Topic: Hepatitis B
V. Araya; R. Restrepo;
D. Ng; R. Koka; K. D. Rothstein; M. Orrego; S. J. Munoz
Background:
Little data exists linking treatment
algorithms with histological severity.
Aim: Determine whether the North American HBV treatment
algorithms and/or patient demographics correlate or predict the severity of
chronic HBV.
Method: Inclusion
criteria:
1. HBV-infected patients with at least
two ALT’s, detectable HBV DNA quantitative levels, and eAg status obtained over
a minimum of 6 months;
2. No prior antiviral therapy;
3. A METAVIR scored liver biopsy within
2 years of the serological data.
Peak ALT and HBV DNA levels were used to define ALT and VL
categorization.
Exclusion criteria:
1. HIV or HCV co-infection;
2. Iron overload;
3. Hepatocellular carcinoma.
Definitions: High viral load (HVL): ≥104
copies/ml (c/ml) if eAg -, or ≥ 105 c/ml if eAg+; low viral load (LVL): < 104 c/ml if eAg -, and < 105 c/ml if eAg+. For
analysis, patients were distributed among 4 groups depending on their viral
load and eAg status.
·
Groups
0: eAg (-) and LVL;
·
Group
1: eAg (-) and HVL;
·
Group
2: eAg (+) and LVL;
·
Group
3: eAg (+) and HVL.
Spearman correlation, Fisher’s exact test, and logistic
regression analysis were employed for statistical modeling.
Results:
425 patients seen between 2001 and 2006 were evaluated. 96
patients met inclusion criteria. 61% were Asian, 59% males, mean age 47 (67%
Age ≥ 40), 58% had persistently normal ALT, 65% were eAg negative.
No correlation existed between biopsy grade or stage, and eAg
status, ALT status, gender, or ethnicity. Groups 0 and 3 correlated with biopsy
grade (P=0.03 Fisher’s Exact Test, FET), but not stage (P=0.46 FET).
In Group 0, 37% had Stage ≥ 3 and 18% had Grade ≥
3. The only variable demonstrating statistically
significant correlation with stage and grade was Age ≥ 40 (P=0.004 FET).
Stage ≥ 3 was seen in 20% age <40 and 51% age ≥
40 and Grade ≥ 3 was seen in 17% age < 40, and 36% age ≥ 40.
Logistic regression did not show that any Group, ALT status, Viral load level, or eAg status was able to predict stage or
grade ≥ 3. Age ≥ 40 had the highest area under the ROC at 0.69 for
advanced histological stages (3 or 4).
Combining the variables Age ≥ 40, Groups 1-3, and
abnormal ALT yielded an area under the ROC of 0.71 for Stage ≥ 3 and 0.77
for Grade ≥ 3.
Conclusion:
Current treatment algorithms for hepatitis B do not correlate
nor predict the severity of chronic HBV. Since available HBV treatment can
improve HBV infection severity, accurate histological diagnosis is important
for risk assessment. Thus, patients age ≥ 40 may
benefit most from a liver biopsy.
740. Contribution of common variants in the complement
factor H gene to fibrogenesis in chronic hepatitis C virus (HCV)
infection.
F. Grünhage; H.
Keppeler; H. Wasmuth; M. Odenthal; U. Drebber; H. P. Dienes; C. Hellerbrand; T.
Sauerbruch; F. Lammert
Topic: Liver Transplantation - General
T1028. The Effect of Liver Transplantation on Autonomic
Dysfunction in Patients with End-Stage Liver Disease.
E. J. Carey; D. D.
Douglas; H. E. Vargas; T. J. Byrne; J. L. Rakela; V. Balan; D. C. Mulligan.
Background:
Autonomic dysfunction is a recognized complication of
end-stage liver disease but there is little information on how liver
transplantation (LT) affects this problem.
Aim:
To prospectively evaluate autonomic
function in patients with end stage liver disease before and after liver
transplantation.
Methods:
Autonomic Reflex Screen (ARS) was performed on 26 patients
with end stage liver disease (ESLD) prior to transplantation. The ARS tests
sudomotor, cardiovagal, and adrenergic nervous system function and includes sudomotor
axon reflex test (QSART) at 4 sites, heart rate response to Valsalva maneuver
and deep breathing, blood pressure and heart rate responses to head-up tilt. A
10-point composite autonomic score (CAS) was calculated from these data.
Results:
26 patients (21M, 5F) with ESLD had ARS prior to liver
transplantation. Average age was 55
years, indication for liver transplant was HCV (14), cryptogenic (4), alcohol
(3), other (5), average MELD score at ARS was 17.
Three patients had diabetes, two without any end-organ damage and one with mild
CAD.
Prior to liver transplantation, 88.5% of patients had
evidence of autonomic dysfunction. Mean CAS was 2.6 (range 0-10), median 2.
Sudomotor function was disturbed in 64%, cardiovagal in 58%, and adrenergic in
38%. No correlation was found between MELD score or presence of diabetes and
pre-LT CAS. There was a trend towards more autonomic dysfunction in patients
whose etiology of liver disease included alcohol abuse, p=0.05.
18 patients had repeat ARS an average of 9 months after liver
transplantation. Pre-LT CAS in this
group was 2.9 (range 1-10) and post-LT CAS was 1.9 (range 0-5). Two patients
with normal pre-LT scores remained normal post-LT. Thirteen patients with pre-LT
autonomic dysfunction had stable or improved scores after LT. Three patients
had worsened autonomic dysfunction after LT.
Conclusion:
Autonomic dysfunction is common in patients with ESLD, with
over 88% affected. Sudomotor or cardiovagal dysfunction is present in over 60%
of patients and adrenergic dysfunction occurs in almost 40%. Although most
patients show improvement in autonomic function after LT, this effect is not
universal. We await the post-LT ARS results of the remaining patients in this
study.
Topic: Cirrhosis - General
T1038. Prevalence of Complications Of Liver Cirrhosis In Patients With HCV Infection And
Diabetes Mellitus.
S. Memon; N. K.
Khatri; U. Soomro; W. Jafri; R. Ghori.
Background:
There is evolving evidence that the presence of diabetes
mellitus (DM) increases the prevalence and severity of various complications of
liver cirrhosis due to HCV infection. Prospectively we evaluated this
previously unreported novel observation in our setting.
Aim:
To evaluate the prevalence of
complications of liver cirrhosis in patients with HCV infection and diabetes
mellitus.
Methods:
Patients with liver cirrhosis were enrolled who visited our
clinic from June 2006 to September 2006. A questionnaire was filled regarding the
presence of diabetes mellitus and other complications of liver cirrhosis,
whether occurred in past or presented in emergency room or clinic.
Results:
Out of total 304 patients, 53 (17.4%) had DM with 181 (59.5%)
men and 123 (40.5%) women. There was no significant difference in mean duration
of cirrhosis, mean age, mean body weight and mean body mass index (BMI) in
diabetes and non-diabetes patients. The prevalence of DM was significantly
higher in men compared to women (p value 0.04). No difference of Child’s class
in both groups. History of variceal bleeding was significantly lower (p value
0.029) in DM patients (13.2%) compared to non diabetic(27.5%),
whereas there was significant difference in the prevalence of ascites, hepatic
encephalopathy and hepatocellular carcinoma due to presence or absence of DM.
Conclusion:
Presence of DM does not increase complications of liver
cirrhosis, rather it decreases the prevalence of variceal bleeding, hence our results do not support the above novel observation.
Topic: Cirrhosis – General
K. Julka; S. L. Flamm.
Background:
Spontaneous bacterial peritonitis (SBP) is a serious
complication of ESLD. In-hospital mortality rates of ~35% are often quoted but
mainly arise from old reports. Because of increased awareness, earlier dx and
therapy and improved abx and ICU care, we speculated that in-hospital mortality
from SBP has improved with contemporary medical management.
Aim:
We sought to assess the current in-hospital mortality from
SBP and to determine which clinical factors currently predict mortality in this
pt population.
Methods:
72 consecutive patients diagnosed with "suppurative
peritonitis" from 1/00 - 12/04 in a tertiary care ctr were identified by
ICD-9 codes. Patients were excluded from analysis if a source of abd infection
was identified such as perforation or abscess. 52 patients had SBP as defined
by diagnostic paracentesis during hospitalization with a cell ct of >250
PMNs in the setting of confirmed cirrhosis. Demographic information and
numerous clinical factors including etiology of ESLD, Child's class, clinical symptoms
including encephalopathy (HE), GI bleeding, renal failure, bacteremia and
hospital day of SBP diagnosis were documented. The endpoint was in-hospital
mortality. Statistical analysis was performed to assess predictive value of
clinical factors related to mortality.
Results:
52 patients (31M:21F) with mean age
56.3 (range 32-81)were analyzed. EtOH (21), HCV (14), and 3 each HBV,HCV, AIH, Cryptogenic,
PSC, and other were etiology of ESLD in the majority of patients. 23 were dx'ed
on day 1 (D1), 16 on D2-D5, and 13 after D5 of hospitalization. The overall
mortality rate was 15/52 (29%). Renal failure (47% vs 5%) bacteremia (50% vs
20%), concomitant GI bleeding (56% vs 23%) and Child's class C vs B (33% vs
10%) were predictive of increased mortality. Presence of clinical symptoms
including HE (31% vs 23%), ascites cx + (35% vs 25%)and
day of diagnosis (30% D1 vs 25% D2-5 vs 31% >D5) were not predictive.
Conclusions:
1. Despite early diagnosis/therapy and
improved abx and ICU care, the in-hosp mortality rate for SBP has not improved.
2. Predictive factors of adverse
outcomes including renal failure, concomitant GI bleeding, bacteremia and
Child's class are unchanged from early reports.
3. New strategies such as more aggressive primary
prophylaxis must be sought to improve mortality from SBP.
Topic: Cirrhosis – General
M. Jang; J. Jang; H.
Kim; H. Kim; W. Shin; J. Lee; K. Kim; J. Park; J. Lee; H. Kim.
Background/Objective:
Endoscopic injection sclerotherapy (EIS) with cyanoacrylate
has been used in conditions with both cardiac (GOV1) and fundal (GOV2/IGV1)
variceal bleeding of gastric varices. However, cardiac varices are very
different from fundal varices both hemodynamically and pathophysiologically.
Therefore, therapeutic strategies should be individualized. This pilot study
was aimed to evaluate the efficacy of endoscopic band ligation (EBL) in active
cardiac variceal bleeding, not fundal variceal bleeding.
Methods:
We consecutively enrolled a total of 23 patients with liver
cirrhosis presenting with active cardiac variceal bleeding. They were treated
by EBL (6/19, EBL group) or EIS (13/19, EIS group). Remained 4 patients could
not undergo therapeutic procedures because of sudden cardiac collapse by
massive bleeding. GOV1 was defined as the varices within 2-5cm of
gastroesophageal junction.
Results:
Total patients were 95% of male and 52 (36-72) years old in
median (range). The causes of liver cirrhosis were alcoholic (62%),
HBV-associated (30%), HCV-associated (4%) and cryptogenic (4%), respectively.
The patients had experienced early rebleeding (within 48 hours) in 17% (1/6) of
the EBL group and 23% (3/13) of the EIS group (P=NS), and late rebleeding(within 6 months) in 17% (1/6) and 46% (6/13) in
each group (P=NS). Rebleeding-free survival was not significantly different
between EBL group and EIS group (165 days (1-450) vs. 90 days (1-870), P=0.39
on Kaplan-Meier curve). Mortality by cardiac variceal bleeding was not
significantly different between 2 groups (17% vs. 8%, P=NS).
Conclusions:
EBL may not be inferior to EIS in controlling an active cardiac
variceal bleeding in this pilot study. Therefore, it will be warranted to
perform the larger-scale study to reevaluate the role of EBL in active cardiac
variceal bleeding, not fundal variceal bleeding.
Topic: Current HCV Treatment – Side Effects
G. M. Dusheiko; J. G.
McHutchison; N. H. Afdhal; M. L. Shiffman; M. Rodriguez-Torres; S. Sigal; M.
Bourliere; T. Berg; N. Blackman; F. M. Campbell; S. White.
Background/Aims
Eltrombopag is an oral, non-peptide, small molecule
thrombopoietin receptor (TPO-R) agonist. The safety, efficacy and
pharmacokinetics of eltrombopag in HCV-infected subjects with thrombocytopenia
precluding initiation of pegylated-interferon (PEG-IFN) and ribavirin have
previously been reported. We have now examined the ability of eltrombopag to
counteract the myelosuppressive effects of PEG-IFN on platelet counts in
HCV-infected patients during treatment. A sub-analysis of data from study
TPL102357 was performed to determine if eltrombopag is able to maintain
platelet counts in thrombocytopenic subjects during PEG-IFN treatment thus
avoiding deleterious dose reductions of PEG-IFN.
Methods
HCV positive subjects with compensated cirrhosis and platelet
counts 20-70,000/uL were randomized (1:1:1:1) to receive 30mg (10 pts), 50mg
(14 pts), 75mg (21 pts) eltrombopag or placebo once daily for 4 weeks
(induction phase). Subjects achieving platelet counts of > 70,000/uL in the
induction phase could initiate PEG-IFN/ribavirin therapy along with study drug
for 12 weeks (maintenance phase). Platelet count assessments made at the
baseline visit were compared to those made at the completion of study drug
concomitant with PEG-IFN/ribavirin (Study Day 113).
Results/Conclusion
A total of 74 subjects were enrolled and 49 of those
successfully initiated PEG-IFN/ribavirin.
·
Eltrombopag
effectively maintained platelet counts above 50,000/uL in up to 81% of patients
during the first 12 weeks of antiviral treatment, counteracting the
myelosuppressive effects of PEG-IFN.
·
Eltrombopag
use avoided the need for PEG-IFN dose modification in approximately 90% of
patients during the first 12 weeks of antiviral treatment.
·
Further
research into the long-term use (48 weeks) of eltrombopag in patients with HCV
–associated thrombocytopenia is warranted.
Topic: Disease Progression – metabolic disorders
T1072. Outcome of Japanese patients with cirrhosis due
to nonalcoholic steatohepatitis(NASH) and hepatitis C.
S. Yatsuji; E.
Hashimoto; A. Kabutake; M. Tobari; M. Taniai; K. Tokushige; K. Shiratori.
Background and aims:
Ethnic differences in the prevalence and features of NASH are
well-documented. But, there is no information on the outcome of Japanese NASH
patients. In this study we compared the outcome of Japanese with liver
cirrhosis due to NASH(LC-NASH) with that of those with
LC associated to hepatitis C virus infection (LC-HCV).
Patients and Methods:
We investigated the long-term morbidity and mortality of 48
patients with biopsy proven LC-NASH and 60 with biopsy proven LC-HCV who were
not treated or did not respond to interferon. The end-points were survival,
appearance of varices and HCC. Time to failure analysis (Kaplan-Meier),
and log-rank analyses were used for across-group comparisons. The impact of
baseline risk factors on survival and the development of specific complications
were evaluated by logistic regression. Specific categorical features across
different subsets were compared using χ2 test. Mann-Whitney test was used
for across-group comparisons of numerical data. The patients were monitored
every 4-6 months clinically, biochemically and ultrasonographically.
Results:
LC-NASH group: the median age was 64 y.o.
(18-89 y.o.). There were 27 women (56%); 12 patients (25%) had a
BMI>30, 32 (67%) a BMI>25, and 29 (60%) had diabetes. Thirty four (71%) patients
were in Child-Pugh class A. During follow up (median 32.5 months; range
0.8-199), 11 patients developed some disease. Three died from HCC and 3 from a
liver unrelated cause. Five patients developed HCC, 5 esophageal varices, 5
ascites, and 4 developed hepatic encephalopathy. The 5-year survival rate was
83%, and the cumulative probability of developing HCC at 5 years was 11%.
LC-HCV group: the median age was 58 y.o. (33-73 y.o.).
There were 31 women (52%); 2 patients (3%) had a BMI>30, 20 (33%) a BMI>25,
and 16 (27%) had diabetes. Forty-three (72%) patients were in Child-Pugh class
A. During follow up (median 50.7 months; range 0.4-189), 19 patients developed
some disease. Six died from HCC and 2 from a liver unrelated cause. Fifteen
patients developed HCC, 17 esophageal varices, 15 ascites, and 8 developed
hepatic encephalopathy. The 5-year survival rate was 79%, and the cumulative
probability of developing HCC at 5 years was 20%. There were no significant
differences between the two groups regarding any parameter.
Conclusions:
In this prospective study, we found no significant
differences between LC-NASH and LC-HCV concerning morbidity, including HCC and
mortality.
Topic: Epidemiology – Psychosocial
G. S. Sayuk; S.
El-Dirani; J. E. Elwing; P. Lustman; M. Lisker-Melman; J. S. Crippin; R. E.
Clouse.
Introduction:
Depression is prevalent in patients with NASH and is
associated with greater degrees of steatosis and inflammation on biopsy
(Psychosom Med 2006; 68:563-9). Depression in patients without liver disease is
associated with insulin resistance and elevated levels of inflammatory markers
(e.g., IL-6, TNFa), a plausible explanation for its relationship with NASH. We
measured current depression symptoms and transaminases to assess whether these
indirect measures of hepatic inflammatory activity vary with degree of
depression symptoms in NASH and in chronic HCV.
Methods:
58 patients with NASH and 115 patients with HCV completed the
21-item Beck Depression Inventory (BDI) at an outpatient visit. Clinical data
were extracted from chart review. AST and ALT were determined contemporaneously
with BDI or extracted from recent laboratory data. Linear regression models
were constructed with transaminases as dependent variables and demographic
(age, sex, BMI) and liver disease factors (MELD score, encephalopathy, interferon) as independent variables that might confound a
relationship with BDI. Both total BDI (tBDI) and the 13-symptom cognitive scale
(cBDI) were examined to avoid confounding by overlap of liver disease with
depression symptoms on the total measure.
Results
AST and ALT correlated in both NASH (r=0.61, p=0.01) and HCV
patients (r=0.68, p=0.01). Mean tBDI scores were similar in NASH and HCV
patients (14.1 ±1.6 vs 15.0 ±1.1, p=0.6).
In NASH, 23 patients (39.7%) had elevated tBDI (≥16)
and 16 (27.6%) had scores ≥10 on the cBDI; in HCV, 49 patients (42.6%)
had elevated tBDI and 32 (27.8%) had high cBDI scores. AST was greater in NASH
patients with elevated tBDI vs those with lower tBDI scores (AST: 59 ±6 vs 43
±3, p<0.01) whereas ALT was not different (72 ±13 vs 61 ±6, p=0.4).
Similar findings were observed in HCV patients (AST: 102 ±13
vs 71 ±7, p=0.02; ALT: 115 ±18 vs 83 ±8; p=0.09). Regression analyses revealed
that, in NASH patients, both tBDI and cBDI predicted AST (p=0.03 for each),
while no other variable was significant. ALT was inversely predicted by age,
the only variable retained in its models (p<0.01 in each). In HCV patients,
tBDI (p=0.04) was the sole predictor of AST, and age again inversely predicted
ALT (p=0.03).
Conclusion:
·
Current
depression symptom activity is associated with AST levels in both NASH and HCV
patients, even after controlling for potentially confounding factors (including
liver disease severity).
·
Correlation
of liver histology and longitudinal measurements of transaminases with
depression activity in HCV and NASH patients will be required to clarify the
significance of the relationship and its causal directionality.
·
Clinical
Implications: These data serve as
preliminary evidence of a potential relationship between depression and a biomarker
of hepatic inflammation in two distinct chronic liver disease populations.
Topic: Epidemiology
E. J. Bini; S. Kritz;
L. S. Brown; J. Robinson; D. Alderson; J. Rotrosen.
Background:
Although substance abuse treatment programs are an important
point of contact to provide health services to diagnose, treat, and prevent
transmission of HIV/AIDS, hepatitis C virus (HCV) infection, and sexually
transmitted infections (STI), many drug treatment programs do not offer these
services. The aims of this study were to determine the proportion of substance
abuse treatment programs that did not offer health services for HIV/AIDS, HCV,
and STI, and to identify barriers to offering these services.
Methods:
We conducted surveys of drug treatment program administrators
and clinicians within the National Drug Abuse Treatment Clinical Trials Network
across the United States to evaluate the availability of 4 medical services
(medical history/physical examination, biological testing, medical treatment,
medical monitoring), 4 non-medical services (provider education, patient education,
patient risk assessment, patient counseling), funding, and other key elements
involved in testing, evaluating, and caring for patients with HIV, HCV, and
STI.
Results:
Completed surveys were received from 269 of the 319 treatment
program administrators (84.3%) and 1,723 of the 2,210 randomly selected
clinicians (78.0%). The majority of substance abuse programs were private
not-for-profit organizations (78.8%) and were free-standing facilities (60.7%).
One or more medical staff was present in 78.9% of programs, and 41.2% of
programs reported a current patient census of more than 500 clients. Of the 8
medical and non-medical services, the median number of health services offered
was 6.0 (interquartile range [IQR], 3.0 – 7.0) for HIV/AIDS, 4.0 (IQR, 2.0 –
7.0) for HCV, and 4.5 (2.0 – 7.0) for STI (p <0.01).
A high proportion of substance abuse treatment programs did
not offer any of the 4 medical services either on-site or by referral for
HIV/AIDS (29.8%), HCV (41.0%), or STI (39.8%) (p = 0.02). In contrast, a lower
proportion of drug treatment programs did not offer any of the 4 non-medical
services on-site or by referral for HIV/AIDS (4.7%), HCV (13.7%), or STI
(13.6%) (p <0.01).
The most common barriers identified by program administrators
and clinicians included funding, patient health insurance benefits, patient
acceptance, and staff training, with funding identified as the single biggest
obstacle to providing health services for these infections.
Conclusions:
Health service delivery for HIV/AIDS, HCV, and STI is less
than optimal in drug treatment programs, and there are numerous barriers to
providing these services. Public health interventions to overcome these
barriers to care afford an opportunity to enhance treatment and prevention.
Topic: Cirrhosis – General
T1333. Predictive Factors Of Hepatocellular Carcinoma In Cirrhosis.
C. Fierbinteanu
Braticevici; L. Ionita; L. Tribus; R. Usvat; A. Petrisor; A. Bengus.
Introduction:
The incidence of hepatocellular carcinoma (HCC) associated with
cirrhosis have increased over the last decade. The recognition of the risk
factors of hepatic carcinogenesis could improve the early diagnosis and
prognosis of HCC.
Aim:
To investigate the predictive factors for HCC occurrence in
cirrhotic patients
Methods:
Between 1998 and 2003, 365 cirrhotic patients, aged 35-65,
admitted to the University Hospital Bucharest, were prospectively followed up
during a 3-year period for early diagnosis of HCC. HCC was diagnosed in 31 of
them. The predictive value of different risk factors was evaluated using the
Kaplan-Meier method and Cox regression model. The clinical and biochemical
parameters consisted of: age, sex, etiology of cirrhosis, body mass index
(BMI), serum aminotransferase, serum glucose, serum lipid profile, INR, serum
glutathione and platelet count.
Results:
The incidence of HCC was 3.6 % in the first year, 1.9% in the
second and 4.7% in the third. Multivariate analysis demonstrated that: age
(>55years), male sex, HCV (hepatitic C virus) etiology of liver disease,
LDL- cholesterol < 100mg/dl, INR>1. 8 and platelet
count <80 × 10 3 /mm 3were important predictors of
HCC.
Comorbidities: obesity and diabetes mellitus also increased
the HCC risk. According to the contribution of each of these factors, a
clinico-biological score ranging between 0 and 5.23 was calculated to allow the
detection of high risk patients.
Conclusions:
·
Not
all patients with cirrhosis had an equal risk for developing HCC.
·
Parameters
like: age, sex, etiology, lipid profile, comorbidity, platelet count and INR
interact to increase the risk of HCC and may be taken into account when
selecting the cirrhotic patients to be screened for this type of tumor.