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HEPATOLOGY WATCH® |
Editorial Board:
Emmet B. Keeffe, MD (Chair); M. Eric Gershwin, MD; Ira S. Goldman, MD; John
L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul Martin, MD; Marion G. Peters,
MD |
HIGHLIGHTS OF THE 55TH
ANNUAL MEETING OF
THE AMERICAN
ASSOCIATION FOR THE STUDY OF LIVER DISEASES
OCTOBER 29 -
HEPATITIS B VIRUS (HBV) INFECTION
Entecavir (ETV) vs. lamivudine
(LVD). The
results of 2 phase III studies showing the superiority of ETV to LVD were
reported. The first study (Daniel Shouval, et al.) was a multicenter, double-blind trial in
which 648 patients with HBeAg(-) chronic hepatitis B
were randomized to receive either ETV 0.5 mg qd or LVD 100 mg qd for 48
weeks. Histological improvement
(≥2-point decrease in Knodell necroinflammatory score with no worsening
of fibrosis) occurred in 70% of ETV-treated patients compared to 61% of
LVD-treated patients (primary endpoint).
In addition, a greater proportion of ETV patients (84%) than LVD
patients (78%) achieved a composite endpoint of serum HBV DNA <0.7 MEq/mL
and ALT normalization. In the second
multicenter, double-blind study (TT Chang, et al.), 716 patients with HBeAg(+) chronic HBV were randomized to receive ETV 0.5 mg
qd or LVD 100 mg qd. Histological
improvement occurred in 72% compared to 62% of ETV and LVD patients,
respectively, and a greater proportion of ETV than LVD patients achieved a
virological response (91% vs. 65%). No
mutations associated with resistance to ETV were detected in either study, and
safety was comparable between ETV and LVD groups in both studies. These studies showed ETV treatment to be
superior to LVD in both HBeAg(-) and HBeAg(+) chronic
hepatitis B. (Abstracts LB-07 and 70)
Peginterferon
(PEG IFN) alfa-2a vs. LVD. George Lau and others conducted a partially double-blind,
multicenter study in which 814 patients with HBeAg(+) chronic hepatitis B were
randomized to receive: 1) PEG IFN alfa-2a 180 ug once
weekly plus placebo qd; 2) PEG IFN plus LVD 100 mg qd; or 3) LVD 100 mg
qd. Patients were treated for 48 weeks
and were assessed after 24 weeks of follow-up.
Significantly greater proportions of PEG IFN-treated patients than
LVD-treated patients achieved HBeAg seroconversion, serum HBV DNA levels
<100,000 copies/mL, HBeAg loss, and ALT normalization. This study showed that PEG IFN therapy was
associated with greater efficacy in HBeAg(+) HBV
patients than LVD therapy and that the addition of LVD to PEG IFN did not
improve the response rate. (Abstract 20)
Adefovir
dipivoxil (ADV) vs. ADV plus emtricitabine (FTC).
George Lau and colleagues investigated novel
anti-HBV therapy by performing a multicenter, double-blind study in which 30
patients with HBeAg(+) chronic hepatitis B were
randomized to receive ADV 10 mg qd plus placebo qd or ADV 10 mg qd plus FTC 200
mg qd. Patients treated with combination
therapy achieved a greater median log10 reduction of HBV DNA
compared to those given ADV alone at both 24 weeks and 48 weeks of
therapy. HBV kinetics were examined and
revealed 2 groups of patients: fast responders who cleared the virus by 12
weeks of treatment and slow responders who did not clear the virus by 12
weeks. Fast response was associated with
enhanced T-cell reactivity, and patients on combination therapy were more
likely to be fast responders than those on ADV monotherapy. HBeAg seroconversion was observed in 3 cases
(all fast responders). These results
indicate that the combination of ADV and FTC therapy result in faster and greater
HBV suppression than ADV alone in patients with HBeAg(+) chronic hepatitis
B. (Abstract 245)
Prevention of
vertical transmission of HBV with LVD treatment.
Wei-Min Xu and coworkers randomized
114 HBsAg (+) mothers (serum HBV DNA >1,000 MEq/mL) seen in several medical
centers in
Occult HBV infection. Manna Zhang
and others screened 241 adult hemodialysis patients for occult HBV to document
the prevalence of HBV infection in an adult hemodialysis population. Two patients (0.8%) were HBsAg(+). Among the remaining 239 HBsAg(-)
patients, 9 patients (3.8%) had detectable serum HBV DNA ranging from 1,000 to
100,000 copies/mL. Seven of these 9
patients were nt 587
mutation (S-mutant) positive. No
demographic factors were predictive for occult HBV infection. These findings indicate the prevalence of
occult HBV is 4-5 times higher than HBsAg testing would suggest. Consideration should be given to utilizing
HBV DNA to screen dialysis patients, and studies are needed to determine the
infectivity and natural history of occult HBV infection. In order to document the prevalence of occult
HBV infection in an isolated community in Canada, Dongfeng
Sun et al. tested sera from 544 (64%) of 850 residents in an Inuit community;
39 cases were already known to be HBsAg(+).
The samples from the remaining 515 subjects were divided into 2 groups:
Group 1 included 108 samples with a serologic profile consistent with resolved
HBV infection (HBsAg(-), anti-HBc(+), and
anti-HBs(+)); and Group 2 was made up of 407 samples that were seronegative for
all HBV markers. Serum HBV DNA was
detected in 14 (13%) samples in Group 1 and 33 (8.1%) samples in Group 2. Viral
loads were low (<106 copies/mL) in all cases, and S variants were
found in 12/14 and 17/33 of HBV DNA(+) individuals in
Groups 1 and 2, respectively. (Abstracts
100 and 1001)
HEPATITIS C VIRUS (HCV) INFECTION
Prevalence in
US. Gregory Armstrong and colleagues
from the Centers for Disease Control and Prevention compared prevalence data
from the ongoing National Health and Nutrition Examination Survey (NHANES)
conducted during 1999-2002 with that from NHANES III conducted 10 years
ago. Serum specimens were obtained from
15,079 participants aged 6 years and older in the current NHANES and tested for
anti-HCV. Compared with NHANES III, the
overall prevalence of anti-HCV (1.6%) was unchanged but peaked in an older age
group (45-49 years) vs. 35-39 years in NHANES III). These data are consistent with a past
epidemic of acute HCV infection resulting in a cohort of people aged 45-49
years with a high prevalence rate of HCV infection. (Abstract 31)
PEG IFN vs.
interferon alfa (IFN) plus ribavirin (RBV) in asymptomatic acute hepatitis C.
Sanaa Kamal
and others prospectively observed 68 asymptomatic patients with proven acute
hepatitis C for up to 20 weeks. At weeks
8 (Group A; n = 21), 12 (Group B; n = 20), and 20 (Group C; n = 20), patients
who did not spontaneously recover were randomized to 12 weeks of treatment with
either PEG IFN monotherapy once weekly or IFN (3 MIU TIW) plus RBV (10.6
mg/kg). Overall a greater proportion of
PEG IFN-treated patients than IFN+RBV-treated patients achieved a virological
response (90% vs. 62%). Early therapy
was associated with a slightly higher virological response rate. Patients receiving PEG IFN had a lower
incidence of influenza-like symptoms, blood changes, and depression than
patients treated with IFN+RBV. The
results of this study suggest that once weekly PEG IFN for 12 weeks is superior
to IFN+RBV as treatment for patients with asymptomatic acute hepatitis C. (Abstract 37)
Is smoking cannabis a risk factor for
fibrosis progression? Cannabis
sativa (marijuana) exerts its effects via CB1 and CB2 receptors. Christophe Hezode et al. have recently demonstrated that CB1 receptors
enhance liver fibrogenesis. These
findings led to an evaluation of the impact of cannabis smoking on fibrosis
progression in chronic hepatitis C. Data
were analyzed from 211 consecutive newly diagnosed patients with chronic
hepatitis C. Multivariate analysis
identified daily cannabis smoking to be independently related to rapid fibrosis
progression. Other predictive factors
were histological activity ≥A2, age >24 years, infection with genotype
3, and alcohol intake ≥30 g/day.
These findings suggest a link between daily cannabis smoking and
progression of fibrosis in patients with chronic hepatitis C. (Abstract 67)
Liver transplantation (LT) in
HIV-HCV co-infected patients. Jean-Charles Duclos-Vallee et al.
prospectively followed 20 HIV-HCV co-infected
patients who underwent LT between December 1999 and May 2004 for end-stage HCV
cirrhosis (median follow-up of 16 months; range, 1-48 months). All patients were treated with HAART. Two patients died after LT due to recurrent
hepatitis C and mitochondrial (mt) toxicity (possibly
secondary to HAART). One patient
succumbed to pancreatic cancer. Ten
patients (50%) required initiation of IFN+RBV therapy for recurrent hepatitis
C. Microvesicular steatosis was observed
in 7 (35%) patients and a low level of mtDNA was
detected in 2 of 5 patients. These
findings indicate that LT is feasible in patients with HIV-HCV co-infection.
However, severe recurrent hepatitis C and mitochondrial toxicity may
develop, requiring IFN+RBV treatment and avoidance of HAART. (Abstract 69)
72 vs 48 weeks
of therapy with PEG IFN alfa-2a and RBV.
Jose Sanchez-Tapias enrolled a total of 517
previously untreated patients with detectable HCV RNA to receive PEG IFN
alfa-2a180 ug/week and RBV 800 mg/day. After 4 weeks of treatment, 327 patients who
had not achieved a rapid virological response (RVR) were randomized to receive
either 48 or 72 total weeks of PEG IFN+RBV therapy. The sustained virological response (SVR) rate
was greater (46% vs. 32%) and the relapse rate was lower (13% vs. 48%) in the
72-week group compared to the 48-week group.
The safety profile of the 72-week treatment group was similar to that of
the 48-week treatment group. These data
showed that extended treatment with PEG IFN+RBV resulted in superior efficacy
without increasing the incidence of adverse events in patients with chronic
hepatitis C who did not achieve RVR.
(Abstract 126)
HEPATOCELLULAR CARCINOMA (HCC)
Epidemiology.
Alex Befeler et al. analyzed data from the
Liver Cancer Network database obtained from 189 patients with HCC in 6 centers
(median follow-up, 193 days). Their data
showed that HCC was almost always associated with chronic liver disease (HCV in
half of cases); almost half of all patients were initially asymptomatic;
asymptomatic patients at diagnosis had a longer survival; and the BCLC and CLIP
staging systems were an improvement over the Okuda and TNM classifications. (Abstract 123)
TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS)
Polytetrafluoroethylene
(PTFE)-covered stents. Previous
data had shown that PTFE-covered stents decreased the rate of TIPS
dysfunction. However, no study has
evaluated the long-term potency of PTFE-covered stents. Christophe Bureau
et al. conducted a multicenter study in which 80 cirrhotic patients requiring
TIPS were randomized to receive either a PTFE-covered stent or a standard
stent. At 2 years, the actuarial rates of
potency were 76% for the PTFE-covered stents and 36% for the uncovered
stents. Shunt dysfunction occurred in 6
(15%) patients with the PTFE-covered stent compared to 18 (44%) patients with
the uncovered stents. The incidences of
portal hypertension and encephalopathy were greater in the group with uncovered
stents and survival was similar in both groups.
These findings show that PTFE-covered stents improve the long-term
potency of TIPS resulting in improved outcomes.
The authors concluded that the role of TIPS therapy in the management of
portal hypertension should be re-assessed utilizing PTFE-covered stents. (Abstract 54)
PRIMARY SCLEROSING CHOLANGITIS (PSC)
Effect of
high-dose ursodeoxycholic acid (UDCA).
There is evidence that high doses (≥ 20 mg/kg/d) of UDCA may be
more effective therapy for PSC than lower doses. This increased effectiveness may be due to
enrichment of biliary bile acids with UDCA.
However, the correlation between UDCA dose and biliary enrichment had
not been previously demonstrated. Daniel
Rost and associates at the
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