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Case report
peer-reviewed

Rapid Intrahepatic Progression of Hepatocellular Carcinoma after Transarterial Chemoembolization: A Case Report



Abstract

The prevalence of hepatocellular carcinoma (HCC) is increasing worldwide. Multiple strategies are available for its management including surgical removal, chemotherapeutic drugs, and ablative and chemoembolization procedures. Transarterial chemoembolization (TACE) is currently being used for the unresectable intrahepatic tumor with no vascular invasion or metastasis to other organs. The common adverse effects associated with this technique involve self-limiting fever, vomiting, and abdominal pain. Liver failure is reported in a few cases. In this report, we present a case of 37-year-old HCC patient who experienced rapid progression of tumor following TACE. Our patient came to the Gastroenterology & Hepatology Department, Nishtar Hospital, Multan, with signs concerning acute liver failure within a few months following TACE. On triphasic computed tomography (CT) scan, there was evidence of multiple new infiltrating lesions in both lobes of the liver and portal vein thrombosis, which were not present before TACE procedure. Hence, we made a diagnosis of acute, chronic liver disease due to the rapid intrahepatic progression of HCC. This is a rare side effect of TACE procedure and highlights the significance of proper counseling of the patients undergoing this intervention.

Introduction

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers all around the world. Most of the patients are diagnosed at the terminal stage when limited options of curative treatment are available. Multiple procedures are available for its management including surgery, chemoembolization, ablation, and chemotherapy. This largely depends on the stage of the tumor and the overall status of the patient. Transarterial chemoembolization (TACE) is considered a good therapeutic option for unresectable tumors which are not metastasized or involved the blood vessels [1]. The common adverse effects associated with TACE in these subsets of patients are reported in a prospective observational study. It mainly comprises self-limiting symptoms including fever, gastrointestinal features like vomiting and pain in the abdomen. Few cases of acute liver failure and deaths are also reported in the study [2]. Rapid recurrence and progression of HCC is a rare occurrence. Herein, we present a case of a 37-year-old HCC patient who developed a rapid progression of his underlying tumor after receiving TACE.

Case Presentation

A 37-year-old male patient presented to the Gastroenterology & Hepatology Department, Nishtar Hospital, Multan, Pakistan in July 2019, with complaints of jaundice and abdominal distention from the last two weeks.

The patient had a history of chronic hepatitis B (CHB) infection diagnosed since 2008. At that time, he had elevated levels of alanine aminotransferase (ALT), detectable hepatitis B virus (HBV) DNA levels, and no evidence of cirrhosis. He was advised tablet Tenofovir 300 mg once daily. However, the patient took treatment with poor compliance and was lost to follow-up.

In March 2019, the patient reported to a physician with the complaints of fatigability, body aches, loss of appetite, and weight loss for the past few weeks. He also had started drinking alcohol for the past few years and was now consuming alcohol on a daily basis. There was no history of illicit drug use. Family history was non-significant with respect to the liver and metabolic diseases. Examination findings included yellow sclera, mildly enlarged tender liver and splenomegaly with no evidence of ascites or peripheral edema. The patient had detectable HBV DNA levels and raised alpha-fetoprotein (AFP) levels. Further workup revealed two arterially enhancing lesions (larger one being 8.5 cm and the smaller one 1.5 cm in size) in the left lobe of liver on Triphasic Computed Tomography (CT) of the abdomen (Figure 1) consistent with hepatocellular carcinoma (HCC). The liver had an irregular surface. Portal vein measured 1.4 cm without evidence of thrombosis. There were no ascites and no evidence of metastasis. The patient was diagnosed with HCC (Barcelona clinic liver cancer [BCLC] stage B, child class B, performance status 0), CHB, and alcohol-related liver disease. As the patient's HCC was outside the resectability and transplant criteria, he was referred for transarterial chemoembolization (TACE). 

The patient underwent successful chemoembolization in April 2019 and was started on Tablet Tenofovir 300 mg once daily with advice to abstain from alcohol. The patient remained well after that. At one-month follow-up, CT abdomen was performed, which showed post-TACE radiological changes in left lobe of the liver (Figure 2) and development of two new small-sized lesions in the right lobe of liver consistent with hepatomas. No change in treatment was done and the patient was called for follow-up after one month.

In July 2019, the patient presented to the Gastroenterology & Hepatology Department, Nishtar Hospital, Multan, Pakistan with complaints of jaundice and abdominal distension from the last two weeks. He also complained of right hypochondrium pain associated with nausea and vomiting. There was no history of fever. There was a history of passing black tarry stools for the last few days. The patient also admitted that he started drinking alcohol again after abstinence of a few weeks. No history of illicit drug intake. Examination showed pallor, palmar erythema, and yellow sclera. Flapping tremors were absent. The abdomen was soft with mild tenderness in right hypochondrium and there was distension with fullness in flanks. The liver was enlarged, hard, and tender with irregular margins. There was evidence of ascites and splenomegaly.

Ultrasound abdomen showed coarse echotexture of the liver. There were multifocal hypoechoic lesions seen in left and right lobes of the liver. Triphasic CT scan abdomen showed newly formed multiple infiltrative lesions suggestive of HCC in both lobes of the liver (Figure 3), portal vein thrombosis, arteriovenous shunting, and moderate ascites.

Laboratory investigations are shown in Table 1. Ascitic fluid routine examination showed high serum ascites albumin gradient (SAAG) ascites with no evidence of spontaneous bacterial peritonitis (SBP). The patient was managed with intravenous antibiotics, dextrose, vasopressors and syrup lactulose. Esophagogastroduodenoscopy (EGD) showed early esophageal varices and portal gastropathy. A diagnosis of acute on chronic liver disease due to the rapid intrahepatic progression of HCC was made. His current child class is C, model for end-stage liver disease (MELD) score 20, performance status 1-2, and BCLC stage D. After a few days of treatment, the patient gradually improved and was discharged on diuretics, beta-blockers and lactulose. He was called for follow-up after two weeks.

Peripheral Blood Results Blood Chemistry Results
WBC 14000 /µL Serum Bilirubin 4.8 mg/dl
Neutrophils 85 % ALT 95 U/L
Lymphocyte 10 % AST 44 U/L
Mixed 5 % ALP 582 U/L
    Serum Albumin 2.0 g/dl
RBC 2.660x 106 / µL Urea 45 mg/dl
Hemoglobin 8.5 g/dl Creatinine 0.7 mg/dl
Hematocrit 26.4 % Sodium 136 mmol/L
Platelet count 67000 /µL Potassium 4.54 mmol/L
Coagulation Test   Serological Tests  
Prothrombin Time (PT)   HBsAg Positive
Patient PT 24 seconds Anti-HCV Negative
Control (PT) 12 seconds HBeAg Positive
INR 2 Anti HIV Negative
    Anti-HDV Negative
Tumor Marker   Anti HAV IgM Negative
AFP Level 968 ng/ml Anti HEV IgM Negative

Discussion

TACE is a good alternative for HCC patients who are not suitable for surgical resection and have no vascular invasion and no metastasis. The association of TACE and the rapid progression of HCC has been discussed in different studies. In an experimental study by Wang GZ et al, HCC was induced in buffalo rats. It demonstrated statistically significant increased metastasis in the transarterial embolization group. It was proposed that hypoxia leads to an increase in a transcriptional factor called Hypoxia-inducible factor-1 (HIF-1) which plays an important role in the breakthrough of the tumor by damaging the extracellular matrix and intracellular adhesion molecules. Other mechanisms like the formation of new blood vessels in response to hypoxia may also play some role [3]. These results were validated by Lai JP et al. study. This, in addition to previous findings, showed that hypoxia is also related to the activation of proteins that are involved in promoting the differentiation of progenitor cells. These factors may result in the manifestation of aggressive behavior by the tumor following TACE [4].

There are multiple studies highlighting the aggressive recurrence of tumor following radiofrequency ablation (RFA), but not many studies could be found in the literature regarding similar association with TACE [5-6]. A retrospective study was conducted to evaluate the frequency of rapid recurrence of HCC when a combination of TACE and RFA was used. Interestingly, the results showed a decline in the overall occurrence of this complication when combined therapy was used [7]. Our patient underwent TACE only and developed features of acute liver failure within a few months of intervention. A study aimed to describe the adverse effects of TACE, demonstrated the complication of acute decompensation in a few cases [2]. In our patient the underlying pathogenesis of rapid intrahepatic progression of tumor leading to acute, chronic disease was unique. This is a rare occurrence following TACE.

Our patient was managed on the lines of acute on chronic liver disease. He was discharged after improvement in symptoms and was called for follow-up after two weeks. In light of this, it is imperative for physicians to discuss this adverse effect with patients who are planning to go for TACE. Further research is required for a deeper understanding of pathogenesis and factors responsible for this complication.

Conclusions

The rapid progression of primary liver tumor in response to TACE therapy is a rare complication. Hypoxia induced by this intervention is considered to play an important role in its manifestation. Herein, we present a case of an HCC patient who developed acute liver failure within a few months after TACE procedure. On triphasic CT scan, multiple new infiltrative lesions suggesting HCC were found, involving both lobes of the liver. This is a unique case of rapid HCC progression following TACE therapy. 


References

  1. Raza A, Sood GK: Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol. 2014, 20:4115-27. 10.3748/wjg.v20.i15.4115
  2. Tasneem AA, Abbas Z, Luck NH, Hassan SM, Faiq SM: Adverse events following transarterial chemoembolization for hepatocellular carcinoma and factors predicting such events. J Pak Med Assoc. 2013, 63:239-44.
  3. Wang GZ, Fang ZT, Zhang W, Qu XD, Qian S, Liu R, Wang JH: Increased metastatic potential of residual carcinoma after transarterial embolization in rat with McA-RH7777 hepatoma. Oncol Rep. 2014, 31:95-102. 10.3892/or.2013.2820
  4. Lai JP, Conley A, Knudsen BS, Guindi M: Hypoxia after transarterial chemoembolization may trigger a progenitor cell phenotype in hepatocellular carcinoma. Histopathology. 2015, 67:442-50. 10.1111/his.12623
  5. Kang TW, Lim HK, Cha DI: Aggressive tumor recurrence after radiofrequency ablation for hepatocellular carcinoma. Clin Mol Hepatol. 2017, 23:95-101. 10.3350/cmh.2017.0006
  6. Kang TW, Lim HK, Lee MW, et al.: Aggressive intrasegmental recurrence of hepatocellular carcinoma after radiofrequency ablation: risk factors and clinical significance. Radiology. 2015, 276:274-85. 10.1148/radiol.15141215
  7. Song KD, Lee MW, Rhim H, Kim YS, Kang TW, Shin SW, Cho SK: Aggressive intrasegmental recurrence of hepatocellular carcinoma after combined transarterial chemoembolization and radiofrequency ablation. AJR Am J Roentgenol. 2016, 207:1122-1127. 10.2214/AJR.16.16080
Case report
peer-reviewed

Rapid Intrahepatic Progression of Hepatocellular Carcinoma after Transarterial Chemoembolization: A Case Report


Author Information

Tanveer H. Siraj

Gastroenterology, Nishtar Medical University & Hospital, Multan, PAK

Asim Tameez Ud Din

Internal Medicine, Rawalpindi Medical University, Rawalpindi, PAK

Farooq Mohyud Din Chaudhary Corresponding Author

Gastroenterology, Nishtar Medical University & Hospital, Multan, PAK

Sultan Ahmad

Gastroenterology, Nishtar Medical University & Hospital, Multan, PAK

Khaleeq H. Siddiqui

Internal Medicine, NewYork-Presbyterian Queens, Flushing, USA


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.


Case report
peer-reviewed

Rapid Intrahepatic Progression of Hepatocellular Carcinoma after Transarterial Chemoembolization: A Case Report


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