Risk Assessment for Hepatocellular

Carcinoma Development in Patients with Chronic

Hepatitis C

Bui Dac Chi,MDMedic Center

• The prognosis of HCC is deemed poor unless the cancer is detected and treated at an early stage. Thus, the assessment of risk for HCC development is essential in the management of patients with chronic liver diseases.

HCV infection typically progresses to chronic infection in more than 60% of patients, and it can lead to cirrhosis in as many as 20% over a 20-year period. Serum aminotransferase levels reflecting hepatocellular injury can fluctuate, as does the viral load.

As the disease evolves, hepatocytes are progressively destroyed and replaced by fibrosis, insidiously leading to the development of bridging fibrosis and ultimately cirrhosis. The course of any individual patient is affected by various factors, such as age at onset of infection, sex, co-infection with other viruses (hepatitis A virus, HBV or HIV), or other medical conditions, as well as risk behavior, such as alcohol consumption. Interferon-based treatment has a varying success rate in clearing the virus, The risk of developing HCC in chronic HCV patients with cirrhosis is as high as 4% per year. . Although successful treatment with interferon-based regimens is associated with a lower rate of liver-related complications or mortality, and perhaps even regression of fibrosis/cirrhosis, patients may still be at risk of development of HCC, even years after SVR.

Lauer and Walker, 2001

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Natural History of HCV Infection: Natural History of HCV Infection: Individual VariabilityIndividual Variability

• Educating patients regarding the natural history of chronic HCV is one of the most important things that a physician can do for a patient with recently diagnosed chronic HCV.

A warning that cirrhosis has developed and that the risk of complications (such as hepatocellular carcinoma) has increased considerably.

• In patients with HCV, the risk for HCC increases with the development of cirrhosis. The risk for HCC in patients with only bridging fibrosis may be < 1% per year. Some patients with HCV who develop HCC in the absence of cirrhosis may also have occult HBV infection. Patients with HCV are more likely to present with multiple hepatic tumors than are patients with HBV] HCV/HBV coinfection, HCV/HIV coinfection, and concomitant diabetes mellitus increase the risk for HCC. Suppression of viral replication with antiviral treatments may not eliminate the risk for HCC in patients with HCV cirrhosis] Routine screening should continue even if a sustained viral response is attained after antiviral treatment. Cirrhosis of any cause carries a risk for development of HCC; hemochromatosis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune hepatitis, primary biliary cirrhosis, and Wilson disease have all been associated. Additional risk factors for HCC in patients with cirrhosis include male sex, age older than 40 years, past or present obesity, diabetes mellitus, nonalcoholic fatty liver disease, cigarette smoking, a family history of HCC, exposure to aflatoxin, and hepatic venous outflow obstruction.

• Genetic Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus

• Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in patients with HCV.

IL28B minor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection

• All HCV patients should be screened to exclude cirrhosis by TE if available. Serum biomarkers can be used in the absence of TE • HCV patients who were diagnosed with cirrhosis based on non-invasive diagnosis should undergo screening for HCC and PH and do not need confirmatory liver biopsy

• The parameters included are commonly recorded in clinics, which indicate that the scoring system could be used routinely in the clinic. The clinical practice.

• Calculation of Laboratory Liver Fibrosis Indices

The following values were obtained through serum sample analysis: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGTP), platelet count, and cholesterol. The APRI [18] was calculated as (AST [IU/L] / upper limit of normal AST [IU/L]) × 100 / platelet count [109/L]. The FIB-4 index [19, 20] was calculated as AST [IU/L] × age [years]/ platelet count [109/L] × ALT [IU/L]1/2. The Forns index [21] was calculated as 7.811–3.131ln(platelet count [109/L]) + 0.781ln(GGT [IU/L]) + 3.467.ln(age)– 0.014 (cholesterol [mg/dL]).

• TE could be useful to identify patients at risk of developing HCC.

• high LS value measured by TE is significantly associated with

• the risk of presence of HCC.

• Finally, it has been recently suggested that SS could predict the occurrence of complications . Thus the potential of LS values for predicting clinical outcomes seems to be greater than that of liver biopsy, probably LS measures ongoing pathophysiological processes and functions that a biopsy cannot. Similarly, serum biomarkers such as FibroTest , ELF ], APRI and FIB-4 [222,331], as well as for models based on standard laboratory tests] have been shown to have prognostic value in various chronic liver diseases.

• As we know, SVR of HCV could reduce the risk of HCC. For the high risk patients who did not achieve SVR before, we have to do more effort to eradicate the HCV virus in order to reduce HCC. In patients who could not achieve SVR or who are still within high risk category even after SVR, selection of an intensive HCC surveillance program is important to early detect HCC, followed by early treatment which could increase patients’ survival.

• CHC patients who respond to peg-IFN combination therapy should be followed even after HCV eradication, and special attention should focus on those who have severe liver fibrosis (F3 or F4), those with low pre-treatment platelet levels (,150 ﾗ109/L) and those who are aged ≥60 years, to detect potentially treatable HCC.

• The most important long-term HCC risk predictors for chronic hepatitis B patients are serum levels of HBV DNA, HBsAg and alanine aminotransferase (ALT), HBeAg serostatus, HBV genotype, HBV basal core promoter A1762T/G1764A mutant, gender, age, family HCC history, habitual alcohol consumption, and co-infection with HCV or HIV.

The long-term HCC risk predictors for chronic hepatitis C patients include increasing age, cirrhosis status, HCV genotype 1, elevated serum levels of HCV RNA and ALT and co-infection with HBV.

• Role of occult hepatitis B virus infection in chronic hepatitis C.

In everyday clinical practice, the detection of anti-hepatitis B core antibody (anti- HBc)

in serum of HBsAg-negative subjects is used as a surrogate marker to identify patients with OBI.

In patients with chronic hepatitis C (CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular

carcinoma (HCC) in patients with CHC.

• Anti-HBc-positive results on serologic testing are a marker of high risk for HCC among patients with HCV-related cirrhosis. Interferon therapy might be less effective in preventing HCC among patients with chronic hepatitis C who are anti-HBc-positive than in those with chronic hepatitis C who are anti-HBc-negative.

• MEDIC Researchers Develop Risk Scores to Prioritize Individuals for Population-wide Hepatocellular Carcinoma Screening Using Liver Ultrasound