| Back
to News Review
Liz Highleyman
To download pdf version click here
In This Issue: Hepatitis C
Noninvasive Markers for Liver
Disease
Hepatocellular Carcinoma
Promising Amantadine Results
Noninvasive
Markers for Liver Disease
Noninvasive Markers for Liver
Disease
Liver biopsy remains the “gold standard” for determining
the extent of liver damage, but the search is underway for
less invasive techniques that can be used to monitor liver
disease progression and the effectiveness of treatment without
the need for repeated biopsies.
In the February 2004 issue of the American
Journal of Gastroenterology, Vincent Leroy and colleagues
looked at whether serum levels of several chemicals were related
to METAVIR fibrosis scores in 194 hepatitis C patients and
194 healthy controls. The researchers found that levels of
hyaluronate, procollagen type III N-terminal peptide (PIIINP),
and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2
were significantly higher in patients than controls. In a
multivariate analysis, PIIINP and matrix metalloproteinase
(MMP)-1 were independently associated with fibrosis. PIIINP
is a marker for fibrogenesis (the production of fibrous tissue),
while MMP-1 reflects fibrolysis (the breakdown of fibrous
tissue). The authors concluded that combining the two markers
“may provide a useful tool for evaluating liver fibrosis.”
Blood levels of gamma-glutamyl transpeptidase
(GGT) are commonly measured along with ALT and AST to gauge
liver disease status, and GGT levels are often elevated in
people with chronic hepatitis C. But GGT is not a direct marker
of liver damage, and its usefulness remains unclear. In the
March 2004 issue of the Jounal of Gastroenterology and
Hepatology, Ivonete Silva and colleagues reported on
a study designed to assess the relationship between GGT and
clinical, biochemical, and histological status in 201 chronic
hepatitis C patients who underwent liver biopsy. Elevated
GGT was seen in about half the patients. No association was
seen between GGT levels and either bile duct damage or steatosis
(fatty liver). But in a multivariate regression analysis,
elevated GGT was associated with grade 3 or 4 inflammatory
activity in the liver and stage 3 or 4 fibrosis. The authors
concluded that GGT “seemed to be useful as an indirect
marker of more advanced liver disease in chronic hepatitis
C.”
Back to top
Hepatocellular
Carcinoma
Hepatocellular carcinoma (HCC) is a type of liver cancer that
develops in some people with chronic hepatitis C or B, usually
after many years. It is the fifth most common cancer worldwide,
and the third most common cause of cancer-related death. Several
recent journal articles have focused on HCC, and the February
2004 issue of Liver Transplantation was devoted to
the topic. In the latter, Masao Omata and Haruhiko Yoshida
presented an overview of the state of knowledge about HCC.
Since hepatitis C and B are the predominant causes of HCC,
better treatments for these diseases as well as widespread
vaccination against hepatitis B can play a key role in reducing
the incidence of liver cancer. For example, in the March 2004
issue of Gut, H. Yoshida and colleagues reported
that interferon therapy delayed the development of HCC, especially
in patients with advanced fibrosis.
Along with progress in therapy for hepatitis C and B, there
have also been advances in HCC diagnosis and treatment. However,
Omata and Haruhiko note, liver cancer recurrence is “extraordinarily
frequent, since the remaining liver is still at a particularly
high risk of HCC.” Also in Liver Transplantation,
Josep Llovet and colleagues described the HCC diagnosis, staging,
and treatment program used by the Barcelona Clínic
Liver Cancer Group. Since HCC usually occurs in people with
cirrhosis (whether due to chronic viral hepatitis or some
other cause), this group should be screened every six months
for liver cancer using ultrasound and blood tests for alpha-fetoprotein.
Other tests are under study; in the February 2004 issue of
Hepatology, Jin Woo Kim and colleagues reported on
a unique genetic pattern in tissue samples of patients with
cirrhosis that may potentially be useful as a marker to help
diagnose early onset HCC.
Surgical resection (removal of the tumor)
is considered the best treatment option for patients with
early HCC if they maintain reasonable liver function (e.g.,
normal bilirubin and no portal hypertension). As Lorenzo Capussotti
and colleagues reported in Liver Transplantation,
even large tumors (greater than 10 cm) and cancer that involves
the portal vein can sometimes successfully be removed.
In patients with poor liver function,
percutaneous ablation (destruction of the tumor in place),
chemoembolization (delivery of drugs directly to the tumor),
or liver transplantation are other possible options. As described
by Riccardo Lencioni and colleagues, percutaneous ablation
works best in people with early-stage HCC. Injection of ethanol
(alcohol) into the tumor is the most common method, but recent
studies show that thermal destruction using radiation (radiofrequency
ablation) appears more effective and requires fewer treatment
sessions. [Radio-frequency] ablation could therefore be considered
as the percutaneous treatment of choice for patients with
early-stage tumors,” the authors concluded. “Further
investigation is warranted to clarify whether current [radiofrequency]
technology could offer improved results in patients with intermediate-stage
HCC.”
HCC survival rates depend on how
early the cancer is detected and how large and extensive the
cancer has grown. Kazuto Inoue and colleagues reported in
Liver Transplantation that the 5-year survival rate
was 93% among patients with early HCC (well-differentiated
cancer, usually less than 2 cm, and not metastasized, or spread);
however, cancer recurred after treatment in 53%. Masakazu
Yamamoto and colleagues reported in the March 2004 Annals
of Surgery that the 5-year survival rate for early HCC
was 85%, significantly better than the outcomes among patients
with even small-sized advanced liver tumors. Tito Livraghi
and colleagues reported, also in Liver Transplantation, that
among 210 patients with early-stage HCC receiving treatment
(radiofrequency ablation, ethanol injection, or chemoembolization)
guided by ultrasound, 3- and 5-year survival rates were 69%
and 49%. Among 164 patients with intermediate-stage HCC, the
corresponding survival rates were 43% and 28%. Dr. Capussotti’s
group reported that patients who underwent removal of large
tumors had a 5-year survival rate of just 17%. Unfortunately,
late-stage liver cancer is not considered treatable, although
patients with advanced HCC may be eligible to join clinical
trials of experimental therapies.
Back to top
Promising
Amantadine Results
Amantadine (Symmetrel), a drug used to treat influenza and
Parkinson’s disease, is also under study as a possible
therapy for hepatitis C. Research to date has been inconclusive,
with several studies showing that amantadine did not appear
particularly effective against HCV. But in the March 2004
issue of the Journal of Hepatology, Alessandra Mangia
and colleagues from Italy reported on a study that produced
more favorable results. The researchers conducted a meta-analysis
of data from nearly 1,000 treatment-naive patients from six
European centers. At the end of therapy, virological response
was seen in 38.5% of subjects receiving interferon plus amantadine,
compared with 29.5% of those using interferon alone. Sustained
virological response (SVR; continued undetectable HCV viral
load six months after the end of treatment) was seen in 23.1%
and 17.3%, respectively. Addition of amatadine improved response
rates in all subgroups except patients with low initial HCV
viral load and those with genotypes 2 or 3. The researchers
concluded that “therapy with amantadine and interferon
is effective and may be an alternative to interferon and ribavirin
in patients who cannot tolerate ribavirin.”
Back to top
Back to News Review |
