Kurikulum Vitae Nama : Prof Dr. Nurul Akbar SpPD KGEH Riwayat

Kurikulum Vitae
Nama
: Prof Dr. Nurul Akbar SpPD KGEH
Riwayat pendidikan : FKUI 1968
Internis 1975
Konsultan 1984
Pekerjaan
: Staf Hepatologi FKUI
Professor 1998
Penghargaan
: Peneliti Terbaik FKUI 1998
Organisasii
: Ketua PPHI 2006
Sekretaris Dewan Guru Besar FKUI 2000
Tata laksana Fibrosis , Sirosis dan Kanker Hati
Komprehensif
Prof Dr Nurul Akbar, SpPD-KGEH,
Hepatitis Kronik dgn ALT normal
juga perlu diobati
High prevalence of significant liver fibrosis and cirrhosis in
chronic hepatitis B patients with normal ALT
in central Europe. Thomas Göbel,
The indication for antiviral treatment of patients with chronic hepatitis B is based on serum HBV DNA levels, transaminases, and
histological grade and stage. The relation of liver fibrosis and inflammation to ALT activity in chronic hepatitis B infection was
investigated in a non-endemic, European setting.
A total of 253 patients with CHB who had undergone liver biopsy at the Clinic of Gastroenterology, Hepatology, and
Infectious Diseases, Düsseldorf, Germany over the past 19 years (1990–2009) were evaluated.
39 had persistently normal ALT, 86 had ALT 1–2 × ULN, and 128 had ALT >2 × ULN.
Liver fibrosis or inflammation was defined as significant for stages or grades ≥ 2 according to the Desmet/Scheuer score.
Significant liver fibrosis (F ≥ 2) was found in 36%, cirrhosis in 18%, and significant inflammation (G ≥ 2) in
27%, of patients with normal ALT. There was no difference in the stage of liver fibrosis and the frequency of cirrhosis
between patients with normal and elevated ALT. The most important factor associated with the presence of cirrhosis in multivariate
analysis was age ≥40 years (P < 0.003). If concomitant factors like elevated GGT or male sex were furthermore present high
prevalences of significant liver disease were found.
The data indicate that, in a European setting, patients with chronic hepatitis B infection, and normal ALT
frequently have significant liver fibrosis or cirrhosis. Therefore, liver biopsy or liver stiffness measurement (LSM)
should be performed in these patients to determine the stage of liver fibrosis.
J. Med. Virol. 83:968–973, 2011.
Need anti-fibrosis treatment
(Fibroles, HpPro PLUS, AHFC
NON-INVASIVE DIAGNOSIS – WHY BOTHER?
•
Liver biopsy
Not always easy
FIBROSCAN
•3.5 MHz ultrasound transmitted from the vibrator toward the tissues
•pulse-echo ultrasound acquisitions are performed which is directly related to tissue stiffness.
•The harder the tissue, the faster the shear wave propagates
•The operator, assisted by ultrasound time-motion images
•liver portion at least 6 cm thick and free of large vascular structures
•The measurement depth is between 25 and 65 mm below the skin surface
100 times larger than liver biopsy
Terapi Causal seringkali tidak berhasil memenuhi harapan
….. diperlukan upaya optimal untuk mencegah komplikasi
Protect
Mitochondrial
Dysfunction
Stop Nekroinflamasi
Stop Fibrosis &
Stop Nekroinflamasi
Terapi Sirosis –
Tingkatkan
Kualitas Hidup
Immune Regulator
Anti Virus
Stop Fibrosis
Fibrosis hati
akumulasi/penumpukan jaringan parut didalam hati
Pembentukan jaringan parut
merupakan respon normal tubuh terhadap kerusakan sel hati,
tetapi dalam fibrosis ini proses penyembuhan berjalan menyimpang
ketika hepatosit rusak akibat infeksi dan peradangan
dengan berbagai penyebab seperti : virus, konsumsi alkohol berat, racun, trauma, atau faktor lain
maka sistem imun akan diaktifkan
untuk memperbaiki kerusakan sel
Kerusakan hati oleh sebab apapun
akan menginduksi nekrosis hepatosit dan apoptosis
Nekrosis melibatkan sinyal inflamasi dan menyebabkan peradangan klasik dan
sinyal fibrogenik dan fibrogenik klasik
Cirrhosis is
REVERSIBLE
Friedmann SL (Shanghai)
Cirrhosis
the most advanced stage of fibrosis
connotes not only more scar than fibrosis alone,
but also distortion of the liver parenchyma associated with
septae and nodule formation, altered blood flow, and risk of liver failure.
However,
cirrhosis still remains a dynamicand evolving state, such that
Interventions even at these advanced stages
could regress scar and improve clinical outcomes
Scott L. Friedman
GASTROENTEROLOGY 2008;134:1655–1669
Masalah
TERAPI ETIOLOGI
1) Chronic Hepatitis B: cccDNA
2) Chronic Hepatitis C: Mutasi
3) Efektifitas
4) Resistensi
5) Efek samping
6) Biaya
Stop Nekroinflamasi
Stop Fibrosis
Primary
TARGET
ETIOLOGI
Secondary
TARGET
NEKROINFLAMASI
FIBROSIS
Fibrosis & Sirosis
“ANYONE
WHO CAN STOP OR DELAY
LIVER FIBROSIS
WOULD BE ABLE TO CURE MOST
CHRONIC LIVER DISEASES.”
PROFESSOR HANS POPPER
A FAMOUS HEPATOLOGIST IN THE U.S.
GASTROENTEROLOGY RESEARCH AND PRACTICE, VOLUME 2012
Telah Ada di Indonesia
Protect
Mitochondrial
Dysfunction
Carnico Q
Stop Nekroinflamasi
Hp Pro
Stop Fibrosis &
Stop Nekroinflamasi
Hp Pro Plus
Terapi Sirosis –
AHFC
Tingkatkan
KualitasHidup
BRM
Immune Regulator
ImReg
Stop Fibrosis
Fibroles
Hp Pro - Mechanism of Actions
1) MAINTAIN MEMBRANE STABILITY OF HEPATOCYTES
through inhibiting lipid peroxidation and covalent binding of toxic metabolite of CCl4 to
lipid and proteins of liver microsomes
2) INCREASES THE DETOXIFICATION FUNCTION OF LIVER
by increasing the liver microsomal cytochrome P-450 content
3) INCREASES RESISTANCE OF THE BODY TO HARMFUL STIMULI
by modifying the pattern of metabolic activation and metabolite-DNA complex profile in
liver microsomes of carcinogenic substance (benzopyrene)
4) INHIBITS HEPATOCARCINOGENESIS INDUCED BY AFLATOXIN B1
as indicated in less and smaller y-GT foci and inhibition of a-FP production in rats after
Hp Pro treatment
5) PROMOTES LIVER CELL REGENERATION
as indicated in increase of RNA and glycogen content, ATPase and cytochrome oxidase in
hepatocyte mitochondria.
Liu Gengtao, Chinese Academy of Medical Sciences, Beijing Chine
FOKUS TERAPI
1)
Regulasi Sistem Imun
2)Hentikan Nekroinflamasi
3)
4)
5)
Hentikan Fibrosis
Terapi Sirosis
Terapi Kanker???
Effectiveness of Hp Pro
in treatment of liver diseases:
an experience in Indonesian patients
Chinese Medical Journal 1998 :
Nurul Akbar, Rino Alvani Gani Taher, Widayat Djoko Santoso, Soemarno
Sumaryono, H M Sjaifoelah Noer, Liu Geng Tao
The effects of HpPro on the level of GPT of Indonesian patients.
An open trial
Nurul Akbar et.al. Chinese Medical Journal 1999; 111 (30): 248-251
U/L
250
Mean of ALT on the first day
200
Acute hepatitis : 194 ± 212 N = 16
150
100
Chronic hepatitis: 69 ± 74
N = 20
Liver cirrhosis
: 45 ± 18
N = 14
Fatty liver
: 43 ± 21
N= 6
Dose
: 3 X 1 capsule
50
0
1st day
1st wk
Acute hepatitis
2nd wk
Chronic hepatitis
3rd wk
Liver cirrhosis
4wk
Fatty Liver
Comparison of therapeutic effect on GPT and GOT decreased between
the HpPro group and the control group in the controlled study
on chronic hepatitis
%
80
*
*
70
60
50
HpPro(GPT)*
Control(GPT)
HpPro(GOT)*
Control(GOT)
40
30
20
10
* : statistically significant
0
1st week 2nd week
Nurul Akbar et.al. Chinese Medical Journal 1999; 111 (30): 248-251
Im-Reg
1.Meningkatkan Jumlah Makrofag
2.Meningkatkan Aktifitas Sel NK (Natural
Killer Cells)
3.Meningkatkan Jumlah Interleukin-2 (IL2)
4.Meningkatkan Jumlah Sel Th (T4) dan
jumlah sel Tc
5.Meningkatkan rasio Th / Ts
6.Anti-Kanker, Sinergis dengan BRM
FOKUS TERAPI
1)Regulasi Sistem Imun
2)Hentikan Nekroinflamasi
3)
4)
5)
Hentikan Fibrosis
Terapi Sirosis
Terapi Kanker???
Peran Sistem Imunologi
dalam menunjang terapi etiologik pada
infeksi virus hepatotropik
dr. Suwardji Haksohusodo
Fak. Kedokteran, Univ. Gadjah Mada
Kongres Nasional IV
Perhimpunan Alergi Imunologi Indonesia
Medan, 29 Maret - 1 April 2001
Stop Nekroinflamasi & Fibrosis
Cegah Sirosis dan Kanker Hati
Stop Fibrosis
Hepatitis Kronik ALT = Normal
Stop Nekroinflamasi & Fibrosis
Hepatitis Kronik ALT > Normal
Fibroles
Hp Pro Plus
Salvianolic Acid B
and its metabolite SMND-309
FIBROLES
Mechanisms of Action
and Therapeutic Effects
1)
2)
3)
4)
5)
Ameliorated liver function
Decreased the elevation of
•
Serum HA, LN, PIIIP
•
Hydroxyproline content in liver tissue
•
MDA
Restored the decrease of
•
Superoxide dismutase (SOD)
•
Glutathione peroxidase (GSH-PX) activities
Reduced liver damage and liver fibrosis grade.
Powerfully down-regulated the expression of CTGF rather
than TGF-B1
Therapeutic effects of SMND-309, a new metabolite of salvianolic acid B, on experimental liver fibrosis.
prevent the development of decompensated cirrhosis
and hepatocellular carcinoma (HCC)
Cirrhosis
is a series of progressive stages
(not a single stage)
Fibroles
HpProPlus
AHFC
prevent the development of decompensated cirrhosis
and hepatocellular carcinoma (HCC)
cpd 861 (AHFC)
•
an aqueous extract of
10 defined herbs based on TCM
• The chief herbs used in cpd 861 are :
‐
‐
‐
‐
Salvia miltiorrhiza (FIBROLES)
Astragalus membranaceous
Spatholobus suberectus
Bupleurum sinens
• The aim of TCM
is resolution of :
- blood stasis and
- liver stagnation
two conditions that form the basis of
liver pathology and patient discomfort
Hepatology, October 1999
Herbal Products for Liver Diseases:
A Therapeutic Challenge for the New Millennium.
D Schuppan, Ji-Dong Jia
AHFC ; The Mechanisms
leading to The Reversal of Fibrosis
 Significantly inhibit LX-2 cell proliferation
 Suppression of fibrogenesis and Concurrent
Enhancement of ECM degradation
• reduced the mRNA levels of
collagen type Ⅲ, MMP-2 and TGF-β1
• enhanced the MMP-1 mRNA levels
• down-regulated the TIMP-1 mRNA expression
increasing the ratio of MMP-1 to TIMP-1
REF
- World J Gastroenterol 2004;10(19): 2831-2835
- World J Gastroenterol 2008 March 21; 14(11): 1790-1794
Cpd 861 (AHFC)
is proved to be
an effective anti-fibrotic herbal compound
1. Animal Experiment
2. Open Clinical Trial
3. Double Blind Cinical Trial
Efficacy Confirmed by
Liver Biopsies
GOLD STANDARD
double-blind
The
AH F C
(n=50) ,
REVERSAL
52%
100
75
SCORE
≥2
53.3%
50
38.9%
25
0
Confirmed by
0%
(Liver Biopsies)
S1 (n=3) S2 (n=18) S3 (n=15) S4 (n=14)
AFTER 6 (SIX) MONTHS TREATMENT
The Overall Reversal Rate
AHFC 52% vs Control 20%
p<0.05
YIN Shan -shan et al.
Rate
Fibrosis
78.6%
Chin J Hepatol, August 2004
100
75
50
25
0
C ontrol (n=50), 20%
0.0%
S1
(n=12)
14.3% 25.0%
S2
(n=14)
S3
(n=12)
41.7%
S4
(n=12)
Treatment with Cpd
861(AHFC)
Patient no 15
Ma, male, 49 year-old
HBsAg(+) for 6 years with increased ALT
Before After Normal
198
54
<40
IV-C (ng/ml)
287.8
133.9
<140
H A (ng/ml)
736.7
109.7
2-110
P-III-P (u/ml)
2.05
1.51
0.3-0.8
Ln
(u/ml)
2.25
1.62
1.0-1.6
PV
(mm)
12.0
11.0
<14
Spleen(mm)
52.0
50.0
<40
ALT
(u/l)
Penelitian di Indonesia
Evaluasi Fibrosis hati secara non invasif
dengan Fibroscan pada
Terapi Anti-Fibrosis
Prof.Dr.Nurul.Akbar,SpPD-KGEH
Bagian Ilmu Penyakit Dalam
FKUI/RSCM. Jakarta
F0: < 5, F1: 5 -7, F2: 7.1-9.4, F3: 9.5-12.4, F4: 12.5-20, Sirosis > 20
BRM
1.Mencegah Pembentukan Lipid Peroksida
Hepar
2.Anti-Fibrogenesis
3.Regenerasi Sel Hepar
(merangsang sintesa DNA,RNA,dan Urea
Pad Sel hepar yang terganggu)
6.Menghambat Sel Hepatoma & Metastasis
7.Memacu Apoptosis Selektif Sel Kanker
8.Mencegah Penurunan Sel lekosit &
Imunitas
Pada Penderita Kanker Yang Menjalani
Kemoterapi / Radioterapi
KESIMPULAN:
Terapi Hepatitis Kronik
1) Terapi Causal


Hepatitis Virus
 Terapi Imun (+ anti virus, sesuai pedoman)
Hepatitis Non-Virus
 Terapi Etiologi (Obesitas, DM, Alkohol, dll)
2) Stop Dysfungsi Mitochondria
 Cegah Hepatic Fat Infiltrasi & Nekroinflamasi
3) Stop Nekroinflamasi
 Cegah Fibrosis
4) Stop Fibrosis
 Cegah Sirosis
5) Terapi Sirosis
 Cegah Sirosis Dekompensata & Kanker Hati
You’re Eating Too Many Herbs!
You’re Eating Too Many Herbs!
Terima Kasih
prevent the development of
decompensated cirrhosis and HCC