How could a patient with chronic hepatitis B who had been undergoing regular checkups and treatments suddenly develop advanced liver cancer?

This is the 3184th article of Da Yi Xiao Hu

Primary liver cancer is called the "king of cancer" mainly because the liver is a relatively silent organ. When there are active lesions in the liver, there may be no discomfort. By the time patients feel unwell and seek medical treatment, the tumor is often in the late stage, large in size, or has already invaded the blood vessels or metastasized to distant sites, and the best time for treatment has been lost. Moreover, more than 80% of liver cancer occurs on the basis of cirrhosis. When liver cancer is discovered, the patient's liver function is already relatively poor, and the patient cannot tolerate treatment, with a high mortality rate.

A patient with advanced liver cancer recently admitted to the department left a deep impression on Dr. Fang.

It was a very ordinary day. Dr. Fang was on his normal outpatient duty and received a 41-year-old male patient named Da Li. The patient looked a little anxious and took a stack of lists to show Dr. Fang.

"Doctor, can you help me check my transaminase levels? Is the virus in my body resistant to drugs? The last time I checked the virus, it was below 100, but this time it was 175. Is it the drug resistance that caused the liver function to deteriorate?"

Doctor Fang carefully reviewed the patient's recent laboratory test results. Indeed, the patient's liver function transaminase has been increasing over the past three months, and the most recent follow-up showed a significant increase in bilirubin. Abdominal ultrasound examination showed diffuse thickening and enhancement of liver spots.

Based on his experience, Dr. Fang felt that this patient's liver function abnormalities were not caused by drug resistance.

She carefully asked the patient whether he had drunk alcohol recently, whether he had taken any suspected liver-damaging drugs (including health products and external drugs), whether he had a cold or diarrhea, etc. The patient shook his head and denied it one by one.

Doctor Fang was also puzzled: Why did the patient's liver function deteriorate while he was receiving antiviral treatment? She thought that the patient might have recently been infected with other hepatitis viruses, or had autoimmune liver damage or other possible causes of liver damage.

Because the liver function was obviously abnormal, Dr. Fang admitted the patient to the hospital.

After Dr. Fang finished his outpatient clinic, he specifically gave instructions to the doctor in charge and asked him to pay attention to the patient's condition.

On Monday morning, Dr. Fang conducted rounds and the patient's test results were all out. B-ultrasound showed space-occupying lesions in the liver, and primary liver cancer was suspected. Although alpha-fetoprotein, the most common liver cancer tumor marker, was normal, another liver cancer tumor marker, abnormal prothrombin, was significantly elevated to greater than 10,000.

Doctor Fang understood why the patient's liver function abnormalities continued to worsen: a tumor had grown in the liver. Doctor Fang carefully reviewed the patient's recent test results again and found that the alpha-fetoprotein had always been normal. The B-ultrasound examination at another hospital three months ago showed that the diffuse light spots in the liver had thickened and enhanced echoes, and had a nodular feel.

Dr. Fang asked the attending physician to apply for an enhanced CT scan for the patient to further understand the nature of the lesion, the extent of the involvement, the presence of vascular invasion and distant metastasis, etc.

Two days later, the CT scan results came out, and the diagnosis of primary liver cancer was clear. Almost the entire right lobe of the liver had been affected, and there were already cancer thrombi in the right and middle hepatic veins. The patient was then given a CT scan of the lungs and head. Fortunately, no metastatic cancer was found in the lungs and head.

Not only was the patient confused, but Dr. Fang was also thinking: the patient's compliance was very good, he took medicine on time and had regular check-ups, so why was liver cancer not detected early?

Dr. Fang summarized the patient's previous medical experience, which has the following characteristics:

1. Although the patient had regular checkups, he had never used a highly sensitive detection method for checking hepatitis B virus DNA replication. Existing quantitative detection of hepatitis B virus includes common methods and highly sensitive methods. The detection limit of the common method is 100 IU/L (it cannot be detected if it is less than 100 IU/L), while the detection limit of the highly sensitive method is 10 or 20 IU/L (it cannot be detected if it is less than 10 or 20 IU/L). The common method is cheap (110 yuan/time), while the highly sensitive method is expensive (500 yuan/time). After some patients have incomplete responses to antiviral treatment, the virus may have been in a low-level replication state. The common method cannot detect it, but the highly sensitive method can still detect it. Outpatient doctors often only prescribe common tests to save costs for patients.

Second, the patient's previous semi-annual follow-up was performed with abdominal color Doppler ultrasound. When the color Doppler ultrasound showed diffuse light spots in the liver with thickened, enhanced, and nodular echoes, no further enhanced CT or enhanced MRI examinations were performed. Although abdominal B-ultrasound examinations are convenient and economical, the sensitivity of detecting liver cancer is not 100%, and it is also limited by the level of the operator, and false negatives may occur. For example: Dr. Fang's friend's father had hepatitis B and alcoholic liver cirrhosis. The B-ultrasound examination at the grassroots hospital only showed cirrhosis; the patient's alpha-fetoprotein was also normal, but the liver's biochemical indicators alkaline phosphatase and gamma-glutamyl transpeptidase (the isoenzymes of these two enzymes are also liver cancer markers) were significantly elevated, so it was recommended to go to a tertiary hospital for enhanced CT examination. It was found that it was already a massive liver cancer with intrahepatic vascular metastasis, and even the indication for liver transplantation had been lost. It was a pity!

3. In the past, the patient had been regularly tested for liver cancer using alpha-fetoprotein, and had never checked for other tumor markers. Alpha-fetoprotein is the most commonly used marker for primary liver cancer, with a sensitivity of 60-70%, but there are still about 30-40% of liver cancer patients with negative alpha-fetoprotein.

In response to the above problems, Dr. Fang recommends that chronic hepatitis B patients pay attention to the following issues during short-term outpatient follow-up:

1. If there are no economic problems, it is recommended to choose a highly sensitive virological detection method to detect the presence of low viremia in a timely manner and adjust the antiviral treatment plan in a timely manner. Currently, international guidelines recommend that the lower limit of antiviral treatment is 10 IU/L or 20 IU/L. Many clinical studies have confirmed that under low-level viral replication, liver inflammation and fibrosis may still continue to progress, and cirrhosis or cancer may occur. Only by maximally suppressing the virus can the disease progression be prevented to the maximum extent, the risk of adverse prognosis can be reduced, the quality of life of patients can be improved, and the survival time of patients can be prolonged.

2. It is recommended that the following high-risk groups undergo enhanced CT or enhanced MRI every six months: patients with liver nodules on B-ultrasound examination, patients with a family history of liver cancer, patients with persistent abnormalities in liver function transaminases, patients with metabolic disorders such as alcoholism, diabetes, obesity, and patients over 30 years old with active replication of the big three positive virus. This is to detect early liver cancer in time and buy time for effective treatment.

3. Monitoring of tumor markers. In addition to alpha-fetoprotein, it is recommended to check abnormal prothrombin, sugar chain antigen Ca 199, etc. Sugar chain antigen Ca 199 is meaningful for the discovery of cholangiocarcinoma in primary liver cancer (cholangiocarcinoma accounts for about 5% of primary liver cancer, and the remaining 95% is primary hepatocellular carcinoma). These indicators combined with alpha-fetoprotein can increase the detection rate of early liver cancer to more than 90%. However, because abnormal prothrombin and sugar chain antigen Ca 199 are not carried out in all hospitals, it is recommended that patients with high-risk factors for liver cancer go to a large hospital for reexamination at least once a year to test the above indicators.

4. For the high-risk groups for liver cancer mentioned above, if conditions permit, use interferon alone or in combination with treatment as much as possible to reduce the risk of liver cancer. Especially for some advantaged groups, try to achieve negative conversion of surface antigen, obtain clinical cure, and reduce the risk of adverse prognosis.

Dr. Fang reminds everyone: Although primary liver cancer is called the "king of cancer", the prognosis will be better if it can be detected, diagnosed and treated early.

Author: Wang Fang, Department of Hepatology II, Shenzhen Third People's Hospital