1. Antiviral Treatment of Egyptian Patients with Advanced
Cirrhosis due to HCV genotype 4 using PegIntron and ribavirin;
Effect on reduced Glutathione.
Shendy Mohammed shendy*, Naema Al-Ashry**, Alaa Awad Taha*, Moetaz Sery Siam*.
*Gastroenterology, Hepatology department, ** Clinical Chemistry Department Theodor
Bilharz Research Institute.
-Journal:-The New Egyptian Journal of Medicine, vol 37; No. 3(S), Sept 2007; 7-21
ISSN:1110-1946
-Conference: 7th International Annual Congress of the Egyptian Society of Tropical
Medicine, Infectious and Parasitic diseases (ESTIP) in collaboration with the Egyptian
Society of Hepatology, Gastroenterology and Infectious Diseases (ESHGID), Sheraton El
Montaza Hotel, Alexandria, Egypt, Sept 21-23, 2005
Abstract:
Little data until now are available regarding the effect of therapy in Egyptian patients with advanced
cirrhosis due to HCV genotype 4, the predominant type. The aim of this work is to assess the therapeutic
effect of combination therapy with pegylated interferon alfa-2b and ribavirin in Egyptian patients with
advanced cirrhosis due to HCV. Patients and methods: 29 patients of advanced cirrhosis due to HCV
genotype 4 were included in the study. All are of Child-Pugh grade B but without any contraindications to
both drugs. They were given treatment and followed by clinical, biochemical, hematological and virological
evaluation in addition to liver biopsy and measurement of its reduced glutathione content. Results: One
male patient died from brain stem hemorrhage due to care accident after 8 weeks of treatment. Four patients
were withdrawn due to severe side effects of therapy within first 2 months (one due to severe
thrombocytopenia, another one due to severe neutropenia and recurrent chest infection, severe Rheumatoid
factor positive polyarthritis in one and thyrotxicosis in the fourth). Treatment is continued in other all
patients for the recommended period of time (24 patients). The virus titer was not significantly reduced after
12 weeks in 8 patients who were considered non-responders and therapy was stopped. Viral response was
detected in the remaining 16 cases (initial responders) who continued treatment for 48 weeks. They all
showed biochemical and virological response at end of treatment (end of treatment responders). Sustained
response was evaluated after 6 months of the end of treatment. Four patients showed virological relapse and
sustained response was present in 12 cases (41.38 % of intention to treat patients, 50 % of the protocol
treatment patients). The only predictive response in these cases was the original viral load which was
significantly less in sustained response cases in comparison to the non-responsive and relapsing cases.
Reduced Glutathione in liver biopsy was significantly reduced after treatment in those with sustained
response (P = 0.002) and in all patients taken together (P < 0.001). There is significant reduction in the HAI
score (histological activity) after treatment in sustained response category and total patients (P =0.001) but
not in other categories or in the fibrosis grade (P >0.05). Conclusion: it is concluded from this study that
patients with advanced cirrhosis but with no contraindication to combination therapy can be managed in the
same way as earlier cases with pegylated IFN and ribavirin showing nearly similar responses, anti-oxidant
effect and tolerability.
Introduction
There are real concerns about patients with cirrhosis after HCV infection and their outcome
because the survival rate after 5 years in patients with decompensated liver disease (Child-Pugh C) is
very poor (only 50%) (Padilla, 2002).
Although clearance of HCV from serum and liver is the main therapeutic target in chronic hepatitis
C, delay in progression of fibrosis may represent a secondary therapeutic target that could be
particularly important in patients with advanced fibrosis who fail to achieve SVR. Several indirect data
suggest that interferon (IFN-α) may have antifibrotic effects. Significant improvements in liver
1

2. histology have been observed not only in patients with sustained virological response (SVR)
(Marcellin et al., 1997 and Camma et al., 1998) but in all patients who achieve sustained biochemical
response (SBR) regardless of virologic response as well (Bruno et al., 1998 and Mathurin et al., 1998).
Moreover, improvements in both the necroinflammatory activity and the extent of fibrosis have been
observed at 6-12 months after the end of therapy in patients with partial virologic response, which are
usually included among the nonresponders (Shiffman el al., 1999).
Besides its potential beneficial effect on liver histology, IFN-α therapy may also be associated with
reduction of hepatocellular carcinoma (HCC) incidence ((Lau et al., 1998 and Shiratori et al., 2000).
In a meta-analysis including studies with patients with HCV cirrhosis, 6-12 months of IFN-α therapy
was found to be associated with almost negligible risk of HCC for patients with a sustained response
(<1% in 4 years) and significantly lower risk of HCC in patients without sustained response (9%)
when compared with untreated patients (21.5%) (Papatheodoridis et al., 2001).
A trial was done to overcome the poor tolerability in patients with advanced chronic hepatitis and
decompensated liver disease, who were awaiting for liver transplantation, using an accelerating
regimen of interferon alfa-2b plus ribavirin. The regimen involved initiating therapy at a lower dose of
interferon alfa-2b of 1.5 MU 3 times per week plus ribavirin 600 mg per day, with a stepwise
incremental change in the doses to achieve the standard regimen of 3 MU of interferon alfa-2b 3 times
per week plus ribavirin 1000-1200 mg per day. Sustained virologic responses were obtained in 17%
(Everson et al., 2000).
Interferon-based maintenance therapies have been proposed for several years for the prevention of
hepatic decompensation and the development of hepatocellular carcinoma in nonresponder patients
with cirrhosis (Poynard et al, 1999 and Shiffman 2003). Although this concept is supported by results
from several retrospective studies, we still lack data from controlled prospective trials. The HALT-C
(pegylated interferon alfa-2a) and EPIC-3 (pegylated interferon alfa-2b) trials are ongoing.
Upon the introduction of the long acting PEG-IFN, a marked improvement was observed, such that
30% of patients with bridging fibrosis or cirrhosis achieved SVR with PEG IFN alpha 2a monotherapy
alone (Heathcote et al., 2000)). Combination of ribavirin with PEG-IFN has improved the chance of
SVR to just over 40% (Manns et al, 2001 and Fried et al., 2002). However, this figure still remains
less than may be achieved in individuals without background cirrhosis (Wright TL, 2002 and Mauss et
al, 2004).
Thus, therapy with pegylated interferon and ribavirin is clearly indicated for patients with
compensated cirrhosis as long as the white cell and platelet counts allow the reduction induced by the
therapy (Padilla, 2002). The results from two recent studies supported treatment of HCV infection in
the setting of decompensated cirrhosis if patients are selected carefully (Fontana et al., 2004 and Lim
and Imperial, 2005).
In Egypt, no data until now are available regarding the effect of therapy in our patients with
advanced cirrhosis due to HCV, particularly genotype 4, the predominant type.
Hepatitis C infection causes a state of chronic oxidative stress and increased reactive oxygen
species (ROS) production which may contribute to fibrosis and carcinogenesis in the liver. This in
turns leads to oxidation of the glutathione pool, a decrease in mitochondrial NADPH content and
inhibition of electron transport. This was believed to be due to direct interaction of core protein with
mitochondria in hepatocytes (Okuda et al. 2002, Otani et al. 2005, Moriya et al. 2001, Wen et al. 2004,
and Masaaki et al. 2005) (45-49). Also, abnormal methionine metabolism occurs in animals fed ethanol
2

3. and in end-stage cirrhotic patients. Expected consequences of these abnormalities include reduced
hepatic S-adenosylmethionine and glutathione (GSH) levels, impaired transmethylation, and reduced
homocysteine catabolism particularly in cirrhotic patients (Lee et al., 2004). It was proved that
oxidative stress mediated activation and stimulated collagen production of cultured hepatic stellate
(Ito) cells initiating a fibrogenesis cascade in the liver of patients with chronic hepatitis C (Houglum et
al., 1997).
The aim of this work is to assess the therapeutic effect of combination therapy including effect on
reduced glutathione concentration in liver biopsy in Egyptian patients with advanced cirrhosis due to
HCV.
Materials and methods:
In this study, 29 patients with advanced cirrhosis due to HCV genotype 4 were enrolled to enter
the study. They were 19 males and 10 females. All patients were subjected to history taking and
clinical examination with special stress on the stigmata of chronic liver disease, abdominal
ultrasonography, and upper endoscopy. Liver biopsy was not mandatory because of fear of
complications in such advanced cases and the clinical diagnosis of cirrhosis. Liver biopsy was done
only for those without contraindications before and after treatment. Blood samples from all patients
were collected after an overnight fast into plain and anticoagulated tubes and transferred immediately
to the lab, and subjected to complete blood picture, Serum ALT, AST, bilirubin, alkaline phosphatase,
albumin, globulins and prothrombin time and concentration. Thyroid functions and antibodies and
autoimmune markers were done only in clinically suspicious cases. Urea, creatinine, blood sugar,
ECG, chest X ray and when indicated cardiac enzymes were done for all patients. Liver biopsy was
done whenever possible and no contraindication, to determine the level of reduced glutathione content
and histopathology before and after treatment in liver tissues. Upper endoscopy and abdominal
ultrasound evaluation of liver, spleen and portal hypertension were done before and after end of
treatment in all patients. Markers for hepatitis B and C viruses were performed by enzyme
immunoassay (EIA) according to the manufacturer’s instructions. The following markers were
performed:
Hepatitis B surface antigen (HBsAg) by Murex version 3, Murex-Biotech Ltd. UK
Hepatitis B core total antibody (anti-HBc total) by ETI-AB-Corek-2 DiaSorin s.r.l., Italy.
Hepatitis C antibody (anti-HCV) by Murex anti HCV version 4 Murex-Biotech Ltd UK
HCV RNA was extracted using acid guanidinium thiocyanate-phenol chloroform single step method
(Chomczynski and Sacchi.1987). HCV-RNA was detected by qualitative nested RT-PCR using two
sets of primers within the 5’ non-coding region. Amplification products were analyzed using 2%
agarose gel electrophoresis (Van Doorn et al., 1994). Quantitative PCR was done by using Light
Cycler (Roche) real time and on line quantification using fluorescein dye with external standard of 4
dilution positive control for calibration curve. Viral load was estimated as follows:
<10,000 copies /ml: weak viraemia
10,000-100,000 copies /ml: mild viraemia
100,000- 1,000,000 copies /ml: moderate viraemia
> 1,000,000 copies /ml: high viraemia
Genotyping of HCV was done using amplified products of specific primers from the 5-UTR region in
a reverse transcription polymerase chain reaction (Roche Diagnostics, Switzerland) followed by a
reverse hybridization technique (Innolipa HCV II [Innogenetics, Belgium])
3

4. Determination of Glutathione Content— Freshly isolated liver tissue samples (50–75 mg) and mitochondrial
samples (2 mg) were sonicated using a Branson Sonifer 450 (VWR Scientific Products, West Chester PA) for 15
s at power setting 3 in ice-cold 5% trichloroacetic acid and centrifuged at 3000 x g at 4 °C for 10 min. The
concentration of reduced GSH was measured by the thioester method using the GSH-400 kit (Oxis International
Inc., Portland, OR). Total glutathione content of samples was measured by the glutathione reductase-DTNB
recycling assay using a commercial kit (GSH-412, Oxis International). (Anderson, 1989 and Masaaki et al.
2005) (49,50).
Inclusion criteria:
Patients with liver cirrhosis due to HCV genotype 4 with detectable virus RNA in serum and elevated
liver enzymes.
Negative HBsAg and anti-HB core antibodies.
No evidences of hepatosplenic schistosomiasis (clinically and by ultrasound).
No history of severe upper gastrointestinal bleeding due to portal hypertension complications.
CBC and prothrombin time are compatible with interferon and ribavirin treatment (Hemoglobin level
≥ 12 g/dl in women and ≥ 13 g/dL in men, White blood cell count ≥ 1500/mm3, Platelet count ≥
100,000/mm3)
No contraindications for interferon therapy such as uncontrolled ascites, or severe, persistent
encephalopathy, ischemic heart disease, autoimmune diseases, persistent infection, uncontrolled
diabetes mellitus, severe neuropsychiatric disorders, pregnancy or inability to practice contraception,
debilitating medical conditions, particularly a history of pulmonary disease, history of cardiovascular
disease, coagulation disorders
Age between 18-65 years
Patients give informed consent to continue medication and follow up.
Treatment of selected cases was done using peginterferon-alfa 2b (pegIntron) 1.5 μg/kg of body
weight subcutaneous once weekly and ribavirin 800-1200 mg/ day according body weight in two
divided doses (800 mg in those <65 kg, 1000 mg in those of 65-85 kg, 1200 mg for those > 85 kg).
Dose adjustment was done during treatment according biochemical and hematological parameters as
advised by the manufacturer as follows:
- reduction of pegIntron to half the dose if neutrophil count was reduced to less than 750/μl ( or total
WBC is less than 1500/μl) or platelet count is less than 50,000/μl, and
- for ribavirin, it is reduced to 600 mg /day if hemoglobin is reduced to < 10 gm/dl or indirect
bilirubin > 5 mg/dl
- both PegIntron and ribavirin are discontinued if neutrophil count is less than 500//μl (or total WBC
is less than 750/μl), or direct bilirubin is more than 2.5 times the upper limit of normal or indirect
bilirubin > 4 mg/dl (for more than 4 weeks), or if serum creatinine is increased to >2mg/dl or the
ALT or AST level is doubled or increased 10 times the upper limit of normal.
- Treatment is discontinued also if no reduction of HCV RNA level by 2 logs after 12 weeks and
considered not responding not responding to treatment (Poynard T et al., 2005)
The following precautions were followed to overcome the common side effects of medications:
a) Acetaminophen or ibuprofen was taken one hour before injection,
b) Patient was encouraged to drink 24 ounces of water before injection to combat dehydration
c) Enough rest (6 to 10 hours each night) was allowed.
d) Light exercise in daily routine to reduce muscle loss (Muscle loss can cause increased fatigue).
e) Balanced diet and daily requirements of vitamins supplementations
f) Relaxation and stress management were added with avoiding stressful situations if possible.
g) Eating small frequent meals, even when not hungry and healthy snacks throughout
the day. Taking a 5-10 minute walk before meals to increase appetite and decrease nausea.
4

5. Liver function tests and CBC, are repeated after 2 weeks, one month, 3 months, 6 months and at end of
treatment. Viral RNA was quantified before treatment, 12 weeks, 24 weeks and at end of treatment (48
weeks) and after 6 months of end of treatment (to detect sustained virologic response).
Patients were grouped in a retrograde manner according treatment complications and response into
four categories:
Category I: (12 patients) with sustained response to therapy for 6 months after the end of treatment
Category II: (8 patients) not responding to treatment with persistent viremia at 12 weeks of treatment
Category III: (4 patients) showing relapse of viremia after 6 months of end of treatment
Category IV: (5 patients) prematurely withdrawn from the study due to severe adverse reactions, due
to accidental events or lost follow up.
Statistical Analysis
Results are expressed as absolute values and mean ± SD. Statistical analysis of the data was carried
out using the ANOVA test. For correlation studies, the Pearson correlation coefficient was used. A p
-value of < 0.05 was considered significant. Statistical analysis was performed using the SPSS 12 for
window statistical Package.
Results:
This study included 29 patients. They were 19 males and 10 females. All had liver cirrhosis of
Child’s B grade. One male patient died from brain stem hemorrhage due to care accident after 8 weeks
of treatment. Four patients were withdrawn due to severe side effects of therapy within first 2 months.
One (a female) was withdrawn due to severe thrombocytopenia. Another one (male) was due to severe
neutropenia and recurrent chest infection. The other two (who are females) were due to severe
autoimmune manifestations, in the form of severe rheumatoid factor positive polyarthritis in one and
thyrotxicosis in the other. Treatment was continued in other all patients for the recommended period of
time (24 patients). After 12 weeks (3 months), treatment was stopped in 8 patients due to persistent
viremia.
The mean age of the patients was 49.92 ± 5.67 and no significant differences in the mean ages
between different response categories. The treatment was tolerated by most patients despite frequent
complaints of flue-like symptoms (such as myalgia, fever, headache, giddiness, malaise, anorexia,
hypersomnia), mild hair loss in 10 patients, mild degrees of irritability and depression in 9 patients
(feelings of deep and constant sadness, hopelessness, crying, changes in mood, loss of interest in
things, trouble concentrating), skin rash and itching in 6 patients, mild thyroiditis in 2 patients (both
are females) without clinical hypo-,hyperthyroidism and development of diabetes mellitus in 2 cases
(tables 3 & 4).
Ascites was found before treatment (at any time during follow up) in 18/29 (62.4 %) patients, but
was controlled in all of them before enrollment. However, some cases, reappear during treatment but
were all controlled by balanced diet with sufficient protein intake, diuretics and salt restriction. In all,
diuretics can be withdrawn again after control of ascites (tables 3 & 4). There was history of small (<3
cm) HCC in one patient proved by liver biopsy and alpha fetoprotein and was treated successfully by
radiofrequency ablation 6 months before enrollment in the study.
History of hepatic encephalopathy of mild grades; I-II, (in the form of personalities changes, sleep
rhythm disturbances, emotional and behavioral changes, some drowsiness, and flapping tremors); were
detected during pretreatment period in 16/29 (55.2 %). These manifestations were all transient for few
5

6. days and were responding to simple measures of mild protein restriction and disaccharides. Similar
attacks reappeared during treatment in 4 cases with similar response to treatment. Mild attacks also
developed in 2 new cases including one case of non-variceal (from congestive gastropathy) upper
gastrointestinal tract bleeding which was mild and responds to conservative treatment
No cases of hepatocellular carcinoma have been developed in patients during the period of
treatment and the 6 months of follow up period (tables 3 & 4).
Viral response to therapy after 12 weeks was evaluated as disappearance or a two log reduction of
the virus. In such cases, therapy is continued for a total of 48 weeks. This was observed in 16 cases. In
8 cases, the virus titer was not reduced to such extent. Therefore therapy was stopped in these 8
patients and considered not responding to therapy. Evaluation of viral response was performed after 6
months of end of treatment. Sustained response was observed in 12 cases, while relapse was detected
in 4 cases. The end of treatment response was observed in 66.67% of cases who were able to continue
medicines for 12 weeks, while sustained response was observed in 50% of such cases (protocol
treatment patients) and in 41.38 % of intention to treat patients. The only predictive response in these
cases was the original viral load which was significantly less in sustained response cases in
comparison to the non-responsive and relapsing cases.
The biochemical response at end of treatment (as defined by normalization of ALT) was observed
in patients responding to therapy including relapsing patients (with very minimal elevation, 2-5 units
above normal, still detected in 2 patients in each group). In relapsing patients, elevation of liver
enzymes recurred in all cases after 6 months after being normalized during the whole course of
treatment.
There were mild but significant reduction in the three blood elements; which is more pronounced
in haemoglobin level and least pronounced in platelet count; after treatment in all patients. However,
except for the female patient withdrawn from treatment due to thrombocytopenia, none of all other
patients reached a level to stop or reduce the doses of any of both drugs.
The liver span in the midline (left lobe) was found to be significantly longer in patients with
sustained response than those not responding to treatment (table2). It was found also to be negatively
correlated with congestive gastropathy, oesophageal varices, short axis of spleen, presence of ascites
and encephalopathy. Liver span in mid-clavicular line was significantly increased and long axis of
spleen was significantly decreased after treatment in patients showing sustained response. Ascites was
significantly less in patients showing sustained response than those not responding to therapy.
Reduced Glutathione was found to be significantly reduced after treatment only in those with
sustained response (P = 0.002) and in all patients taken together (P < 0.001)( table 17). There is
significant reduction in the HAI score (histological activity) after treatment in sustained response
category and total patients (P =0.001) but not in other categories or in the fibrosis grade (P >0.05)
(table18).
Discussion
In all published trials the greater the degree of hepatic fibrosis the lower the response to antiviral
therapy. When standard IFN monotherapy was used, there was a negligible response seen in patients
with cirrhosis (Schalm et al., 1999), but upon the introduction of the long acting PEG-IFN, a marked
improvement was observed, such that 30% of patients with bridging fibrosis or cirrhosis achieved
SVR with PEG IFN alpha 2a monotherapy alone (Heathcote et al., 2000)). Combination of ribavirin
with PEG-IFN has improved the chance of SVR to just over 40% (Manns et al, 2001 and Fried et al.,
6

7. 2002). However, this figure still remains less than may be achieved in individuals without background
cirrhosis (Wright TL, 2002 and Mauss et al, 2004). The results from two recent studies supported
treatment of HCV infection in the setting of decompensated cirrhosis if patients are selected carefully
(Fontana et al., 2004 and Lim and Imperial, 2005).
Most of the previous studies included patients with genotypes 1, 2 & 3. Few studies were
performed including patients with genotype 4 which is predominant in Egypt. It constitutes about 91-
94 % of cases of HCV ( Ray et al., 2000 and El-zayadi et. al., 1999).
Treatment trials in patients with genotype 4 passed in three stages. The first stage was in the early
era of the use of standard interferon monotherapy. Two studies in France demonstrated very low
sustained response rate of 10-11% in comparison to 35% in genotype 3 (Remy et al., 1998 and
Zylberberg et al., 2000). Then, the addition of ribavirin to interferon has slightly improved the
sustained response rate to the range of 5-42% with the average response around 20% (El-faleh et al.,
1998 and 2000; El-Zayadi et al., 1999 and Sheha and Salem 2002). Lastly, the introduction of the long
acting pegylated interferon in preliminary studies, has placed genotype 4 midway between type 1 on
one side and types 2 & 3 on the other side as regards the sustained response rate to new combination
therapy. In these studies, the sustained response rate ranged between 40 to 69% vs. 16 to 39 % for the
standard combination therapy using usual interferon (Diago et al., 2002; Shobokshi et al., 2002 and
2003; Hasan et al., 2003; Thakeb et al., 2003; and Esmat et al., 2003). In all of these studies, patients
with as early as possible active disease with mild fibrosis were selected to avoid side effects and
improve the sustained response rate as has been concluded from the previous experiences with usual
interferon. No studies until now have included patients with advanced fibrosis or cirrhosis.
The improvement in liver histology and the reduced rate of complications including hepatocellular
carcinoma in old studies of patients with sustained response and to a lesser extent in partial responders
or even in non-responders to the combination therapy (Lau et al., 1998; Shiratori et al., 2000;
Heathcote, 2003 and Everson et al., 2004), might push as to make such new therapy with pegylated
interferon available to as much of the at-risk population as possible.
In this study, advanced cases of liver cirrhosis were selected. Twenty nine patient of Child-Pugh
grade B underwent treatment with long acting pegylated interferon and ribavirin. Unfortunately, five
cases had been withdrawn due to side effects or accidental death. The other 24 cases continued under
the trial for the first 12 weeks when re-evaluation of viral response was done. They were tolerant to the
therapy with the side effects neither more nor severer than usual particularly if usual precautions were
taken to manage such effects. Reappearance or development of new ascites, encephalopathy, or
bleeding occurred in an expected rate; even less; and were easily managed and controlled. Also,
hepatocellular carcinoma didn’t develop in any of the patients during the period of follow up despite
being advanced. This might add another evidence of the protective effect of therapy against HCC in
patients with sustained response and even relapsing or partial responders if given in late advanced
cases.
The tolerability to combination therapy in these advanced patients might allow us to add these
cases to our treatment protocols of HCV and give good news to some patients who feel hopeless about
their cure.
Secondly, the mean age of this group of patients was higher than in previous studies. This again
will open the way for somewhat older ages to take their chances of treatment whenever no general
medical illness or contraindication to therapy exists.
7

8. Despite the encouraging observations in this study, it was not a controlled study, the number of
patients is somewhat small and liver biopsy was not obtained before and after treatment in most cases.
Liver biopsy was not feasible and might be serious in these advanced patients. Our study opinion, is
that biopsies are not essential and it was not expected to have significant histological changes within
the treatment period in such advanced cases. Also it is not essential neither for diagnosis nor staging of
patients with clear clinical, biochemical, ultrasonographic and endoscopic manifestations of cirrhosis
in addition to the virological diagnosis.
The concept of the three month trial for viral response was applied in this study and found
reasonable. Non-responding cases can be withdrawn to avoid the cost and side effects of medicines.
Those who didn’t respond (8 patients) were similar to those responding in all parameters except the
pretreatment viral load. Thus, high viral load was found to be the only predicting factor for failure of
treatment in such patients. This is logic and accepted because the other known predicting factors are
not working in this group of patients such as age (mostly old), duration of illness (probably long in
all), degree of fibrosis (marked in all cases, mostly cirrhotic).
Viral response to therapy after 12 weeks was observed in 16 cases in which therapy is continued
for a total of 48 weeks. It was not detected in 8 cases in which therapy was stopped and considered not
responding to therapy. The evaluation of patients responding to treatment 6 month later showed
sustained response in 12 cases, while relapse was detected in 4 cases. At the end of treatment response
was observed in 66.67% of cases who were able to continue medicines for 12 weeks, while sustained
response was observed in 50% of such cases (protocol treatment patients) and in 41.38 % of intention
to treat patients. These findings are similar to findings observed in compensated cirrhosis in which the
sustained response rate ranged from 26% (low dose ribavirin: 800 mg/day) to 37% (standard dose
ribavirin: 1000-1200 mg/day) in genotype 1 and from 69% to 75% in genotypes 2/3 with overall
response rate of 36 to 45% (Marcellin P et al., 2004).
Virological response was associated with biochemical response in all patients even in relapsing
patients in this study. This means that the biochemical response follows virological response even if
transient. Therefore, these patients get benefit from treatment whatsoever and it was assumed that even
those not responding at week 12 could be given maintenance doses for longer time to get such
benefits.
The presence of significantly larger left lobe of liver (span in midline) in patients with sustained
response may indicate that higher liver volume and regeneration is a good sign in these patients. This
also can be understood from the increased liver span in mid-calvicular line and decreased size of
spleen after treatment in the same category of patients.
The recent AASLD Practice Guideline on Diagnosis, Management, and Treatment of Hepatitis C
(2005) dealt with the topic of antiviral therapy in patients with decompensated cirrhosis. In their
recommendations, Strader et al. suggest that antiviral therapy might be initiated at low dose in
hepatitis C virus (HCV) infected patients with mild degrees of hepatic compromise, preferably in
patients who have been accepted as candidates for liver transplantation. Studies are ongoing using
standard IFN daily (3MU/day) and ribavirin (800mg/day) when the expected time for liver
transplantation was around 4 months. The rational is to produce virological response by the week 12
when the patients approach transplantation aiming at reducing the infection of the graft. After a
median treatment duration of 12 weeks, 9 (30%) of 30 patients achieved on-treatment virological
response, which persisted in 6 (20%) after transplantation (Forns et al., 2004).
The effect of therapy on the manifestations of portal hypertension (PH) in our patients was subtle
and not significant but because this is not a controlled study, we can’t evaluate such effect properly.
8

9. However, no remarkable complications aroused during treatment and follow up period. Studies are
ongoing to explore the effect of maintenance therapy with pegylated interferon on portal hypertension
and its complication (COPILOT Study). The initial 2 years of follow up demonstrated that the survival
of these patients with PH was superior compared to the colchicine arm. IFN-treated subjects had a
lower incidence of variceal bleeding. In addition, the development of PH at 2 years of follow-up was
lower in the group of IFN-treated individuals (12/95, 12%) than in the colchicine group (24/92, 28%)
(p= 0.025). In a subgroup of patients who underwent measurements of hepatic venous pressure
gradient (HVPG), a reduction of 41% in their HVPG values was observed after 24 weeks of therapy
with pegylated IFN-a-2b (Curry M. et al., 2005). If this is confirmed in more studies and longer follow
up, maintenance therapy with small dose of pegylated IFN 0.5 μg/kg/week may be advised in this
critical group of patients. Also, if patients are selected carefully, treatment of HCV infection in the
setting of decompensated cirrhosis is possible (Lim and Imperial 2005 and Annicchiarico et al.,
2005)). This suggestion is now becoming a reality as has been observed in this study.
It was found that hepatitis C infection causes a state of chronic oxidative stress due to production
of reactive oxygen species. This may contribute to fibrosis and carcinogenesis in the liver. In this
study, reduced glutathione was estimated in liver biopsy in those for whom liver biopsy was done.
Significant reduction in the reduced Glutathione after treatment was found only in those with sustained
response (P = 0.002) and in all patients taken together (P < 0.001) but not in other categories because
of the lower number of cases that did not reach statistical significance. The reduction of reduced
glutathione in all patients after treatment can explain some of the beneficial effect of antiviral
treatment particularly IFN despite absence of virological response in some patients. This reduction is
due to reduction in the oxidative stress in the liver after treatment. Numerous studies have shown that
oxidative stress is present in chronic hepatitis C to a greater degree than in other inflammatory liver
diseases (Barbaro et al., 1999 and Valgimigli et al., 2002) and a prospective study showed
improvement in liver injury in chronic hepatitis C with antioxidant treatment (Houglum et al., 1997). It
was found that HCV core protein expression caused an increase in mitochondrial ROS production, an
oxidation of the mitochondrial glutathione pool, inhibition of electron transport, and an increase in
ROS production by mitochondrial electron transport complex (Masaaki et al. 2005). Low glutathione
levels are found in people with cataracts, HIV infection, chronic HCV, and cirrhosis. People with
cirrhosis of the liver may have difficulty in synthesising glutathione. This may explain why
glutathione levels are 30% below normal in people with cirrhosis (white et al., 1994 and Burgunder
and Lauterberg 1987).
Levels of the most important form of glutathione (reduced glutathione) are significantly below
normal in people who have alcoholic hepatitis or hepatitis C. Studies have shown that people with
hepatitis C who had the lowest glutathione levels also had the highest viral loads and more evidence of
liver damage. Glutathione has been shown to have direct antiviral effects (Loguercio et al., 1999 and
Barbaro et al., 1996). Although no research has been done with the hepatitis C virus (HCV),
glutathione has been shown to inhibit HIV in the test tube. Although this research does not prove that
raising glutathione levels leads to lower viral loads, it does indicate that optimal levels of glutathione
may be an important factor in controlling HCV infection (Staal et al., 1992).
Also significant reduction in the HAI score (histological activity) after treatment was found in in
sustained response category and total patients but was insignificant in those with non-response or in
the fibrosis grade. However, there was some reduction in the fibrosis score and HAI activity in all
these patients whether showing sustained response or not. However, the small number of cases for
whom biopsy was performed did not allow having any conclusion regarding the effect of treatment on
the liver pathology as shown by histopathological examination.
9

10. Conclusion:
As patients with cirrhosis due to hepatitis C have a high chance of dying from progressive liver
disease they have much to gain from successful antiviral therapy. The highest sustained virological
response in patients with cirrhosis has been achieved using pegylated interferon alfa plus ribavirin.
Patients who do not achieve sustained virologic response can still show clinical, biochemical and
probably histological improvement with lesser chance to develop HCC. They also had less oxidative
stress which can explain many beneficial effects apart from antiviral response. Thus, it is concluded
from this study that patients with advanced cirrhosis but with no contraindication to combination
therapy can be managed in the same way as earlier cases with pegylated IFN and ribavirin. Longer
controlled studies and follow up may direct the light to the long term benefits and survival in such
patients.
Table 1: Number, sex, age and grade of liver disease in all patient categories.
Parameter Total patients Patients with
Sustained R
Patients not
responding
Patients with
relapse
Patients withdrawn
early due side effects
Numbers
% of ITT
% of PT
29
24/29 (82.76%)
24/24 (100%)
12
12/29 (41.38%)
12/24 (50.00%)
8
8/29 (27.59%)
8/24 (33.33%)
4
4/29 (13.79%)
4/24 (16.67%)
5
5/29(17.24%)
5/24 (20.83%)
Males 19 10 5 2 2
Females 10 2 3 2 3
Mean age 50.17 ± 5.51 49.67± 6.59 49.88 ± 5.11 50.75 ± 4.99 51.40 ± 5.03
Grade of
liver cirrh. B B B B B
ITT: intention to treat. PT: Protocol treatment.
No differences in mean of age and grade of liver disease between all category groups
Table 2: Ultrasonographic findings of liver, PV and collaterals in different patient categories
(means) before and after treatment.
sustained
response
non-response
relapse
withdrawn due
to side effects
total patients
10.33 .29 9.14 .36 9.80 .63 10.40 .30 9.94 .20
5.88 .22 4.84 .12 4.83 .19 5.30 .24 5.34 .14
14.00 .30 13.69 .34 13.63 .38 14.00 .63 13.86 .19
1.75 .25 2.25 .25 2.25 .25 1.80 .37 1.97 .14
10.55 .31 9.29 .29 9.68 .60 10.34 .33 10.04 .20
5.78 .18 4.91 .15 5.25 .13 5.36 .25 5.40 .11
13.83 .23 13.25 .37 13.50 .29 14.00 .45 13.66 .16
1.75 .22 2.63 .18 2.50 .29 2.00 .45 2.14 .15
liver /MCL/before ttt
liver/ML/before ttt
PV diam/before ttt
collaterals/before ttt
liver/MCL/after ttt
liver/ML/after ttt
PV/after ttt
collaterals/after ttt
Mean SE
Mean SE
Mean SE
Mean SE
Mean SE
response categories
*The span of the liver in midline is significantly longer in sustained response category than in none
response category (p =0.005)
*The span of the liver in MCL is significantly increased after treatment in responding patients only
(P=0.05) not in other groups or total patient evaluation.
Table 3: Ultrasonographic findings of spleen and splenic vein in different patient categories
(means) before and after treatment.
10

11. sustained
response
non-response
relapse
withdrawn due
to side effects
total patients
16.15 .43 17.74 .73 17.08 .55 17.26 .71 16.91 .32
5.79 .28 7.20 .27 7.00 .29 6.84 .14 6.53 .18
10.42 .47 11.63 .71 10.50 .65 10.50 .71 10.78 .31
15.43 .39 17.27 .53 15.98 .41 15.60 .61 16.04 .28
6.05 .25 7.18 .18 6.98 .23 6.78 .12 6.61 .15
10.67 .47 11.50 .63 11.25 .48 10.40 .68 10.93 .29
axis of spleen/before ttt
width of spleen/before ttt
SV/before ttt
spleen/longaxis/after
spleen/shortaxis/after
SV/after
Mean SE
Mean SE
Mean SE
Mean SE
Mean SE
response categories
*The long axis of spleen is significantly decreased after treatment in sustained responders (P=0.03)
and total patient (P=0.0001) evaluation but not in other patient categories.
*Also the short axis is decreased significantly after treatment in sustained responders only (P=0.01).
Table 4: Clinical data (OV, gastropathy, collaterals, ascites, and HE) of patient categories
response categories
3 3
3 2 1 2 8
5 5 2 3 15
1 1 1 3
2 2
7 3 2 4 16
3 5 2 1 11
6 1 2 9
3 4 3 2 12
3 3 1 1 8
6 1 2 2 11
6 7 2 3 18
7 2 2 2 13
5 6 2 3 16
none
grade I
grade II
grade III
OV
none
mild
severe
cong. gastropathy
none
one site
two sites
collaterals
absent
controlled
ascites grade
none
mild
enceph grade
sustained
response non-response relapse
withdrawn
due to side
effects total patients
11

12. *There are more significant ascites in none-response cases than SR cases (P=0.002)
**Two-tailed partial correlation according response category classification showed significant
correlation between each of:
1- Grade of oesophageal varices and each of age (P< 0.05), grade of PH gastropathy (P=0.002),
long axis (P=0.049) and short axis of spleen (P=0.002) and negatively with span of liver in
midline (P=0.046)
2- Grade of gastropathy and short axis of spleen (P=0.04) and negatively with liver span in
midline (P=0.033)
3- Portal vein diameter and grade of congestive gastropathy (P=0.002)
4- Length of short axis of spleen and OV, gastropathy, negatively with liver span in midline
(P=0.004), absence of ascites (P=0.004), absence of encephalopathy (P=0.034) and
collaterals (P=0.002).
Table 5: complications reappearing or newly developed in all patients during treatment.
Parameter Sustained
Response
Patients not
responding
Relapsing
Patients
withdrawn early
due side effects
Total pts
after ttt
Total pts
before ttt
Bleeding
Upper GIT:
Others :
15 Oesoph. Varices
02
1 (mild ,non-variceal)
1
01
03
17
None;
Grade I
Grade II
Grade III:
4341
2420
0130
0112
69
10
3
38
15
3
Cong. Gastrop
None
Mild
Severe
372
026
031
013
3
13
12
2
16
11
Encephalopathy
Recurrence
New
01
20
10
10
5(17.24%)
41
16(55.17%)
HCC 0 0 1 0 0 1
There is one small HCC in one patients of relapse category treated successfully by radiofrequency
Table 6: complications appearing in all patients during treatment.
Parameter Patients with
Sustained R
Patients not
responding
Patients with
relapse
withdrawn early due
side effects
Total patients
Flue-like symptoms 12 8 4 5 29 (100%)
Ascites:
Reappearance
New
11
31
10
10
(27.59%)
62
Depression (mild) 3 3 1 2 9(31.03%)
Hair loss 5 2 2 1 10(34.48%)
Thyroiditis (clinical):
Thyroid antibodies
13
11
01
1:(with
hyperthyroidism)
2
3 (10.34%)
7(24.14%)
Development of DM 1 0 1 0 2(6.9%)
Skin rash/itching 2 1 2 1 6(20.7 %)
12

13. Table 7: ALT levels before, during and after treatment in all patient categories (mean and
standard error)
sustained
response
non-response
relapse
withdrawn due
to side effects
total patients
93.58 6.94 90.25 9.19 127.50 12 114.40 12.4 100.93 5.10
56.17 4.13 98.25 6.14 61.00 3.5 61.60 5.12 69.38 4.21
44.67 3.12 90.75 5.11 45.75 2.7 52.60 7.35 58.90 4.35
36.50 1.43 84.88 4.12 39.00 1.6 . . 53.04 4.93
36.83 1.27 . . 38.00 1.8 . . 37.13 1.03
34.75 1.21 . . 70.25 6.1 . . 43.63 4.29
ALT/before treatment (ttt)
ALT/after one month of ttt
ALT after 3 months of ttt
ALT/after 6 month of ttt
ALT/ at end of ttt
ALT/ 6 month after end of ttt
Mean SE
Mean SE
Mean SE
Mean SE
Mean SE
response categories
*ALT was significantly lowered in sustained R cases after one month of treatment than in
non-response cases.
Table 8: AST levels (U/dL) before, during and after treatment in all patient categories
(mean and standard error)
sustained
response
non-response
relapse
withdrawn due
to side effects
total patients
113.75 7.55 127.75 6.92 149.75 12 130.40 6.28 125.45 4.57
67.92 4.52 72.00 4.71 72.25 4.87 59.40 5.31 68.17 2.57
52.58 3.85 71.25 4.86 57.50 1.32 61.60 9.42 59.97 2.89
55.00 3.98 71.00 4.22 53.75 3.79 . . 60.13 2.91
54.67 4.02 . . 50.00 1.83 . . 53.50 3.05
51.67 2.55 . . 88.00 7.63 . . 572.06 513
AST/before ttt
AST/after one month of ttt
AST/ after 3 months of ttt
AST/ after 6 months of ttt
AST/at end of ttt
AST/after 6 months of end of ttt
Mean SE
Mean SE
Mean SE
Mean SE
Mean SE
response categories
Figure 1: Biochemical response in all patients.
140
120
100
80
60
40
20
0
1 2 3 4 5 6
treatment months
ALT (U/dl)
SR NR Relapse Intolerant
13

14. Figure 2: Biochemical response in all patients (AST)
160
140
120
100
80
60
40
20
0
before 1m 3m 6m 12m 6m later
Month of treatment
AST
SR NR relapse intolerant
Table 9: Bilirubin levels(mg/dL) before, during and after treatment in all patient
categories (mean and standard error)
sustained
response
non-respons
e
relapse
withdrawn
due to side
effects
total patients
2.68 .96 3.75 .93 3.48 .77 3.08 .48 3.16 .94
4.08 1.04 5.13 1.16 4.60 1.01 3.98 .30 4.42 1.05
2.28 .73 4.99 .75 4.80 .57 3.90 .37 3.65 1.39
1.70 .47 4.16 .60 2.53 .43 . . 2.66 1.23
1.73 .36 . . 1.73 .22 . . 1.73 .32
1.69 .33 . . 2.85 .51 . . 1.98 .63
BIL/before treatment (ttt)
BIL/after one month of ttt
BIL/after 3 months of ttt
BIL/after 6 month of ttt
BIL/ at end of ttt
BIL/ 6 month after end of ttt
Mean SD
Mean SD
Mean SD
Mean SD
Mean SD
Response categories
*Bilirubin before treatment is significantly less in SR cases than relapse cases (P= 0.024)
Table 10: Albumin levels(g/dL) before, during and after treatment in all patient categories
(mean and standard error)
14

15. sustained
response
non-respons
e
relapse
withdrawn due
to side effects
total patients
2.98 .52 2.66 .22 2.78 .28 3.02 .38 2.87 .41
3.23 .58 2.95 .36 2.85 .45 3.08 .19 3.08 .46
3.42 .46 2.96 .14 2.88 .43 3.10 .20 3.16 .41
3.57 .36 2.93 .21 3.25 .44 . . 3.30 .43
3.68 .53 . . 3.20 .50 . . 3.56 .55
3.63 .48 . . 3.18 .40 . . 3.51 .50
Albumin/before treatment (ttt)
Alb/after one month of ttt
Alb/after 3 months of ttt
Alb/after 6 month of ttt
Alb/ at end of ttt
Alb/ 6 month after end of ttt
Mean SD
Mean SD
Mean SD
Mean SD
Mean SD
response categories
Table 11: Globulins levels(g/dL) before, during and after treatment in all patient
categories (mean and standard error)
sustained
response
non-respon
se
relapse
withdrawn
due to side
effects
total patients
5.36 .55 5.26 .27 5.25 .31 4.92 .13 5.24 .42
5.03 .46 5.24 .40 4.90 .41 5.08 .40 5.08 .42
4.38 .69 5.10 .28 4.88 .28 4.78 1.04 4.72 .68
4.59 .56 4.95 .31 4.55 .48 . . 4.70 .49
4.56 .83 . . 4.45 .33 . . 4.53 .72
4.52 .57 . . 4.78 .48 . . 4.59 .54
Globulin before treatment (ttt)
Glob/after one month of ttt
Glob/after 3 months of ttt
Glob/ after 6 months of ttt
glob/ at end of ttt
glob/ 6 month after end of ttt
Mean SD
Mean SD
Mean SD
Mean SD
Mean SD
response categories
*From the third month of treatment improvement of all parameters of liver function was
significantly better in SR cases than non-response cases (P< 0.01).
Table 12: PT prolongation(seconds) before, during and after treatment in all patient
(mean & SE).
sustained
response
non-respons
e
relapse
withdrawn due
to side effects
total patients
3.08 .79 3.49 .44 3.28 .51 2.84 .32 3.18 .62
2.64 .64 4.10 .52 3.20 .37 2.92 .31 3.17 .80
2.21 .66 4.13 .43 3.03 .17 2.40 .38 2.88 .96
1.83 .46 4.04 .45 1.68 .24 . . 2.54 1.16
1.70 .28 . . 2.08 .22 . . 1.79 .31
1.44 .39 . . 2.13 .30 . . 1.61 .47
PT/before treatment (ttt)
PT/after one month of ttt
PT/after 3 months of ttt
PT/after 6 month of ttt
PT/ at end of ttt
PT/ 6 month after end of ttt
Mean SD
Mean SD
Mean SD
Mean SD
Mean SD
response categories
Table 13: Haemoglobin levels (g/dl) before, during and after treatment
15

16. sustained
response
non-response
relapse
withdrawn due
to side effects
14.22 .25 14.23 .26 14.40 .50 14.16 .34
12.74 .34 12.79 .22 12.85 .29 13.36 .28
12.76 .24 12.78 .25 13.38 .40 13.02 .19
12.75 .25 12.85 .20 13.38 .27 12.90 .23
HB before ttt
HB, 2-4
weeks
HB, 24 weeks
HB, after ttt
Mean SE
Mean SE
Mean SE
Mean SE
response categories
Figure 3: Haemoglobin levels (g/dl) before, during and after treatment
Hb levels before and during treatment
18
16
14
12
10
8
6
4
2
0
1 2 3 4 time
Hb level (g/dl)
Sr NR Relapse Intolerant
Table 14: Platelet count (thousands/mm3) before, during and after treatment
sustained
response
non-response
relapse
withdrawn due
to side effects
130.42 6.51 119.75 6.96 129.00 16.1 108.40 7.09
131.58 5.23 113.88 7.06 130.75 13.9 105.20 6.34
124.92 4.83 111.38 5.65 125.25 13.7 92.60 11.74
130.17 4.89 112.00 5.71 108.50 11.1 89.40 9.45
Platelets,before ttt
Platelet, 2-4 weeks
Platelets,24 weeks
Platelets,after ttt
Mean SE
Mean SE
Mean SE
Mean SE
response categories
Table 15: Leukocytic count (thousands/mm3) before, during and after treatment
16

17. sustained
response
non-response
relapse
withdrawn due
to side effects
5.63 .36 5.04 .38 5.10 .24 6.16 .49
5.10 .25 5.26 .19 4.70 .55 4.86 .35
3.99 .16 3.98 .25 3.75 .14 4.18 .24
3.93 .15 3.76 .18 3.68 .11 4.06 .19
WBCs, before ttt
WBCs, 2-4 weeks
WBCs, 24 weeks
WBCs, after ttt
Mean SE
Mean Se
Mean SE
Mean SE
response categories
*There are mild but significant decrease in the three blood elements; which is more pronounced
in Hb level and least pronounced in platelet count; after treatment in all patients.
Table 16: Viral levels(copies/ml) before, during and after treatment in all patient categories
(mean and standard error)
sustained response
non-response
relapse
total patients
528333.33 462435.91 2416875 1024098.69 2107500 932313.43 1543621 1120856.57
20000.00 27879.61 1508750 704707.39 82500.00 117862.91 526666.67 810584.42
6666.67 16143.30 1975625 751643.14 12500.00 25000.00 663958.33 1034308.19
.00 .00 . . 162500.0 325000.00 40625.00 162500.00
.00 .00 . . 545000.0 676880.10 136250.00 388636.51
viremia/before ttt
viremia/3 mon
viremia/6mon
viemia /end
viremia/6m.later
Mean SD
Mean SD
Mean SD
Mean SD
response categories
*There is significant correlation between levels of viremia before treatment and levels at end of
treatment and 6 months later on in all patients.
Table 17: Reduced Glutathione concentration in liver biopsy (nmol/mg protein of liver tissue).
6 1.78 .24
6 1.38 .32
4 2.03 .18
4 2.00 .17
5 1.83 .26
5 . .
2 1.88 .11
2 . .
17 1.87 .23
17 1.63 .41
GTH before Treatment
GTH after treatment
Sustained response
GTH before Treatment
GTH after treatment
Non-response
GTH before Treatment
GTH after treatment
Relapse
GTH before Treatment
GTH after treatment
Withdrwan due to side
effects
Group
GTH before Treatment
GTH after treatment
Group Total
Count Mean Std Deviation
count: number of patients for whom liver biopsy was done in each category.
It was found that there is significant reduction in the reduced Glutathione after treatment only
in those with sustained response (P = 0.002) and in all patients taken together (P < 0.001)
Table 18: Results of Liver biopsy in patients without contraindications.
17

18. 14.5000 12.3333 3.3333 3.3333
1.04881 1.03280 .51640 .51640
14.7500 14.0000 3.5000 3.5000
1.50000 1.82574 .57735 .57735
15.4000 3.6000
1.34164 .54772
14.5000 3.5000
.70711 .70711
14.8235 13.0000 3.4706 3.4000
1.18508 1.56347 .51450 .51640
Mean
Std. Deviation
Mean
Std. Deviation
Mean
Std. Deviation
Mean
Std. Deviation
Mean
Std. Deviation
Group
Sustained response
Non-response
Relapse
Withdrwan due to
side effects
Total
Histolog.
activity before
treatment
Histolog.
activity after
treatment
Grade of
fibrosis
before
treatment
Grade of
fibrosis after
treatment
There is significant reduction in the HAI score (histological activity) after treatment in
sustained response category and total patients (P =0.001) but not in other categories or in the
fibrosis grade (P >0.05)
Figure 4: Viral load in responding patients
viremia during treatment in SR
1600000
1400000
1200000
1000000
800000
600000
400000
200000
0
1 2 3 4
Months of treatment
viral titer
Figure . 5: viral levels in non-responding patients
18

19. viral loads in nonresponding patients
5000000
4500000
4000000
3500000
3000000
2500000
2000000
1500000
1000000
500000
0
1 2 3
time of measurement
viral load
Figure 6: Viral load in relapsing patients
viremia during treatment in relapsing patients
3500000
3000000
2500000
2000000
1500000
1000000
500000
0
1 2 3 4 5
Months of treatment
viral titer
Figure 7: Viral load in all 24 patients continuing treatment
19

20. viremia in all patients
5000000
4500000
4000000
3500000
3000000
2500000
2000000
1500000
1000000
500000
0
1 2 3 4 5
time of treatment
vira l titer
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علج المرضى المصريين المصابين بالتليف الكبدى المتقدم نتيجة الصاببابة بببالفيروس
الكبدى ج النوع الوراثى ٤ وذلك باستخدام النترفيرون طويل المفعول مع الريبافيرين
شندى محمد شندى شريف* و نعيمة العشرى** وعلء عوض* و معتز صايام *
* قسمى المببراض المتوطنبة والكبببد والجهباز الهضبمى و** الكيميباء الكللينيكيبة معهببد تيبودور بلهبارس
للبحاث
حيث أنه ل يوجد معلومات كلافية حتى الن عببن نتائببج علج المرضبى المصببريين المصبابين بببالتليف الكبببدى المتقببدم
الناتج عن الفيروس الكبدى ج النوع الوراثى الرابع ولذلك كلان الهدف مببن البحببث هببو تقيببم العلج باسبتخدام النبترفيرون
طويل المفعول والريبافيرين معا فى هؤلء المرضى. وقد تم البحث علي ۲٩ مريض جميعهم مصنفين مببن النببوع ب حسببب
تقسيم "اتشيلد بوف" ول يوجد موانع لديهم لستخدام هذه الدوية. وقد تم متابعتهم تحت العلج بالفحوص اللزمة.
وكلانت نتيجة البحث أن هناك خمسة مرضى خرجوا من البحث قبل ثلث شهور لظهور مضباعفات شببديدة مثبل نقبص
الصفائح الدموية و كلرات الدم البيضاء والتهابات المفاصال ( موجب الروماتيد) وزيادة وظائف الغدة الدرقية و وفاة مريض
بنزيف دماغى أثر حادث سيارة. أما باقى المرضى فقد اسبتمروا ببالعلج حبتى ثلث شبهور حيببن أوقببف العلج فبى ثمانيبة
مرضى وذلك لعدم استجابتهم للعلج وعدم انخفاض مستوى الفيروس فى الببدم واعتببروا غيببر مسبتجيبين للعلج . والسبتة
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24. عشر المرضى الباقون فقد استجابوا مبدئيا للعلج الذي استمر حتى ٤٨ أسبوع واعتبروا مستاجبين للعلج عند نهببايته. و
بعد ستة أشهر من إيقاف العلج حدث انتكاسة بظهور الفيروس فى 4 مرضى واستمر الشفاء التام فى 12 مريببض الببباقين
و الذين يمثلون ٨٣,٤١ % من جميع المرضى و ٥٠ % من المرضى الذين استمروا بالعلج .
وكلان العامل الوحيد الدال على الستجابة التامة هو مستوى الفيببروس فبى الببدم قببل العلج حيببث كلبان أقبل فبى الببذين
استمرت استجابتهم.
وقد انخفض تركليز الجلوتاثيون المختزل انخفاضا ذو دللة احصائية وكلذلك كلان التحسن النسيجى فى عينات الكبببد فبى
المرضى ذي الستجابة الدائمة فقط وليس فى باقى المرضى
يستنتج من هذا البحث أن المرضى ذوي التليف المتقدم والذين ليس عندهم موانع لستخدام هببذه الدويبة مببن الممكببن
علجهم بنفس الدوية والتى تستخدم فى الحالت المبكرة بنفس درجة الستجابة وتحمل العلج تقريبا.
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