50541

Sex- and age-specific carriers of hepatitis B and C viruses in Japan

estimated by the prevalence in the 3,485,648 first-time blood donors
during 1995-2000
Tanaka J, Kumagai J, Katayama K, Komiya Y, Mizui M, Yamanaka R,
Suzuki K, Miyakawa Y, Yoshizawa H
Intervirology
47(1):32-40, 2004
Objective: Carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Japan were
estimated on a national basis. Methods: Sera from the first-time blood donors aged 1664 years in eight jurisdictions of the Japanese Red Cross Blood Center during 1995-2000
were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV).
Viremia with HCV was estimated to be present in 70% of donors with anti-HCV. Results:
HBsAg was detected in 22,018 of 3,485,648 (0.63%) blood donors including 12,990 of
1,780,149 (0.73%) men and 9,028 of 1,705,499 (0.53%) women, and anti-HCV in 17,010
(0.49%) including 8,504 (0.48%) men and 8,506 (0.50%) women. Multiplying the carrier
rate by the population registered in the Census 2000, the total HBV carriers aged 15-65
years were estimated at 967,753 (95% confidence interval 806,760-1,128,745), of
whom 571,210 (479,267-663,152) were men and 396,543 (327,494-465,593) were
women. Likewise, the total HCV carriers were estimated at 884,954 (95% confidence
interval 725,082-1,044,826), of whom 464,363 (377,927-550,799) were men and
420,591 (347,156-494,027) were women. Conclusion: Estimated numbers of HBV and
HCV carriers would help plan to prevent the development of hepatocellular carcinoma in
Japan.

50542
Impact of occult hepatitis B virus infection in HIV patients naive for
antiretroviral therapy
Filippini P, Coppola N, Pisapia R, Scolastico C, Marrocco C, Zaccariello
A, Nacca C, Sagnelli C, De Stefano G, Ferraro T, De Stefano C,
Sagnelli E
AIDS
20(9):1253-60, 2006
OBJECTIVE: To study the impact of occult hepatitis B virus (HBV) infection in 115
consecutive anti-HIV-positive, hepatitis B surface antigen-negative patients, naive for
antiretroviral treatment. METHODS: Of these 115, 86 patients were followed for at least
6 months (range 6-36) with serial determinations of HIV RNA and HBV DNA by
polymerase chain reaction and other laboratory tests. RESULTS: Of the 86 patients
having a follow-up, plasma HBV DNA was detected in 17 (19.8%), 13 on admission and
four during follow-up. HBV DNA was more frequently found in patients with isolated antihepatitis B core (HBc; 35.5% of 31 cases) than in those lacking anti-HBc and antihepatitis B surface (8.8% of 41, P < 0.005), or showing both (21.4% of 14). Twenty-eight
patients (32.5%) experienced a hepatic flare during the follow-up; this event was more
frequent in the 17 HBV-DNA-positive patients than in the 69 negative (64.7% versus
24.6%, P < 0.005). Of the 13 HBV-DNA-positive patients on admission, 11 receiving
HAART containing lamivudine became HBV-DNA negative, but two of these again
became positive and experienced a hepatic flare during treatment and two both during
and after lamivudine treatment. A hepatic flare also occurred under lamivudine
treatment in two of the four patients in whom HBV DNA became detectable during
follow-up. The role of immune reconstitution inflammatory syndrome and HAART in
inducing a hepatic flare was found to be marginal in 49 patients with no HBV or hepatitis
C virus marker. CONCLUSION: The study suggests that HBV occult infection, relatively

frequent in anti-HIV-positive patients, is associated with hepatic flares.

50543
HIV therapy, hepatitis C virus infection, antibiotics and obesity, a
mitochondria killer mix? [letter]
Cote H C, Brumme Z L, Chan J W, Guillemi S, Montaner J S, Harrigan P R
AIDS
20(9):1343-5, 2006
50544
Genetic polymorphisms of interleukin-1-beta in association with
sustained response to anti-viral treatment in chronic hepatitis B in
Chinese
Chan H L, Tse A M, Zhang M D, Wong V W, Chim A M, Hui A Y, Sung J J
Aliment Pharmacol Ther
23(12):1703-11, 2006
BACKGROUND: Interleukin-1beta is a pro-inflammatory cytokine that may influence
host defence against viral infection. AIM: To investigate the impact of interleukin-1beta
gene polymorphism on the response to anti-viral treatment. METHOD: Hepatitis B e
antigen-positive chronic hepatitis B patients who have completed a randomized study of
peginterferon alpha-2b and lamivudine combination vs. lamivudine monotherapy were
included. Sustained responders were patients who had persistent hepatitis B e antigen
loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any
time up to week 76 post-treatment. Polymorphisms at interleukin-1beta-511, -31 and
-3954 and interleukin-1 receptor antagonist (RN) were studied. RESULTS: Eighty-eight
patients were studied and 18 (20%) patients developed sustained response. Near
complete linkage disequilibrium was observed between interleukin-1beta-511 and -31
loci. After adjustment for the potential confounding effects of treatment allocation,
hepatitis B virus genotype, pre-treatment alanine aminotransferase and hepatitis B virus
DNA levels, genotype C/T at interleukin-1beta-511 was found to be associated with
higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1,
96.9, P = 0.040). The proportion of sustained responders tend to be higher among
patients with allele T at interleukin-1beta-511 (83%) than those without (70%) (P =
0.058). CONCLUSION: High interleukin-1beta production genotype at position -511 has
a favourable response to anti-viral treatments.

50545
Lamivudine response of IgM anti-HBc chronic hepatitis B patients [letter]
Gomez-Dominguez E, Garcia-Buey L, Gisbert J P, Moreno-Otero R
Aliment Pharmacol Ther
23(12):1757-8, 2006
50546
Lamivudine response of IgM anti-HBc chronic hepatitis B - Reply [letter]
Chen J J, Tsai S L
Aliment Pharmacol Ther
23(12):1758-60, 2006

50547
Concomitant interferon-alpha therapy and tumor necrosis factor alpha
inhibition for rheumatoid arthritis and hepatitis C
Niewold T B, Gibofsky A
Arthritis Rheum
54(7):2335-7, 2006
2

50548
Anti-C1q antibodies in hepatitis C virus infection
Saadoun D, Sadallah S, Trendelenburg M, Limal N, Sene D, Piette J C,
Schifferli J A, Cacoub P
Clin Exp Immunol
145(2):308-12, 2006
Autoantibodies against C1q have been described in many immune-complex diseases
including hypocomplementaemic urticarial vasculitis and systemic lupus erythematosus
(SLE). No study has focused on the role of anti-C1q antibodies in hepatitis C virus (HCV)
infection. The aim of this study was (i) to evaluate the prevalence of anti-C1q antibodies
in HCV infection; and (ii) to analyse the association of anti-C1q antibodies with clinical
and biological features of HCV?mixed cryoglobulinaemia (MC) vasculitis. We searched
for anti-C1q antibodies using an enzyme-linked immunosorbent assay (ELISA) test in
111 HCV patients (75 had cryoglobulin and 23 systemic vasculitis), 60 SLE patients and
109 blood donors. Anti-C1q antibodies were detected in 26% of HCV patients compared
to 10% of healthy donors (P < 0.01), and 38% in patients with SLE. Although there was a
higher prevalence of anti-C1q antibodies among HCV patients with type III cryoglobulin
(50%, P < 0.01), the overall prevalence of anti-C1q antibodies was similar in HCV
patients being cryoglobulin-positive or cryoglobulin-negative (26% versus 25%, P =
0.98). A significant association was found between anti-C1q antibodies and low C4
fraction of complement (P < 0.05). No association was found between anti-C1q
antibodies and HCV genotype, severity of liver disease or with specific clinical signs of
HCV-MC vasculitis. This study shows an increased prevalence of anti-C1q antibodies in
HCV-infected patients. Anti-C1q antibodies were associated with low C4 levels. No
association was found between anti-C1q antibodies and HCV-MC vasculitis, nor between
anti-C1q antibodies and cryoglobulinaemia.

50549
Hepatic steatosis is associated with fibrosis, nucleoside analogue use,
and hepatitis C virus genotype 3 infection in HIV-seropositive patients
McGovern B H, Ditelberg J S, Taylor L E, Gandhi R T, Christopoulos K A,
Chapman S, Schwartzapfel B, Rindler E, Fiorino A M, Zaman M T, Sax
P E, Graeme-Cook F, Hibberd P L
Clin Infect Dis
43(3):365-72, 2006
BACKGROUND: We conducted a study to determine the prevalence and factors
associated with hepatic steatosis in human immunodeficiency virus (HIV)-seropositive
patients with hepatitis C and to investigate whether steatosis is associated with liver
fibrosis. METHODS: Retrospective chart reviews were conducted in 4 hospitals that
serve community-based and incarcerated HIV-infected patients who had undergone a
liver biopsy for evaluation of hepatitis C virus (HCV) infection during the period of 20002003. Demographic characteristics and medication and laboratory data were collected
from the time of the biopsy. A pathologist blinded to all clinical data evaluated the
specimens. The primary outcome was presence or absence of steatosis. RESULTS: Of
260 HIV-HCV-coinfected patients, 183 met inclusion criteria and had a biopsy specimen
adequate for review. Steatosis was present in 69% of patients (graded as minimal in
31%, mild in 27%, moderate in 18%, and severe in 1%). Factors associated with
steatosis included use of dideoxynucleoside analogues, such as didanosine and
stavudine (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.55-13.82). There was a
trend toward presence of steatosis and use of other nucleoside analogues or infection
with HCV genotype 3 (OR, 2.65 [95% CI, 0.95-7.41] and 3.38 [95% CI, 0.86-13.28],
respectively). The presence of steatosis was associated with fibrosis (OR, 1.37; 95% CI,
1.03-1.81). CONCLUSIONS: In this multiracial population of HIV-HCV-coinfected
patients, steatosis was prevalent and was associated with severity of liver fibrosis. Use
of nucleoside analogues (particularly didanosine and stavudine) and HCV genotype 3
infection were associated with hepatic steatosis. The development of steatosis is

multifactorial in nature and may play a contributory role in the progression of liver
disease in HIV-infected patients.

50550
Lymphadenopathy resulting from acute hepatitis C infection mimicking
metastatic breast carcinoma on FDG PET/CT
Jacene H A, Stearns V, Wahl R L
Clin Nucl Med
31(7):379-81, 2006
We report a case documenting fluorodeoxyglucose (FDG) accumulation in upper
abdominal lymph nodes resulting from acute hepatitis C infection. A 42-year-old AfricanAmerican female with a history of metastatic breast carcinoma was found to have
hypermetabolic porta hepatic, peripancreatic, and paraaortic lymphadenopathy and
hypermetabolism in the spleen on a surveillance FDG positron emission
tomography/computed tomography (PET/CT) scan. Concurrently, she was diagnosed
with acute hepatitis C infection. Antiviral therapy was not recommended secondary to
the low level of detectable virus at the time of diagnosis. Her breast cancer therapy
regimen was continued unaltered. FDG PET/CT scan was repeated 2 months later as a
result of concern that the hypermetabolic lymph nodes represented metastatic disease;
however, the scan revealed complete resolution of the previously abnormal findings.
The resolution of the lymphadenopathy and the patient's clinical course led to the
conclusion that the most likely explanation for the FDG PET/CT findings was
inflammation secondary to acute hepatitis C infection and not metastatic breast
carcinoma. Inflammatory and infectious processes accumulate FDG, occasionally
resulting in false-positives for malignancy. Infected macrophages in the lymph nodes
draining the liver in this case and stimulation of a cellular immune response by the
hepatitis C virus, with resultant cytokine production by cytotoxic and T-helper cells, offer
possible explanations for the findings seen on FDG PET/CT in this case. This case
highlights the importance of clinical history and laboratory correlation for the proper
interpretation of FDG PET scans.

50551
Successful treatment with novel triple drug combination consisting of
interferon-gamma, interferon alfacon-1, and ribavirin in a nonresponder
HCV patient to pegylated interferon therapy
Balan V, Rosati M J, Anderson M H, Rakela J
Dig Dis Sci
51(5):956-9, 2006
Despite major advances in therapy of hepatitis C over the past decade, nearly half of
the patients treated with the currently available regimens do not clear the virus.
Therefore, there is a large unmet need for more effective therapy for patients who have
failed pegylated interferon plus ribavirin therapy. We describe a case of a HCV genotype
1b patient who had failed previous combination therapies of interferon plus ribavirin and
pegylated interferon plus ribavirin and was subsequently successfully treated with a
novel triple drug combination consisting of interferon-gamma plus interferon alfacon
plus ribavirin with the outcome of a sustained virologic response. This triple drug
therapy combination could be an option for patients who have failed therapies with
currently available pegylated interferons plus ribavirin. Prospective randomized studies
are required to evaluate the effectiveness and tolerability of this regimen in this patient
population.

50552
4

Anti-HBs-positive liver failure due to hepatitis B virus reactivation

induced by rituximab
Sera T, Hiasa Y, Michitaka K, Konishi I, Matsuura K, Tokumoto Y,
Matsuura B, Kajiwara T, Masumoto T, Horiike N, Onji M
Intern Med
45(11):721-4, 2006
A 59-year-old man developed acute hepatitis with reactivated hepatitis B virus (HBV)
following administration of rituximab (anti-CD20 monoclonal antibody). The patient was
diagnosed with malignant lymphoma in 1998, and virus marker testing indicated HBV
surface antigen (HBsAg)-negative and anti-HBs antibody (anti-HBs)-positive results
when chemotherapy including rituximab was started. Levels of aminotransferases were
elevated, and HBsAg results turned positive. Despite therapy for late-onset hepatic
failure, the patient died. Rituximab appears likely to have induced HBV reactivation in
this case. Anti-viral agents should be administered for both HBsAg-positive and antiHBs-positive patients who are scheduled to receive rituximab.

50553
Seroprevalence of hepatitis C in patients with type 2 diabetes mellitus
and non-diabetic on haemodialysis
Ocak S, Duran N, Kaya H, Emir I
Int J Clin Pract
60(6):670-4, 2006
Type 2 diabetes mellitus (DM) has emerged as the commonest cause of end-stage renal
disease. Haemodialysis (HD) treatment constitutes a high-risk environment for the
transmission of hepatitis C virus (HCV). The aim of this study was to establish a potential
relationship between type 2 DM and HCV infection in HD patients. Of the 267 HD
patients, 67 (25.1%) had type 2 DM and 200 (74.9%) were with diverse aetiology for
end-stage renal disease. The serum markers of HCV infection were tested by a secondgeneration enzyme-linked immunosorbent assay test for antibodies and by qualitative
reverse-transcription polymerase chain reaction technique for viral RNA. The overall
prevalence of anti-HCV antibodies and HCV RNA was found to be 12.7% (34/267) and
10.1% (27/267), respectively. Patients with type 2 DM were found to have a higher HCV
prevalence compared with non-diabetic patients [20.8% (14/67) vs. 10% (20/200)] (p <
0.05). The mean period on dialysis of anti-HCV-positive patients with type 2 DM was
shorter than that observed for anti-HCV-positive non-diabetic patients (43.9 +/- 9.8
months vs. 59.7 +/- 28.4 months) (p < 0.05). This study has shown that although the
period on dialysis of diabetic patients are shorter than non-diabetic patients, the
prevalence of HCV in HD patients with type 2 DM is higher than that detected in nondiabetic HD patients.

50554
Steatosis in chronic hepatitis C: relationship to the virus and host risk
factors
Matos C A L, Perez R M, Pacheco M S, Figueiredo-Mendes C G, LopesNeto E, Oliveira E B, Lanzoni V P, Silva A E B, Ferraz M L G
J Gastroenterol Hepatol
21(8):1236-9, 2006
5

Background: Steatosis occurs frequently in hepatitis C. However, the mechanisms

leading to this lesion are still unknown, and the role of steatosis in the progression of the
disease remains controversial. The aim of the present paper was to determine the
prevalence of steatosis in hepatitis C and its association with hepatitis C virus (HCV)
genotype, viral load and the presence of risk factors for steatosis, and to analyze the
association between steatosis and the intensity of liver disease. Methods: Patients
infected with HCV who underwent liver biopsy were included. Patients coinfected with
hepatitis B virus and/or human immunodeficiency virus and those previously treated for
hepatitis C were excluded. The following risk factors for steatosis were investigated:
obesity (body mass index [BMI] > 25 kg/m(2)), diabetes mellitus, hyperlipidemia,
alcoholism, and use of potential steatosis-inducing drugs. Histological analysis
evaluated the presence of steatosis, the degree of periportal activity and staging.
Patients with and without steatosis were compared regarding demographic,
epidemiological, laboratory and histological characteristics. Logistic regression analysis
was applied to identify variables that were independently associated with the presence
of steatosis. Results: Ninety patients (55 men, 35 women) with a mean age of 45 +/- 13
years were included. The prevalence of steatosis was 67%. Variables that remained
independently associated with steatosis were age, female gender, obesity and genotype
3. Conclusions: The prevalence of steatosis in hepatitis C was high. Risk factors usually
related to steatosis such as age, female gender and obesity, as well as genotype 3, were
independently associated with the presence of steatosis. Steatosis was not
independently associated with the intensity of histological liver disease.

50555
Metabolic factors involved in the therapeutic response of patients with
hepatitis C virus-related chronic hepatitis
Tarantino G, Conca P, Sorrentino P, Ariello M
J Gastroenterol Hepatol
21(8):1266-8, 2006
Background: The purpose of the present paper was to investigate the factors possibly
involved in the failure of pegylated interferon (Peg IFN) plus ribavirin treatment at
standard dosage in hepatitis C virus (HCV) 1b patients, with chronic hepatitis. Methods:
A fully screened population of 40 virological non-responders (NR) to combined antiviral
therapy was selected and matched, 1:1, with a similar cohort of end-therapy virological
responders (R). Results: Waist circumference, glucose metabolic impairment, body
mass index, non-genetic iron overload, steatosis and fibrosis severity and, finally,
arterial hypertension were statistically more frequent in the NR group on Peg IFN plus
ribavirin. Increased waist circumference was the strong independent predictor of
therapeutical failure. Interestingly, the concomitant presence of cofactors was more
significantly represented in NR, whereas in the R cohort this association was found in a
few cases only. Conclusion: Insulin-resistance syndrome could contribute to nonresponse in treated chronic HCV patients, suggesting the presence of dysmetabolic
factors that frequently cluster in a critical combination.

50556
417-2alpha-Tocopherol and ascorbic acid attenuates the ribavirin-induced
decrease of eicosapentaenoic acid in erythrocyte membrane in chronic
hepatitis C patients
Hino K, Murakami Y, Nagai A, Kitase A, Hara Y, Furutani T, Ren F,
Yamaguchi Y, Yutoku K, Yamashita S, Okuda M, Okita M, Okita K
J Gastroenterol Hepatol
21(8):1269-75, 2006
6

Background: Oxidative damage of the erythrocyte membrane plays an important role

in ribavirin-induced anemia. The purpose of the present paper was to assess whether
supplementation of alpha-tocopherol and ascorbic acid (vitamins) causes changes in the
erythrocyte membrane fatty acid composition during interferon and ribavirin
combination therapy for chronic hepatitis C patients. Methods: Fatty acid compositions
in erythrocyte membrane phospholipids were determined by gas chromatography at 0,
2, 4, 8 weeks, and at the end of combination therapy (26 weeks) for interferon with
ribavirin in 32 patients with chronic hepatitis C who were randomized to receive
vitamins or not (controls). Results: Good compliance with orally administered vitamins
and ribavirin were confirmed by their concentrations in erythrocytes or plasma. The
hemoglobin level was negatively correlated with the ribavirin concentration at 8 weeks
(r = 0.59, P = 0.01) after initiation of therapy in controls, but not in the vitamin group.
Among the 26 kinds of fatty acids analyzed, only eicosapentaenoic acid (EPA)
significantly decreased at 8 weeks after initiation of therapy (P = 0.03) and at the end of
therapy (P = 0.004) in controls. Vitamins did not inhibit ribavirin-induced anemia, but
attenuated the decrease of EPA in erythrocytes. The EPA level was negatively correlated
with the drop in hemoglobin levels at 8 weeks after initiation of therapy in controls (r =
0.58, P = 0.015), but not in the vitamin group. Conclusions: Supplementation of alphatocopherol and ascorbic acid attenuates the ribavirin-induced decrease of EPA in
erythrocyte membrane phospholipids in chronic hepatitis C patients.

50557
Early intrahepatic CD8 responses in HBV pathogenesis: a new piece of
the puzzle [editorial]
Missale G
J Hepatol
45(2):169-71, 2006
50558
Antiviral effect of peginterferon alfa-2b and alfa-2a compared [editorial]
Jansen P L M, Reesink H W
J Hepatol
45(2):172-3, 2006

50559
Analysis of intrahepatic HBV-specific cytotoxic T-cells during and after
acute HBV infection in humans
Sprengers D, Molen R G, Kusters J G, Man R A, Niesters H M, Schalm S
W, Janssen H L
J Hepatol
45(2):182-9, 2006
BACKGROUND/AIMS: Characteristics of the intrahepatic virus-specific T-cell response
in patients with acute hepatitis B virus (HBV) infection have not been studied due to the

risk of complications associated with standard liver biopsies. In this study we aimed to
characterize the virus-specific CD8+T-cell response in the liver of patients with acute
HBV infection using the fine-needle aspiration-biopsy (FNAB). METHODS: In HLA-A2
positive patients with acute HBV infection a FNAB was performed at first presentation, at
the time of HBsAg-seroconversion and 3 months after HBsAg-seroconversion. HLA-A2
tetramers were used to identify HBV-specific CD8+T-cells in FNAB-cytology and
peripheral blood (PB). RESULTS: At first presentation there was a correlation between
the frequency of intrahepatic CD8+T-cells and the degree of liver damage. At all time
points there was sequestering of HBV-specific CD8+T-cells in the liver, and the
percentage of intrahepatic HLA-DR expressing HBV-specific CD8+T-cells was higher than
in PB. Three months after HBsAg-seroconversion the frequency of intrahepatic HBVspecific CD8+T-cells remained high. CONCLUSIONS: HBV-specific CD8+T-cells are
compartmentalized in the liver during acute HBV infection. Their presence in the liver
may suggest a role in the resolution of the infection. Intrahepatic HBV-specific CD8+T
cells remain detectable at high frequencies after HBsAg-seroconversion.

50560
Enhanced ability of peripheral invariant natural killer T cells to produce
IL-13 in chronic hepatitis C virus infection
Inoue M, Kanto T, Miyatake H, Itose I, Miyazaki M, Yakushijin T,
Sakakibara M, Kuzushita N, Hiramatsu N, Takehara T, Kasahara A,
Hayashi N
J Hepatol
45(2):190-6, 2006
BACKGROUND/AIMS: Human invariant natural killer T (iNKT) cells express a TCR
Valpha24-JalphaQ paired with Vbeta11 and are activated by a surrogate ligand, alphagalactosylceramide (alphaGalCer). The iNKT cells are involved in the regulation of antiviral immune responses, however, little is known about their roles in hepatitis C virus
(HCV) infection. METHODS: We compared the frequency of peripheral iNKT cells and
their cytokine producing capacity reactive to alphaGalCer between chronically HCVinfected patients and healthy subjects. Cytokine production of freshly isolated iNKT cells
were analyzed by ELISPOT. Activated iNKT cells were obtained by culture with
alphaGalCer-loaded dendritic cells (DCs) and re-stimulated with them for the
measurement of cytokine production. RESULTS: The frequencies of iNKT cells were not
different between HCV-infected patients and healthy subjects. The number of fresh IFNgamma-producing iNKT cells reactive to alphaGalCer was not different between the
patients and controls, whereas fresh iNKT cells produced negligible amounts of Th2
cytokines regardless of HCV infection. In response to alphaGalCer, expanded iNKT cells
from the patients secreted IFN-gamma comparable in amount to controls, whereas they
released significantly more IL-13 than cells from controls. CONCLUSIONS: Activated
iNKT cells from HCV-infected patients gain more ability to secrete IL-13 than those from
healthy subjects.

50561
Cancer incidence in people with hepatitis B or C infection: a large
community-based linkage study
Amin J, Dore G J, O'Connell D L, Bartlett M, Tracey E, Kaldor J M, Law M
G
8

J Hepatol

45(2):197-203, 2006

BACKGROUND/AIMS: Risks of hepatocellular carcinoma (HCC) following hepatitis B

and/or hepatitis C virus (HBV/HCV) infection are well known, those for other cancers are
less well understood. The aim was to quantify the risk of cancers among persons
diagnosed with HBV/HCV infections. METHODS: The data from a cohort of 39109 HBV,
75834 HCV, and 2604 HBV/HCV co-infected persons notified to the State health
department, 1990-2002, were probabilistically linked to the Cancer Registry and
standardised incidence ratios (SIRs) for cancer were calculated. RESULTS: The match
rate for any cancer was 2.7%, 2.3% and 3.3% for HBV, HCV and HBV/HCV co-infected
notifications. SIRs for HCC were 30.6 (95% CI 25.7-36.5), 22.7 (95% CI 19.1-26.5) and
30.3 (95% CI 13.6-67.5), respectively. Increased risk was detected for Burkitt's
lymphoma and HBV (SIR 12.9, 95% CI 5.4-30.9) and immunoproliferative malignancies
following HCV (SIR 5.6, 95% CI 1.8-17.5). CONCLUSIONS: The risk of HCC in the
infected cohort was 20-30 times greater than in the uninfected population with SIRs two
to three times greater than those for the other HBV/HCV infection associated cancers.
The modest though significant risk of immunoproliferative malignancies associated with
HCV infection is consistent with recent findings.

50562
A randomised trial to compare the pharmacokinetic, pharmacodynamic,
and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in
patients with chronic hepatitis C (COMPARE)
Silva M, Poo J, Wagner F, Jackson M, Cutler D, Grace M, Bordens R,
Cullen C, Harvey J, Laughlin M
J Hepatol
45(2):204-13, 2006
BACKGROUND/AIMS: To compare the pharmacokinetics, pharmacodynamics, and
antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with
chronic hepatitis C virus genotype 1. METHODS: Thirty-six patients were randomised to
peginterferon alfa-2b (1.5mug/kg/week) or peginterferon alfa-2a (180mug/week) for 4
weeks, then in combination with ribavirin (13mg/kg/day) for a further 4 weeks. The
pharmacokinetic profile of both peginterferons, mRNA expression of a selected group of
interferon-induced gene transcripts, and serum HCV-RNA levels were assessed.
RESULTS: Patients receiving peginterferon alfa-2b had significantly greater upregulation of interferon-alfa response genes compared with those receiving
peginterferon alfa-2a. Correspondingly, patients treated with peginterferon alfa-2b also
had a significantly greater log(10) maximum and log(10) time-weighted average
decrease in serum HCV-RNA. A greater proportion of peginterferon alfa-2b patients
achieved a 2.0 log(10) reduction in serum HCV-RNA levels by week 8 (72% vs 44% of
peginterferon alfa-2a patients, P=0.09). There was an approximately 16-fold greater
exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a.
CONCLUSIONS: These findings suggest that the biological activity, measured by early
interferon-induced gene transcripts and early antiviral responsiveness, may have been
greater in patients treated with peginterferon alfa-2b despite their lower exposure to the
drug compared with patients treated with peginterferon alfa-2a.

50563
9

Replication of hepatitis C virus (HCV) RNA in mouse embryonic

fibroblasts: protein kinase R (PKR)-dependent and PKR-independent
mechanisms for controlling HCV RNA replication and mediating
interferon activities
Chang K S, Cai Z, Zhang C, Sen G C, Williams B R G, Luo G
J Virol
80(15):7364-74, 2006
Hepatitis C virus (HCV) infection causes chronic hepatitis and is currently treated with
alpha interferon (IFN-alpha)-based therapies. The underlying mechanisms of chronic
HCV infection and IFN-based therapies, however, have not been defined. Protein kinase
R (PKR) was implicated in the control of HCV replication and mediation of IFN-induced
antiviral response. In this report, we demonstrate that a subgenomic RNA replicon of
genotype 2a HCV replicated efficiently in mouse embryonic fibroblasts (MEFs), as
determined by cell colony formation efficiency and the detection of HCV proteins and
both positive- and negative-strand RNAs. Additionally, the subgenomic HCV RNA was
found to replicate more efficiently in the PKR knockout (PKR(-/-)) MEF than in the wildtype (PKR(+/+)) MEF. The knockdown expression of PKR by specific small interfering
RNAs significantly enhanced the level of HCV RNA replication, suggesting that PKR is
involved in the control of HCV RNA replication. The level of ISG56 (p56) was induced by
HCV RNA replication, indicating the activation of PKR-independent antiviral pathways.
Furthermore, IFN-alpha/beta inhibited HCV RNA replication in PKR(-/-)MEFs as efficiently
as in PKR(+/+) MEFs. These findings demonstrate that PKR-independent antiviral
pathways play important roles in controlling HCV replication and mediating IFN-induced
antiviral effect. Our findings also provide a foundation for the development of transgenic
mouse models of HCV replication and set a stage to further define the roles of cellular
genes in the establishment of chronic HCV infection and the mediation of intracellular
innate antiviral response by using MEFs derived from diverse gene knockout animals.

50564
Identification of a naturally occurring recombinant genotype 2/6 hepatitis
C virus
Noppornpanth S, Lien T X, Poovorawan Y, Smits S L, Osterhaus A D M
E, Haagmans B L
J Virol
80(15):7569-77, 2006
Hepatitis C viruses (HCVs) display a high level of sequence diversity and are currently
classified into six genotypes and an increasing number of subtypes. Most likely, this
heterogeneity is caused by genetic drift; evidence for recombination is scarce. To study
the molecular heterogeneity of HCV in Vietnam, we analyzed 58 HCV RNA-positive sera
from Vietnamese blood donors by sequence analysis of the CORE and NS5B regions.
Phylogenetic analyses revealed the presence of genotype 1 (38%), genotype 2 (10.3%),
and genotype 6 viruses (51.7%). All samples showed concordant results except for two
(D3 and D54). Sample D54 was a mixed infection of genotype 2i and 6h viruses. Wholegenome analysis and bootscan analysis of sample D3, on the other hand, revealed a
recombinant virus with genotype 2i and genotype 6p sequences at the 5' and 3' ends,
respectively. The crossover point was located between nucleotide positions 3405 to
3464 (numbering according to prototype strain HCV-H, M67463) at the NS2/NS3
junction. The identification of this naturally occurring recombinant virus strengthens the
concept that recombination may play a role in HCV epidemiology and evolution.
Furthermore, the location of the recombination breakpoint may be relevant for
constructing infectious chimeric viruses.

10

50565
Native hepatitis B virions and capsids visualized by electron
cryomicroscopy
Dryden K A, Wieland S F, Whitten-Bauer C, Gerin J L, Chisari F V, Yeager
M
Mol Cell
22(6):843-50, 2006
Hepatitis B virus (HBV) infects more than 350 million people, of which one million will die
every year. The infectious virion is an enveloped capsid containing the viral polymerase
and double-stranded DNA genome. The structure of the capsid assembled in vitro from
expressed core protein has been studied intensively. However, little is known about the
structure and assembly of native capsids present in infected cells, and even less is
known about the structure of mature virions. We used electron cryomicroscopy (cryoEM) and image analysis to examine HBV virions (Dane particles) isolated from patient
serum and capsids positive and negative for HBV DNA isolated from the livers of
transgenic mice. Both types of capsids assembled as icosahedral particles
indistinguishable from previous image reconstructions of capsids. Likewise, the virions
contained capsids with either T=3 or T=4 icosahedral symmetry. Projections extending
from the lipid envelope were attributed to surface glycoproteins. Their packing was
unexpectedly nonicosahedral but conformed to an ordered lattice. These structural
features distinguish HBV from other enveloped viruses.

50566
Hepatitis in primary care: what NPs can do to save lives
Stonsifer E, Burke A, Simwale O
Nurse Pract
31(6):53, 55, 2006
50567
Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and
hepatitis C endemicity
Seeff L B, Hoofnagle J H
Oncogene
25(27):3771-7, 2006
Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide.
It evolves from several chronic liver diseases, most of which culminate in cirrhosis. As
the most common causes, other than alcoholic cirrhosis, are chronic hepatitis B and C
infections, its prevalence worldwide is linked to the prevalence of these two viruses.
Thus, the highest rates are in southeast Asia and sub-Saharan Africa, the world's most
populous nations, where hepatitis B virus infection is endemic. In most western
countries, hepatitis C virus infection is the predominant cause, and hepatitis B-related
liver cancer occurs largely among immigrants from countries of high hepatitis B
endemicity. In most western countries, the incidence and mortality from HCC is
increasing as a consequence of the chronic sequelae of the 'epidemic' of hepatitis C of
the 1960-1980s. In the US, modeling of this infection predicts a continued rise in liver
cancer over the next decade. Surveillance by the National Cancer Institute and the
Centers for Disease Control confirms the increasing incidence of and mortality from HCC
to the year 2000, although subsequent analyses suggest a slowing or possibly decline in
the rate of increase. Whether this trend will continue requires further evaluation.

11

50568
Hepatitis B virus-related hepatocellular carcinoma: paradigms for viralrelated human carcinogenesis [review]
Kremsdorf D, Soussan P, Paterlini-Brechot P, Brechot C
Oncogene
25(27):3823-33, 2006
As discussed in detail in other chapters of this review, chronic hepatitis B (HBV) infection
is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the
evolution of an active or inactive cirrhosis. However, some tumors occur on livers with
minimal histological changes; the prevalence of such cases varies from one
geographical region to the other, being much higher in the southern half of Africa
(around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are
associated with the cirrhosis. This heterogeneity is probably a reflection of different
environmental and genetic factors. This review will summarize the current knowledge on
the mechanisms involved in HBV-related liver carcinogenesis. It will show in particular
how viruses can be viewed as tools to discover and dissect new cellular pathways
involved in cancer development and emphasize the potential synergistic effects
between HBV and hepatitis C virus, as well as between viral infections and other
environmental factors, such as alcohol.

50569
Viral hepatitis and liver cancer: the case of hepatitis C [review]
Levrero M
Oncogene
25(27):3834-47, 2006
Chronic infection with the hepatitis C virus (HCV) is a major risk factor for the
development of hepatocellular carcinoma (HCC) worldwide. The pathogenesis of HCC in
HCV infection has extensively been analysed. Hepatitis C virus-induced chronic
inflammation and the effects of cytokines in the development of fibrosis and liver cell
proliferation are considered as one of the major pathogenic mechanisms. Increasing
experimental evidence suggests that HCV contributes to HCC by directly modulating
pathways that promote the malignant transformation of hepatocytes. Hepatitis C virus is
an RNA virus that does not integrate into the host genome but HCV proteins interact
with many host-cell factors well beyond their roles in the viral life cycle and are involved
in a wide range of activities, including cell signaling, transcription, cell proliferation,
apoptosis, membrane rearrangements, vesicular trafficking and translational regulation.
At least four of the HCV gene products, namely HCV core, NS3, NS4B and NS5A, have
been shown to exhibit transformation potential in tissue culture and several potentially
oncogenic pathways have been shown to be altered by the expression of HCV proteins.
Both HCV core and NS5A induce the accumulation of wild-type beta-catenin and the
Wnt-beta-catenin pathway emerges as a common target for HCV (and HBV) in human
HCCs, also independently from axin/beta-catenin gene mutations. Induction of both
endoplasmic reticulum stress and oxidative stress by HCV proteins might also contribute
to HCV transformation. Most of the putative transforming functions of the HCV proteins
have been defined in artificial cellular systems, which may not be applicable to HCV
infection in vivo, and still need to be established in relevant infection and disease
models.

50570
Does cyclosporine have a beneficial effect on the course of chronic
hepatitis C infection after renal transplantation?
Kamar N, Selves J, Sandres-Saune K, Durand D, Izopet J, Rostaing L
Transplant Proc
38(5):1329-32, 2006
12

The aim of our study was to assess the long-term liver histology in renal transplant
patients infected with hepatitis C virus (HCV) who were treated with a cyclosporinebased regimen. Among 55 anti-HCV(+)/RNA(+) patients, liver biopsies (LB) were
requested every 3 to 4 years after transplantation: two LBs (n = 55); three LBs (n = 44);
four LBs (n = 10). Overall, the rate of liver fibrosis progression was 0.07 +/- 0.03 Metavir
U/y. Only three patients out of 55 (5.4%) developed cirrhosis. Liver fibrosis remained
stable throughout follow-up in 21 patients; increased in 21 patients; and improved in the
remaining 13 patients. The incidence of posttransplant diabetes mellitus was low (9%).
We concluded that HCV infection is not harmful to liver histology in more than 50% of
renal transplant patients with grafts functioning more than 6 years. Cyclosporine might
have beneficial effects on the natural course of HCV infection after renal transplantation.

50571
The impact of nonalcoholic fatty liver disease and the metabolic
syndrome on progression of fibrosis in patients with recurrent HCV after
liver transplantation
Mindikoglu A L, Regev A, Casanova-Romero P Y, Bejarano P A, Martinez
E J, Tzakis A G, Schiff E R
Transplant Proc
38(5):1440-4, 2006
Nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MS) have been
shown to play a role in disease progression and response to therapy in patients with
chronic hepatitis C virus (HCV) infection. The primary objective of this study was to
evaluate the impact of coexisting NAFLD and MS on the progression of fibrosis in
patients with recurrent HCV treated with interferon (IFN)/ribavirin after orthotopic liver
transplantation (OLT). From 1998 to 2004, a total of 418 patients underwent OLT in our
center for HCV-related cirrhosis. Thirty-five patients with recurrent HCV on IFN/ribavirin
treatment, who had at least 2 posttransplant liver biopsies at least 6 months apart, were
included in the study. Patients who had MS at the time of their first posttransplant
biopsy were identified. The first and last posttransplant biopsies were assessed for the
presence and severity of NAFLD, grade of inflammation, and stage of fibrosis. The
fibrosis progression rate (FPR) was calculated and expressed in fibrosis units per month
(FU/mo). Among 35 patients, 34% were diagnosed with NAFLD in the first posttransplant
biopsy. The mean FPR was 0.05 +/- 0.16 FU/mo in the presence of NAFLD compared to
0.07 +/- 0.10 FU/mo in its absence (P = .68) and 0.03 +/- 0.06 FU/mo in the presence of
MS versus 0.10 +/- 0.15 FU/mo in its absence (P = .06). When FPR values were divided
into two categories of <0.16 FU/mo or >/=0.16 FU/mo (below/above the 25% upper
quartile) or <0.08 FU/mo or >/=0.08 FU/mo (below/above the 50% upper quartile), there
was no correlation between FPR categories and the presence of NAFLD with or without
MS, only MS, or the absence of both in the first liver transplant biopsy (P = .13).
Coexisting NAFLD or MS had no significant effect on the progression of fibrosis after OLT
in patients with treated hepatitis C after OLT.

50572
Impact of double-filtration plasmapheresis in combination with interferon
and ribavirin in living donor liver transplant recipients with hepatitis C
Taniguchi M, Furukawa H, Shimamura T, Suzuki T, Yamashita K, Ota M,
Todo S
Transplantation
81(12):1747-9, 2006
Double-filtration plasmapheresis (DFPP) selectively removes high molecular weight
substances including hepatitis C virus (HCV). Four live donor liver transplantation (LDLT)

13

recipients with HCV received combination therapy with low-dose interferon (IFN) and
ribavirin with DFPP. Three patients underwent this therapy for prophylaxis of HCV
recurrence, and one for treating fibrosing cholestatic hepatitis (FCH). The combination
therapy and DFPP decreased HCV RNA levels to 8.2% +/- 2.9% and 0.7% +/- 0.5% by
the 5 and 30 day of treatment, respectively. Three patients who underwent DFPP for
prophylaxis showed no evidence of HCV recurrence for >1 year after treatment. The
patient whose graft showed FCH, recovered dramatically after the DFPP treatment. DFPP
appeared to be effective in reducing HCV viremia and preventing HCV recurrence in
patients with high HCV RNA levels after LDLT. Moreover, it may become a rescue therapy
for FCH in a liver transplant recipient with hepatitis C.

50573
Identification of a specific gene expression pattern associated with HCVinduced pathogenesis in HCV- and HCV/HIV-infected individuals
Walters K A, Smith M W, Pal S, Thompson J C, Thomas M J, Yeh M M,
Thomas D L, Fitzgibbon M, Proll S, Fausto N, Gretch D R, Carithers R L,
Shuhart M C, Katze M G
Virology
350(2):453-64, 2006
Gene expression profiling was performed on liver biopsies from 28 patients (12 HCV and
16 HCV/HIV infected) in an attempt to understand the mechanisms of HCV liver disease
in the presence and absence of HIV coinfection. The data were compared with clinical
observations and a gene expression database obtained for transplant HCV-infected
samples. This is the first report of functional genomics being used to compare
intrahepatic gene expression profiles of HCV- and HCV/HIV-infected individuals.
Significantly, the intrahepatic global gene expression profiles do not differ between HCVand HCV/HIV-infected individuals. However, a subset of patients was identified who
share a specific pattern of gene expression, termed the enhanced gene expression
(EGE) pattern. Specifically, the EGE (+) patients show a dramatic decreased expression
of multiple genes associated with the FAS-apoptosis pathway and increased expression
of lymphocyte adhesion molecules and lymphocyte-specific genes. The EGE (+) patients
also have partially impaired Type I and II IFN-mediated antiviral responses, including a
lack of induction of the anti-fibrogenic cytokine IFN-gamma. Importantly, the pattern of
gene expression observed in EGE (+) patients has similarities to patients who developed
fibrosis within 1 year of receiving a liver transplant.

50574
Suppression of mRNA accumulation by the duck hepatitis B virus reverse
transcriptase
Cao F, Tavis J E
Virology
350(2):475-83, 2006
Hepadnaviruses establish chronic liver infections, but the mechanisms of persistence
and immune evasion are poorly understood. We previously found that the duck hepatitis
B virus (DHBV) and hepatitis B virus reverse transcriptases (P protein) unexpectedly
accumulate in the cytoplasm where they could affect function(s) beyond viral DNA
synthesis, such as gene expression. Therefore, we measured effects of DHBV P on gene
expression from reporter constructs and the viral genome. P reduced reporter
expression at the mRNA level to approximately 30-40%, independent of reporter tested.
Accumulation of the viral pregenomic RNA from its native promoter was suppressed

14

three-to four-fold by P, and accumulation of the capsid protein and intracellular core
particles was similarly suppressed because the pregenomic RNA encodes the capsid
protein. Therefore, suppression of the pregenomic RNA by DHBV P creates a negative
feedback loop to limit viral antigen accumulation and replication, possibly contributing
to maintenance of chronic infection.

50575
Hepatitis E virus genotyping based on full-length genome and partial
genomic regions
Zhai L, Dai X, Meng J
Virus Res
120(1-2):57-69, 2006
Some genomic regions for hepatitis E virus (HEV) genotyping have been reported to
correlate well with the results from the phylogenetic analyses on the basis of the
complete genome. However, few studies have systemically investigated the genomic
regions for HEV genotyping using a combined phylogenetic and statistical approach. A
consensus region for HEV genotyping has not been determined. In this study the
nucleotide identities and genetic distances of 24 partial genomic regions and the
complete genome sequences of 37 HEV strains were compared statistically. It was
demonstrated with both one-way ANOVA and two-way ANOVA that only one genomic
region in RNA-dependent RNA polymerase domain (4254-4560nt) for which there were
no significant differences when compared with the full-length genome (P>0.05). The
same four genotypes were identified by phylogenetic analysis based on this statistically
predicted region identified as for the complete genome. RT-PCR amplification of HEV
strains from all four genotypes confirmed conservation of the flanking primer sites of
this region. Serum samples from 20 patients with a clinical diagnosis of hepatitis E were
further analyzed by PCR using the same primers, 13 were positive and could be
classified into genotype 4. These data strongly suggested that this newly identified
region could be used for future HEV genotyping.

50576
Prevalence of mutations in hepatitis C virus core protein associated with
alteration of NF-kappaB activation
Mann E A, Stanford S, Sherman K E
Virus Res
121(1):51-7, 2006
The hepatitis C virus (HCV) core protein is a key structural element of the virion but also
affects a number of cellular pathways, including nuclear factor kappaB (NF-kappaB)
signaling. NF-kappaB is a transcription factor that regulates both anti-apoptotic and proinflammatory genes and its activation may contribute to HCV-mediated pathogenesis.
Amino acid sequence divergence in core is seen at the genotype level as well as within
patient isolates. Recent work has implicated amino acids 9-11 of core in the modulation
of NF-kappaB activation. We report that the sequence RKT is highly conserved (93%) at
this position across all HCV genotypes, based on sequences collected in the Los Alamos
HCV database. Of the 13 types of variants present in the database, the two most
prevalent substitutions are RQT and RKP. We further show that core encoding RKP fails
to activate NF-kappaB signaling in vitro while NF-kappaB activation by core encoding

15

RQT does not differ from control RKT core. The effect of RKP core is specific to NFkappaB signaling as activator protein 1 (AP-1) activity is not altered. Further studies are
needed to assess potential associations between specific amino acid substitutions at
positions 9-11 and liver disease progression and/or response to treatment in individual
patients.

50577
Hepatitis C virus E2 links soluble human CD81 and SR-B1 protein
Heo T H, Lee S M, Bartosch B, Cosset F L, Kang C Y
Virus Res
121(1):58-64, 2006
Limited information is available regarding hepatitis C virus (HCV) entry events. Viral
attachment and infection studies have been performed using HCV envelope
glycoprotein (E2) and HCV pseudo-particle (HCVpp) models to obtain general
information about the early entry events. However, the details involved in each step of
viral entry into human cells are still obscure. This study provides molecular clue for the
formation of a heteromultimeric complex as a possible post-attachment step. Among
several putative receptors, human CD81 and scavenger receptor class B type 1 (SR-B1)
have been demonstrated as considerable determinants in infectious outcome as well as
attachment. In this study, we provide molecular evidence demonstrating that HCV E2
links soluble CD81 and SR-B1 protein together. This physical neighboring might explain
why both CD81 and SR-B1 are indispensable factors for HCVpp infection. These data
further elucidate our understanding of HCV entry and provide new insight into directing
future studies identifying novel liver-specific fusion receptor(s).

50578
Risk factors for retinopathy associated with interferon alpha-2b and
ribavirin combination therapy in patients with chronic hepatitis C
Okuse C, Yotsuyanagi H, Nagase Y, Kobayashi Y, Yasuda K, Koike K, Iino
S, Suzuki M, Itoh F
World J Gastroenterol
12(23):3756-9, 2006
AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic
hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We
prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who
underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4,
12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%)
developed retinopathy, which was initially diagnosed by the appearance of a cotton
wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient
complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite
the continuation of combination therapy. However, retinopathy persisted in 5 patients
with retinal hemorrhage. A comparison of the clinical background between the groups
with and without retinopathy showed no significant differences in age, gender, viral
genotype, RNA level, white blood cell count, platelet count, prothrombin time,
complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic
changes in the optic fundi. However, multiple logistic regression analysis revealed that
complication by hypertension was observed with a high frequency in the group with
retinopathy (P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2). CONCLUSION:
Retinopathy associated with combination therapy of interferon alpha-2b and ribavirin
tends to develop in patients with hypertension.

16

50579
Increased hepatic expression of insulin-like growth factor-I receptor in
chronic hepatitis C
Stefano J T, Correa-Giannella M L, Ribeiro C M, Alves V A, Massarollo P
C, Machado M C, Giannella-Neto D
World J Gastroenterol
12(24):3821-8, 2006
AIM: Although increased insulin-like growth factor-I receptor (IGF-IR) gene expression
has been reported in hepatocellular carcinoma, studies assessing IGF-IR in chronic
hepatitis C (CHC) and cirrhosis are scarce. We therefore aimed to evaluate IGF-IR and
IGF-I mRNA expression in liver from patient with CHC. METHODS: IGF-IR and IGF-I mRNA
content were determined by semi-quantitative RT-PCR and IGF-IR protein expression was
determined by immunohisto-chemistry in hepatic tissue obtained from patients with
CHC before (34 patients) and after (10 patients) therapy with interferon-alpha and
ribavirin. RESULTS: An increase of IGF-IR mRNA content was observed in hepatic tissue
obtained from all CHC patients as well as from 6 cadaveric liver donors following
orthopic transplantation (an attempt to evaluate normal livers) in comparison to normal
liver, while no relevant modifications were detected in IGF-I mRNA content. The
immunohistochemical results showed that the raise in IGF-IR mRNA content was related
both to ductular reaction and to increased IGF-IR expression in hepatocytes. A decrease
in IGF-IR mRNA content was observed in patients who achieved sustained virological
response after therapy, suggesting an improvement in hepatic damage. CONCLUSION:
The up-regulation of IGF-IR expression in hepatocytes of patients with CHC could
constitute an attempt to stimulate hepatocyte regeneration. Considering that liver is the
organ with the highest levels of IGF-I, our finding of increased IGF-IR expression after
both acute and chronic hepatic damage highlights the need for additional studies to
elucidate the role of IGF-I in liver regeneration.

50580
Significance of serum IgA in patients with acute hepatitis E virus
infection
Tian D Y, Chen Y, Xia N S
World J Gastroenterol
12(24):3919-23, 2006
AIM: To study the significance of serum anti-hepatitis E virus (HEV) IgA in patients with
hepatitis E. METHODS: A new method was established to assay anti-HEV IgA, which
could be detected in the middle phase of the infection. We compared anti-HEV IgA assay
with anti-HEV IgM and anti-HEV IgG assay in sera from 60 patients with positive HEVRNA. RESULTS: The 60 patients with positive HEV-RNA had both anti-HEV IgA and antiHEV IgM and 410 patients with negative HEV-RNA were used as control. Periodic serum
samples obtained from 60 patients with hepatitis E were tested for HEV RNA, anti-HEV
IgM, anti-HEV IgA and anti-HEV IgG. Their HEV-RNA was detectable in the serum until 20
+/- 11 d. We used anti-HEV IgM and anti-HEV IgA assay to detect HEV infection and
positive results were found in 90 +/- 15 d and 120 +/- 23 d respectively, the positive
rate of anti-HEV IgA was higher than that of anti-HEV IgM and HEV-RNA (P < 0.05).
CONCLUSION: The duration of anti-HEV IgA in serum is longer than that of anti-HEV
IgM, and anti-HEV IgA assay is a good method to detect HEV infection.

17