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ZADAXIN, LAMIVUDINE, REBETRON,

               INTERFERÓN

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***** DERMAGIC-EXPRESS No 10 ********* 

****** 29 OCTUBRE DE 1.998 ******* 

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EDITORIAL ESPAÑOL:

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Amigos de la red, los saludo de nuevo, DERMAGIC, en esta ocasión, hace una revisión sobre algunos productos recientemente usados para el tratamiento de la hepatitis B y C

Bien es conocido por todos nosotros, el riesgo que TODO personal médico tiene de contraer hepatitis. Los productos son el denominado ZADAXIN de la casa SciClone Pharmaceuticals aprobado por la FDA en Mayo 1.998 el cual es efectivo en el tratamiento de la hepatitis B y C, químicamente se denomina thymosisn alfa 1. EL REBETRON, una terapia combinada de ribavirin e interferón alfa2b recombinante para la hepatitis C, aprobado por la FDA en Junio 1.998. 

El LAMIDUVINE, de la casa GLAXO WELLCOME, para la hepatitis B, nombre comercial EPIVIR. El INTERFERÓN ALFA ha mostrado ser útil en el tratamiento de la hepatitis B, C, D y G.

Pero en combinación con el RIBAVIRIN, pareciera tener mayor efectividad. También se esta utilizando la vacuna para hepatitis B, como inmunoterapia en la misma enfermedad. Estas 25 REFERENCIAS nos aclaran algo este interesante tema de las hepatitis y sus tratamientos. 

PRODUCTOS:

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LAMIVUDINE: (EPIVIR) TABS 150 MGRS GLAXO WELLCOME

RIBAVIRIN: (VIRAZOLE, TRIBAVIRIN)) AMPS 6 GRS (CANADA), REBETOL(R) Caps.

THYMOSIN ALFA 1: (ZADAXIN:) No encontré datos sobre presentación del producto en las bases de datos. Fue recientemente aprobado.

REBETRON: Rebetron is a combination of Rebetol(R) (ribavirin, USP) Capsules and

Intron(R) A (interferon alfa-2b, recombinant) Injection. Schering-Plough Corp.

INTERFERON ALFA:

tipos:

1) Interferon Alfa-2a, Recombinant; 2) Interferon Alfa-2b, Recombinant; 3) Interferon Alfa-n1(lns)a; 4) Interferon Alfa-n3b.

NOMBRES COMERCIALES:

1.) Alferon N4

2.) Intron A2

3.) Roferon-A1

4.) Wellferon3

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HEPATITIS B VACCINE RECOMBINANT 

Derivada del antigeno de superficie del virus de la hepatitis B (HBsAg) y producida en células de la levadura (Saccharomyces cerevisiae), esta vacuna protege contra hepatitis D tambien.

NOMBRES COMERCIALES:

1.) Engerix-B (SmithKline Beecham)

2.) Recombivax HB;

3.) Recombivax HB Dialysis Formulation.

...Y la vacuna contra la hepatitis A, HAVRIX, (SmithKline Beecham)

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Hasta la próxima edición amigos dermágicos...

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DERMAGIC/EXPRESS(10)

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ZADAXIN, LAMIVUDINE, REBETRON, INTERFERON ================================================================

REFERENCIA 1: thymosin alfa 1

REFERENCIA 2: thymosin alfa 1 e interferon en hepatitis C

REFERENCIA 3: thymosin alfa 1 y hepatitis B

REFERENCIA 4: thymosin alfa 1 y hepatitis B

REFERENCIA 5: lamiduvine y hepatitis B

REFERENCIA 6: lamiduvine y hepatitis B

REFERENCIA 7: lamiduvine y hepatitis B

REFERENCIA 8: lamiduvine y hepatitis B

REFERENCIA 9: thymosyn alfa 1 en LA WEB: Study Says Zadaxin Is Effective And Safe In The Treatment Of Chronic Hepatitis B

REFERENCIA 10: interferon y ribavirin en hepatitis C

REFERENCIA 11: interferon y ribavirin en hepatitis C

REFERENCIA 12: interferon y ribavirin en hepatitis C

REFERENCIA 13: interferon y ribavirin en hepatitis C

REFERENCIA 14: interferon y ribavirin en en la WEB: FDA Approves Rebetron Combination Therapy For Chronic Hepatitis C

REFERENCIA 15: hepatitis virus (A,B,C,D,E)

REFERENCIA 16: interferon y hepatitis D

REFERENCIA 17: hepatitis A innmunización

REFERENCIA 18: interferon alfa y hepatitis C y G

REFERENCIA 19: sarcoidosis en terapia con interferon para hepatitis C

REFERENCIA 20: interferon beta en hepatitis C resistente a interferon alfa

REFERENCIA 21: interferon alfa 2b en hepatitis B

REFERENCIA 22: inmunoterapia para hepatitis B con vacuna para hepatitis B

REFERENCIA 23: interferon alfa y lamivudine en hepatitis B resistente a interferon alfa

REFERENCIA 24: hepatitis E, aspectos tropicales

REFERENCIA 25: hepatitis E

====================================================

1.) Thymosin-alpha 1, but not interferon-alpha, specifically inhibits anchorage-

independent growth of hepatitis B viral transfected HepG2 cells.

====================================================

Moshier JA; Mutchnick MG; Dosescu J; Holtz TK; Akkary S; Mahakala K; Merline JR; 

Naylor PH

Department of Internal Medicine, Wayne State University School of Medicine, 

Detroit, Michigan, USA.

J Hepatol (DENMARK) Dec 1996 25 (6) p814-20 ISSN: 0168-8278

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9706

Subfile: INDEX MEDICUS

BACKGROUND: Thymosin-alpha 1 is a biological response modifier that has been used 

clinically, alone and in combination with interferon-alpha for the treatment of 

chronic hepatitis B viral infection. Both immunomodulatory and immediate 

intracellular mechanisms have been postulated to explain the effect of these two 

agents on HBV-infected hepatocytes. METHODS: In this study, hepatitis B transfected 

HepG2 hepatoblastoma cells (HepG2-Nu2), derived from 2.2.15 cells, were used as an in 

vitro model to determine the efficacy of thymosin-alpha 1 and interferon-alpha, 

individually and combined, as proliferation inhibitors of HBV-infected cells. For 

comparison, parental HepG2 cells and an SV40-transfected HepG2 cell line (HepG2P9T2) 

were also evaluated. RESULTS: In a clonogenic soft agar assay, thymosin-alpha 1 

inhibited the anchorage-independent growth of the HepG2-Nu2 cells by 40% compared 

with untreated controls, but did not inhibit parental HepG2 or HepG2P9T2 clonal 

growth. The response was dose dependent over concentrations spanning three log units. 

In comparison, 10000 units/ml of interferon-alpha inhibited parental HepG2, HepG2-N4Z 

and HepG2P9T2 by 33%, 41% and 87%, respectively. The combination of thymosin-alpha 1 

and interferon-alpha consistently inhibited HepG2-Nu2 clonal growth more effectively 

than either treatment alone, reaching maximum inhibition levels of 51%. CONCLUSIONS: 

Thymosin-alpha 1 specifically inhibits the tumorigenic growth of HBV-transfected 

HepG2 cells in contrast to the general inhibition displayed by interferon-alpha. 

This panel of cell lines may be an important resource for dissecting the mechanism by 

which thymosin, alone or in combination with other drugs, influences HBV-infected 

hepatocytes and/or HBV-associated carcinoma.

====================================================

2.) Combination thymosin alpha 1 and lymphoblastoid interferon treatment in chronic 

hepatitis C [see comments]

====================================================

Rasi G; DiVirgilio D; Mutchnick MG; Colella F; Sinibaldi-Vallebona P; Pierimarchi P; 

Valli B; Garaci E

Istituto di Medicina Sperimentale, CNR-Roma, Italy.

Gut (ENGLAND) Nov 1996 39 (5) p679-83 ISSN: 0017-5749

Note: Comment in: Gut 1996 Nov;39(5 ):769

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9704

Subfile: AIM; INDEX MEDICUS

BACKGROUND: Monotherapy for chronic hepatitis C using interferon (IFN) results in a 

very small proportion of patients exhibiting a sustained response. Clinical trials 

assessing the benefit of combination drug therapy may provide evidence of improved 

treatment response over that seen with single drug treatment. AIM: To assess the 

response in patients with chronic hepatitis C to one year of combination treatment: 

thymosin alpha 1 (T alpha 1), 1 mg twice weekly, and lymphoblastoid (L)-IFN, 3 MU 

thrice weekly. PATIENTS AND METHODS: Fifteen patients with serum HCV RNA positive 

chronic hepatitis C were studied. Eleven patients were treatment naive and four had 

failed previous standard IFN therapy. Thirteen patients were HCV RNA serotype 1b. 

All patients were given combination T alpha 1 and L-IFN therapy for one year with a 

six month follow up period. RESULTS: Six months after initiation of treatment seven 

patients (47%) were sera HCV RNA negative and at completion of the one year treatment 11 (73%), including two who had failed previous standard IFN treatment, had negative serum HCV RNA. Six months after treatment, six patients (40%), including five with 

HCV type 1b, showed a sustained response characterized by a negative serum HCV RNA. 

CONCLUSIONS: The results of this open label trial suggest that there may be a 

potential benefit to combining an immune modulator (T alpha 1) with an antiviral 

(IFN) in the treatment of chronic hepatitis C. Verification of the observations in 

this study require completion of a randomised controlled study.

====================================================

3.) Emergence of an S gene mutant during thymosin alpha1 therapy in a patient with chronichepatitis B. 

====================================================

Author 

Tang JH; Yeh CT; Chen TC; Hsieh SY; Chu CM; Liaw YF 

Address 

Department of Pathology, Chang Gung Memorial Hospital and University, Taipei, Taiwan. 

Source 

J Infect Dis, 178(3):866-9 1998 Sep 

Abstract 

The presence of a hepatitis B virus S gene mutant was investigated in a patient being treated with thymosin alpha1. He was seropositive for hepatitis B e antigen throughout therapy but was intermittently seronegative for hepatitis B surface antigen (HBsAg) by an RIA. Sequence analysis revealed an S gene mutant in HBsAg-seronegative serum with two consecutive amino acid substitutions: threonine115-to-isoleucine and threonine116-to-asparagine, whereas no amino acid substitution or deletion was found in the pre-S region. A site-directed mutagenesis experiment confirmed that these mutations were responsible for the failure to detect HBsAg. In summary, an S gene mutant was identified in an HBsAg-seronegative patient. The mutations were located outside the putative "a"

determinant. The emergence of an S gene mutant during thymosin alpha1 treatment suggests that enhanced host immunity against HBsAg may play a role in its antiviral activity.

====================================================

4.) Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. 

====================================================

Author 

Chien RN; Liaw YF; Chen TC; Yeh CT; Sheen IS 

Address 

Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University, Taipei,

Taiwan. 

Source 

Hepatology, 27(5):1383-7 1998 May 

Abstract 

Thymosin alpha1 (Talpha) is an immune modifier that has been shown in a pilot study to be effective for chronic hepatitis B; this requires confirmation. Ninety-eight patients with clinicopathologically proven chronic hepatitis B were randomly allocated to 3 groups: 1) group A received a 26-week course of Talpha with a 1.6-mg subcutaneous injection two times a week (T6 group); 2) group B received the same regimen as group A, but Talpha therapy extended for 52 weeks (T12 group); and 3) group C served as a control group and was followed up for 18 months without specific treatment (T0 group). The three groups were comparable in clinicohistological features at entry. The complete virological response rate (clearance of serum hepatitis B virus [HBV] DNA and hepatitis B e antigen [HBeAg]) was higher in group A (40.6%) and group B (26.5%) than in group C (9.4%) (group A vs. group

C: P=.004; group B vs. group C: P=.068) when assessed 18 months after entry,

although complete response rates among these three groups were similar when first assessed at the end of therapy. There was a trend for complete virological response to increase or accumulate gradually after the end of Talpha therapy. None of the responders lost hepatitis B surface antigen. Blinded histological assessment showed a significant improvement in treated patients, particularly in lobular necroinflammation and scores excluding fibrosis. No significant side effects were observed. These results suggest that a 26-week course of Talpha therapy is effective and safe in patients with chronic hepatitis B. 

=======================================================

5.) Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and 

patterns.

=======================================================

Honkoop P; Niesters HG; de Man RA; Osterhaus AD; Schalm SW

Department of Internal Medicine II, Erasmus University Hospital Rotterdam, The 

Netherlands.

J Hepatol (DENMARK) Jun 1997 26 (6) p1393-5 ISSN: 0168-8278

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9711

Subfile: INDEX MEDICUS

BACKGROUND: Lamivudine is a non-toxic, potent inhibitor of hepatitis B virus 

replication. Recently, hepatitis B virus resistance to lamivudine has been described 

in patients using immunosuppressive drugs after liver transplantation. METHODS: From 

our cohort of 81 consecutive patients treated with lamivudine, we selected all 

immunocompetent patients who received lamivudine monotherapy for a period over 26 

weeks (n=14). RESULTS: Lamivudine resistance with the characteristic mutation in the 

YMDD motif was observed in four patients (actuarial cumulative incidence: 39%). Two 

patterns of viral resistance were observed: incomplete response (n=2) and viral 

breakthrough (n=2). CONCLUSIONS: The observed high frequency of lamivudine 

resistance may have implications for the concept of long-term virus-suppressive 

therapy of chronic hepatitis B by lamivudine monotherapy.

=======================================================

6.) Lamivudine treatment of advanced and decompensated liver disease due to hepatitis 

B.

=======================================================

Van Thiel DH; Friedlander L; Kania RJ; Molloy PJ; Hassanein T; Wahlstrom E; Faruki 

H

Department of Medicine, University of Kentucky School of Medicine, Lexington, USA.

Hepatogastroenterology (GREECE) May-Jun 1997 44 (15) p808-12 ISSN: 0172-6390

Language: ENGLISH

Document Type: CLINICAL TRIAL; JOURNAL ARTICLE 

Journal Announcement: 9711

Subfile: INDEX MEDICUS

The purpose of this study was to evaluate the effectiveness and safety of 

lamivudine treatment in patients with advanced and end-stage liver disease caused by 

hepatitis B. Nine cases of advanced or end-stage liver disease due to hepatitis B 

infection were treated with lamivudine. Four received liver transplants while 

receiving lamivudine. Moreover, each of these four has been maintained on lamivudine 

therapy post-transplantation while receiving immunosuppression. No cases of HBV 

reactivation have been seen. More importantly, the allograft liver tissue has been 

HBc and HBs antigen negative as well as HBV-DNA negative by PCR. This report 

suggests that: 1) lamivudine can be given safely to liver transplant candidates; 2) 

lamivudine suppresses HBV replication, so much so that HBV-DNA becomes undetectable 

in the serum; 3) despite powerful immunosuppression associated with transplantation, 

HBV reactivation does not occur under lamivudine therapy; and 4) the observations 

should cause transplant physicians, surgeons and third-party payers to reconsider 

their positions relative to transplantation of individuals with HBV-associated 

cirrhosis.

=======================================================

7.) Effect of lamivudine on morphology and function of mitochondria in patients with 

chronic hepatitis B.

=======================================================

Honkoop P; de Man RA; Scholte HR; Zondervan PE; Van Den Berg JW; Rademakers LH; 

Schalm SW

Department of Internal Medicine II, Erasmus University Hospital, Rotterdam, The 

Netherlands.

Hepatology (UNITED STATES) Jul 1997 26 (1) p211-5 ISSN: 0270-9139

Language: ENGLISH

Document Type: CLINICAL TRIAL; JOURNAL ARTICLE 

Journal Announcement: 9710

Subfile: INDEX MEDICUS

Nucleoside analogues can induce mitochondrial dysfunction leading to severe 

clinical syndromes. Lamivudine, a new nucleoside analogue, is an active inhibitor of 

hepatitis B viral replication without apparent clinical toxicity. To assess 

subclinical mitochondrial toxicity, we studied the morphology and function of the 

mitochondrial system in 15 patients treated with lamivudine. Morphology was 

investigated by routine histological evaluation and electron-microscopic studies of 

mitochondria in liver biopsy specimens. Mitochondrial function was assessed by 2-

keto[1-14C] isocaproic acid decarboxylation (KICA breath test) and by measuring the 

activity in liver biopsy specimens of the mitochondrial enzymes encoded by nuclear 

and mitochondrial DNA (mt-DNA) (complex I and IV) as well as a mitochondrial and a 

cytosolic enzyme both encoded by nuclear DNA only (complex II and lactic 

dehydrogenase [LDH]). All 15 patients underwent a liver biopsy before treatment and 

a KICA breath test before and during treatment; 13 agreed to undergo a repeat liver 

biopsy during lamivudine treatment. Liver tissue with no or minimal fibrotic changes 

from 7 patients treated for 6 months with lamivudine was suitable for assessment of 

the mitochondrial enzyme activity. We observed no signs of toxicity by routine 

histological or electron-microscopic evaluation. KICA breath tests revealed no 

differences in either peak exhalation or the area under the curve from 0 to 60 

minutes between healthy controls (3.0% and 19.3%), untreated patients with chronic 

hepatitis B (3.4% and 19.3%), and patients treated with lamivudine (3.1% and 20.6%). 

The activities of the mt-DNA-encoded enzymes remained normal after lamivudine therapy. 

Unexpectedly a significant decrease in the activity of nuclear-DNA-encoded enzymes in 

patients with chronic hepatitis B in comparison with normal controls was found. The 

mean activity of complex II dropped from 45.3 to 20.0 micromol x min(-1), that of 

lactic dehydrogenase from 106 to 44 micromol x min(-1) (Wilcoxon rank sum; P < .05). 

In conclusion, no subclinical signs of mitochondrial toxicity resulting from 

lamivudine therapy for 6 months were observed.

=======================================================

8.) Histological improvement in patients with chronic hepatitis B virus infection 

treated with lamivudine.

=======================================================

Honkoop P; de Man RA; Zondervan PE; Schalm SW

Department of Internal Medicine II, (Section Hepatology), Erasmus University 

Hospital, Rotterdam, The Netherlands.

Liver (DENMARK) Apr 1997 17 (2) p103-6 ISSN: 0106-9543

Language: ENGLISH

Document Type: CLINICAL TRIAL; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; 

MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL 

Journal Announcement: 9709

Subfile: INDEX MEDICUS

Lamivudine is an oral nucleoside analogue with strong antiviral activity against 

hepatitis B virus (HBV). In previous clinical studies, a course of lamivudine for 4-

12 weeks induced a profound decrease in HBV viraemia with excellent tolerance, but 

data on histology have not yet been reported. We studied the liver histology of 13 

patients with stable chronic HBV infection treated with 25 mg, 100 mg or 300 mg 

lamivudine daily for 6 months. All patients became HBV-DNA negative during treatment. 

The paired biopsies taken at entry and during treatment were scored by two 

independent observers, using the components of the histology activity index (HAI) and 

fibrosis (modified Knodell). The items scored were piecemeal necrosis, focal 

necrosis, confluent necrosis, portal inflammation and fibrosis. Before treatment, 

the biopsies yielded a mean HAI of 4.4 (+/- 0.8), which decreased to HAI 2.8 (+/- 

0.5) during treatment. An analysis of the individual components of the 

classification system showed a significant decrease in piecemeal necrosis from a pre-

treatment 1.4 (+/- 0.3) to 0.8 (+/- 0.1) during treatment (p = 0.02). Although a 

trend was found for the other components, it was not statistically significant, 

probably due to the number of pairs examined. In conclusion these results suggest 

that prolonged suppression of viral replication by lamivudine can improve liver 

histology. In contrast to previously published reports on alpha-interferon therapy, 

this study indicates that the improvement in liver histology with lamivudine is 

independent of HBe-seroconversion.

====================================================

9.) Study Says Zadaxin Is Effective And Safe In The Treatment Of Chronic Hepatitis B

====================================================

SAN MATEO, CA -- May 29, 1998 – Phase III clinical trial results of

SciClone Pharmaceuticals’ Zadaxin® thymosin alpha 1 show that the drug is

safe and effective in the treatment of chronic hepatitis B.

The trial results are published in this month’s issue of Hepatology.

Importantly, the Zadaxin complete virologic response rate (the conversion from

both hepatitis B virus positive to negative and hepatitis B e antigen positive to

negative) in the study continues to increase even when measured one year after

the end of treatment.

The publication on the study's primary site data, written by professor Yun-Fang

Liaw, M.D. and his colleagues of the Chang Gung Memorial Hospital, Taiwan,

included 98 Asian patients with chronic hepatitis B. At the start of the study,

patients were randomised to receive 1.6 mg of Zadaxin two times per week for

26 weeks, 52 weeks or no treatment. Patients were followed for a total of 18

months.

The publication highlights that patients receiving ZADAXIN showed

statistically-significant increase in conversion from both hepatitis B virus positive to negative and hepatitis B e antigen positive to negative.

At the end of the study, 40.6 percent of patients receiving 1.6 mg of Zadaxin

twice per week for 26 weeks tested negative for both hepatitis B virus and

hepatitis B e antigen (an immune response to the hepatitis B virus that can

indicate long lasting remission of the disease) compared to 9.4 percent of

patients in the control group, a statistically significant result.

Patients responding to Zadaxin showed statistically significant improvement in

liver histology (inflammation of the liver), consistent with the ultimate goals of

therapy for hepatitis B – to prevent progression to serious liver disease,

including liver cancer and cirrhosis.

"Thymosin alpha 1 is safe and effective in the treatment of chronic hepatitis B.

The thymosin alpha 1 response rate is statistically significant in the six month

treatment group when compared to control," the researchers write. "It also

reduces liver inflammation. Thymosin alpha 1 therapy offers renewed hope in

the fight against chronic hepatitis B."

Hepatitis B is a potentially deadly liver disease and one of the most common

causes of death in the world. According to the World Health Organization,

approximately 350 million people, or five percent of the world's population, are

chronic carriers of the hepatitis B virus in their blood. These carriers of the

hepatitis B virus have a 200-fold increased chance of developing serious liver

disease, including liver cancer, the most common cancer in the world, and

cirrhosis.

Currently, Zadaxin and interferon (a drug that produces a sustained response in

less than one third of Asian patients treated and causes debilitating side effects)

are the only established therapies for hepatitis B in certain Asian markets,

including the People's Republic of China.

====================================================

10.) Moving towards the optimal treatment of chronic hepatitis C.

====================================================

Camma C; Giunta M; Almasio P; Di Marco V; Craxi A

ISMEDA-CNR, University of Palermo, Italy.

Ital J Gastroenterol Hepatol (ITALY) Feb 1997 29 (1) p69-74

Language: ENGLISH

Document Type: JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE 

Journal Announcement: 9711

Subfile: INDEX MEDICUS

Almost 10 years after the first report of the effectiveness of interferon (IFN) for 

chronic NANB hepatitis, the optimal treatment for chronic hepatitis C is still a 

matter of debate. The issue of the relative importance of higher doses versus a 

longer period of therapy remains unsettled, since the long-term response may be a 

function of the total dose received. Controlled studies have shown that high doses 

of IFN (5-6 MU t.i.w.), a long period of therapy (> 12 months) and the administration 

of a large total dose are all associated with a higher cure rate. However, these 

measures can cause more adverse effects and certainly cost more than the current 

schedule of 3 MU t.i.w. for a period of 6 months. The standard schedule may be 

appropriate for subjects with pre-treatment features predictive of a good response 

(non-Ib genotype, low viraemia, absence of cirrhosis). Alternative treatment 

schedules or combination therapy with interferon/ribavirin should be considered in 

subjects with normalized alanine aminotransferase (ALT) levels, but who are still 

viremic after three months of therapy, as well as in relapsers and in non-responders.

====================================================

11.) [The effect of interferon in combination with ribavirin on the plus and minus 

strands of hepatitis C virus RNA in patients with hepatitis]

====================================================

He Y; Liu W; Zeng L

Department of Infectious Diseases, Xiehe Hospital, Tongji Medical University, 

Wuhan.

Chung Hua Nei Ko Tsa Chih (CHINA) Jan 1996 35 (1) p32-5 ISSN: 0578-1426

Language: CHINESE Summary Language: ENGLISH

Document Type: 

JOURNAL ARTICLE English Abstract

Journal Announcement: 9711

Subfile: INDEX MEDICUS

The effect of interferon in combination with ribavirin on the plus and minus 

strands of hepatitis C virus (HCV) RNA in patients with chronic hepatitis C (CHC) was 

studied by means of nested RT-PCR. The results showed that in those who respond to 

the combination of antiviral therapy, their increased serum ALT levels decreased to 

normal range, but more than half (55.56%) of these patients relapsed 24 weeks after 

cessation of the antiviral therapy. The positive rate of the plus strand HCV RNA in 

serum (92.31%) decreased significantly to 38.46% (P < 0.005) and that of the minus 

strands HCV RNA in peripheral blood mononuclear cells (PBMC, 76.92%) to 38.46% (P < 

0.05) at the end of the treatment, but little effect on the plus strand HCV RNA in 

PBMC in these patients was found. Relapse occurred in patients whose plus and minus 

strands of HCV RNA in PBMC remained positive during treatment. These data indicated 

that absence of HCV RNA in serum do not mean complete clearance of HCV and can not 

predict a sustained therapeutic response. For evaluating the antiviral effect and 

prognosis it is essential to measure the plus and minus strands of HCV RNA in serum 

and PBMC simultaneously. The results of the combined antiviral therapy were similar 

to that of single interferon treatment; it seems that rib-a-virin do not enhance the 

antiviral effect of interferon.

====================================================

12.) effect of interferon-alpha and ribavirin therapy on serum GB virus C/hepatitis G 

virus (GBV-C/HGV) RNA levels in patients chronically infected with hepatitis C virus 

and GBV-C/HGV.

====================================================

Lau JY; Qian K; Detmer J; Collins ML; Orito E; Kolberg JA; Urdea MS; Mizokami M; 

Davis GL

Department of Medicine, University of Florida, Gainesville 32610, USA.

J Infect Dis (UNITED STATES) Aug 1997 176 (2) p421-6 ISSN: 0022-1899

Contract/Grant No.: RR-0082--RR--NCRR; AI-41219--AI--NIAID

Language: ENGLISH

Document Type: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL 

Journal Announcement: 9710

Subfile: AIM; INDEX MEDICUS

GB virus C/hepatitis G virus (GBV-C/HGV) is a newly described virus associated with 

hepatitis in humans, and GBV-C/HGV coinfection is common in patients chronically 

infected with hepatitis C virus (HCV). To determine the clinical impact of GBV-C/HGV 

infection in such patients and the effect of interferon-alpha and ribavirin therapy 

on serum GBV-C/HGV RNA levels, GBV-C/HGV RNA was detected and quantitated in serum 

samples from 62 chronically infected HCV patients by a combination of a qualitative 

nested reverse transcription-polymerase chain reaction and a newly developed 

quantitative branched DNA assay: 10 patients were positive for serum GBV-C/HGV RNA. 

There were no differences in the clinical, biochemical, and histologic features of 

the patients with GBV-C/HGV-HCV coinfection compared with those with HCV infection 

alone. Interferon-alpha treatment caused a marked but usually transient reduction in 

serum GBV-C/HGV RNA, and ribavirin had, at most, a modest antiviral effect.

====================================================

13. Ribavirin and interferon-alpha combination therapy vs interferon-alpha alone in the retreatment of chronic hepatitis C: a randomized clinical trial.

====================================================

Bellobuono A; Mondazzi L; Tempini S; Silini E; Vicari F; Ideo G

Crespi Division of Medicine, Niguarda Hospital, Milan, Italy.

J Viral Hepat (ENGLAND) May 1997 4 (3) p185-91 ISSN: 1352-0504

Language: ENGLISH

Document Type: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL 

Journal Announcement: 9710

Subfile: INDEX MEDICUS

Interferon-alpha (IFN-alpha) induces sustained remission of chronic hepatitis C in 

approximately 25% of patients. In patients who are non-responders to the first 

course of therapy, retreatment with IFN-alpha is of limited efficacy. Ribavirin has 

also been used to treat chronic hepatitis C, but it induces only a transient response. 

In this study, we evaluated the efficacy of ribavirin and IFN-alpha combination 

therapy for IFN-alpha resistant chronic hepatitis C. Twenty-four IFN-alpha non-

responders and 24 relapsers were randomized to receive either ribavirin (1000 mg per 

day) together with IFN-alpha (3-6 million units (MU) thrice weekly) or the same dose 

of IFN-alpha alone, for 6 months. Both at the end of treatment and 6 months later, 

normal transaminase levels were more common in the patients receiving combination 

therapy than in the group receiving IFN-alpha alone: 17 (70.8%) vs seven (29.2%) 

patients (P = 0.009) and six (25%) vs one (4.2%) patient (P = 0.034), respectively. 

At the end of treatment and 6 months later, serum HCV RNA was no longer detectable in 

eight (33.3%) and five (20.8%) patients in the combination therapy group and in six 

(25%) and one (4.2%) patient in the IFN-alpha therapy group, respectively. Three 

patients (12.5%) were withdrawn prematurely from combination therapy because of side-

effects; ribavirin therapy was ceased or dosage reduced in six other patients (25%), 

again because of side-effects. In conclusion, this combination treatment was more 

effective than retreatment with IFN-alpha, alone, in inducing sustained biochemical 

remission of chronic hepatitis C that was resistant to a previous course of IFN-alpha. 

The combination treatment, however, was frequently associated with significant side-

effects.

====================================================

14.) FDA Approves Rebetron Combination Therapy For Chronic Hepatitis C

====================================================

MADISON, NJ -- June 3, 1998 -- The United States Food and Drug

Administration has approved Schering-Plough Corp.’s Rebetron™, a

combination therapy for chronic hepatitis C in patients with compensated liver

disease who have relapsed following alpha interferon therapy

Rebetron is a combination of Rebetol(R) (ribavirin, USP) Capsules and

Intron(R) A (interferon alfa-2b, recombinant) Injection. Prior to Rebetron

combination therapy, the only drugs approved in the U.S. for treating hepatitis

C had been alpha interferons.

The FDA decision was based in part on clinical data from two pivotal

multicentre Phase III studies involving patients with hepatitis C who had

relapsed following alpha interferon therapy. Results of these studies showed

that Rebetron combination therapy resulted in a 10-fold increase in the number

of patients showing eradication of detectable [HCV-RNA (qPCR)-negative]

hepatitis C virus as compared to patients receiving Intron A alone.

"Rebetron combination therapy is an exciting treatment breakthrough," said

Willis Maddrey, M.D., professor of medicine at the University of

Texas-Southwestern Medical Center in Dallas. "We've learned from research

in viral diseases such as AIDS that combination therapies rather than

monotherapy offer the best potential for effective treatment."

Some four million Americans are chronically infected with the hepatitis C virus,

according to the Centers for Disease Control and Prevention (CDCP). The

CDCP has estimated that 20 to 50 percent of chronically infected hepatitis C

patients will develop liver cirrhosis and 20-30 percent of those will go on to

develop liver cancer or liver failure requiring liver transplant.

Hepatitis C infection contributes to the deaths of 8,000 to 10,000 Americans

each year. This toll is expected to triple by the year 2010 and exceed the

number of annual deaths due to AIDS, according to the CDCP. The American

Liver Foundation has reported that liver failure due to hepatitis C infection is the

leading cause of liver transplants in the U.S. 

The safety and efficacy of Rebetron combination therapy were evaluated in two

identical controlled double-blind clinical trials involving 345 chronic hepatitis C

patients who had received previous treatment with alpha interferon and

relapsed after having an initial response. Relapse patients were defined as

patients who had a normal serum alanine aminotransferase (ALT) level at the

end of up to 18 months of alpha interferon therapy with abnormal ALT values

within one year following the end of the most recent course of therapy.

Patients in the clinical trials were randomised to receive subcutaneous injections

of Intron A three million international units (MIU) three times a week and either

oral Rebetol 1,000-1,200 mg daily or a matched placebo for 24 weeks of

treatment. At six months post-treatment, 79 of 173 patients (45.7 percent) who

received the combination therapy had undetectable virus levels compared to

eight of 172 patients (4.7 percent) who received Intron A and placebo. Patient

tolerance of the combination therapy was good, with six percent of patients

treated with Rebetron discontinuing therapy due to adverse events versus three

percent of patients treated with Intron A and placebo.

The most common adverse experiences associated with Rebetron combination

therapy are flu-like symptoms, such as headache, fatigue, myalgia and fever,

which appear to decrease in severity as treatment continues. Psychiatric

disorders have been reported during Rebetron combination therapy, both in

patients with a previous psychiatric history and in patients with no history.

These adverse events include depression, which may be severe, and rare cases

Of suicide ideation and suicidal attempt. Rebetron combination therapy is

associated with a significant risk of abnormal fetal development. Women of

childbearing potential should not begin therapy until a report of a negative

pregnancy test has been obtained. 

===================================================================

15.) Hepatitis viruses: changing patterns of human disease (published erratum appears in Proc Natl Acad Sci U S A 1994 Sep 13;91(19):9195)

==================================================================

Journal: Proc Natl Acad Sci U S A 91:2401-6, 1994

Publication Date: 1994 March 29

Author(s): Purcell RH

Abstract: Viral hepatitis is a disease of antiquity, but evidence for more than one etiologic agent has been recognized only since the 1940s, when two viruses (hepatitis A virus and hepatitis B virus) were thought to account for all disease. In the past 20 years, three additional hepatitis agents (hepatitis C virus, hepatitis D virus, and hepatitis E virus) have been discovered, and there is evidence for at least one additional virus. Each of the five recognized hepatitis viruses belongs to a different virus family, and each has a unique epidemiology. The medical impact of these viruses on society has been strongly influenced by changes in human ecology. This has resulted in some cases in diminished disease and in others in increases in the incidence of disease.

============================================================

16.) Treatment of chronic hepatitis D with interferon alfa-2a (see comments)

============================================================

Journal: N Engl J Med 330:88-94, 1994

Publication Date: 1994 January 13

Author(s): Farci P, Mandas A, Coiana A, Lai ME, Desmet V, Van Eyken P, Gibo Y, Caruso L, Scaccabarozzi S, Criscuolo D, et al

Abstract: 

BACKGROUND AND METHODS. Chronic hepatitis D is a severe and rapidly progressive liver disease for which no therapy has been proved effective. To evaluate the efficacy of treatment with interferon, we studied 42 patients with chronic hepatitis D who were randomly assigned to receive either 9 million or 3 million units of recombinant interferon alfa-2a (three times a week for 48 weeks) or no treatment.

RESULTS. By the end of the treatment period, serum alanine aminotransferase values had become normal in 10 of 14 patients receiving 9 million units (71 percent), as compared with 4 of 14 treated with 3 million units (29 percent, P = 0.029) and 1 of 13 untreated controls (8 percent, P = 0.001). Seven patients treated with the higher dose of interferon (50 percent) had a complete response (normal levels of alanine aminotransferase and no detectable serum hepatitis delta virus (HDV) RNA), as compared with three of those who received the lower dose (21 percent, P = 0.118), and none of the controls (P = 0.004). Treatment with 9 million units of interferon was associated with a marked improvement in the histologic findings (reduced periportal necrosis and portal and lobular inflammation), whereas in the untreated controls there was considerable histologic deterioration. In 5 of the 10 patients treated with 9 million units of interferon whose alanine aminotransferase values became normal, the biochemical responses persisted for up to 4 years (mean, 39 months), but the effects of treatment on viral replication were not sustained. In contrast, none of those who received 3 million units and none of the untreated controls had a sustained biochemical or virologic response.

CONCLUSIONS. In about half the patients with chronic hepatitis D treated with high doses of interferon alfa-2a (9 million units three times a week for 48 weeks), the serum alanine aminotransferase level becomes normal, HDV RNA becomes undetectable in serum, and there is histologic improvement. However, a relapse is common after treatment has been stopped.

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17.) Long-term persistence of anti-HAV antibodies following active immunization with hepatitis A vaccine.

======================================================================

Maiwald H; Jilg W; Bock HL; Loscher T; Sonnenburg F

Department of Infectious Diseases and Tropical Medicine, University of Munich, 

Germany.

Vaccine (ENGLAND) Mar 1997 15 (4) p346-8 ISSN: 0264-410X

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9709

Subfile: INDEX MEDICUS

Seventy-one anti-hepatitis A virus (HAV) negative volunteers were immunized against 

hepatitis A. An inactivated hepatitis A vaccine (HAVRIX, SmithKline Beecham), derived 

from tissue cell cultures, at single doses of 720 ELISA units was used following a 

schedule of vaccinations at month 0.1 and 6. The vaccines were tested for the 

presence of HAV antibodies 1 month after each vaccination and then after 2, 3, 4 and 

5 years. The annual decrease of anti-HAV titres was 25%. Five years after 

vaccination a protective antibody titre, varying between 20 and 5200 mIU ml-1, could 

be demonstrated in all 47 retested volunteers with a geometric mean titre (GMT) of 

442 mIU ml-1. Levels of anti-HAV-antibodies following active immunization were 

significantly higher in female volunteers. This could be consistently demonstrated 

throughout the observation period. Based on these data the antibody persistence was 

calculated over time. GMTs at protective levels higher than 20 mIU ml-1 can be 

expected to persist for at least 15 years.

=====================================================================

18.) Hepatitis C and G co-infection: response to interferon therapy and quantitative changes in serum HGV-RNA. 

=====================================================================

Author 

McHutchison JG; Nainan OV; Alter MJ; Sedghi-Vaziri A; Detmer J; Collins M; Kolberg J 

Address 

Division of Gastroenterology/Hepatology, Scripps Clinic and Research Foundation, La Jolla,

CA 92037, USA. 

Source 

Hepatology, 26(5):1322-7 1997 Nov 

Abstract 

Hepatitis G virus (HGV), a positive sense RNA virus, is distantly related to hepatitis C

virus (HCV): its genetic organization and identity are consistent with the Flaviviridae family.

Coinfection with HGV occurs in 10% to 20% of HCV-infected subjects. These similarities

raise two theoretical questions. First, could HGV coinfection play any role in the response of

HCV to antiviral therapy and second, would this coinfected population have changes in

serum HGV-RNA induced by interferon. To address these questions, 98 patients with

documented chronic HCV underwent interferon therapy (3 million units three times a week)

for 6 months. Response to therapy was categorized using standard biochemical criteria.

Changes in HGV-RNA levels were evaluated before, during, and after interferon therapy by

a quantitative branched DNA amplification research-based assay. Eleven of 98 (11%)

patients with HCV infection had detectable serum HGV-RNA. There was no difference

between the groups (HGV+ vs. HGV-) when baseline alanine aminotransferase (ALT)

values, HCV-RNA levels, HCV genotype, histological severity, or other demographic

features were analyzed. Interferon response was similar in both groups and HGV was not

associated with outcome following therapy. Antiviral therapy appeared to induce a

reduction in HGV-RNA load in five of nine patients coinfected with HCV serially tested. In

two patients, the fall in serum HGV-RNA correlated with biochemical response, independent

of changes in HCV-RNA. These observations indicate that a larger study of an HGV

population is required to more clearly define the relationship between HCV and HGV

coinfection and their response to antiviral therapy. 

====================================================================

19.) Sarcoidosis associated with interferon-alpha therapy for chronic hepatitis C. 

====================================================================

Author 

Hoffmann RM; Jung MC; Motz R; G¨ossl C; Emslander HP; Zachoval R; Pape GR 

Address 

Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany. 

Source 

J Hepatol, 28(6):1058-63 1998 Jun 

Abstract 

BACKGROUND/AIMS: Pulmonary side effects of interferon-alpha therapy of chronic

hepatitis C seem to be rare. So far, only two cases of sarcoidosis in association with

interferon-alpha treatment of chronic hepatitis C have been described.

METHODS/CASES: We report on three patients who were treated with recombinant

interferon-alpha2a for chronic hepatitis C, two of them in combination with ribavirin. These

patients developed pulmonary sarcoidosis 12, 20 and 21 weeks, respectively, after beginning

interferon therapy, one patient with L¨ofgren's syndrome. In one patient sarcoidosis emerged

only after discontinuation of interferon therapy because of treatment failure. Clinical

symptoms of sarcoidosis in the three patients were suggestive of side effects of

interferon-alpha. Interferon therapy was discontinued and spontaneous remission was

observed in all three cases 5, 6, and 8 months, respectively, after the onset of symptoms.

CONCLUSION: The occurrence of sarcoidosis in association with interferon-alpha therapy

for chronic hepatitis C may have been underestimated so far. This could be due to the fact

that symptoms of sarcoidosis and common side effects of interferon are similar, and

sarcoidosis may occur after the end of interferon therapy. We hypothesize that

interferon-alpha as a potent stimulator for T-helper 1 (Th1) immune responses may trigger

the compartmentalized Th1 reaction that has been shown to take place in sarcoidosis. 

==================================================================

20.) Pilot study on the safety and efficacy of intravenous natural beta-interferon therapy in patients with chronic hepatitis C unresponsive to alpha-interferon. 

==================================================================

Author 

Mazzoran L; Grassi G; Giacca M; Gerini U; Baracetti S; Fanni-Canelles M; Zorat F;

Pozzato G 

Address 

Department of Internal Medicine, University of Trieste, Italy. 

Source 

Ital J Gastroenterol Hepatol, 29(4):338-42 1997 Aug 

Abstract 

BACKGROUND: Since a large fraction of patients affected by chronic hepatitis C do not

respond to alpha-interferon therapy, we planned a pilot study of intravenous beta-interferon

therapy in Italian patients non responsive to several courses of alpha-interferon.

METHODS: Ten Italian patients with chronic hepatitis C were treated intravenously with

beta-interferon to assess the biochemical and virological responses. Each patient received

intravenously 6 MU of beta-interferon daily for 7 days a week for a period of 2 months; in

responders, this treatment was followed by intramuscular beta-interferon administration 6

MU three times a week for an additional 8 weeks. RESULTS: All the patients were infected

by the genotype 1b of hepatitis C virus and had a high serum concentration of HCV-RNA

(4.1 +/- 3.3 x 10(7) copies/ml). During intravenous therapy, 4 patients (40%) showed a

complete return to normal of alanino-aminotransferase and 3 cases became HCV-RNA

negative. During intramuscular beta-interferon administration, two patients breakthrough. At

the end of the follow-up (six months after the end of the treatment) two patients only showed

return to normal of alanino-aminotransferase, but one of them remained HCV-RNA positive.

CONCLUSIONS: These results indicate that even genotype 1b of hepatitis C virus can be

suppressed by intravenous beta-interferon therapy, as previously described in similar cases

in Japan. The rate of sustained biochemical and virologic response was, however, low,

suggesting that further studies are needed to define the best regimen to achieve eradication of

hepatitis C virus infection. 

======================================================================

21.) Interferon-alpha2b therapy is efficacious in Asian-Americans with chronic hepatitis B infection: a prospective controlled trial. 

======================================================================

Author 

Martin P; Hann HW; Westerberg S; Mu~noz SJ; Rubin R; Maddrey WC 

Address 

UCLA School of Medicine, Los Angeles, California 90095-1749, USA. 

Source 

Dig Dis Sci, 43(4):875-9 1998 Apr 

Abstract 

Chronic hepatitis B virus infection is endemic in Asian communities in the United States. The

purpose of the current study was to compare the antiviral efficacy of interferon-alpha2b in a

group of adult Asian patients chronically infected with hepatitis B with active replication

compared to a control group of Caucasian patients treated with the same regimen. Patients

with entry aminotransferase (ALT) levels greater than three times the upper limit of normal

received interferon-alpha2b, 5 million units, subcutaneously daily for 16 weeks. Patients with

pretreatment ALT levels 1.5-3 times the upper limit of normal received prednisone for a total

of six weeks prior to interferon starting at 60 mg daily with reduction in dosage by 20 mg

every two weeks with a two-week period between finishing prednisone and starting

interferon-alpha2b. Eight (62%) of the 13 Asians and six (60%) of the 10 Caucasians

cleared HBeAg and HBV DNA from serum (NS). By the end of one year of follow-up after

therapy, four (67%) of six Caucasian responders but none of the Asian responders had

cleared hepatitis B surface antigen from serum (P < 0.05). Loss of serum markers of active

replication appeared less durable in the Asian responders compared to the Caucasians with

reappearance of serum HBeAg in two (25%) of eight of the former but only one (17%) of

the latter group. Three other Asian patients subsequently redeveloped HBeAg in serum. It is

concluded that adult Asian-Americans have an identical initial response rate to antiviral

therapy with interferon-alpha2b; however, the response may be less durable and does not

usually lead to loss of HBsAg. 

======================================================================

22.) Immunotherapy of chronic hepatitis B by anti HBV vaccine. 

======================================================================

Author 

Pol S; Couillin I; Michel ML; Driss F; Nalpas B; Carnot F; Berthelot P; Br´echot C 

Address 

Unit´e d'H´epatologie, H^opital Necker, Paris, France. 

Source 

Acta Gastroenterol Belg, 61(2):228-33 1998 Apr-Jun 

Abstract 

Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV)

leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis

which may result in cirrhosis and hepatocellular carcinoma. The partial efficacy of antiviral

therapies (40% of sustained inhibition of HBV replication), their cost, their possible side

effects and the immune-mediated pathology of HBV infection explain the need of new

immune therapies in treating HBV infection. Experimental and clinical evidences suggest the

usefulness of vaccine therapy in HBV chronic infection. In a pilot and opened study,

forty-six consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum

HBV DNA were given 3 standard injections of the GenHevac B vaccine at one month

interval. Six months after the first injection, 12 patients (26.1%) had undetectable HBV DNA

while 8 others showed significant decrease (more than 50%) in HBV DNA titers. Six of

these 12 responders received a standard course of alpha-Interferon (5 MU thrice weekly

subcutaneously for 4 months) and all six had still undetectable HBV replication at the end of

follow-up. Among the 34 non responders to vaccine, 20 were given alpha-interferon and 2

the monophosphate derivate of Vidarabine: 12 of these 22 patients stopped HBV replication

and in all 12, vaccine therapy had induced a significant decrease of HBV replication before

the antiviral treatment with a decrease of mean serum HBV DNA from 392 pg/ml before to

217 pg/ml after vaccine therapy. In an ongoing controlled study, using the same vaccine

schedule, serum HBV DNA disappeared more frequently after 6 months, in patients who

were given a preS2/S vaccine (7/35) than in patients who received a S vaccine (1/21) or no

vaccine (1/32). In responders to vaccine, an induction of specific proliferative responses was

observed and this may contribute to the potential efficacy of anti-HBV vaccine therapy. No

side-effect or vaccine-induced escape-mutants occurred during the follow-up. In summary,

serum HBV DNA disappeared in 28 of the 46 patients (60.9%) who were given vaccine

therapy, with (64.2%) or without (55.6%) Interferon. These results are not different at 6

months and at the end of follow-up from those of 43 HBsAg chronic carriers who were given

only an antiviral treatment. Active immune therapy against HBV appears efficient and less

expensive than antiviral therapies in stopping HBV replication. Such results need to be

confirmed by the completed results of our controlled, randomized trial which is now

conducted in our unit. 

======================================================================

23.) Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study. 

======================================================================

Author 

Mutimer D; Naoumov N; Honkoop P; Marinos G; Ahmed M; de Man R; McPhillips P;

Johnson M; Williams R; Elias E; Schalm S 

Address 

Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK. 

Source 

J Hepatol, 28(6):923-9 1998 Jun 

Abstract 

BACKGROUND/AIMS: Alpha-interferon achieves seroconversion in about one third of

naive patients. Attempts to achieve seroconversion in patients who have previously failed

alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon

with a nucleoside analogue) might provide a treatment alternative for these patients. We have

undertaken a phase 2 study in 20 patients who had previously failed at least one course of

alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the

combination. Methods: All patients were treated for 16 weeks with alpha-interferon in

combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16

weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant

pharmacokinetic drug interaction. RESULTS: The combination was well tolerated, and

side-effects of the combination were indistinguishable from the recognised side-effects of

alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any

significant interaction. All patients achieved HBV DNA clearance during treatment, but 19

relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four

patients, but was sustained for a single patient (who also had sustained DNA clearance).

CONCLUSIONS: Combination therapy with alpha-interferon and lamivudine given for 16

weeks appears safe and is well tolerated. However, for this group of patients who had

previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine

therapy appears disappointing, and other treatment strategies should be investigated. 

======================================================================

24.) Tropical aspects of viral hepatitis. Hepatitis E.

======================================================================

Skidmore SJ

Public Health Laboratory, Birmingham Heartlands Hospital, Birmingham, UK.

Trans R Soc Trop Med Hyg (ENGLAND) Mar-Apr 1997 91 (2) p125-6 ISSN: 0035-9203

Language: ENGLISH

Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL 

Journal Announcement: 9709

Subfile: INDEX MEDICUS

Hepatitis E (HEV) is a faeco-orally transmitted hepatitis virus. It has many 

features similar to hepatitis A but some differences, notably the high mortality 

caused by HEV in pregnant women. A vaccine is being developed but at the moment only 

a clean water supply will reduce the number of cases in areas where the virus is 

endemic. (9 References)

======================================================================

25.) [Viral hepatitis E]

======================================================================

L'hepatite virale E.

Molinie C; Desrame J

Service de Pathologie Digestive, Hopital d'Instruction des Armees Begin, Saint-

Mande, France.

Med Trop (Mars) (FRANCE) 1996 56 (3) p285-8 ISSN: 0025-682X

Language: FRENCH Summary Language: ENGLISH

Document Type: 

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL English Abstract

Journal Announcement: 9704

Subfile: INDEX MEDICUS

Thanks to progress in serologic techniques evidence was obtained in 1980 showing 

that acute hepatitis epidemics observed in India were due to neither virus A nor 

virus B. The presence of another virus was confirmed and its genome was cloned and 

sequenced in 1991. Hepatitis virus E is a small RNA virus that differs from other 

known human viruses. Man and probably a few animal species maintain dissemination by 

the fecal route. Subjects not previously contaminated are susceptible and produce 

protective antibodies. Contamination occurs by the fecal-oral route general from 

water or tainted food. Direct contamination is rare. Vertical transmission from 

mother to fetus can also be observed. Outbreaks of the disease are characterized by 

epidemic proportions, preferential involvement of adolescent and young adults, and 

high incidence of fulminant cases especially in pregnant women. Outbreaks have been 

observed in endemic settings in southern Asia, Africa, and Mexico where sporadic 

cases are observed. Endemic areas are found in all developing countries. Hepatitis 

E is not clinically different from other acute viral hepatitis. Asymptomatic forms 

are common especially in children. The course of the disease is usually benign with 

little risk of development of chronic symptoms and cirrhosis. However hepatitis E is 

associated with a high incidence of severe cases with a mortality of 1 to 2% from 

icteric forms which occur in 15 to 20% of cases involving women contaminated during 

the last three months of pregnancy. Diagnosis can be made using either synthetic 

proteins or recombinant peptides. for the epitopes of the virus. Prevention depends 

on protection of the water supply and proper sewage disposal. Successful active 

immunization of monkeys holds promise for development of a vaccine. Due to its 

magnitude and high mortality rate hepatitis E is a major health problem for numerous 

regions around the world including Southeast Asia. (15 References)

======================================================================

DATA-MEDICOS/DERMAGIC-EXPRESS No (10) 29/10/98 DR. JOSE LAPENTA R. DERMATOLOGO

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