A fifty-year-old man saw his family doctor complaining of a pain in his side. A native of Vietnam he had lived in the United States since 1975. From the time he moved here and sought medical attention it was noted that he had minimally abnormal liver function tests indicating chronic liver injury.
In the 1980’s his family doctor obtained additional blood tests that revealed he had chronic Hepatitis B with evidence of active infection. No further action was taken. Over the next twenty years his liver tests remained mildly abnormal. He voiced no complaints referable to his liver and on physical examination his liver was never tender or enlarged.
At the time of this visit to his primary care physician (PCP) he had marked tenderness in the right upper quadrant of the abdomen and a slightly enlarged liver particularly in the most lateral aspect of the liver, corresponding to the right lobe.
Concerned about these new findings his doctor ordered an ultrasound that revealed a ten-centimeter (four-inch) tumor in the right lobe of his liver and a one cm tumor in the left lobe. He was referred to a liver specialist, who ordered an alpha-feto protein blood test for liver cancer. The test result was 41,000, with upper limit of normal 25. A liver biopsy showed hepatocellular carcinoma (HCC). He was referred to an oncologist and placed on the liver transplant list through UNOS, the national clearinghouse for organ availability (typically hearts, kidneys and livers).
He was treated with the best available drug treatment for his cancer but died before a liver became available. Before his death he sued his PCP for not screening him for liver cancer and not referring him for anti-viral therapy. His family carried on the suit after his death.
Unraveling the Case and National Liver Cancer Trends
The attorney representing the PCP contacted me to help him evaluate the case and possibly give expert testimony. The issues that were important to me were: whether there was evidence that following patients with chronic Hepatitis B for the development of cancer resulted in an improved outcome if the cancer were detected early and whether treatment with anti-viral therapy could have prevented the development of liver cancer. A lesser issue for me, more the province of the family doctor who would support the PCP’s actual practice patterns, was what other family doctors in the US did for such patients, i.e., the so-called standard of care.
One would think that these questions would be easy to answer once one searched the available medical literature. Most of the Hepatitis in the US today is Hepatitis C, transmitted by blood products (much less so recently with improved blood screening), contaminated needles, and sex with infected individuals – especially male homosexuals. Several well-done studies have shown that careful surveillance of these patients with serial alpha-feto protein tests (typically every six months) and liver ultrasound (every six to twelve months) can improve outcome with respect to mortality from HCC. In fact, the disease can be detected early with an improved outcome from surgery and can actually be prevented in some of those patients whose virus can be eliminated from the blood with drug treatment (a substantial minority of all patients with chronic Hepatitis C).
Even though this information is readily available, most patients in the US today with chronic Hepatitis C do not receive optimal care – either surveillance or anti-viral therapy. Nonetheless one could reasonably conclude that if a doctor did nothing for a patient with Hepatitis C he would be vulnerable to an accusation that he violated the accepted standard of care.
The story for Hepatitis B is somewhat different. This disease is endemic in Southeast Asia; most of the good studies looking at the benefit of surveillance and therapy have come from large hospitals in Taiwan and Mainland China. There is good research that treatment of chronic Hepatitis B and surveillance with alpha-feto protein and liver ultrasound and can reduce mortality from HCC in China.
HCC is the most common cause of cancer death in Southeast Asia. The percentage of people with chronic Hepatitis B infection is very high compared to that of the US. The relatively common frequency of that disease makes it relatively easy to do good clinical research because patients are readily available for study. No comparable studies have been reported in the United States.
Clinical Trial Controversy
Clinical trials are conducted all the time that never get reported in the peer-reviewed literature. When a study is negative – i.e., the intervention tried doesn’t work – the temptation is for the investigators to bury it. Reputations are not enhanced and promotions not given for negative studies.
What does this mean? It is possible that cancer prevention strategies for Hepatitis B have been tried in the US and found ineffective. There is no way to know. Critics have repeatedly tried to force bodies that conduct large clinical trials to report their data. This approach has intellectual and ethical appeal, and since most large clinical trials are funded with public (NIH) money one could argue that taxpayers are entitled to know where their tax dollars are going.
Nonetheless the American Association for the study of Liver Diseases (AASLD) recommends that Asian men living in the US with chronic Hepatitis B should be in a program of active surveillance for HCC, acknowledging the paucity of data. They use an arbitrary cutoff of 0.2%/year incidence above which screening is cost effective. As such they are effectively practicing public policy. Nonetheless, based on this figure, they judge it is cost-effective to screen Asians but not Caucasians with chronic Hepatitis B because for whatever reason their incidence of HCC is lower.
Whether successful elimination of the Hepatitis B virus from the blood prevents HCC is also controversial. Most authorities agree that if liver cirrhosis (severe scarring) has developed then eliminating the virus does not eliminate a patient’s risk. Whether eliminating the infection before there is cirrhosis can prevent HCC is basically unknown.
Back At Trial
I discussed the paucity of data in the US regarding the value of active surveillance and treatment of people with Hepatitis B with the defendant’s attorney and suggested to him that this approach would be a fairly weak defense of his client. We tried to find national compliance data, the percentage of people with chronic active Hepatitis B in the US who are actually in surveillance and treatment programs, but these numbers are not readily available. In the absence of data, the doctor’s lawyer found experts in family practice who were willing to testify that it was not the standard of care to follow people with chronic Hepatitis B with anti-viral therapy and serial blood tests and ultrasounds despite the AASLD recommendations stated above.
At his deposition the PCP did not make a very good showing. He showed a substantial lack of knowledge about the natural history of treated and untreated Hepatitis B, did not know of the potential benefits of surgery or liver transplant for HCC, and did not have any patients in his practice with Hepatitis B who he was currently following with active surveillance. There is a saying among trial lawyers that “a doctor can’t win his case at his deposition, but he can lose it.”
After reading his deposition I was worried that he had lost it. I felt that his lawyer, who was a veteran medical malpractice defense lawyer, had done an inadequate job of preparing his client.
Still, the PCP and his lawyer were not inclined to settle this case out of court. The trial took place in a medium-sized, midwestern city where juries traditionally like doctors and give them the benefit of the doubt. After a four-day trial, the jury returned a verdict in favor of the doctor.
Can We Learn Anything From This Sad Case?
There are thousands of Vietnamese refugees in the US with chronic Hepatitis B and thousands of American-born drug addicts, sex trade workers and others who are also infected with chronic Hepatitis B. The poverty rate is so much higher in Southeast Asia than in the US that it would be difficult but not impossible to try to eliminate the large reservoir of Hepatitis B from this part of the world. New cases continue to be imported into the US and continue to occur among Americans who were not immunized as children. The excess mortality from cirrhosis of the liver and HCC is a huge burden to liver disease sufferers and to society as a whole.
Immunization against Hepatitis B is available and effective but is not widely practiced in the US outside of health-care workers, all of whom should be immunized when they join the profession. In theory, with immunization, HCC from Hepatitis B is entirely preventable. HCC from Hepatitis C is partially preventable (see above), and HCC from other causes of liver damage (such as Hereditary Hemochromatosis) is also largely preventable with appropriate interventions.
The lack of data on patients in the US with chronic Hepatitis B on HCC prevention and mortality reduction with active surveillance and anti-viral therapy should not be an excuse not to treat and follow carefully these patients. The absence of data does not mean that such a policy would be futile. The primary care doctor in this case was exonerated on fairly narrow grounds and on the basis of the accumulated good will of the medical profession in his hometown. His victory should not be interpreted as a triumph.
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Dr. James Stark is the founder of StarkOncology, where he practiced Oncology in Hampton Roads for thirty-four years. He is now a health-care consultant specializing in topics such as breast cancer, colon cancer, lung cancer, chemotherapy complications, and failure to screen. In addition to this new venture he continues to serve as Professor of Medicine at Eastern Virginia Medical School.