Liver Cancer and HCV-infected individuals who do not have cirrhosis

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Liver Cancer and HCV-infected individuals who do not have cirrhosis

Liver cancer is more common in older people. Over half of people newly diagnosed with liver cancer are age 65 and over. Liver cancer is more common in men than in women. Liver cancer rates are highest among Asians and Pacific Islanders, most likely because of higher prevalence of viral Hepatitis infection. Liver cancer rates are lower among whites than Blacks or Asians and Pacific Islanders. At this time, we do not know exactly what causes cancer of the liver. There are several different types of liver cancer.

The most common type is associated with long-term excessive alcoholic beverage use, scarring of the liver (cirrhosis), and Hepatitis B virus or Hepatitis C virus infection. Long-term use of anabolic steroids can also increase the risk of getting liver cancer. Smoking is also believed to increase the risk of getting liver cancer.

Hepatitis B and hepatitis C are highly contagious blood borne viruses that cause liver disease, liver cancer, and premature death. Chronic hepatitis B is treatable when detected early and properly managed.

In about 50% of the cases, chronic hepatitis C can be cured. It is estimated that 2,000,000,000 people worldwide have been infected with the hepatitis B virus, 400 million chronically. Approximately 170 million people worldwide are chronically infected with the hepatitis C virus. An estimated 5.3 million people living in the United States are infected with either hepatitis B or hepatitis C; tragically more than half are unaware of their status.

Overwhelming majority of the liver cancers is the hepatocarcinoma (or hepatoma). Most hepatoma developed from a cirrhotic liver, which is a liver damaged by repeated inflammation by many causes among them viral hepatitis. Viral hepatitis B & C accounts for more than 80% of all the liver cancers. Hepatitis B virus is unique because hepatoma may develop from a fairly healthy liver without much cirrhosis. About 30-50% of hepatoma from Hepatitis B viral infection developed from a non cirrhotic liver. In Asia, 80% of the liver cancer is from the hepatitis B infection.

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— Asian Liver Center at Stanford University.

http://www.livercancerfree.org/livercancer.php

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Hepatitis C Virus May Persists at Low Levels after Sustained Response to Treatment; Liver Cancer May Develop Years Later

..http://www.hivandhepatitis.com/hep_c/news/2009/020609_a.htmlBy Liz Highleyman2/06/09Hepatitis C patients who maintain an undetectable plasma HCV RNA level 6 months after completion of interferon-based therapy are generally considered "cured." But 2 recent studies indicate that HCV may persist at low levels in the body, and successfully treated patients remain at risk for liver disease progression.

Low Level HCV

In the first study, reported in the December 23, 2008 advance online edition of Hepatology, Canadian researchers aimed to assess the infectivity of HCV persisting at very low levels using a previously established HCV infection system in human T-cells.

As background, the investigators noted that HCV can persist in the liver, lymphoid cells, and serum of individuals with apparently complete spontaneous or treatment-induced resolution of hepatitis C.

In this study, naive lymphoid cells were exposed to plasma and/or supernatants from cultured peripheral blood mononuclear cells from 9 individuals with apparent sustained virological response (SVR) after completion of antiviral therapy. Exposed cells were analyzed for HCV RNA positive and negative strands. In selected cases, the researchers also assessed the presence of HCV non-structural protein 5a (NS5a), the appearance of HCV variants, and the release of virions (virus particles) using immunoelectron microscopy. Results11 of the 12 established cultures were HCV RNA positive strand-reactive. 4 also expressed the viral replicative strand. The NS5a protein was detected in the newly infected cells. Clonal sequencing revealed HCV variants not found in the inoculated plasma or supernatants. Immunoelectron microscopy demonstrated enveloped HCV particles in plasma used as inocula and in culture supernatant from T-cells exposed to that

plasma. Overall, HCV carried by 3 of the 9 study participants elicited productive infection in vitro.

Based on these findings, the study authors concluded, "HCV persisting at very low levels long after therapy-induced resolution of chronic hepatitis C can remain infectious.""The retained biological competence of the virus might have implications with respect to the mechanisms of its persistence and the epidemiology of HCV infection," they added.Molecular Virology and Hepatology Research Group, Division of Biomedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. 's, Newfoundland, Canada; Discipline of Laboratory Medicine, Faculty of Medicine, Health Sciences Centre, Memorial University, St. 's, Newfoundland, Canada

Liver Cancer

Hepatocellular carcinoma (HCC) is a form of primary liver cancer that can develop over time in people with chronic hepatitis C. While effective antiviral treatment has been shown to dramatically lower the risk of HCC, it does not eliminate it completely.

In the January 7, 2009 issue of Cases Journal, Japanese authors described a case of a patient who developed HCC more than a decade after successful treatment. While there have been several recent reports of HCC developing in chronic hepatitis C patients even after attaining a sustained response to interferon-based therapy, it is not common for HCC to develop more than 10 years after achieving SVR, the authors noted as background.The present case report involved a 73-year-old Japanese man with chronic hepatitis C who achieved SVR with interferon therapy 13 years ago.

The man was admitted to the hospital after he developed multiple large liver tumors, along with marked elevation of tumor biomarkers. After several diagnostic methods strongly suggested HCC, the authors performed histopathological (tissue) examination, confirming a diagnosis of well-differentiated HCC. Since the man's tumors were well-differentiated, he was able to be successfully treated with intensive combination therapy.

In conclusion, the authors wrote, "Our report highlights the need for careful follow-up for more than 10 years even if the patients with chronic hepatitis C achieve SVR to interferon therapy."Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan2/06/09ReferencesT Mashitani, H Yoshiji, M Yamazaki, and others. Development of hepatocellular carcinoma in a patient 13 years after sustained virological response to interferon against chronic hepatitis C: a case report. Cases Journal 2(1): 18. January 7, 2009.

SEE CASE JOURNAL AND COMPLETE STUDY

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Modern Pathology (2010) 23, 276–283; doi:10.1038/modpathol.2009.174;

published online 20 November 2009

,.Hepatitis C-associated hepatocellular carcinomas in non-cirrhotic livers

M Yeh1, Hubert Darius-J 2 and son2

AbstractChronic hepatitis C viral infection can lead to cirrhosis and hepatocellular carcinoma. It is generally believed that hepatitis C infection is not oncogeneic per se, but that the presence of cirrhosis determines the increased risk for hepatocellular carcinoma. However, a search of surgical pathology files from two large tertiary care centers for the years 2001–2008 identified a total of 18 hepatocellular carcinomas in non-cirrhotic livers with chronic hepatitis C infection.

In six cases the background livers showed bridging fibrosis, while the remainder showed lower stages of fibrosis. Cases were negative for clinical and serological evidence of hepatitis B co-infection, and occult hepatitis B test was negative by PCR of formalin-fixed, paraffin embedded tissues. The tumors were also negative for TP53, exon 7, codon 249 mutations, a characteristic mutation strongly linked to aflatoxin exposure.

The hepatocellular carcinomas had typical histology with no enrichment for unusual growth patterns or histological features. Among all resected hepatocellular carcinomas in non-cirrhotic livers over this time period, the prevalence of 16% with HCV infection was significantly greater than that expected by chance. In conclusion, these results demonstrate that hepatocellular carcinomas can arise in livers chronically infected with hepatitis C but without cirrhosis.

,These findings raise the possibility that in some cases hepatitis C infection and inflammation can be directly oncogeneic. It is also possible that established cirrhosis may have regressed in some cases. Regardless of the mechanism, these findings highlight an important and previously under-recognized risk for hepatocellular carcinoma in HCV-infected individuals who do not have cirrhosis...

Correspondence: Dr MM Yeh, MD, PhD, Department of Pathology, University of Washington School of Medicine, 1959 NE Pacific Street, NE140D, Box 356100, Seattle, WA 98195, USA. E-mail: myeh@...

http://www.nature.com/modpathol/journal/v23/n2/abs/modpathol2009174a.html

also see:Liver Cancer In HCV Cirrhosis and Interferon Feb 2010

http://Hepatitis Cnewdrugs.blogspot.com/2010/03/liver-cancer-and-hcv-infected.html