University of Alabama at Birmingham 2006 Case #3 Universidad Peruana Cayetano Heredia
The following patient was seen by course participants in the outpatient department at the Tropical Medicine Institute.
Image for 02/20/06History: 28 yo female with 2 months of epigastric pain, early satiety, and nausea with progression to abdominal swelling.  Previously in good health.  On no medications, no oral contraceptives.  No fever, chills, or weight loss.

Epidemiology: Housewife with 1 child from Paramonga on the coast.  Non-smoker, non-drinker, no use of illegal drugs.  No TB exposure.  Received all routine childhood vaccinations.

Physical Examination: Afebrile.  Well nourished and hydrated.  Right upper quadrant of the abdomen painful on deep palpation, firm liver edge felt 15 cm below the right costal margin.

Laboratory Examination: Hct 37.  WBC 12.9 with 88 segs, 5 bands, 3 lymphs, 4 monos.  INR 2.1.  Albumin 1.2.  Alkaline phosphatase 153, ALT 120, AST 495, GGT 96, LDH 1338.  Bilirubin 2.0.  Electrolytes normal.  HIV, RPR negative.  CXR, lungs clear with elevated right hemidiaphragm.  Abdominal MRI is shown in Image A.





Diagnosis: Chronic infection with hepatitis B complicated by hepatocellular carcinoma.
Image for 02/20/06 DiscussionDiscussion: A right hemi-hepatectomy was performed [Image B].  Histology of the large tumor [Images C, D] disclosed moderately differentiated hepatocellular carcinoma with both a solid and trabecular pattern.  Intravascular infiltration by tumor with areas of necrosis as well as hepatic capsular infiltration was seen.  Chronic periportal inflammation and steatosis was also noted.  HbsAg positive, HbeAg negative, anti-Hepatitis C negative.  Alpha-fetoprotein 78,770 (N=0-10).  One younger brother of the patient was HbsAg positive and two other brothers had anti-HBsAg indicating prior infection but not carriage.  The patient?s mother has not been tested.

The official MRI report described a solid 20 cm diameter lesion with ill-defined borders and of heterogeneous density occupying the entire right lobe of the liver.  The mass was noted to be indenting the hepatic flexure of the colon but there was no indication of any invasion of the kidney or other organs and there was no evidence of any peri-hepatic or intra-abdominal fluid.  The right hemi-azygous vein was noted to be dilated but MR flow studies indicated no thrombus in this vein or in the portal vein or vena cava.  The only differential diagnosis based on the imaging study was between hepatocellular carcinoma and hepatocarcinoma of the fibro-lamellar type.

More than 400 million people worldwide are chronic carriers of hepatitis B virus (HBV).  Over 80% of the half-million annual cases of liver cancer are caused by viral hepatitis with two-thirds of these due to HBV.  Up to one-third of the world’s population has been infected at some time with HBV and 5% are chronically infected.  Three-quarters of those with chronic HBV in the world are from China and sub-Saharan Africa with southeast Asia also having very high rates.  Prevalence of chronic HBV carriage in those regions is 10-20% with most infections occurring in the neonatal period or during early childhood, thus emphasizing the importance of peri-natal vaccination strategies.  In contrast, in countries of North America, Europe and Australia where infections occur primarily during adolescence or adulthood, prevalence rates are <0.5%.

While none of the South American countries as a whole qualify as highly endemic for HBV, rates as high as those found in China can be found amongst native Amerindian populations from the Amazon basin and related ecosystems [Cad Saúde Pública. 2003 Nov-Dec;19(6):1583-91].  Of note, there is also an association with a high level of infection with hepatitis D virus among the chronic HBV carriers in the Amazon.  In samples taken from various sites in the Maranon and Madre de Dios regions of Peru, prevalence of HBV infection at some time during life (rate of Anti-HBc) is from 69-74% with an HBsAg carriage rate of 3.9-12.1%, and Anti-HDV rates of 2.5-9.0% amongst HBsAg carriers.  In the transition Andean valleys and the high jungle surrounding the Peruvian Amazon (Huanta, Abancay) rates are 82% for Anti-HBc, 16% for HBsAg, and 18% of HBsAg carriers are positive for Anti-HDV.  Our patient was not born in a typical endemic area but a complete epidemiologic history on parents and grandparents was not available.

The risk of chronicity with HBV varies greatly according to age of acquisition of the infection.  For neonates and children younger than 1 year, the risk of the infection becoming chronic is 90%.  Between ages 1-5 years, the risk is 30% and for those older than 5 years at time of infection the risk decreases to about 2%.  Large powerful epidemiologic studies support the relationship between chronic HBV infection and hepatocellular carcinoma.  A minimum of 20-30 years seems to be required for the development of cancer so that cases appear in the 20-30 age group in hyperendemic areas with predominant peri-natal infection, and in the 6th decade of life in lower endemic areas.  The male:female ratio is 3:1 and risk is higher in those who are HBeAg positive.  While most hepatocellular cancer due to HBV develops on a background of pre-existing cirrhosis, from 15-45% does not.

Hepatocellular carcinoma is an aggressive malignancy, usually detected late, with median survival from 6-20 months.  Partial hepatectomy in situations where cure is possible (no radiologic evidence of vascular invasion or metastases) is the optimal treatment for hepatocellular carcinoma.  Long-term relapse-free survival rates average 40 percent or better in carefully selected patients with small (<5 cm="" tumors="" and="" good="" underlying="" liver="" function="" nbsp="" however="" there="" is="" no="" general="" rule="" regarding="" tumor="" size="" for="" selection="" of="" patients="" resection="" advanced="" or="" non-resectable="" disease="" a="" number="" options="" including="" combination="" chemotherapy="" radiofrequency="" ablation="" embolization="" exist="" but="" none="" optimal="" infectious="" agents="" are="" associated="" with="" at="" least="" 16="" different="" cancers="" among="" which="" hepatocarcinoma="" hbv="" cervical="" cancer="" hpv="" gastric="" em="">H. pylori) are the most important.

Follow-up MRI 7 months post-operatively [Image E] showed compensatory hypertrophy of the left lobe with formation of a large nodule in the surgical bed consistent with recurrent disease.  No retroperitoneal or mesenteric adenopathy.  AFP levels were rising once again.

We wish to thank Drs. Raul Gutierrez (Infectious Diseases), Luis Tacsa (Pathology), and Eloy Ruiz (Surgery) of the INEN (Instituto Nacional de Enfermedades Neoplasticas) in Lima for discussion, advice, and the images for this case.