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A Bi-Monthly Publication of the Hepatitis Support Project

January 25, 2008
Volume 5, Issue 2

Liz Highleyman

To download pdf version click here

In This Issue:

Hepatitis C

• HCV Transmission via Crack Pipes

• Liver Transplant Survival

• Genetic Variation in Liver Disease Progression

• CT Scans for Monitoring Liver Fibrosis

• Elastography and Acute Hepatitis

• Antiretroviral Therapy for Coinfected Patients

HCV Transmission via Crack Pipes
It is well-known that HCV is transmitted through sharing needles for drug injection, but a study in the January 2008 European Journal of Gastroenterology and Hepatology added to the evidence that the virus can also be spread via non-injection drug use. B. Fischer and colleagues attempted to detect HCV RNA on pipes used by 51 street crack users, within one hour after use. Study participants provided saliva samples for HCV antibody testing and had their mouths photographed to assess the presence of oral lesions. In total, 22 participants (43%) tested HCV antibody positive, and a minority had oral sores. HCV was detected on one of the 51 pipes (2%). This pipe had a glass stem, and its owner was HCV antibody positive and had mouth sores. “HCV transmission from an infected host onto paraphernalia as a precondition of HCV host-to-host transmission via shared crack paraphernalia use seems possible,” the researchers concluded, recommending larger studies to confirm their findings.

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Liver Transplant Survival
Chronic hepatitis C can progress to advanced liver disease, including cirrhosis and hepatocellular carcinoma (HCC), which may necessitate a liver transplant. In the December 2007 Journal of Hepatology, E. Melum and colleagues reported outcomes in 288 hepatitis C patients wait-listed for liver transplants in the Nordic countries over a 17-year period, and a comparison group of 1,552 people without viral hepatitis who needed liver transplants for other reasons. Among the HCV patients, 253 (90%) received new livers, and HCC was found in 38% of the old removed livers. Survival rates in the HCV group at 1, 3, and 5 years were 82%, 69%, and 61%. This compared with 85%, 80%, and 76%, respectively, in the comparison group. In the HCV group, survival rates were 73%, 52%, and 46% for people with HCC versus 88%, 80%, and 71% for those without liver cancer. The researchers concluded that hepatitis C is associated with significantly impaired survival in liver transplant recipients. While this effect was seen even in HCV positive patients without liver cancer, HCC and older donor age were the two factors that most strongly contributed to reduced survival.

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Genetic Variation in Liver Disease Progression
There is wide individual variability in the progression of hepatitis C, from spontaneous viral clearance to end-stage liver disease. Human genetic variations may help explain these differences, according to a study in the December 2007 issue of Hepatology. P. Hraber and colleagues assessed whether specific human leukocyte antigen (HLA) variations were statistically linked to liver disease progression in hepatitis C patients. At each genome location, individuals have two gene variations, or alleles, one from each parent; these two alleles may either be the same (homozygous) or different (heterozygous). Looking at data from more than 22,000 recipients of liver transplants due to various causes, the investigators found that people with HCV were significantly less likely than uninfected individuals to be heterozygous for the HLA-DRB1 allele; they did not find significant associations for other HLA locations. “These findings constitute evidence for an advantage among carriers of different supertype HLA-DRB1 alleles against HCV infection progression to end-stage liver disease,” the researchers concluded.

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CT Scans for Monitoring Liver Fibrosis
In an effort to reduce the need for repeated biopsies, researchers have explored alternative ways to diagnose and monitor liver fibrosis, including various blood markers and non-invasive imaging methods. As reported in the December 20, 2007, advance online edition of Hepatology. M. Romero-Gomez and colleagues evaluated conventional digitized helical computed tomography (CT) scans as a method for assessing liver fibrosis in 141 chronic hepatitis C patients. On a scale of F0 to F4, fibrosis scores according to CT imaging correlated with histology scores as determined from liver biopsies by two blinded pathologists. Receiver operating characteristics curve values (a measure of accuracy) were 0.83 for diagnosing significant fibrosis (stage F2 or higher) and 0.86 for diagnosing advanced fibrosis (stage F3 or higher). The correlation between CT and biopsy findings was higher for patients with homogeneous fibrosis distribution throughout their livers than for those with inconsistent distribution. The investigators concluded that, “Fibro-CT is a simple to use, readily available, and useful method for the diagnosis of fibrosis in patients with chronic hepatitis C.”

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Elastography and Acute Hepatitis
In another December advance article in the same journal, researchers looked at a different non-invasive method – liver stiffness determined by transient elastography (FibroScan) – in patients with acute viral hepatitis. This technique was developed to assess fibrosis, but results may be influenced by other types of liver injury. U. Arena and colleagues evaluated 18 patients with no history of previous liver disease who were admitted to an Italian hospital with acute viral hepatitis. Elastography and aminotransferase (ALT and AST) measurements were performed on the same day at the point of peak aminotransferase increase, when aminotransferase levels were 50% or less than the peak level, and again when levels fell to 2 times the upper limit of normal. In all patients, liver stiffness values at the aminotransferase peak exceeded the cutoffs proposed for predicting significant fibrosis or cirrhosis. Liver stiffness progressively declined over time as aminotransferase levels fell. The researchers recommended that the extent of necroinflammatory activity (as indicated by ALT and AST) must be carefully considered when using transient elastography to assess liver fibrosis, particularly in patients with absent to moderate fibrosis (stages F0-F2). “Liver stiffness measurement does not represent a reliable instrument to detect the presence of advanced fibrosis and cirrhosis in patients presenting with a clinical picture of acute hepatitis,” they concluded.

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Antiretroviral Therapy for Coinfected Patients
Certain antiretroviral drugs, including nevirapine (Viramune), have been linked to liver toxicity in some people with HIV, but prior studies have produced inconsistent data. HIV/HCV coinfected individuals are at greater risk of hepatotoxicity, and also tend to experience more rapid liver fibrosis progression. As described in the January 1, 2008, issue of Clinical Infectious Diseases, J. Berenguer and colleagues retrospectively assessed the association between two classes of anti-HIV drugs – non-nucleoside reverse transcriptase inhibitors (NNRTIs, including nevirapine and efavirenz [Sustiva]) and protease inhibitors (PIs) – and fibrosis progression in 201 coinfected patients. The odds of having absent or minimal fibrosis (stage F0-F1) versus severe fibrosis (F3-F4) increased with each additional year of exposure to antiretroviral therapy overall, NNRTIs as a class, and efavirenz or nevirapine specifically; however, this effect was not seen with PIs. The odds of having significant (F2) versus severe fibrosis increased with longer exposure to NNRTIs or nevirapine, but not antiretroviral therapy overall, PIs, or efavirenz. Further, longer exposure to antiretroviral therapy overall, NNRTIs, or nevirapine was associated with slower fibrosis progression. These data suggest that, on the whole, the benefits of antiretroviral therapy in reducing liver disease progression outweigh the risk of liver toxicity.

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