Response to interferon alfa is hepatitis B virus genotype
dependent: genotype A is more sensitive to interferon than
A Erhardt, D Blondin, K Hauck, A Sagir, T Kohnle, T Heintges, D Ha ¨ussinger
See end of article for
Dr A Erhardt, Klinik fu ¨r
Du ¨sseldorf, Moorenstr 5,
D-40225 Du ¨sseldorf,
Revised version received
20 February 2005
Accepted for publication
9 March 2005
Gut 2005;54:1009–1013. doi: 10.1136/gut.2004.060327
Background an aims: Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The
role of hepatitis B virus (HBV) genotypes for response to IFN was investigated.
Patients and methods: HBV genotype was determined by direct sequencing of the HBV X gene in 165
consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D
was found in 144 cases.
Results: Sustained response (six months after treatment) to standard IFN therapy was higher in HBV
genotype A compared with HBV genotype D infected patients (49% v 26%; p,0.005). Sustained response
to IFN was 46% versus 24% (p,0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n=99) and 59%
versus 29% (p,0.05) in HBeAg negative hepatitis (n=45) for HBV genotype A compared with HBV
genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression
identified HBV genotype A and high pretreatment alanine aminotransferase levels (.26upper limit of
normal) as independent positive predictive parameters of IFN response.
Conclusions: The present study indicates that HBV genotypes A and D are important and independent
predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may
further improve treatment efficacy in chronic hepatitis B.
for chronic hepatitis B.3Hepatitis B e antigen (HBeAg)
seroconversion is associated with increased survival in
patients with chronic hepatitis B.4However, HBeAg serocon-
version is only achieved in 30–40% of HBeAg positive patients
using standard interferon therapy. Treatment of HBeAg
negative hepatitis B apparently gives even poorer sustained
responses.5Treatment regimens with nucleos(t)ide analogues
have not proved superior to IFN treatment.
Alanine aminotransferase (ALT) levels, HBV-DNA titres,
and degree of liver inflammation have been associated with
prediction of IFN response in chronic HBV infection.4 6
However, the immunological disposition of the host and
genetic factors of the virus itself may be major determinants
of IFN response.7 8Virus genotypes are strongly related to IFN
response in chronic hepatitis C.9 10Unlike the role of hepatitis
C virus genotypes, the role of HBV genotypes on the response
to IFN treatment is not as clear.
To date, eight HBV genotypes (A–H) have been identi-
fied.11–13HBV genotypes are classified by more than 8%
divergence of the full nucleotide sequence.14Determination of
amino acid variability at amino acids 122 and 160 of the HBV
surface protein allows subtyping of HBV. Several mutations
in the nucleotide sequence of HBV are associated with
specific HBV genotypes such as the precore stop codon
mutation (G1896A).15 16The precore mutation that prevents
translation of the precore polypeptide and thereby eliminates
HBeAg production is particularly found in HBV genotypes B,
C, and D.17
The geographic distribution of HBV genotypes varies
significantly.13HBV genotype A is common in Northern
Europe and North America whereas HBV genotype D is found
mainly in the Mediterranean area, Middle East, and India.
HBV genotypes B and C are frequent in Asia. HBV genotype E
hronic hepatitis B affects approximately 360 million
persons worldwide.1 2Interferon alfa (IFN) and nucleo-
s(t)ide analogues are the currently approved treatments
has mainly been found in West Africa and South Africa and
HBV genotype F in South America and Central America.
Geographic distribution of HBV genotypes G and H is less
well studied; both HBV genotypes seem to be rare in Europe.
The aim of the present study was to investigate the role of
HBV genotypes in a large cohort of patients with chronic
hepatitis B for response to standard IFN treatment.
PATIENTS AND METHODS
A total of 165 consecutive patients seen between 1988 and
2002 with chronic hepatitis B were investigated. Among
these, 119 patients (72%) had HBeAg positive and 46 (28%)
HBeAg negative hepatitis B infection. None of the patients
had markers of hepatitis D virus (HDV), hepatitis C virus
(HDV), or human immunodeficiency virus (HIV) infection.
Markers of HBV, HCV, and HIV (hepatitis B surface antigen,
antibody to hepatitis B surface antigen, antibody to hepatitis
B core antigen, HBeAg, antibody to hepatitis B e antigen,
anti-HDV, anti-HCV, and anti-HIV) were tested by commer-
cial immunoassays. All patients were HBV DNA positive. HBV
DNA was measured by a commercial hybridisation assay
(Digene 2.0; Murex Diagnostika, Burgwedel, Germany). The
detection limit of the quantitative HBV DNA assay was
2.5 pg/ml. Ninety six per cent of patients (159/166) had
elevated ALT levels.
Patients had received 364.5–10 million units (MU) or
764.5 MU of IFN-a2b or IFN-a2a weekly for at least four
months (range 4–15 months). The vast majority of patients
(92.5%) had received 364.5–6 MU IFN-a weekly. A daily
Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HDV,
hepatitis D virus; HIV, human immunodeficiency virus; IFN-a, interferon
alfa; ETR, end of treatment response; SR-6, sustained response six
months post treatment; SR-12, sustained response 12 months post
treatment; HBeAg, hepatitis B e antigen; ALT, alanine aminotransferase;
ULN, upper limit of normal
IFN-a schedule was given to 5% of patients and 369–10 MU
IFN-a were administered to 2.5% of patients. Distribution of
treatment schedules did not differ between HBV genotypes A
For HBeAg positive patients, sustained response was
defined as negative HBV-DNA in the hybridisation assay,
normalisation of ALT levels, and seroconversion from HBeAg
to anti-HBeAg at six months after stopping IFN treatment
(SR-6). For HBeAg negative patients, sustained response was
defined as persistent loss of HBV-DNA in the hybridisation
assay and normalisation of ALT levels at six months after
stopping IFN treatment (SR-6). In addition to SR-6,
sustained response 12 months after stopping treatment
(SR-12) was also determined for HBeAg negative and
HBeAg positive patients. Data for the 12 month follow up
were available in 142 patients; two patients were lost to
follow up. Liver biopsy at the time of IFN treatment was
available for 100 of 165 patients (61%). Histological scoring
was performed according to Desmet and colleagues.18The
diagnosis of liver cirrhosis was based on pretreatment liver
histology. Data on disease duration were obtained by medical
history (date of blood transfusion, needle stick injury,
appearance of clinical signs and symptoms such as jaundice,
HBV genotype was determined by direct sequencing of the
HBV X gene in all patients, as described previously.8The HBV
X gene sequences of patients were compared with HBV
databank entries of known HBV genotypes A–H with the
AF160510, AF160501, D00329, D00330, D00331, D00630;
X02496, X02763, X04615, X52939, X59795, X69798, X75656,
X75657, X75658, X75663, X75664, X75665, X97848, Z35716,
Z35717. Alignments of DNA sequences were performed with
Lasergene Megalign software (DNAStar Inc., Madison,
Statistical analysis was done using SPSS software (SPSS
Inc., Munich, Germany). The Student’s t test was used for
analysis of continuous variables, the Mann-Whitney test for
non-continuous variables, and the x2test for analysis of
categorical variables. Logistic regression models were used to
examine the association between HBV genotype and IFN
response. A p value ,0.05 was considered significant.
Of 165 patients investigated, 47.3% were infected with HBV
genotype A, 40.0% with HBV genotype D, 6.7% with HBV
genotype C, 3.6% with HBV genotype B, 1.8% with genotype
E, and 0.6% with genotype G. HBV genotypes H and F were
not encountered. HBV genotype D was found significantly
more often in HBeAg negative hepatitis B than in HBeAg
positive hepatitis B (p,0.01) (table 1). HBV genotype A was
the predominant HBV genotype in HBeAg positive hepatitis B
(table 1). Due to insufficient power, HBV genotypes B, C, E,
and G were not included in further statistical analysis.
Baseline HBV-DNA, cumulative IFN dose, and cirrhosis
prevalence did not differ significantly between HBV geno-
types (table 2). Infection with HBV genotype B or C was
characterised by a longer disease duration and a higher rate
of females compared with other HBV genotypes. ALT levels
according to hepatitis B e antigen (HBeAg) status
Hepatitis B virus (HBV) genotype distribution
HBeAg positive (%)
HBeAg negative (%)
*HBV genotype D distribution between HBeAg negative and HBeAg
positive patients was significantly different (p,0.01).
Characteristics of patients with chronic hepatitis B according to hepatitis B virus
HBeAg positive (%)
Mode of acquisition (%)
Cumulative IFN dose (MU) 418 (21)
1078 (2072) 459 (135)
450 (15) 447 (20)
*The patient with HBV genotype G was not included in the analysis.
?Diagnosis of liver cirrhosis was made on liver histology. Liver histology was available in 100 patients.
`Sex distribution, age, and ALT levels were significantly different in HBV genotype B patients compared with HBV
genotype A or D (all p,0.05).
1Perinatal infection rate was higher among patients with HBV genotypes B, C, and D compared with HBV genotype
HBeAg, hepatitis B e antigen; ALT, alanine aminotransferase; ND, not determined.
1010Erhardt, Blondin, Hauck, et al
were significantly lower in patients with HBV genotype B
compared with HBV genotype A, C, or D. Disease duration
was not different between patients with HBV genotype A
compared with HBV genotype D (78 (10) v 74 (15) months)
despite a higher frequency of perinatal infections in genotype
D. Disease duration was determined in 74% of patients.
Neither frequency of liver cirrhosis (table 2) nor mean stage
of liver fibrosis (2.2 v 2.1) or mean grade of inflammatory
activity (2.3 v 2.0) differed significantly between HBV
genotypes A and D.
Mean treatment duration and cumulative IFN dose were
not different between patients with HBV genotype A and
HBV genotype D (table 3). Treatment duration and cumula-
tive IFN dose were slightly higher among patients with
HBeAg negative hepatitis compared with HBeAg positive
hepatitis (7.0 v 6.1 months (p,0.03); 473 v 413 MU IFN
(p,0.06)). In HBeAg positive hepatitis, 16.9% of patients
compared with 37% of HBeAg negative patients were treated
for longer than six months. For HBeAg positive hepatitis B,
treatment duration and cumulative IFN dose were slightly in
favour of HBV genotype D whereas in HBeAg negative
hepatitis B, treatment duration and cumulative IFN dose
were slightly in favour of HBV genotype A (table 3).
Overall sustained response to IFN six months post
treatment (SR-6) was 35%. SR-6 rates to IFN therapy varied
greatly between the different HBV genotypes (table 3).
Despite administration of slightly lower cumulative IFN
doses compared with other HBV genotypes, patients with
HBV genotype A showed the best end of treatment response
(ETR) and SR-6 rates. Among patients with HBV genotype B
(n=6), HBV genotype C (n=11), and HBV genotype E
(n=3), SR was 0%, 18% and 0%, respectively. ETR was 50%,
46%, and 0% among patients with HBV genotypes B, C, and
E. The only patient with HBV genotype G achieved a
sustained IFN response.
A significantly better SR-6 rate was observed in patients
with HBV genotype A (49%) compared with patients with
HBV genotype D (26%; p,0.005). This was also the case for
the subgroups of HBeAg positive (46 v 24%; p,0.03) and
negative (59 v 29%; p,0.05) patients with HBV genotype A or
D. The higher SR-6 in patients with HBV genotype A
compared with HBV genotype D was the result of both a
higher primary IFN response rate and a lower relapse rate in
HBV genotype A hepatitis patients. In HBeAg positive
hepatitis, relapse rates were comparably low in both HBV
genotypes (13% for HBV genotype A v 18% for HBV genotype
D; NS) but ETR differed significantly (53% for HBV genotype
A v 29% for HBV genotype D; p,0.02). HBeAg negative
hepatitis was characterised by higher and more divergent
relapse rates between HBV genotype A and D (29% v 58%;
p,0.09) and by higher but less different ETR (82% v 68%;
NS) compared with HBeAg positive hepatitis B.
Data on sustained response 12 months post treatment (SR-
12) were available in 142 patients with HBV genotype A or D.
hepatitis B according to hepatitis B virus (HBV) genotype
Response rates (SR-6) to interferon alfa (IFN) therapy in patients with chronic
Genotype AGenotype Dp Value
Cumulative IFN dose (MU)
Treatment duration (months)
Relapse (% of ETR)
Cumulative IFN dose (MU)
Treatment duration (months)
Relapse (% of ETR)
Cumulative IFN dose (MU)
Treatment duration (months)
Relapse (% of ETR)
SR-6, sustained response six months post treatment; ETR, end of treatment response; HBeAg, hepatitis B e antigen.
response (SR-6) among patients with hepatitis B virus (HBV) genotype A and D
Univariate logistic regression analysis of factors associated with sustained
(n=89) p ValueOR 95% CI
Genotype A (%)
Genotype D (%)
HBeAg positive (%)
Sex, male (%)
SR-6, sustained response six months post treatment; HBeAg, hepatitis B e antigen; ALT, alanine aminotransferase;
ULN, upper limit of normal; OR, odds ratio; 95% CI, 95% confidence interval.
Parameters were categorised for univariate analysis. ALT, (26ULN versus .26ULN; HBV-DNA level, (200
versus .200 pg/ml.
HBV genotype and IFN response1011
SR-12 was 47% for HBV genotype A compared with 23% in
HBV genotype D (p,0.002). Among HBeAg positive patients,
SR-12 was 44% compared with 24% (p,0.04) and among
HBeAg negative patients SR-12 was 59% versus 21%
(p,0.01) for HBV genotype A and HBV genotype D,
Univariate regression analysis revealed no effect of sex,
cirrhosis, HBeAg status, or HBV-DNA titre on response rate to
IFN (table 4). HBV genotype A and ALT levels were relevant
predictive parameters of IFN response and were further
included in the multivariate analysis. SR-6 was 45% among
patients with ALT levels .26upper limit of normal (ULN)
but only 20% in patients with ALT levels (26ULN
(p,0.001). SR-6 for patients with HBV genotype A and
ALT.2 ULN was 56% compared with 26% for ALT (26ULN
(p,0.03), and 31% and 14%, respectively, in patients with
HBV genotype D.
Multivariate logistic regression analysis identified HBV
genotype A (odds ratio (OR) 2.7 (95% confidence interval
(CI) 1.3–5.8); p,0.009) and elevated pretreatment ALT level
((26ULN v .26ULN; OR 3.0 (95% CI 1.2–7.5); p,0.02) as
independent parameters for sustained response. Low pre-
treatment HBV-DNA level ((200 pg/ml v .200 pg/ml), sex,
or cirrhosis were not found to be independent factors
associated with sustained response (table 4).
In the present study, we demonstrated that in chronic
hepatitis B, response to standard IFN was HBV genotype
dependent. HBV genotype A was associated with a signifi-
cantly higher SR to IFN than HBV genotype D and showed
better SR rates than HBV genotype C, B, or E. Furthermore,
our findings indicate that HBeAg negativity per se is not a
negative predictor of IFN response. The reported low SR rates
in HBeAg negative patients compared with HBeAg positive
patients seem to be the result of a higher prevalence of low
IFN responding HBV genotype D patients in HBeAg negative
hepatitis B. We focused on IFN treatment as IFN is still
recommended as the firstline treatment for chronic hepatitis
B in most cases.5
In chronic hepatitis C, viral genotypes have been identified
as major determinants of IFN or IFN/ribavirin responsive-
ness, and treatment regimens are adapted to HCV genotype.10
Unlike HCV genotypes, the role of HBV genotypes on the
response to IFN treatment is not as clear. In a study from
China involving 73 HBeAg positive patients, HBV genotype B
was associated with a better SR to IFN or a combination of
IFN with prednisone priming than HBV genotype C (39% v
17%; p,0.03).19A study from Taiwan comprising 58 HBeAg
positive patients also demonstrated a better SR rate in HBV
genotype B compared with HBV genotype C infection (41% v
15%; p,0.05).20A small study, with only HBeAg negative
patients treated with highly variable IFN doses of 361 MU to
368 MU weekly, suggested a better SR rate for HBV
infections with HBV genotype A compared with HBV
genotype D or E.21In the present study we investigated IFN
response in 144 patients with HBV genotype A or D, among
them 99 HBeAg positive and 45 HBeAg negative patients.
Twenty one patients with HBV genotype C, B, E, or G were
not included in the analysis of IFN response due to
insufficient statistical power. The overall IFN response rate
of 35% in the present study was in line with that of a larger
meta-analysis.22The study demonstrates that IFN response in
chronic hepatitis B is HBV genotype dependent. HBV
genotype A was found to be an independent positive
predictor whereas HBV genotype D was an independent
negative predictor of IFN response. Although HBV genotypes
correlated with viral dynamics and mutational patterns
during treatment with nucleoside analogues,23differences
in response rates have not been observed to date.24 25One
limitation of the present study, related to its retrospective
character, was that patients did not receive a standardised
IFN dose. However, cumulative IFN dose and treatment
duration did not differ significantly among patients with
HBV genotypes A and D. Prospective studies will have to
further address the role of HBV genotypes for IFN response.
The genotype dependent response to IFN may explain the
highly divergent sustained response rates to IFN therapy
among different geographic regions as a result of the
geographic variability in HBV genotype prevalence. This
holds true for HBeAg negative hepatitis B in particular. In
the present study, 89% of patients of Mediterranean origin
carried HBV genotype D and 61% of HBeAg negative patients
were infected with HBV genotype D. In contrast, HBV
genotype A was the predominant genotype (78%) in patients
of German origin and only 37% of HBeAg negative patients
were carriers of HBV genotype A. Low sustained response
rates of even less than 10% have been reported for HBeAg
negative patients; most of the studies in these patients were
performed in the Mediterranean area.26–29In contrast, we did
not find a significant difference in SR between HBeAg
positive and HBeAg negative patients (37% v 40%; NS).
Higher relapse rates were observed in HBeAg negative
hepatitis B confirming the results of previous studies. Even
after stratification for HBV genotype A or D, no differences in
SR were found between HBeAg negative and HBeAg positive
patients (table 3). Thus in view of the present data, the low
response rate for HBeAg negative patients observed so far in
some geographic areas appears to be the result of a high
prevalence of a low IFN responder HBV genotype (for
example, D and E) than that of HBeAg status itself.
Because of the small patient numbers it is difficult to draw
conclusions regarding IFN response for HBV genotypes B, C,
E, and G. The response rate for HBV genotype C reported in
the present investigation is consistent with that reported in
studies from Taiwan and China.19 20The unresponsiveness of
HBV genotype B patients may be due to a high proportion of
patients with normal ALT levels, as reflected by the low mean
ALT values (table 2). The primary non-response of patients
carrying HBV genotype E (all from Africa) should give rise to
further investigations. It has recently been demonstrated in
hepatitis C that Black Americans have a significantly lower
HCV genotype independent response to IFN/ribavirin combi-
nation treatment, indicating that ethnic factors may play a
role in IFN responsiveness.30
Current interferon treatment of chronic hepatitis B has
limited efficacy. Treatment regimens with nucleos(t)ide
analogues have not proved superior to IFN treatment
although nucleos(t)ide analogue therapy has negligible side
effects.31–34Based on the present data it would be useful to
evaluate HBV genotype adapted IFN treatment regimens as
they may provide clues to further improve IFN response rates
in chronic hepatitis B.
The study was supported by a grant from the Forschungskommission
der Heinrich-Heine-Universita ¨t Du ¨sseldorf
A Erhardt, D Blondin, K Hauck, A Sagir, T Kohnle, T Heintges,
D Ha ¨ussinger, Klinik fu ¨r Gastroenterologie, Hepatologie und
Infektiologie, Heinrich-Heine-Universita ¨t Du ¨sseldorf, Du ¨sseldorf,
Conflict of interest: None declared.
1 Lai CL, Ratziu V, Yuen MF, et al. Viral hepatitis B. Lancet 2003;362:2089–94.
2 Lee WM. Hepatitis B virus infection. N Engl J Med 1997;337:1733–45.
1012 Erhardt, Blondin, Hauck, et al
3 Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the Download full-text
management of chronic hepatitis B virus infection in the United States. Clin
Gastroenterol Hepatol 2004;2:87–106.
4 Niederau C, Heintges T, Lange S, et al. Long-term follow-up of HBeAg-positive
patients treated with interferon alfa for chronic hepatitis B. N Engl J Med
5 EASL International Consensus Conference on Hepatitis B. 13–14 September,
2002: Geneva, Switzerland. Consensus statement (short version). J Hepatol
6 Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000—
summary of a workshop. Gastroenterology 2001;120:1828–53.
7 Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical
consequences. N Engl J Med 2004;350:1118–29.
8 Erhardt A, Reineke U, Blondin D, et al. Mutations of the core promoter and
response to interferon treatment in chronic replicative hepatitis B. Hepatology
9 Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b
plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus
placebo for 48 weeks for treatment of chronic infection with hepatitis C virus.
International Hepatitis Interventional Therapy Group (IHIT). Lancet
10 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin
for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–82.
11 Arauz-Ruiz P, Norder H, Robertson BH, et al. Genotype H: a new Amerindian
genotype of hepatitis B virus revealed in Central America. J Gen Virol
12 Kidd-Ljunggren K, Miyakawa Y, Kidd AH. Genetic variability in hepatitis B
viruses. J Gen Virol 2002;83:1267–80.
13 Norder H, Courouce AM, Coursaget P, et al. Genetic diversity of hepatitis B
virus strains derived worldwide: genotypes, subgenotypes, and HBsAg
subtypes. Intervirology 2004;47:289–309.
14 Okamoto H, Tsuda F, Sakugawa H, et al. Typing hepatitis B virus by
homology in nucleotide sequence: comparison of surface antigen subtypes.
J Gen Virol 1988;69:2575–83.
15 Miyakawa Y, Okamoto H, Mayumi M. The molecular basis of hepatitis B e
antigen (HBeAg)-negative infections. J Viral Hepat 1997;4:1–8.
16 Bartholomeusz A, Schaefer S. Hepatitis B virus genotypes: comparison of
genotyping methods. Rev Med Virol 2004;14:3–16.
17 Li JS, Tong SP, Wen YM, et al. Hepatitis B virus genotype A rarely circulates as
an HBe-minus mutant: possible contribution of a single nucleotide in the
precore region. J Virol 1993;67:5402–10.
18 Desmet VJ, Gerber M, Hoofnagle JH, et al. Classification of chronic hepatitis:
diagnosis, grading and staging. Hepatology 1994;19:1513–20.
19 Wai CT, Chu CJ, Hussain M, et al. HBV genotype B is associated with better
response to interferon therapy in HBeAg(+) chronic hepatitis than genotype C.
20 Kao JH, Wu NH, Chen PJ, et al. Hepatitis B genotypes and the response to
interferon therapy. J Hepatol 2000;33:998–1002.
21 Zhang X, Zoulim F, Habersetzer F, et al. Analysis of hepatitis B virus
genotypes and pre-core region variability during interferon treatment of HBe
antigen negative chronic hepatitis B. J Med Virol 1996;48:8–16.
22 Wong DK, Cheung AM, O’Rourke K, et al. Effect of alpha-interferon treatment
in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-
analysis. Ann Intern Med 1993;119:312–23.
23 Zo ¨llner B, Petersen J, Puchhammer-Stockl E, et al. Viral features of lamivudine
resistant hepatitis B genotypes A and D. Hepatology 2004;39:42–50.
24 Westland C, Delaney WT, Yang H, et al. Hepatitis B virus genotypes and
virologic response in 694 patients in phase III studies of adefovir dipivoxil1.
25 Yuen MF, Tanaka Y, Lai CL. Hepatitis B genotypes in chronic hepatitis B and
lamivudine therapy. Intervirology 2003;46:373–6.
26 Brunetto MR, Oliveri F, Colombatto P, et al. Treatment of chronic anti-HBe-
positive hepatitis B with interferon-alpha. J Hepatol 1995;22:42–4.
27 Brunetto MR, Giarin M, Saracco G, et al. Hepatitis B virus unable to secrete e
antigen and response to interferon in chronic hepatitis B. Gastroenterology
28 Pastore G, Santantonio T, Milella M, et al. Anti-HBe-positive chronic hepatitis
B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid
interferon. J Hepatol 1992;14:221–5.
29 Hadziyannis S, Bramou T, Makris A, et al. Interferon alfa-2b treatment of
HBeAg negative/serum HBV DNA positive chronic active hepatitis type B.
J Hepatol 1990;11(suppl 1):S133–6.
30 Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for
the treatment of chronic hepatitis C in blacks and non-Hispanic whites.
N Engl J Med 2004;350:2265–71.
31 Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Adefovir dipivoxil for
the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med
32 Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of
hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med
33 Lai CL, Chien RN, Leung NW, et al. A one-year trial of lamivudine for chronic
hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med
34 Dienstag JL, Schiff ER, Wright TL, et al. Lamivudine as initial treatment for
chronic hepatitis B in the United States. N Engl J Med 1999;341:1256–63.
EDITOR’S QUIZ: GI SNAPSHOT ..................................................................
From question on page 1002
The clue to the diagnosis in this case is the inverted orientation between the superior
mesenteric artery (SMA) and the superior mesenteric vein (SMV). Due to the normal 270˚
counter clockwise rotation of the midgut during embryological development, the SMA is
normally positioned left of the SMV. Here the ultrasound scan demonstrated the SMA to the
right of the SMV. In addition, a dilated small bowel was present. These features are
characteristic of an intestinal malrotation (non-rotation) of the midgut. Endoscopy followed
by upper gastrointestinal contrast series revealed duodenal obstruction. A contrast enhanced
computed tomography scan showed complete malrotation with an obstruction in the distal
duodenum. This was confirmed at laparatomy and a gastrojejunostomy and resolving of
adhesions were performed. A gastrointestinal contrast series four days postoperatively
demonstrated correct contrast passage into the jejunum. After oral refeeding, the patient’s
postprandial complaints were improved.
Intestinal malrotation occurs in approximately 1 in 1000 live births. Symptomatic
malrotation is estimated to occur in 1/6000 live births, with an increased risk for volvulus,
twisting, small bowel obstruction, or other anomalies. Approximately 90% of patients
present within the first months of life. It has to be considered an uncommon diagnosis in
adult patients presenting with signs and symptoms of acute or chronic small bowel
HBV genotype and IFN response1013