Journal of Medicine and Medical Science Vol. 3(4) pp.263-269, April 2012
Available online http://www.interesjournals.org/JMMS
Copyright © 2012 International Research Journals
Full Length Research Paper
Clinic and laboratory analysis of patients with hepatitis
delta in Amazon region, Brazil
Mariana Vasconcelos1, Dhélio Batista Pereira1, Raymundo Paraná R2,
Juan Miguel Villalobos-Salcedo*1
1
Ambulatório de Hepatites Virais, Centro de Pesquisa em Medicina Tropical (CEPEM), Instituto de Pesquisa em
Patologias Tropicais (IPEPATRO), Porto Velho, Rondônia, Brazil.
2
Unidade de Gastro-Hepatologia da Universidade Federal da Bahia, Brazil.
Accepted 18 April, 2012
The hepatitis delta virus (HDV) is a defective RNA virus that needs the Hepatitis B virus (HBV). In Brazil,
endemic areas correspond to Western Amazon States, including Rondonia state. Preliminary data
shows that Hepatitis D in Brazil seems to be more severe as compared to other regions; however, there
are few studies to reinforce this observational evidence. The current study reports results from a
clinical and laboratory analysis for chronic hepatitis delta patients followed in a Hepatology outpatient
service in Brazilian Amazon Basin. We reviewed and analyzed a series of cases for all HDV patients’
medical files from November 1993 to September 2010. All patients had positive anti-HDV IgG serology
and had clinical follow-up documented in their files. A clinical and epidemiological questionnaire was
used to collect information, including laboratory and treatment data. Data from 141 patients was
collected, but only 77 patients were selected because they had regular follow-up. Fifty patients (64.9%)
were male with a mean age of 32 (6 to 57 years old) and 16 patients (20%) were considered Amerindian.
Leukopenia was detected in 28 patients (36.7%). ALT level was above the upper normal in more than
half of the patients. Seven (16.4%) had cirrhosis, 9 (20.9%) had F0 and the rest had different stages of
fibrosis in liver biopsy. Twelve patients (16%) presented with chronic hepatic disease without portal
hypertension in Ultrasonographie. 22 (84.6%) used Interferon as monotherapy, 3 (11.5%) used
lamividine as monotherapy and 1patient received a combination of lamivudine with Interferon. In
Amazonia, the diagnosis is often delayed and advanced liver disease observed in young patients.
These results indicate an imperative requirement to intensify education and prevention campaigns
focused on the early diagnosis of this neglected disease.
Keywords: Hepatitis delta, clinical, laboratory, Amazon region.
INTRODUCTION
The hepatitis delta virus (HDV) was discovered in 1977
by Rizzetto et al (Rizzetto, Canese et al. 1977). HDV is a
defective RNA virus that needs the Hepatitis B virus
(HBV) envelope for its life cycle. Both viruses interact
throughout different stages of replication (Rizzetto,
Canese et al., 1977). HDV can infect the individual simul-
*Corresponding Author E-mail: juanitto2001@yahoo.com.br;
Phone: +55 69 32165444 Fax: +55 69 32196012
taneously with HBV, characterizing the co-infection, or it
can infect a chronic B HBV carrier, characterizing a
superinfection. The co-infection usually evolves into
complete recovery, while the superinfection evolves
toward chronicity in about 90% of cases. Chronicity is
associated with an increased risk of developing advanced
liver disease hepatitis, premature cirrhosis and
hepatocarcinoma (Smedile et al., 1994; Farci, 2003; Silva
et al., 2010).
HDV has a heterogeneous world distribution,
exhibiting prevalence rates as high as 24% in the south
of Italy, Africa and the Middle East (Gaeta et al., 2000). In
264 J. Med. Med. Sci.
the north of Europe and the United States, where HDV is
not endemic, the virus is mostly limited to risk groups
such as intravenous drug users and hemophiliacs
(Novick et al., 1988; Madejon et al., 1994). According to
some authors (Bensabath et al., 1987; Hadler et al.,
1987), at least 300,000 people are infected with this virus
in Latin America, with lower prevalence in the tempered
zones. The prevalence of infection increases in the
equatorial subtropical and tropical zones, concentrating in
certain population groups which are considered high
endemicity models (Torres, 1996).
In Brazil, the hepatitis delta endemic areas correspond
to the Western Amazon states, including Rondonia State
(Bonino et al., 1985; Fonseca et al., 1988; Liaw et al.,
1990; Torres, 1996). Preliminary data shows that
hepatitis delta in Brazil seems to be more severe
compared to other regions; however there are few
studies in our Hepatitis referral centers that reinforce this
observational evidence. The current study aims to report
on the clinical outcome of patients followed in a Referral
Outpatient Unit for Hepatitis in the Brazilian Amazon
Basin.
METHODOLOGY
We reviewed a series of cases followed at the Referral
Unit for chronic viral hepatitis in the Tropical Medicine
Research Center of Rondonia (CEPEM), Porto Velho. All
HDV patients’ medical files from November 1993 to
September 2010 were analyzed. All patients had positive
anti-HDV IgG serology and had clinical follow-up
documented in their files. A clinical and epidemiological
questionnaire (admission sheet) was used to collect
epidemiological and clinical information, including
laboratory and treatment data. In addition, the
ultrasonography, upper digestive endoscopy and liver
biopsy results from admission date or closer were
collected and registered from the medical files. We used
the following reference value parameters for analysis of
laboratory abnormalities: prothrombin time (PTA) lower
than 50% (or INR over 1.7), Albumin lower than 3.5 g/dL,
alanine amino transferase (ALT) above 35 IU/L,
hemoglobin lower than 13.5g/dL in men and 11.5g/dL in
women, leucocytes lower than 5,000/nm and platelet
count lower than 150,000/mm.
The ultrasound tests were categorized as: 1) normal;
2) chronic liver disease without evidence of portal
hypertension; and 3) chronic liver disease with evidence
of portal hypertension.
Results of upper digestive
endoscopy (esophagogastroduodenoscopy), performed
in patients with clinical signs of chronic liver disease or
portal hypertension, were classified as: 1) No evidence of
Portal Hypertension, or 2) Esophageal/Gastric varices
and/or hypertensive gastropathy. Results of liver biopsy
were reviewed according to Metavir score (Bedossa and
Poynard, 1996).
Statistical Analysis: Chi-square tests were conducted
to compare the frequency of results and the T-student
test was used to compare the averages. This study was
done according to principles stipulated by the 1975 World
Medical Assembly and the Brazilian Health Ministry
(Resolution 196/1996). This project was submitted and
approved by the Research and Ethics Committee of
CEPEM.
RESULTS
Data from 141 patients infected with HDV was collected,
but only 77 patients were selected because they had
regular follow-up in the outpatient unit. As presented in
Table 1, 50 patients (64.9%) were male with a mean age
of 32 (6 to 57 years old). Household contact with chronic
HDV carriers was significant, reported in 36 (46.7%) of
our patients. Only 16 (20%) of the patients were
considered Amerindian.
The hematologic and biochemical results are shown in
Table 2. Leukopenia was detected in 28 patients (36.7%).
Regarding the biochemistry results, the ALT level was
above the upper normal in more than half of the patients.
Data of the serological results are summarized in
Table 3. The results indicate that only 9.1% of the coinfected patients have positive HBeAg.
Regarding histopathological data, only 43 (55.8%) of
the 77 studied patients had a liver biopsy. Of those, 7
(16.4%) had cirrhosis, 9 (20.9%) had F0 and the rest had
different stages of fibrosis (Table 4).
Ultrasonography was performed on 75 patients.
Twelve (16%) of the patients presented with chronic
hepatic disease without portal hypertension, 16 (21.3%)
had chronic liver disease with portal hypertension, and 47
(61%) had no liver abnormalities.
Of the 27 patients who had upper digestive
endoscopy, 12 (44.4%) had normal results and 15
(55.5%) showed differing degrees of portal hypertension
with esophageal varices and/or hypertensive gastropathy
(Table 5).
Treatment data revealed that 26 patients received
treatment: 22 (84.6%) used Interferon as monotherapy, 3
(11.5%) used lamividine as monotherapy and 1 patient
received a combination of lamivudine with Interferon
(Table 6).
DISCUSSION
The natural history of chronic hepatitis delta virus is
characterized by different clinical courses, varying from
accelerated rapid progressive fibrosis to lower progress-
Vasconcelos et al. 265
Table 1. Hepatitis delta patient distribution and epidemiologic
characteristics –Viral Hepatitis Outpatient Unit in Rondonia
N
%
50
27
64.9
35.1
8
35
34
10.4
45.4
44.2
16
20.8
36
33
21
10
3
46.7
42.9
27.3
13.0
3.9
67
10
13.0
Sex:
Men
Women
Age:
Less than 18
between 18-35
Over 35
Special Population:
Amerindians
Risk Factors:
Household contact
Dental treatment
Surgical procedure
Blood transfusion
Tattoo
Birthplace
Amazonic Region
Non Amazonic
Table 2. Results for the main laboratory exams of the HDV carrier patients - Viral Hepatitis Outpatient
Unit in Rondonia
Hemogram:
Anemia
Leucopenia
Plateletopenia
Biochemistry:
Prolonged PTA
Increased ALT
Increased AST
Serum Albumin
N
%
Average (D.P.)
Variation
18
28
28
23.4
36.7
36.7
13.3
5.383
175.584
8.1 – 16.6
1.500 – 13.000
44.000 – 440.000
19
51
53
10
24.7
66.2
68.8
12.9
81%
124.4
137.0
4.0
37% - 100%
17 – 2600
15 – 4740
2.5 – 5.6
Table 3. Results for the serological markers of HDV carrier
patients – Viral Hepatitis Outpatient Unit of in Rondonia
Serology:
Anti-HDV
HBsAg
HBeAg
Anti-HBe
sive fibrosis (Rizzetto, 1983). In addition, some HDV
patients without liver disease have been described in
some countries (Saracco et al., 1987). The clinical course
of the infection also varies regionally, most likely
N (+)
%
77
77
7
70
100
100
9.1
90.9
associated to the prevalent genotype in each region
(Parana et al., 2006).
In the Amazon Basin, there are few studies that
correlated clinical and epidemiological data with comple-
266 J. Med. Med. Sci.
Table 4. Result for histopathological liver biopsy for Hepatitis Delta
patients - Viral Hepatitis Outpatient Unit in Rondonia
Biopsy*:
Fibrosis:
F0
F1
F2
F3
F4
No classification
TOTAL
Activity:
A0
A1
A2
A3
No classification
TOTAL
No exam**
N
%
9
5
10
6
7
6
43
20.9
11.6
23.3
13.9
16.4
13.9
100
6
9
13
9
6
43
34
13.9
20.9
30.2
20.9
13.9
100
44.2
* METAVIR classification
** Two of these are transplanted
Table 5. Ultrasound and endoscopy results of Hepatitis Delta patients - Viral
Hepatitis Outpatient Unit in Rondonia
Ultrasound:
Normal
DHC Signs without cirrhosis
DHC Signs with cirrhosis
TOTAL
High digestive endoscopy:
Normal
Esophageal Varices – isolated VE
Hypertensive Gastropathy – isolated GH
VE associated to GH
TOTAL
mentary tests in HDV carriers. Concerning transmission
routes, we found in this study that HDV infection in
Amazonia is most prevalent among young patients, with
a mean age of 32. No cases were related to drug
addiction, strongly contrasting with chronic hepatitis delta
cases in Western Europe and the United States.
Although sexual transmission could not be ruled out
(Braga, Brasil et al. 2001), it is possible that HDV has the
same transmission routes of hepatitis B in Amazonia,
N
%
47
12
16
75
62.7
16.0
21.3
100
12
9
1
5
27
44.4
33.3
3.7
18.5
100
since it probably involves horizontal intrafamilial
transmission in early age, as recently reported (Lobato et
al., 2006). Among our patients, almost half reported a
household contact with an infected member of their
family. However, because the study was a descriptive
study, we could not investigate risk factors deeply
(Roingeard et al., 1993; Braga et al., 1994; Niro et al.,
1999).
As described in other epidemiological studies
Vasconcelos et al. 267
Table 6. Therapeutic situation of Hepatitis Delta patients- Viral Hepatitis
Outpatient Unit in Rondonia
Patients without treatment
Patients with treatment
Interferon
Lamivudine
Association Interferon + Lamivudine
(Fonseca et al., 1988; Soares and Bensabath 1991;
Braga et al., 2001), indigenous populations from northern
Brazil seem to have a high prevalence of HDV. In July
2009, we finished a “Seroprevalence Survey of viral
Hepatitis” in Guajará-Mirim village. This area is an
indigenous special Public Health District of Porto Velho
composed of “Wari” Amerindians belonging to a large
ethnic group. From a total of 3,276 samples, 182 were
positive for HBsAg, a 5.6% rate of infection (Brasil, 2010),
indicating high prevalence rates in this population. (non –
published data).
The majority of the reviewed cases showed evidence
of chronic hepatitis with hepatocellular injury, portal
hypertension and/or low blood cells count (Sherlock,
1997) Leukopenic (36.7%), thrombocytopenic (36.7%)
and anemia (23.4%) were the most common findings.
Moreover, a recent study in HDV patients in the
neighboring state of Acre found similar results: 39.7%
leukopenia, 33% thrombocytopenia and 13.4% anemia
(Silva et al., 2010). Of all hepatotropic viruses, HDV is
considered the most aggressive. While HBV can present
as an inactive chronic carrier and HCV can exhibit
minimal liver disease, HDV usually shows continuous
necro-inflammatory activity that can be explained by
direct cytopathic effect in the host cell. Although the
pathogenesis of HDV infection has still not been totally
understood, this direct cytopathic effect has been
described (Cole et al., 1991). In experimental models, it
was not possible to find highly suggestive aspects of
direct hepatocyte aggression caused by HDV (Guilhot et
al., 1994; Wang et al., 2001). On the other hand, the
immune-mediated disease mechanism, clearly identified
in B and C hepatitis, does not seem to be involved in liver
injury during HDV infection (Nisini et al., 1997). Either
through direct injury or immune-mediated mechanism,
evidence of necroinflammatory activity was observed in
more than 60% of the patients.
The suppressive effect of HDV on HBV replication is a
well recognized phenomenon (Jardi et al., 2001;
Fonseca, 2002). Different reports indicate that 70 to 90%
of patients co-infected with HBV-HDV show HBeAg
negative and low HBV-DNA levels in serum (Sagnelli et
al., 2000). Our results confirm this data, as only 7
patients (10%) presented positive HBeAg, showing that,
N
51
26
22
3
1
%
66.2
33.8
84.6
11.5
3.8
although the genotypes are different from those common
in Asia and Eastern Europe (genotype I and II), HDV from
Amazon region (genotype III) could have the same
suppressive action over HBV (Parana et al., 2006;
Parana et al., 2008). In contrast, other Hepatitis Referral
Centers in the Amazon region (unpublished data) report
elevated numbers of AgHBe positive patients. This
aspect deserves further study due to the possibility of
Hepatitis D heterogeneity in the Amazonia, whereas it
had been described as two different circulating genotypes
(Parana et al., 2006).
Only 43 of the 77 patients in our study, (55.8%)
submitted to liver biopsy. Samples were not collected
from the other 34 patients, of which 22 had some
contraindication, either for coagulation alteration with
prolonged INR (over 1.7) or low platelet count (lower than
80,000). These conditions may reflect the rapid
deterioration of liver function. When the 7 patients who
showed fibrosis level 4 are considered along with the
patients with liver biopsy contraindications, more than
half of all patients had delayed diagnosis, while only 14
patients (adding patients with fibrosis level 0 or 1) or less
than a third of all patients, had early diagnosis. These
results indicate an imperative requirement to intensify
education and prevention campaigns focused on the
early diagnosis of this neglected disease.
The analysis of ultrasound data is always difficult, due
to operator dependence. This aspect may explain why
more than 60% of patients did not show any sign of
chronic liver disease, contrasting with clinical, laboratorial
and histopathological data.
Some patients did not have upper digestive
endoscopy done (27 or 35%), either because there was
not an indication suggesting they needed one or because
they had difficulty accessing this procedure in the
Rondonia State Health System. Regardless, it is
remarkable that more than half of the patients who
submitted to upper digestive endoscopy showed
esophageal varices and/or hypertensive gastropathy.
These findings confirm the fact that hepatitis delta
diagnosis in Rondonia is delayed.
Among the chronic viral hepatitides, hepatitis delta is
the only one for which there is not a standardized
treatment. In clinical practice, the aim of the treatment is
268 J. Med. Med. Sci.
to maintain the suppression of the HDV replication to
obtain liver disease remission and improve the patient’s
clinical condition. The endpoints of the treatment is
usually to keep ALT below the upper normal limit and / or
low HDV viral load (Garripoli et al., 1994; Honkoop et al.,
1997). In this context, the Interferon alpha (IFN) has
been used for the treatment of hepatitis D since the mid
1980s (Niro et al., 2005). Our analysis of the patient
records continued until November 2009. On October 26th,
2009, the Brazilian Health Ministry published new
guidelines for treating patients with hepatitis delta (Brasil
2010). At that point, all of the patients in this review were
treated with conventional Interferon. It should be noted
that only a third of the patients have received treatment,
the majority with IFN in monotherapy (84.6%) or
associated with Lamivudine. Most patients cannot initiate
treatment with interferon because of advanced liver
disease or clinical and laboratorial conditions that
contraindicate this therapy.
In conclusion, the hepatitis delta virus represents a
public health problem in many countries worldwide,
including Brazil, where most cases are concentrated in
western Amazonia. In Amazonia, the diagnosis is often
delayed and advanced liver disease is observed in young
patients. We need health education programs and
educational campaigns to focus on this neglected
disease in Brazil.
REFERENCES
Bensabath G, Hadler SC, Soares MC, Fields H, Dias LB, Popper H,
Maynard JE (1987). Hepatitis delta virus infection and Labrea
hepatitis. Prevalence and role in fulminant hepatitis in the Amazon
Basin. JAMA 258(4): 479-483.
Bonino F, Caporaso N, Dentico P, Marinucci G, Valeri L, Craxi A,
Ascione A, Raimondo G, Piccinino F, Rocca G (1985). Familiar
clustering and spreading of hepatitis delta virus infection. J Hepatol
1(3): 221-226.
Braga WSM, Brasil LM, Souza RABd, Castilho MdC, Fonseca JCd
(2001). Ocorrência da infecção pelo vírus da hepatite B (VHB) e delta
(VHD) em sete grupos indígenas do Estado do Amazonas. Revista
Da Sociedade Brasileira De Medicina Tropical 34: 349-355.
Brasil LM, Braga WSM, Botelho R, Castilho MC, Fonseca JCF
(1994). The Prevalence of Hepatitis-B Virus (Hbv) Markers within
Household in the State of Amazonas, Brazil. Hepatology 19(4): I45I45.
Brasil MdS (2010). Protocolo clínico e diretrizes terapêuticas para o
tratamento de hepatite viral crônica B e coinfecções. Secretaria de
vigilância em saúde. Departamento de DST e Hepatites Virais.
Brasília, DF
Brasil MdS (2010). Relatório final das hepatites virais. . Fundação
Nacional de Saúde. Coordenação Regional de Rondônia. Distrito
Sanitário Especial Indígena de Porto Velho. Brasilia, DF
Cole SM, Gowans EJ, Macnaughton TB, Hall PD, Burrell CJ (1991).
Direct evidence for cytotoxicity associated with expression of
hepatitis delta virus antigen. Hepatology 13(5): 845-851.
Farci P (2003). Delta hepatitis: an update. J. Hepatol. 39 Suppl.
1: S212-219.
Fonseca JC, Castejon M, Cesario A (1988). Prevalência da infecção
pelos vírus das hepatites B e delta em indígenas da nação Tikunas,
alto rio Solimões, Amazonas, Brasil. Resumos do X Congresso
Brasileiro de Hepatologia: E-084.
Fonseca JCF (2002). Hepatite D. Revista Da Sociedade Brasileira De
Medicina Tropical 35: 181-190.
Fonseca JCF, Simonetti SRR, Schatzmayr HG, Castejon MJ,
Cesario ALO, Simonetti JP (1988). Prevalence of Infection with
Hepatitis Delta Virus (Hdv) among Carriers of Hepatitis-B SurfaceAntigen in Amazonas State, Brazil. Transactions of the Royal Society
of Tropical Medicine and Hygiene 82(3): 469-471.
Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G,
Lobello S, Sagnelli E, Brunetto MR, Rizzetto M (2000). Chronic
hepatitis D: a vanishing Disease? An Italian multicenter study.
Hepatology 32(4 Pt 1): 824-827.
Garripoli A, Di Marco V, Cozzolongo R, Costa C, Smedile A, Fabiano
A, Bonino F, Rizzetto M, Verme G, Craxi A (1994). Ribavirin
treatment for chronic hepatitis D: a pilot study. Liver 14(3): 154-157.
Guilhot S, Huang SN, Xia YP, La Monica N, Lai MM, Chisari FV
(1994). Expression of the hepatitis delta virus large and small
antigens in transgenic mice. J. Virol. 68(2): 1052-1058.
Hadler SC, Fay OH, Pinheiro FdP, Maynard JE (1987). La hepatitis en
las Américas : informe del grupo colaborador de la OPS / Hepatitis in
the Americas: report of the PAHO collaborating group. Boletín de la
Oficina Sanitaria Panamericana 103(3): 16.
Honkoop P, deMan RA, Niesters HGM, Heijtink RA, Schalm RW
(1997). Lamivudine treatment in patients with chronic hepatitis Delta
infection. Hepatology 26(4): 1219-1219.
Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Galimany R,
Esteban R, Guardia J (2001). Role of hepatitis B, C, and D viruses in
dual and triple infection: influence of viral genotypes and hepatitis B
precore and basal core promoter mutations on viral replicative
interference. Hepatology 34(2): 404-410.
Liaw YF, Chiu
KW, Chu CM, Sheen IS, Huang MJ (1990).
Heterosexual transmission of hepatitis delta virus in the general
population of an area endemic for hepatitis B virus infection: a
prospective study. J. Infect. Dis. 162(5): 1170-1172.
Lobato C, Tavares-Neto J, Rios-Leite M, Trepo C, Vitvitski L, Parvaz
P, Zoulim F, D'Oliveira A, Jr., Parana R (2006). Intrafamilial
prevalence of hepatitis B virus in Western Brazilian Amazon region:
epidemiologic and biomolecular study. J. Gastroenterol. Hepatol.
21(5): 863-868.
Madejon A, Cotonat T, Bartolome, J, Castillo I, Carreno V (1994).
Treatment of chronic hepatitis D virus infection with low and high
doses of interferon-alpha 2a: utility of polymerase chain reaction in
monitoring antiviral response. Hepatology 19(6): 1331-1336.
Niro GA, Casey JL, Gravinese E, Garrubba M, Conoscitore P,
Sagnelli E, Durazzo M, Caporaso N, Perri F, Leandro G,
Facciorusso D, Rizzetto M, Andriulli A (1999). Intrafamilial
transmission of hepatitis delta virus: molecular evidence. J. Hepatol.
30(4): 564-569.
Niro GA, Rosina F, Rizzetto M (2005). Treatment of hepatitis D. J.
Viral Hepatitis 12(1): 2-9.
Nisini R, Paroli M, Accapezzato D, Bonino F, Rosina F, Santantonio
T, Sallusto F, Amoroso A, Houghton M, Barnaba V (1997). Human
CD4+ T-cell response to hepatitis delta virus: identification of multiple
epitopes and characterization of T-helper cytokine profiles. J. Virol.
71(3): 2241-2251.
Novick DM, Farci P, Croxson TS, Taylor MB, Schneebaum CW, Lai
ME, Bach N, Senie RT, Gelb AM, Kreek MJ (1988). Hepatitis D virus
and human immunodeficiency virus antibodies in parenteral drug
abusers who are hepatitis B surface antigen positive. J. Infect. Dis.
158(4): 795-803.
Parana R, Kay A, Molinet F, Viana S, Silva LK, Salcedo JM,
Tavares-Neto J, Lobato C, Rios-Leite M, Matteoni L, D'Oliveira A,
Tauil P, Trepo C (2006). HDV genotypes in the Western Brazilian
Amazon region: A preliminary report. Am. J. Trop. Med. Hygiene
75(3): 475-479.
Parana R, Vitvitski L, Pereira JE (2008). Hepatotropic viruses in the
Brazilian Amazon: a health threat. Braz J Infect Dis 12(3): 253-256.
Rizzetto M (1983). The Delta-Agent. Hepatology 3(5): 729-737.
Rizzetto M, Canese MG, Arico S, Crivelli O, Trepo C, Bonino F,
Verme G (1977). Immunofluorescence detection of new antigen-
Vasconcelos et al. 269
antibody system (delta/anti-delta) associated to hepatitis B virus in
liver and in serum of HBsAg carriers. Gut 18(12): 997-1003.
Roingeard P, Diouf A, Sankale JL, Boye C, Mboup S, Diadhiou F,
Essex M (1993). Perinatal transmission of hepatitis B virus in
Senegal, west Africa. Viral Immunol 6(1): 65-73.
Sagnelli E, Coppola N, Scolastico C, Filippini P, Santantonio T,
Stroffolini T, Piccinino F (2000). Virologic and clinical expressions of
reciprocal inhibitory effect of hepatitis B, C, and delta viruses in
patients with chronic hepatitis. Hepatology 32(5): 1106-1110.
Saracco G, Rosina F, Brunetto MR, Amoroso P, Caredda F, Farci P,
Piantino P, Bonino F, Rizzetto M (1987).
Rapidly Progressive Hbsag-Positive Hepatitis in Italy - the Role of
Hepatitis Delta Virus-Infection. J. Hepatol. 5(3): 274-281.
Silva NMSM, Castro TM , Silva RSU (2010). Perfil epidemiológico,
clínico e laboratorial de portadores do vírus das hepatites B e delta
atendidos em serviço especializado no Acre. XLVI Congresso da
Sociedade Brasileira de Medicina Tropical. Foz do Iguaçu, Revista
da Sociedade Brasileira de Medicina Tropical. 41.
Smedile A, Rizzetto M, Gerin JL (1994). Advances in hepatitis D virus
biology and disease. Prog Liver Dis 12: 157-175.
Soares MCP, Bensabath G (1991). Tribos indígenas da Amazônia
Oriental como população de risco para a hepatite D (Delta). Revista
do Instituto de Medicina Tropical de São Paulo 33: 241-242.
Torres JR (1996). Hepatitis B and hepatitis delta virus infection in South
America. Gut 38 Suppl 2: S48-55.
Wang D, Pearlberg J, Liu YT, Ganem D (2001). Deleterious effects of
hepatitis delta virus replication on host cell proliferation. J. Virol.
75(8): 3600-3604.