Hepatitis B-associated hepatocellular carcinoma in a young Haitian man: a review of screening guidelines

Abstract

Hepatocellular carcinoma (HCC) is a terminal, yet preventable, outcome of untreated infection with hepatitis B virus (HBV). HBV is endemic in many areas of Latin America and the Caribbean, including Haiti. Haitians have the highest incidence of liver cancer among Caribbean immigrants. Unfortunately, many of these patients are not screened, despite current guidelines. As HBV is treatable, screening of high-risk populations is crucial to early intervention and prevention of poor outcomes. We highlight the case of a young Haitian male immigrant who presented with unintentional weight loss and epigastric pain and found to have HCC associated with HBV. Despite chemotherapy, the patient died 15 months after diagnosis. Increased awareness of HBV among patients from high-incidence countries may result in early recognition of this disease and reduced morbidity and mortality from devastating complications.

Background

In developed countries, approximately 20% of cases of hepatocellular carcinoma (HCC) can be attributed to hepatitis B virus (HBV) infection.¹ Liver cancer is the third leading cause of cancer-related mortality, with HCC responsible for 70%–85% of primary liver malignancies.^2–4 In Latin America and the Caribbean (LAC), 7–12 million people are infected with HBV, with the greatest prevalence being among those 20–40 years old.⁵

HBV is a leading cause of severe chronic liver disease in Haiti with estimated seroprevalence of 2.0%–8.0%, compared with 0.27% in USA.^{6 7} In 2012, Haiti introduced the hepatitis B vaccine into its routine immunisation schedule for children at ages 6, 10 and 14 weeks.⁸ However, the country has yet to include a birth dose, and in the absence of vaccination 20% of HBV-related deaths are attributable to perinatal infection.⁹ In a 2007 study, Haitian immigrants to the USA had the highest incidence of liver cancer among all Caribbean immigrant populations. Following the earthquake in 2010, Haitian immigrants are also among the fastest growing immigrant communities in USA.¹⁰

In USA, there are scant data on HCC associated with HBV (HBV-HCC) in young adults. Immigrants from areas of LAC, especially those from Haiti, represent an endemic and high-risk population who should be screened for HBV. To increase awareness of this disease entity, we present the case of a Haitian immigrant in his early thirties with biopsy-proven HBV-HCC. We then review HBV screening recommendations.

Case presentation

A Haitian man in his early thirties with no known medical history presented to the emergency department with a 2-week history of epigastric pain. The pain was non-colicky and not associated with exacerbating or relieving factors. The patient had a 20-pound unintentional weight loss in 2 months before presentation. He denied fever, jaundice, nausea, vomiting, steatorrhoea, melena, haematochezia and changes in stool frequency, consistency or colour. He denied alcohol consumption, significant non-steroidal anti-inflammatory drug use and recent infection.

The patient was born in Haiti and moved to USA at age 17. He did not receive childhood hepatitis B vaccination. Approximately 7 months prior to presentation, he returned to Haiti for 3 months. Family history is notable for early death of his mother due to unknown causes but, to the patient’s knowledge, was negative for liver disease. He had not been screened for HBV.

No history of sexually transmitted diseases, injection drug use or blood transfusion was noted. The patient reported over a dozen sexual partners in the last year with consistent condom use.

At presentation, the patient had normal vital signs. He appeared generally well nourished without cachexia. He had no scleral or subglossal icterus. Pulmonary and cardiac examinations were unremarkable. His abdomen was soft and non-distended without caput medusa. He had normoactive bowel sounds, with moderate pain elicited on deep epigastric palpation. Periumbilical lymph nodes were not palpable; inguinal nodes were no larger than 1 cm, mobile and non-tender and the spleen was non-palpable with the liver margin about 1 cm below the right subcostal margin at the midclavicular line. He had a negative Murphy sign, Courvoisier sign, Castle sign and no fluid wave. No pedal oedema was noted. There was no jaundice, ecchymosis, purpura, petechiae or palmar erythema. The remainder of the dermatological examination did not reveal any pigmentary changes or puncta consistent with intravenous injection. On neurological examination, the patient was fully alert and oriented with intact mentation, sensation, motor function, reflexes and cranial nerves. He did not demonstrate asterixis.

Investigations

Given the patient’s epigastric pain and weight loss, the admitting physician ordered a CT scan of the abdomen and pelvis which revealed multiple lesions in the liver. Laboratory evaluation showed a normal complete blood count, normal transaminases, bilirubin and alkaline phosphatase. He had a positive hepatitis B surface antigen (HBsAg) without hepatitis core or envelope antigens or antibodies to surface, core or envelope antigens. Otherwise, the patient had negative studies for sexually transmitted diseases, such as HIV. Alpha fetoprotein (AFP) was 801.6; carcinoembryonic (CEA) antigen and cancer antigen (CA) 19–9 were normal. Subsequent abdominal MRI (figure 1) revealed findings concerning for possible multifocal HCC on T2-weighted sequences, later confirmed by core biopsy (figure 2). Moderately differentiated HCC was confirmed by histopathological stains. Positron emission tomography showed diffuse metastasis.

Figure 1.

MRI abdomen with contrast showed a 10.2×9.4 cm hyperintense heterogeneously enhancing mass lesion occupying the majority of segment VII of the liver. Additionally, there was a 3.8×4.1 cm T2 hyperintense heterogeneously enhancing lesion in segment VIII of the liver, consistent with a possible neoplastic process.

Figure 2.

Core biopsy of affected liver with pleomorphic nuclei, prominent nucleoli, high nuclei-to-cytoplasm ratio and occasional mitotic figures consistent with neoplastic pathology.

Differential diagnosis

The initial differential diagnosis for abdominal pain and unintentional weight loss is broad. Common aetiologies include gastrointestinal and other malignancies, malabsorptive diseases (eg, celiac disease), inflammatory bowel disease, irritable bowel syndrome, chronic infectious diarrhoea and postoperative complications (eg, short gut syndrome). In addition to basic laboratory studies, patients with abdominal pain and unintentional weight loss should receive imaging.

Causes of mass lesions in the liver include cysts, hepatic infections and pyogenic abscesses, benign lesions (eg, cavernous angiomas, focal nodular hyperplasia and adenomas) and malignancies (eg, HCC, fibrolamellar carcinoma, cholangiocarcinoma and metastatic disease). Subsequent workup depends on the clinical scenario and radiological characteristics of the lesions.¹¹ For patients with chronic liver disease or infection with HBV or hepatitis C virus (HCV), experts recommend obtaining AFP as well as contrasted MRI liver or triple phase CT. In these imaging modalities, early uptake of contrast during the arterial phase with washout in the portovenous phase strongly suggests HCC.¹¹ While serological studies, such as AFP, CEA and CA 19–9, provide helpful supplemental information, biopsy may be needed for definitive diagnosis.¹¹

Treatment

The patient was not a surgical candidate. He received gemcitabine and oxaliplatin, followed by a clinical trial of sorafenib.

Outcome and follow-up

Despite treatment, the patient died 15 months after diagnosis.

Discussion

HBV is endemic in parts of LAC and especially in Haiti.^{6 7} HBV-HCC is a preventable outcome of HBV infection.¹² As recommended by current guidelines, these and other high-risk populations should be screened for HBV infection.¹³ At present, these patients are not routinely screened, providing an opportunity to improve their care, within USA and abroad, and to prevent devastating complications from untreated HBV infection.¹⁴

Per the American Association of Liver Disease, HBsAg screening and hepatitis B vaccination are recommended for inmates, pregnant women, patients with chronically elevated transaminases, patients on dialysis, patients co-infected with HCV or HIV, patients with high-risk sexual practices and patients from countries with intermediate (HBsAg 2%–7%) or high (HBsAg >8%) HBV prevalence.¹³ The patient in this case had two of these risk factors. His sexual practices—more than a dozen partners in the last year—put him at increased risk for HBV infection and transmission. Likewise, his immigration from a high-prevalence country, Haiti, which lacked routine hepatitis B vaccination until 2012 and still lacks neonatal vaccination, increased his risk.⁸ While not cost effective for the US-born patients without risk factors, testing is recommended and cost effective in immigrants from Africa, the South Pacific Islands, Middle East and many countries in LAC (including Haiti).^{8 14–17} Assuming the patient had access to primary care services, he should have been screened for HBV.

A larger question raised by this case is whether US physicians have a sufficiently high index of suspicion for HBV and its complications among foreign-born patients. Although HBV prevalence in USA has decreased to <0.5%, these data are based on the National Health and Nutrition Examination Surveys that do not capture representative samples of immigrant, homeless and incarcerated patients who are more likely to have the disease.¹⁸ In addition, immigrants to USA, though screened for tuberculosis and HIV, are not tested for HBV.^{14 18} By some estimates, however, 1.3 million foreign-born persons in USA are infected with HBV, with the largest populations from Asia and Latin America and the Caribbean.^{19 20} Clinicians and public health officials may thus be underestimating the prevalence of HBV among foreign-born patients.

In closing, this case highlights a rare presentation of HBV-HCC in a young Haitian immigrant to USA. Given the severe consequences of untreated HBV, healthcare providers must have a high index of suspicion for the disease, particularly among immigrants. From a public health perspective, the case highlights the importance of active screening programmes for HBV in high-risk populations and the need for HBV vaccination at birth in developing countries.

Learning points.

• Hepatitis B virus infection is treatable, and if untreated, infection has devastating complications, including hepatocellular carcinoma.

• American Association of Liver Disease guidelines recommend screening patients from endemic countries, including those from Latin America and the Caribbean and Haiti. However, many of these patients are not screened.

• Public health efforts must focus on awareness of these high-risk populations to promote screening, which can lead to life-saving intervention.