, No. 1 Wadhawan et al
© 2012, Indraprastha Medical Corporation Ltd
rates decrease with higher fibrosis scores at the start of
treatment (48% vs 19%).52
The duration of treatment is rec-
ommended to be 48 weeks irrespective of the genotype.
PROBLEMS IN HEPATITIS C VIRUS
TREATMENT POST-LIVERTRANSPLANT
Treatment of HCV recurrence post-liver transplant is diffi-
cult. Problems can be related to drug discontinuation/dose
reduction of PEG-IFN and/or ribavirin, the risk of graft
rejection, or other miscellaneous issues like post transplant
diabetes mellitus (PTDM), CMV, and occult hepatitis B
virus (HBV).
Anemia is seen in 36–81% LT recipients treated for
chronic hepatitis C.53
The mechanisms can be multiple:
ribavirin induces hemolysis by the accumulation of phos-
phorylated ribavirin in RBCs causing oxidative injury,54
Interferon induces myelosuppression contributing to ane-
mia,55
HCV interference in erythropoietin production (EPO)
by direct inhibition as well as ribavirin-induced renal insuf-
ficiency.56
Treatment is by using weight-based dosing of
ribavirin, the use of EPO which is started pre-emptively
when hemoglobin (Hb) ≤10g% or when there is ≥2g%
reduction in Hb. More vigilance is required in elderly and in
those on concurrent MMF.
Neutropenia and thrombocytopenia are reported in up
to 50% of patients on treatment with PEG-IFN+Riba.
Treatment discontinuation is reported in 0–40% of patients
in various studies.57–61
Usual management is by reducing
the dose/frequency of PEG-IFN and restarting normal dos-
age once it comes back to normal. Gm-CSF is also used
concurrently to increase counts while on treatment.
One of the most important risks of treatment for HCV is
graft rejection. It has been variously reported between 0% and
25% in various published studies.57–61
The proposed mecha-
nisms of rejection is that interferon enhances the expression
of HLA-DR antigens on donor bile duct epithelial cells and
hepatocytes. Further, antiviral therapy improves hepatocyte
microsomal function leading to decreased immunosuppres-
sion levels.53
Median time to rejection has been reported to
be 3.5 months (range 0.3–15.7 months) after HCV-RNA
becomes undetectable.62
The incidence of rejection is shown
to be higher in responders vs nonresponders.62
Another study
has reported a higher incidence of fibrosing cholestatic hepa-
titis (FCH) in nonresponders after stopping IFN therapy.63
Risk of chronic rejection is miniscule and overstated.
The PTDM is seen in 7.2% of liver transplant recipients
at 6 months post transplant. Incidence is higher with TAC
than with cyclosporine, and 4–8-fold higher prevalence is
seen in HCV-related liver transplants than in nonHCV
transplants. Exact mechanism is not known but both HCV
direct effect and immune-mediated effects have been pro-
posed. It is recommended that insulin be used in thin
patients and oral hypoglycemics in overweight patients.64
Sulfonylureas and thiazolidinediones have been found to be
safe.64–66
Metformin is not to be used post-liver transplant
for the concern of lactic acidosis.
Cytomegalovirus infection does not increase the risk of
HCV recurrence post transplant. There is no difference in
HCV viral load, degree of liver injury, and fibrosis in CMV
PCR positive vs negative patients with HCV-related liver
transplant.67
On the other hand, CMV viral load is similar
between HCV-related and nonHCV liver transplants.67
CONCLUSION
Hepatitis C infection accounts for maximum end-stage liver
disease patients. Management of chronic hepatitis C in per-
itransplant period requires specialized care by dedicated
hepatologists. Patients with compensated/Child’s A cirrho-
sis due to HCV infection should be treated like chronic
hepatits C patients without cirrhosis. The risk of treatment
associated complications is much higher in this group.
Decompensated cirrhotics have a very high-risk of compli-
cations including the risk of further worsening of liver dis-
ease and death. After liver transplant, immunosuppression
should be adjusted to prevent/delay recurrent HCV disease.
There is no difference in the incidence and severity of
recurrent HCV disease as well as patient and graft survival
between LDLT and DDLT. It is currently recommended to
treat established recurrent hepatitis C post-liver transplant.
The minimum criteria for treatment are raised ALT
with HAI >4 and/or F >1 on liver biopsy. Pre-emptive/
Prophylactic antiviral therapy is poorly tolerated and has
low efficacy. Standard dose regimen (PEG-IFN 1.5μg/Kg
or 180μg weekly + ribavirin 800–1200mg/day) for 48 weeks
irrespective of the genotype is the recommended treatment
protocol. Therapy is associated with a high complication
rate in the form of anemia, neutropenias, higher risk of
rejection, and fibrosing cholestatic hepatitis.
REFERENCES
1. Mishra S, Chayani N, Sarangi G, Mallick B, Pati SB.
Seroprevalence of anti-HCV antibody in and around Cuttack,
Orissa. Ind J Med Microbiol 2002;20:40–1.

7. Management of chronic hepatitis C before and after liver transplant Review Article 29
© 2012, Indraprastha Medical Corporation Ltd
2. Bhatia R. Blood transfusion services in developing countries
of South-east Asia. Transfus Today 2005;65:4–5.
3. Kapoor D, Saxena R, Sood B, Sarin SK. Blood transfusion prac-
tices in India: results of a national survey. Indian J Gastroenterol
2000;19:64–7.
4. Issar SK, Ramakrishna BS, Ramakrishna B, Christopher S,
Samuel BU, John TJ. Prevalence and presentation of hepatitis
C related chronic liver disease in southern India. J Trop Med
Hyg 1995;98:161–5.
5. Berry N, Chakravarti A, Das U, Kar P, Das BC, Mathur MD.
HCV seroreactivity and detection of HCV RNA in cirrhotics.
Diagn Microbiol Infect Dis 1999;35:209–13.
6. Ray G, Ghoshal UC, Banerjee PK, et al.Aetiological spectrum
of chronic liver disease in eastern India. Trop Gastroenterol
2000;21:60–2.
7. Hissar SS, Goyal A, Kumar M, et al. Hepatitis C virus geno-
type 3 predominates in North and Central India and is associ-
ated with significant histopathologic liver disease. J MedVirol
2006;78:452–8.
8. Chandra M, Thippavuzzula R, Ramachandra Rao VV, et al.
Genotyping of hepatitis C virus (HCV) in infected patients
from South India. Infect Genet Evol 2007;7:724–30.
9. Amarapurkar D, Dhorda M, Kirpalani A, Amarapurkar A,
Kankonkar S. Prevalence of hepatitis C genotypes in Indian
patients and their clinical significance. JAssoc Physicians India
2001;49:983–5.
10. Sood A, Midha V, Hissar S, et al. Comparison of low-dose
pegylated interferon versus standard high-dose pegylated inter-
feron in combination with ribavirin in patients with chronic
hepatitisCwithgenotype3:anIndianexperience.JGastroenterol
Hepatol 2008;23:203–7.
11. Gupta R, Ramakrishna CH, Lakhtakia S,Tandan M, Banerjee R,
Reddy DN. Efficacy of low dose peginterferon alpha-2b with
ribavirin on chronic hepatitis C. World J Gastroenterol 2006;
12:5554–6.
12. Hazari S, Panda SK, Gupta SD, Batra Y, Singh R, Acharya
SK. Treatment of hepatitis C virus infection in patients of
northern India. J Gastroenterol Hepatol 2004;19:1058–65.
13. Sarin SK, Goyal A, Kumar S, et al. A randomized trial of a
4- vs 12-week daily interferon dose regimen combined with
ribavirin in treatment of patients with chronic hepatitis C.
Hepatobiliary Pancreat Dis Int 2004;3:42–8.
14. Sood A, Midha V, Sood N, Bansal M. Pegylated interferon
alfa 2b and oral ribavirin in patients with HCV-related cir-
rhosis. Ind J Gastroenterol 2006;25:283–5.
15. Amarapurkar DN, Patel ND, Kamani P. Antiviral therapy of
decompensated cirrhosis due to hepatitis C viral infection.
Trop Gastroenterol 2005;26:119–22.
16. Kumar R, Kumar S, Sharma BC, Singh J, Sarin SK. Antiviral
therapy in advanced chronic liver disease due to hepatitis C
virus infection: pilot study. J Gastroenterol Hepatol 2005;
20:527–35.
17. McHutchison JG, Lawitz EJ, Shiffman ML, et al.
Peginterferon alfa-2b or alfa-2a with ribavirin for treatment
of hepatitis C infection. N Engl J Med 2009;361:580–93.
18. Tekin F, Gunsar F, Karasu Z, Akarca U, Ersoz G. Safety, toler-
ability, and efficacy of pegylated-interferon alfa-2a plus riba-
virin in HCV-related decompensated cirrhotics. Aliment
Pharmacol Ther 2008;27:1081–5.
19. Russell H, Wiesner, Michael Sorrell, et al for the International
Liver Transplantation Society. Expert panel report of the
First International Liver Transplantation Society Expert
Panel Consensus Conference on Liver Transplantation and
Hepatitis C. Liver Transpl 2003;9:S1–9.
20. Everson GT, Trotter J, Forman L, et al. Treatment of advanced
hepatitis C with a low accelerating dosage regimen of antivi-
ral therapy. Hepatology 2005;42:255–62.
21. Forns X, Garcia-Retortillo M, Serrano T. Antiviral therapy of
patients with decompensated cirrhosis to prevent recurrence
of hepatitis C after liver transplantation. J Hepatol 2003;39:
389–96.
22. Thomas RM, Bremms JJ, Guzman-Hartman G. Infection
with chronic hepatitis C virus and liver transplantation: a role
for interferon therapy before transplantation. Liver Transpl
2003;9:905–15.
23. Crippin JS, McCashland T, Terrault N, Sheiner P, Charlton
MR. A pilot study of the tolerability and efficacy of antiviral
therapy in hepatitis C virus-infected patients awaiting liver
transplantation. Liver Transpl 2002;8:350–5.
24. Carrión JA, Martínez-Bauer E, Crespo G, et al. Antiviral
therapy increases the risk of bacterial infections in HCV-
infected cirrhotic patients awaiting liver transplantation: a
retrospective study. J Hepatol 2009;50:719–28.
25. Iacobellis A, Siciliano M, Perri F, et al. Peginterferon alfa-2b
and ribavirin in patients with hepatitis C virus and decompen-
sated cirrhosis: a controlled study. J Hepatol 2007;46:
206–12.
26. Gane EJ, Naoumov NV, Qian KP, et al. A longitudinal analy-
sis of hepatitis C virus replication following liver transplanta-
tion. Gastroenterology 1996;110:167–77.
27. Everson GT, Trouillot T, Wachs M, et al. Early steroid with-
drawal in liver transplantation is safe and beneficial. Liver
Transpl Surg 1999;5(4 Suppl 1):S48–57.
28. Burroughs AK. Posttransplantation prevention and treatment
of recurrent hepatitis C. Liver Transpl 2000;6(Suppl 2):
S35–40.
29. Samonakis DN, Triantos CK, Thalheimer U, et al.
Immunosuppression and donor age with respect to severity of
HCV recurrence after liver transplantation. LiverTranspl 2005;
11:386–95.

8. 30 Apollo Medicine 2012 March; Vol. 9, No. 1 Wadhawan et al
© 2012, Indraprastha Medical Corporation Ltd
30. Berenguer M,AguileraV, Prieto M, et al. Significant improve-
ment in the outcome of HCV-infected transplant recipients by
avoiding rapid steroid tapering and potent induction immuno-
suppression. J Hepatol 2006;44:717–22.
31. Kato T, Yoshida H, Sadfar K, et al. Steroid-free induction and
preemptive antiviral therapy for liver transplant recipients
with hepatitis C: a preliminary report from a prospective
randomised study. Transplant Proc 2005;37:1217–9.
32. Marubashi S, Dono K, Nagano H, et al. Steroid-free living
donor liver transplantation in adults: impact on hepatitis C
recurrence. Clin Transplant 2009 [Epub ahead of print].
33. Martin P, Busuttil RW, Goldstein RM, et al. Impact of tac-
rolimus versus cyclosporine in hepatitis C virus-infected liver
transplant recipients on recurrent hepatitis: a prospective,
randomized trial. Liver Transpl 2004;10:1258–62.
34. Zervos XA, Weppler D, Fragulidis GP, et al. Comparison of
tacrolimus with microemulsion cyclosporine as primary
immunosuppression in hepatitis C patients after liver trans-
plantation. Transplantation 1998;65:1044–6.
35. Berenguer M, Aguilera V, Prieto M, et al. Effect of calcineurin
inhibitors on survival and histologic disease severity in HCV-
infected liver transplant recipient. Liver Transpl 2006;12:
762–7.
36. Firpi RJ, Abdelmalek MF, Soldevila-Pico C, et al.
Combination of interferon alfa-2b and ribavirin in liver
transplant recipients with histological recurrent hepatitis C.
Liver Transpl 2002;8:1000–6.
37. Germani G, Pleguezuelo M, Villamil F, et al. Azathioprine in
liver transplantation: a reevaluation of its use and a compari-
son with mycophenolate mofetil. Am J Transplant 2009;
9:1725–31.
38. Manousou P, Samonakis D, Cholongitas E, et al. Outcome of
recurrent hepatitis C virus after liver transplantation in a ran-
domized trial of tacrolimus monotherapy versus triple ther-
apy. Liver Transplant 2009;15:1783–91.
39. Walter T, Dumortier J, Guillaud O, Hervieu V, Scoazec JY,
Boillot O. Factors influencing the progression of fibrosis in
patients with recurrent hepatitis C after liver transplantation
under antiviral therapy: a retrospective analysis of 939 liver
biopsies in a single center. Liver Transpl 2007;13:294–301.
40. Berenguer M, Prieto M, Rayón JM, et al. Natural history of
clinically compensated hepatitis C virus-related graft cirrho-
sis after liver transplantation. Hepatology 2000;32:852–8.
41. Charlton M, Ruppert K, Belle SH, et al. Long-term results
and modeling to predict outcomes in recipients with HCV
infection: results of the NIDDK liver transplantation data-
base. Liver Transpl 2004;10:1120–30.
42. Guo L, Orrego M, Rodriguez-Luna H, et al. Living donor
liver transplantation for hepatitis C-related cirrhosis: no dif-
ference in histological recurrence when compared to deceased
donor liver transplantation recipients. Liver Transpl 2006;12:
560–5.
43. Gaglio PJ, Malireddy S, Levitt BS, et al. Increased risk of
cholestatic hepatitis C in recipients of grafts from living ver-
sus cadaveric liver donors. Liver Transpl 2003;9:1028–35.
44. Thuluvath PJ, Yoo HY. Graft and patient survival after adult
live donor liver transplantation compared to a matched cohort
who received a deceased donor transplantation. Liver Transpl
2004;10:1263–8.
45. Shiffman ML, Stravitz RT, Contos MJ, et al. Histologic recur-
rence of chronic hepatitis C virus in patients after living
donor and deceased donor liver transplantation. Liver Transpl
2004;10:1248–55.
46. Rodriguez-Luna H, Vargas HE, Sharma P, et al. Hepatitis C
virus recurrence in living donor liver transplant recipients.
Dig Dis Sci 2004;49:38–41.
47. Bozorgzadeh A, Jain A, Ryan C, et al. Impact of hepatitis C
viral infection in primary cadaveric liver allograft versus primary
living-donor allograft in 100 consecutive liver transplant recip-
ients receiving tacrolimus. Transplantation 2004;77:1066–70.
48. Gallegos-Orozco JF,Yosephy A, Noble B, et al. Natural history
of post-liver transplantation hepatitis C: a review of factors that
may influence its course. Liver Transplant 2009;15:1872–81.
49. Shergill AK, Khalili M, Straley S, et al. Applicability, tolera-
bility and efficacy of preemptive antiviral therapy in hepatitis
C-infected patients undergoing liver transplantation. Am J
Transplant 2005;5:118–24.
50. Tamura S, Sugawara Y, Makuuchi M, et al. Pre-emptive anti-
viral therapy in living donor liver transplantation for hepatitis
C: observation based on a single-center experience. Transpl
Int 2009 [Epub ahead of print].
51. Wang CS, Ko HH, Yoshida EM, Marra CA, Richardson K.
Interferon-based combination anti-viral therapy for hepatitis
C virus after liver transplantation: a review and quantitative
analysis. Am J Transplant 2006;6:1586–99.
52. Carrión JA, Navasa M, García-Retortillo M, et al. Efficacy of
antiviral therapy on hepatitis C recurrence after liver trans-
plantation: a randomized controlled study. Gastroenterology
2007;132:1746–56.
53. Saab S, Oh MK, Ibrahim AB, et al. Anemia in liver transplant
recipients undergoing antiviral treatment for recurrent hepati-
tis C. Liver Transpl 2007;13:1032–8.
54. De Franceschi L, Fattovich G, Turrini F, et al. Hemolytic ane-
mia induced by ribavirin therapy in patients with chronic hep-
atitis C virus infection: role of membrane oxidative damage.
Hepatology 2000;31:997–1004.
55. Sulkowski MS, Wasserman R, Brooks L, Ball L, Gish R.
Changes in haemoglobin during interferon alpha-2b plus
ribavirin combination therapy for chronic hepatitis C virus
infection. J Viral Hepatol 2004;11:243–50.

9. Management of chronic hepatitis C before and after liver transplant Review Article 31
© 2012, Indraprastha Medical Corporation Ltd
56. Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after
transplantation of a nonrenal organ. N Engl J Med 2003;349:
931–40.
57. Dumortier J, Scoazec JY, Chevallier P, Boillot O. Treatment
of recurrent hepatitis C after liver transplantation: a pilot study
of peginterferon alfa-2b and ribavirin combination. J Hepatol
2004;40:669–74.
58. Castells L, Vargas V, Allende H, et al. Combined treatment
with pegylated interferon (alpha-2b) and ribavirin in the acute
phase of hepatitis C virus recurrence after liver transplanta-
tion. J Hepatol 2005;43:53–9.
59. Neumann U, Puhl G, Bahra M, et al. Treatment of patients
with recurrent hepatitis C after liver transplantation with
peginterferon alfa-2B plus ribavirin. Transplantation 2006;82:
43–7.
60. Berenguer M, Palau A, Fernandez A, et al. Efficacy, predic-
tors of response, and potential risks associated with antiviral
therapy in liver transplant recipients with recurrent hepatitis C.
Liver Transpl 2006;12:1067–76.
61. Sharma P, Marrero JA, Fontana RJ, et al. Sustained virologic
response to therapy of recurrent hepatitis C after liver
transplantation is related to early virologic response and dose
adherence. Liver Transpl 2007;13:1100–8.
62. Kugelmas M, Osgood MJ, Trotter JF, et al. Hepatitis C virus
therapy, hepatocyte drug metabolism, and risk for acute cel-
lular rejection. Liver Transpl 2003;9:1159–65.
63. Kornberg A, Küpper B, Tannapfel A, Thrum K, Bärthel E,
Settmacher U. Antiviral treatment withdrawal in viremic
HCV-positive liver transplant patients: impact on viral loads,
allograft function and morphology. Liver Int 2006;26:
811–6.
64. Salvadori M, Bertoni E, Rosati A, Zanazzi M. Post-transplant
diabetes mellitus. J Nephrol 2003;16:626–34.
65. Villanueva G, Baldwin D. Rosiglitazone therapy of posttrans-
plant diabetes mellitus. Transplantation 2005;80:1402–5.
66. Luther P, Baldwin D Jr. Pioglitazone in the management of
diabetes mellitus after transplantation. Am J Transplant 2004;
4:2135–8.
67. Nebbia G, Mattes FM, Cholongitas E, et al. Exploring the
bidirectional interactions between human cytomegalovirus
and hepatitis C virus replication after liver transplantation.
Liver Transpl 2007;13:130–5.

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