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HEPATOLOGY WATCH® |
Editorial Board:
Emmet B. Keeffe, MD (Chair); |
HIGHLIGHTS OF DIGESTIVE DISEASE WEEK
CHRONIC HEPATITIS B VIRUS (HBV)
INFECTION
Treatment with adefovir dipivoxil
(ADV). Prior
studies have demonstrated that ADV is effective treatment for a broad range of
patients with chronic HBV infection. The
following 3 investigations provide further evidence that ADV is efficacious
when used as long-term therapy or as salvage treatment. In the first study Yves Benhamou et al.
report the results of 192 weeks of treatment with ADV 10 mg daily, in addition
to lamivudine (LAM) 150 mg bid, in 22 patients with LAM-resistant HBV
co-infected with HIV. This trial showed
that up to 4 years of ADV therapy was well tolerated and resulted in sustained
reductions in serum HBV and ALT levels.
Furthermore, no ADV-associated mutations were identified. In a second study, Stephanos Hadziyannis et
al. followed HBeAg-negative HBV patients treated with ADV for up to 144
weeks. At 96 and 144 weeks of treatment,
HBV DNA was undetectable by PCR in 71% (50 of 70 patients) and 79% (53 of 67
patients) of patients, respectively. The
cumulative incidence of ADV resistance after 144 weeks of treatment was
5.9%. In a third study, Fasiha Kanwal et
al. compared the cost-effectiveness of interferon monotherapy vs. LAM monotherapy
vs. LAM therapy followed by ADV salvage therapy for the development of LAM
resistance by utilizing decision analysis with Markov modeling. The patient population was a cohort of
40-year-old patients with chronic HBV infection and elevated liver enzymes
without cirrhosis. The ADV salvage
strategy resulted in a greater number of life years saved than the monotherapy
treatment options at an acceptable cost. Gastroenterology
2004;126:(Suppl 2) Abstracts 1, 3, 411.
CHRONIC HEPATITIS C VIRUS (HCV)
INFECTION
Darbepoetin-alfa (DA) for ribavirin
(RBV)-induced anemia. Zobair
Younossi et al. reported preliminary data from 39 patients with chronic HCV
infection receiving peginterferon and RBV therapy with adjunctive DA. Patients who developed a hemoglobin level £10.5 g/dL
were given DA 3 mcg/kg every 2 weeks.
Among 13 patients requiring DA, an increase in hemoglobin level of 1.27
± 0.73 g/dL occurred within 6 weeks of starting DA therapy and 83% of patients
were able to maintain their RBV dose.
These data show that DA improved anemia and allowed for RBV dose
maintenance. Gastroenterology 2004;126: (Suppl 2) Abstract 83.
Viramidine. Viramidine is a pro-drug of
RBV. Preclinical studies have shown that
compared to RBV, viramidine yields higher RBV levels in liver tissue and lower
concentrations in plasma and red blood cells.
Sanjev Arora et al. conducted a study in which 180 previously untreated
patients with HCV infection received 3 different doses of viramidine or
RBV. Serum HCV RNA reductions were
similar for viramidine- and RBV-treated patients. The mean red blood cell concentration of RBV
was lower in patients receiving viramidine and was associated with a lower rate
of hemoglobin reduction than patients treated with RBV. None of the viramidine-treated, versus 13% of
RBV-treated patients, required dose reductions.
Gastroenterology
2004;126:(Suppl 2) Abstract 84.
Frequency of peginterferon alfa-2b
(Peg-Intron) dosing. Francesca
Lodato and associates enrolled 65 patients with chronic HCV infection into a
study of combination Peg-Intron plus RBV therapy. Twenty-two patients received Peg-Intron once
a week and 43 patients received Peg-Intron twice weekly. Patients with genotype 1 and genotype 2
infections were treated for 48 weeks and 24 weeks, respectively. The rates of sustained virological response
were higher in previously untreated patients and patients with genotype 1 who
received the twice weekly administration of Peg-Intron. Tolerability was also greater in the twice a
week group, possibly due to tachyphylaxis caused by continuous drug
exposure. Gastroenterology 2004;126:(Suppl 2) Abstract 122.
HIV coinfection. Prospectively collected data by
Edmund Bini and colleagues from 4,364 HCV RNA-positive patients undergoing
evaluation for HCV therapy in 24
Prevalence of renal
insufficiency. Sorin
Petri and coworkers reviewed the records of consecutive patients with HCV
infection seen at their medical center from July 2000 to August 2003 (N = 531
evaluable patients) and found that 32% of these patients had evidence of renal
impairment. The findings of this review
indicate the need to screen HCV patients for renal insufficiency. Gastroenterology
2004;126:(Suppl 2) Abstract 179.
PROGRESSION OF HEPATIC FIBROSIS
Serum markers. Serum markers of hepatic fibrosis
may reduce the need for liver biopsy.
Yonas Getachew et al. analyzed paired serum markers of fibrosis
(FibroSpect II; Prometheus Labs) and liver biopsy specimens obtained from 10
patients with PBC. The values of the
serum markers were expressed in a regression equation to give a serum marker of
fibrosis index (SMF). Their results
showed that the SMF correlated with degree of liver fibrosis seen on liver
biopsy and that the baseline SMF was better than liver biopsy at identifying
subjects who subsequently developed a clinical complication. Keyur Patel et al. prospectively utilized the
FibroSpect II panel to differentiate minimal from severe fibrosis in patients
with chronic HCV infection from 3
NONALCOHOLIC FATTY LIVER DISEASE
(NAFLD)
Relationship of alcohol intake and
obesity association with cardiac abnormalities.
Alcohol and obesity are associated with hepatic steatosis. Constance Ruhl and James Everhart analyzed
data from 13,607 adult participants in the third US National Health and
Nutrition Examination Survey to examine the relationship of alcohol drinking
and obesity with abnormal serum ALT levels.
Participants with HBV, HCV, or iron overload were excluded. Multivariate analysis identified an
association between elevated serum ALT levels and drinking among persons who
were overweight or obese, but not in those of normal weight. The authors concluded that the risk of
alcohol-related liver injury was limited to patients who were overweight. In another provocative study, Sorel Goland
and coworkers compared the prevalence of cardiac abnormalities in 26 patients
with NAFLD to that of an age- and gender-matched control group. Patients with diabetes mellitus,
hypertension, and morbid obesity were excluded.
Intraventricular septum thickness and left ventricular mass were found
to be significantly greater in the NAFLD patients than in controls. In addition, measurements of left ventricular
diastolic function were significantly lower in patients with NAFLD compared to
controls. These findings suggest that
ventricular diastolic dysfunction may be an early feature associated with
NAFLD. Gastroenterology 2004;126:(Suppl 2) Abstracts 414 and 415.
TRANSPLANTATION
Impact of structured management on
patients after transplantation for alcoholic liver disease (ALD). Structured management consists of
a dedicated team of professionals who apply a treatment plan for alcohol
dependency and abuse before and after liver transplantation for ALD. In an analysis of patients with ALD who had
undergone liver transplantation at a single center (N = 103) in Sweden
(Gothenburg) and survived for at least 3 months, Einar Bjornsson and others
discovered that a greater proportion of patients transplanted prior to the
establishment of structured management resumed alcohol use compared to those transplanted
after the start of a structured management program (54% vs. 22%). In addition, the authors reported that the
overall survival rates at 1 and 5 years after transplantation were similar
between ALD patients and a control group of non-ALD patients matched for
gender, age, and year of transplantation.
These findings demonstrated that ALD and non-ALD patients derived
similar benefit from liver transplantation and that a structured management
approach minimized the risk of recidivism in the ALD population. Gastroenterology 2004;126:(Suppl 2)
Abstract 12.
Treatment regimens for recurrent HCV
after orthotropic liver transplantation (OLT). Interferon
plus RBV therapy is tolerated poorly by patients who develop recurrent HCV
infection after OLT. These results led
Nicholas Kontorinis et al. to conduct a pilot study in which 25 patients with
recurrent HCV after OLT were initially treated with low doses of
peginterferon-2a and ribavirin. A
standard protocol was used to escalate the doses of both agents to full
therapeutic doses by the third month of treatment. This treatment strategy was well tolerated,
although the aggressive use of hematopoietic growth factors was necessary to
achieve adequate dosing of interferon and RBV.
A virological response at 6 months of treatment was realized in 13 (52%)
patients, suggesting that a reasonable sustained virological response rate
would be likely. Gastroenterology 2004;126:(Suppl 2) Abstract 45.
Liver allograft half-life. Alastair Smith and associates
reviewed data from the United Network for Organ Sharing scientific registry
(19,717 liver allografts from January 1, 1988 to December 31, 1996) and found
that patients with immune forms of chronic liver disease had the longest graft
and patient half-lives following OLT.
The data also showed that graft half-lives were short (1.5 years) for
patients receiving second or subsequent allografts, indicating that
retransplantation should be reserved for only those patients with excellent
functional status. Gastroenterology 2004;126:(Suppl 2) Abstract 48.
Liver transplantation for HCV
recurrence. James
Burton and Hugo Rosen conducted a survey of US liver transplant centers to
elucidate the current practice patterns regarding the treatment of HCV
recurrence after first liver transplantation.
Most transplant medical directors responded that practice patterns have
changed over the past 5 years, and 60% of directors were less likely to offer
retransplantation to patients with HCV recurrence due to their poor long-term
survival rates. Gastroenterology 2004;126:(Suppl 2) Abstract 211.
PRIMARY BILIARY CIRRHOSIS (PBC)
Alendronate Therapy. Osteoporosis is a known
complication of PBC. Claudia Zein et al. conducted a double-blind,
placebo-controlled, randomized trial and observed that treatment with the oral
bisphosphonate alendronate for a year was associated with a significant
increase in spine bone mineral density (BMD).
A significant increase in femur BMD was not achieved with alendronate therapy
compared to placebo. Gastroenterology 2004;126:(Suppl 2)
Abstract 170.
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