Friday, March 29, 2024

Liver Cancer And Hepatitis C

What Are The Signs & Symptoms Of Hcv Infection

Hepatitis C and Other Risk Factors for Liver Cancer

Most people with HCV have no symptoms. But even without symptoms, they can develop health problems decades later and can still pass the disease to others.

If symptoms do happen, itâs usually when the disease is very advanced. Symptoms can be similar to those of hepatitis A and hepatitis B and include:

  • darker than usual urine or gray-colored stools

Risk Factors For Development Of Hcc In Chronic Hcv Infection

Approximately 20% of chronic HCV-infected individuals develop liver cirrhosis within 2030 years and once cirrhosis is established, the rate of HCC development is 14% annually.18 The predominant risk factors for the development of HCC in chronic HCV infection include concurrent liver disease, viral genotype, lifestyle factors and the presence of obesity and diabetes mellitus. Coinfection with HBV and human immunodeficiency virus significantly increases the risk of HCC in HCV-infected patients. In HBV-HCV coinfection, HBV replication status is the crucial factor affecting the risk for HCC. Coinfected patients with undetectable HBV DNA have HCC risk equal to that of patients only infected with HCV.19 On the other hand, HCV patients with active HBV replication have twice the risk of HCC and a 21% increase in mortality compared to those with latent HBV and HCV.19 Similarly, there is a substantial increase in HCC prevalence in HIV-HCV coinfected patients compared with HCV patients, with HCC occurring at a younger age in this population.20 This increase is attributed to amplified HCV replication, decreased immune response in HIV, and a more rapid progression to cirrhosis.21 In HIV-HCV coinfection, older age, cirrhosis, and low current CD4 cell count are associated with a higher incidence of HCC.22

Local Impact Of Hepatitis C And Chronic Liver Disease

Hepatitis C is one of the most common liverdiseases in the U.S. and the Western world. An estimated 2.4 million peoplelive with the disease, and approximately 70% to 85% of cases are consideredchronic. The World Health Organization estimates that nearly 400,000 patientsdied from hepatitis C in 2016, mostly due to cirrhosis and HCC.

Texas has a high volume of aging patientswho are living with hepatitis C. Many were infected in the 1980s or 1990s, andthe infection can lie dormant for 25 years or longer before it begins to damagethe liver. Texas is home to many people of Hispanicdescent. Individuals with this ethnicity are at up to double the risk of developing infection-related cancers, such as livercancer. Other factors for the high rates ofliver cancer in Texas include a prevalence of obesity, diabetes, and a highrate of alcohol use.

‘At UT Southwestern, we are well equipped to treat the potential complications of Hepatitis C including cirrhosis or liver cancer. We have a multidisciplinary liver cancer program that offers cutting edge treatment options and compassionate care as well as a large and robust liver transplantation program.’

Amit G. Singal, M.D.

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Epidemiology Of Chronic Hcv Infection In Relation To Hcc: Prevalence And Mortality

The main causes of HCC in different geographical areas around the world have been related to infective agents such as HCV. Of the total number of cancer cases, HCV caused 160,000 cases of HCC in 2018, which is equivalent to 7.1% of cases worldwide caused by infectious agents. Of these, 3900 were reported in Central America, 7400 in South America and 782 cases in the Caribbean.

Other data show that in 2016, of 7.2 million people worldwide who were living with chronic hepatitis C, 57% corresponded to Latin America and 3% were from the Caribbean . The number of people diagnosed and treated for chronic HCV infection in the Americas is very low – only around 25% of all cases are diagnosed but just 14% are from Latin America and the Caribbean. Approximately 301,000 were treated in 2016, which is equivalent to only 16% of the diagnosed population in America, whereas in Latin America and the Caribbean, just 5% were under treatment. Determining the precise number of patients with known HCV status and receiving care has been difficult.

Figure 1. Map of the estimated hepatitis C virus viremic population in countries from Latin America and the Caribbean. Countries that are not shown or are in white color do not have available data

Latin America and the Caribbean 4.1 million

HCV: hepatitis C virus

Liver Cancer Risk Factors

The Viral Time Bomb: Hepatitis C

A risk factor is anything that increases your chance of getting a disease, such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But having a risk factor, or even several risk factors, does not mean that you will get the disease. And some people who get the disease may have few or no known risk factors.

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How Does Hiv Infection Affect Liver Cancer Risk

In contrast, infection with HIV significantly lowered the risk of hepatocellular carcinoma by 98% and hyperlipidemia by 93%.

While these were also the main risk and protective factors among those without hemophilia, alcoholism was associated with a four times higher risk of the liver cancer in this population.

The cancer risk linked to NASH and more comorbidities was higher among men with hemophilia than in men without the disease, in whom HCV infection was linked to a higher risk.

Age, smoking, and transfusions were not risk factors for the cancer in either group.

In contrast to past evidence that HIV promoted progression of HCV infection to end-stage liver disease we found HIV was protective against in both groups, the team wrote.

This likely reflects the effectiveness of antiretroviral therapy and lack of new HIV infection in these groups, they added.

These findings highlight that with the reduction in HCV by direct-acting antiviral agents , NASH is now the most important risk factor for HCC in hemophilic men, as previously shown in nonhemophilic men, the researchers wrote, but NASH is not as common as HCV.

HCV remains a major risk factor for HCC in hemophilic populations despite the wide availability of DAAs, the researchers wrote.

These results also confirm the need for continuing surveillance and prospective study in this high-risk population, the team concluded.

Hepatitis C And Liver Cancer: What To Know

Several viruses besides HPV have been linked to cancer, includinghepatitis C, which is linked to liver cancer.

If you think HPV is the only virus that causes cancer, think again. Several other viruses have been linked to cancer, including hepatitis C.

Hepatitis C is the most common blood-borne infection in the United States. Its also the leading cause of liver cancer.

About 30 percent of people who get exposed to the hepatitis C virus will clear it on their own. The rest will go on to have chronic hepatitis C.

This ongoing infection causes inflammation in the liver. This extended inflammation can cause scarring, called cirrhosis, and can ultimately lead to liver cancer.

Chronic hepatitis C also increases the risk of non-Hodgkin lymphoma and head and neck cancers.

Unlike hepatitis A and B, there is no vaccine against hepatitis C, and there are few if any symptoms, says Harrys Torres, M.D., associate professor of Infectious Diseases.

Its a silent infection, he says. And its a very clever virus that mutates very fast, so it has been difficult to develop a vaccine.

Knowing the risk factors and getting screened are your best defenses against cancers caused by hepatitis C. Treatment of this virus can reduce your risk of liver cancer by 75%.

Risk factors

About 75% of those infected with hepatitis C in the United States are baby boomers people born between 1945 and 1965.

Other risk factors for hepatitis C infection include:

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Impact On Mortality Rates

The lack of access to DAAs not only affects the health of people with hepatitis but also has a direct relationship to liver cancer deaths, according to a 2020 study from the Baylor College of Medicine.

The study reported the rate of liver cancer deaths steadily declined from 1978 to 1998 prior to the introduction of combination hepatitis C therapies. Although more Black people were affected overall, the rate of decline was equal among all groups despite race.

As newer, more effective drugs were being released starting in 1996, the trend shifted dramatically. From 1998 to 2016, over 16,700 liver cancer deaths were reported among Black people in the United States. Moreover, the excess of deaths among Black people compared to White people increased from 27.8% in 1998 to 45.7% by 2016.

Among older adults, who are at the highest risk of liver cancer, the disparity was even greater. While White people 55 and over experienced a 2% per year increase in liver cancer deaths between 2000 and 2016, Black people 55 and over experienced a 4.2% per year increase during the same period.

According to the study, the disparities in liver cancer deaths largely mirror the disparities in treatment access among Black people in the United States.

In the United States, the median age of people newly diagnosed with liver cancer is 62. Less than 15% of cases are seen in people under 55.

Disclosure Of Potential Conflicts Of Interest

Hepatitis and Liver Cancer Statistics | Did You Know?

N. Batyrbekova is a statistician at Scandinavian Development Services AB. S. Aleman reports receiving commercial research grants from Gilead and AbbVie and speakers bureau honoraria from AbbVie, Gilead, Bristol-Myers Squibb, and MSD. C. Lybeck reports receiving speakers bureau honoraria from MSD. A.-S. Duberg reports receiving speakers bureau honoraria from AbbVie, Gilead, and MSD and is a consultant/advisory board member for Gilead and AbbVie. No potential conflicts of interest were disclosed by the other author.

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Progression Of Hcv To Hcc

HCC development due to HCV is a stepwise process spanning over 20 to 40 years .36 HCV carcinogenesis is mediated by viral-induced factors and host-induced immunologic response. While evidence of a direct oncogenic effect of HCV on liver cells is limited to animal models, studies have shown that the HCV core protein may drive lipogenesis and impair oxidative stress metabolism.37 HCV viral proteins can act directly on cell signaling pathways to promote HCC by inhibiting tumor suppressor genes and cell cycle check points or by causing activation of signaling pathways that up-regulate growth and division.38 Specific tumor suppressor genes inhibited by HCV core protein include retinoblastoma protein and p53 tumor suppressor. The loss of p53 and retinoblastoma is synergistic, leading to a greater degree of carcinogenesis.39 HCV nonstructural protein genes also promote fibrosis and the development of HCC through inducing transforming growth factor-beta and activating hepatic stellate cells.40

HCV mechanisms for carcinogensis.

HCV induces mitogenic, angiogenic and metastatic pathways, blocks cell death, triggers persistent inflammation and ROS production, and dysregulates host lipid metabolism. Copied with permission under CC 4.0 from Vescovo et al.36

Hepatitis C Treatment Can Cut Risk Of Liver

Breakthrough findings from a 2019 study showthat not only is hepatitis C treatment safe but it is recommended for patientswith a history of liver cancer treatment can reduce the risk of liver-relateddeath by approximately 50%.

In 2017, data from a study in Europe suggestedpatients with a history of hepatocellular carcinoma, the most common type of liver cancer, who had been cured of hepatitis C withantiviral drugs might have a higher risk of HCC recurrence. The hypothesiswas that, for all its harmfulness, hepatitis C activated a patient’s immunesystem when it infected the liver, keeping cancer recurrence at bay.

We know antiviral drug treatment can cure hepatitisC in morethan 95% of cases, and we know that having chronic hepatitis C greatlyincreases the risk of cirrhosis of the liver a major cause of liver cancer. Something wasn’t adding up for ourmultidisciplinary liver cancerteam at the Harold C. SimmonsComprehensive Cancer Center.

These findings led to another question anda groundbreaking discovery. We wanted to determine theextent to which hepatitis C treatment might impact a patient’s risk of liverdisease progression, thereby reducing the risk of liver-related mortality.

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What Are The Risk Factors For Getting Hepatitis B

Due to the way that hepatitis B spreads, people most at risk for getting infected include:

  • Children whose mothers have been infected with hepatitis B.
  • Children who have been adopted from countries with high rates of hepatitis B infection.
  • People who have unprotected sex and/or have been diagnosed with a sexually transmitted infection.
  • People who live with or work in an institutional setting, such as prisons or group homes.
  • Healthcare providers and first responders.
  • People who share needles or syringes.
  • People who live in close quarters with a person with chronic hepatitis B infection.
  • People who are on dialysis.

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Effects Of Hepatitis B Virus And Hepatitis C Virus On Hepatocellular Micrornas

Possible Complications of Hepatitis C

MicroRNAs are small non-coding RNAs that regulate diverse cell functions including cell proliferation, differentiation and apoptosis. Recent reports highlight aberrant expression of miRs in hepatic tissue from subjects with liver disease and HCC , and provide exciting possibilities for the discovery of bio-markers for early diagnosis of viral-associated HCC .

For CHB, aberrant expression of multiple miRs has been reported to be associated with HCC development. MIR196A2 polymorphism was associated with susceptibility to HBV-related HCC in a male Chinese population . HBx expression may negatively interfere with DNA repair and tumour suppressors by altering expression of multiple miRs through upregulation of HBxAg-upregulated gene 11 . HBx- and URG11-induced upregulation of miR-148a has been shown to drive cell cycle progression and cell migration by suppressing phosphatase and tensin homologue, thus increasing AKT mTOR signalling . Altered miR-122a expression inhibits HBV replication, changes the cell cycle by affecting cyclin G1 expression and inhibits expression of p27 .

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Prognosis Of Persons Diagnosed With Hcc

The overall prognosis for persons diagnosed with HCC in the United States has improved in the past 15 years, but it remains poor, with an overall 5-year survival of approximately 20%. In general, persons who have HCC detected after the onset of symptoms have an even worse prognosis, with an overall 5-year relative survival less than 10%. Symptoms associated with HCC may include abdominal pain, anorexia, early satiety, weight loss, obstructive jaundice, fever, watery diarrhea, and bone pain . In contrast, detection of very early-stage HCC can be cured with an excellent long-term prognosis. Unfortunately, the vast majority of individuals diagnosed with HCC have cancer that is advanced beyond the stage where surgical cure with surgical resection or locoregional ablative therapy is an option.

Can Primary Liver Cancer Be Prevented

Prevention is the best defence against primary liver cancer. Worldwide, the most common risk factors for primary liver cancer are chronic hepatitis B and C infections. Therefore, the prevention of these forms of liver disease is essential. The Canadian Liver Foundation recommends that all children, as well as adults at high risk of being exposed to the virus, should be vaccinated against hepatitis B.

Since there is no vaccine against hepatitis C, it is crucial to prevent the spread of this disease and to identify and assess all those who are already infected with the hepatitis C virus for treatment. The Canadian Liver Foundation recommends that all people with risk factors and adults born between 1945 and 1975 should get tested for hepatitis C.

Alcohol intake should be limited to no more than one to two standard drinks per day. Drinking alcohol every day, as well as binge drinking, can be harmful to your liver. If you already have a liver disease, the safest amount of alcohol is no alcohol at all.

As mentioned earlier, non-alcoholic fatty liver disease and its most severe form, non-alcoholic steatohepatitis is a big risk factor for liver cancer. It is important to maintain a healthy body weight, eat a well-balanced diet, and introduce physical activity into your daily routine.

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Ii Diagnostic Confirmation: Are You Sure Your Patient Has Hepatitis C

Most people are asymptomatic or have only nonspecific symptoms in the acute phase after initial infection. Diagnosis of acute hepatitis C is therefore rarely made. Chronic hepatitis C may be identified at the time of workup for causes of aminotransferase elevations however, the majority of people with chronic HCV infection remain asymptomatic until the disease progresses to advanced stages of fibrosis or cirrhosis.

Presence of anti-HCV antibodies confirms prior infection with HCV. To determine if a patient has current HCV infection, HCV RNA is measured. A patient with detectable serum HCV RNA has chronic HCV infection. A patient with a positive HCV Ab but undetectable HCV RNA was previously exposed to HCV but either spontaneously cleared the infection or was cured by prior treatment . During the early phases of an acute infection, patients may not have developed HCV antibodies therefore, if acute HCV infection is suspected, HCV RNA should be checked despite a negative HCV Ab result. Additionally, patients who are immunocompromised may have negative antibody testing but active infection as indicated by a positive HCV RNA test. In such patients with aminotransferase elevations that remain unexplained after typical causes are excluded, HCV infection should be fully excluded by RNA testing.

Risk Becomes Reality For Dr Coates

Hepatitis C and liver cancer: What baby boomers need to know

The first warning signs of trouble ahead for Dr. Coates came in 2005, when a liver biopsy detected stage 5 fibrosis advanced scarring caused by hepatitis C that eventually developed into cirrhosis.

Screening of all patients with cirrhosis is critical due to the high risk of developing hepatocellular carcinoma which we estimate is roughly as high as 6% per year, Dr. Shah explained.

Various treatments for his hepatitis C infection were attempted to bring the virus under control. Some did not produce enough of a response to continue, while others like an experimental three-drug regimen attempted around 2012, took a toll on his body.

I had a good biological response, but I started shedding skin and had to get blood transfusions twice, Dr. Coates said. When the prescription medication finally rid him of the disease in 2017, he was still monitored because of his elevated liver cancer risk tied to the hepatitis C virus and cirrhosis.

In January 2019, that risk turned into reality.

An abnormal growth was detected on an ultrasound. Another was detected by an MRI. A third was found during surgery to remove them.

A year would go by, and more abnormal growths and lesions appeared.

I talked about a transplant, but they said that was not going to happen, Dr. Coates said.

The tumors kept growing. Radiation therapy was added to the treatment plan. It wasnt working.

Fortunes changed when Dr. Coates nephew relayed the story to Dr. Shah.

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