|Year : 2022 | Volume
| Issue : 1 | Page : 21-25
Hepatocellular carcinoma in a healthy liver; Case report and literature review
Ghaida A Almasaad1, Mohammed A Alkarbi1, Weam S Hussein2, Faisal Al-Alem3, Ahmad M Madkhali3, Abdulaziz A Bazuhair4, Mazen M Hassanain3
1 Department of Anesthesia, King Saud University, Riyadh, Saudi Arabia
2 Liver Disease Research Center, King Saud University Medical City, Riyadh, Saudi Arabia
3 Department of Surgery, King Saud University Medical City, Riyadh, Saudi Arabia
4 Department of Surgery, Arabian Gulf University, Manama, Bahrain
|Date of Submission||27-Sep-2021|
|Date of Acceptance||12-Oct-2022|
|Date of Web Publication||16-Nov-2022|
Dr. Ghaida A Almasaad
Department of Surgery, King Saud Unveracity, Riyadh
Source of Support: None, Conflict of Interest: None
Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide with high mortality rate, and it most commonly develops in the presence of cirrhosis and chronic liver diseases, most commonly in hepatitis. In some cases, however, it may present in noncirrhotic liver or healthy liver without any chronic disease. Our case is a 60-year-old male with primary HCC with no liver disease and negative hepatitis serology. Presented with multiple liver masses in four different segments. Managed with embolization and staged liver resection.
Keywords: Healthy liver, hepatectomy, Hepatocellular carcinoma, non-cirrhotic liver
|How to cite this article:|
Almasaad GA, Alkarbi MA, Hussein WS, Al-Alem F, Madkhali AM, Bazuhair AA, Hassanain MM. Hepatocellular carcinoma in a healthy liver; Case report and literature review. Saudi J Laparosc 2022;7:21-5
|How to cite this URL:|
Almasaad GA, Alkarbi MA, Hussein WS, Al-Alem F, Madkhali AM, Bazuhair AA, Hassanain MM. Hepatocellular carcinoma in a healthy liver; Case report and literature review. Saudi J Laparosc [serial online] 2022 [cited 2023 Feb 8];7:21-5. Available from: https://www.saudijl.org/text.asp?2022/7/1/21/361356
| Introduction|| |
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and it is considered one of the leading causes of cancer-related mortality worldwide.,,,,,,
The most common risk factors to develop HCC are liver cirrhosis and chronic liver diseases. Numerous medical conditions can lead to liver cirrhosis, however, hepatitis B, C, and nonalcoholic fatty liver are considered the most common causes. In 20% of cases, HCC develops in noncirrhotic liver attributed to hepatitis B carrier with a certain demographic background. Moreover, HCC can be developed in 10%–12% of the patients with healthy liver.
| Case Report|| |
A 62-year-old male, with a past history of nasopharyngeal carcinoma 20 years ago that was treated with chemotherapy, presented to a local hospital complaining of abdominal pain.
A computed tomography (CT) image of the abdomen showed two hepatic lesions, which were suggestive of HCC. Therefore, he was referred to a liver specialized center, King Khalid University Hospital, for further workup.
Upon admission, on October 1, 2012, the patient reported 18 kg weight loss over the past few months. The patient's medical history did not reveal any identifiable risk factors for developing HCC including any chronic liver diseases, alcohol consumption, steroid abuse, and no family history of HCC. The physical examination was unremarkable. Laboratory analysis showed high alpha-fetoprotein levels (81.010 KIU/L) with normal liver function values, international normalized ratio, and platelet count. The patient tested negative for viral and autoimmune hepatitis. Upper and lower gastrointestinal endoscopy were done to exclude any gastrointestinal tumors and it was unremarkable. A triphasic CT was done, and it revealed two hypervascular hepatic lesions with washout in portovenous and in the delayed phase: one located in segments 2 and 3 measuring 5.9 cm × 5.6 cm, and the second one located in segments 7 and 8 measuring 7 cm × 6 cm [Figure 1], demonstrating the signs of impending rupture and mild hemorrhagic ascites. Otherwise, the liver parenchyma does not demonstrate any signs of liver cirrhosis or fatty liver disease. There was no major vascular invasion, and no metastatic pulmonary nodules were detected.
|Figure 1: A triphasic CT two hypervascular hepatic lesions with washout in portovenous and in the delayed phase|
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Given the patient's medical history, a Tru-cut biopsy was performed for both masses and normal hepatic tissue, which confirmed the diagnosis of moderately differentiated HCC. The surrounding hepatic tissue demonstrated normal liver parenchyma with no elements of fibrosis or cirrhosis.
The patient underwent transarterial chemoembolization (TACE) for the right hepatic lobe mass with doxorubicin-loaded DC beads. An angiogram obtained postembolization showed complete devascularization of the mass. The patient was discharged, and treatment with sorafenib 200 mg twice a day was initiated due to the risk of metastasis after the primary presentation.
A follow-up triphasic CT was done, which showed almost complete cystic transformation measuring approximately 6.8 cm × 5.4 cm in the right hepatic lobe [Figure 2] with a stable size and the previously noted hypervascular lesion in segment 3/2. Furthermore, two newly developed small lesions measuring 1.1 cm × 1 cm and 1.4 cm × 0.8 cm were observed in segments 3 and 6, and interval complete resolution of the mild free fluid. The routine blood tests, a normal platelet count, a normal international normalized ratio, and a normal liver function test. The case was discussed in the HCC combined meeting, and a staged liver resection was scheduled.
Laparoscopic left lateral liver resection was carried out with uneventful postoperative recovery and discharged on day 5 postoperatively with close follow-up plan.
Six weeks postoperatively, a follow-up CT image of the abdomen showed a mild decrease in the size of the remaining lesion in segments 7 and 8, from 5.5 cm × 6.3 cm to 5.2 cm × 5.6 cm. As for segment 6, it was viewed as arterioportal shunt. No other newly developed hypervascular lesions were observed.
The patient underwent right hepatectomy, leaving him with segments 4 and 1. The surgery was performed uneventfully. He was discharged on postoperative day 9 in good condition. The patient was being followed regularly in the clinic with frequent CT scans and AFP levels with no significant findings.
Four months after the surgery, a CT image showed no new focal hepatic lesions but two pulmonary nodules measuring approximately 1 mm in the left and right lower lobes. Decision was to observe these nodules.
After 1 year and a half, one of the pulmonary nodules showed increase in size reaching 8 mm [Figure 3] which was suspicious for metastasis.
The patient underwent thoracoscopic lung biopsy of the right lower lobe. Histopathological analysis of the specimen confirmed metastatic HCC. The postoperative course went uneventfully; the patient was discharged and started on sorafenib.
Three months after the surgery, a follow-up triphasic CT image showed interval progression in size of the previously noted pulmonary nodule and multiple newly developed pulmonary nodules with multiple peritoneal metastatic masses, which were progressed further on follow-up CT.
On October 11, 2015, the patient presented with dysphagia. No other gastrointestinal symptoms were observed. The upper gastrointestinal endoscopy revealed minimal esophageal stricture, biopsy taken showed fibrosis with no evidence of malignancy, and the patient underwent uneventful esophageal dilatation and discharged few days later.
Further investigation revealed a large left upper quadrant mass originating from the peritoneum compressing the stomach supplied by the left hepatic artery [Figure 4].
|Figure 4: Left upper quadrant mass originating from the peritoneum compressing the stomach supplied by the left hepatic artery |
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A transarterial bland embolization with polyvinyl alcohol particles 200–500 micro was done resulted in necrosis of the mass with no regression in size. Meanwhile, the patient was kept on sorafenib.
The patient's condition deteriorated over the following few months in terms of dysphagia and poor oral intake which was attributed to sorafenib for which it was held, and he died on 25-5-2016.
| Discussion|| |
HCC is the most common primary liver cancer with a very high mortality rate worldwide., It develops generally in cirrhotic livers. However, in 20% of the patients, it arises in noncirrhotic livers, and 10%–12% of cases arise in patient with healthy liver.,,,, Almost half of cirrhotic patients are infected with either hepatitis B or C infection. Other risk factors include high alcohol consumption, diabetes mellitus, and nonalcoholic steatohepatitis.,,, Moreover, chronic liver diseases and some medical conditions are important causes for its development.,
According to our literature review, few articles were found for the development of HCC in completely healthy liver. The cases showed a variety of attributable risk factors, including alcohol abuse, family history of malignancy, chronic use of some medications, as well as some medical conditions [Table 1].
Among the reported patients, a couple of cases were in healthy people without any identifiable risk factor for liver disease. One of the cases described a pregnant woman that found to have HCC in a completely normal liver during a routine prenatal ultrasound., Some of the reported cases were receiving immunosuppressive therapy, two of them were in renal transplant patients, and another one in a young man with Crohn's disease., Moreover, a 76-year-old patient was on hypoglycemic medication and developed HCC with diffuse extensive fatty changes in a normal liver. Some of the cases reported HCC in healthy liver with unusual risk factors, one case report was in a patient with hypercalcemia, the other case was in HIV patient with negative hepatitis B and C virus infection., In addition, a 55-year-old female patient presented with late recurrence of HCC originating in normal liver tissue following repeated complete resections, which raises the issues of genetic screening.
In our case, our patient developed HCC in a completely normal liver with a past history of cured esophageal cancer. Other than that, we investigated for the known risk factors, and all were unremarkable; negative family history, neither steroids administration nor alcohol abuse were noted. Moreover, the patient tested negative for viral and autoimmune hepatitis.
Furthermore, we reviewed two cohort articles by Lubrano et al. and Young et al. that evaluated HCC in normal liver over a long period of time with a sample size of 20 and 80 patients, respectively. They studied the presentation in terms of demographics, presenting symptoms, and tumor characteristics [Table 2].
|Table 2: Summary of cohort studies about the presentation of hepatocellular carcinoma in a normal liver|
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Similarities were found between our case and the reported cases by Lubrano et al. and Young et al., as they frequently reported elderly males who came with a large tumor size in the first presentation, which could be due to the lack of surveillance because of the absence of usual risk factors. In addition, most of the previous cases were unilobar, whereas our patient presented with bilobar lesions. Moreover, as for the presenting symptoms, abdominal pain was commonly reported but weight loss was rarely mentioned.,,
In regard to the management, according to the current NCCN guidelines, TACE is the recommended first-line therapy for patients with unresectable HCC or as a downstaging therapy to reduce the tumor burden in selected patients with more advanced HCC (without distant metastasis) who are beyond the accepted transplant criteria.
In terms of surgical intervention, studies showed that liver resection for noncirrhotic HCC patients provides good long-term outcomes and found to have low perioperative morbidity and mortality. Laparoscopic approach is as safe as the open approach for elderly patients with HCC.
Moreover, also in the current NCCN guidelines, the use of sorafenib in patients with residual or recurrent tumor post-TACE might be an appropriate option if liver function is normal.
Based on the recommendations in the literature, the treatment strategy for our case was to start with downstaging of the tumor using locoregional therapy, followed by staged resection of the tumor. However, the patient developed new liver lesions along with distant metastasis during his management.
This work was funded by the National Plan for Science, Technology and Innovation plan (MAARIFAH), King Abdul-Aziz City for Science and Technology, Kingdom of Saudi Arabia, grant Number 08-MED512-02”. This study was possible with the support of the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia, Riyadh.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kew MC. Hepatocellular carcinoma: Epidemiology and risk factors. J Hepatocell Carcinoma 2014;1:115-25.
Ascione A, Fontanella L, Imparato M, Rinaldi L, De Luca M. Mortality from cirrhosis and hepatocellular carcinoma in Western Europe over the last 40 years. Liver Int 2017;37:1193-201.
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012;142:1264-73.e1.
Trevisani F, Frigerio M, Santi V, Grignaschi A, Bernardi M. Hepatocellular carcinoma in non-cirrhotic liver: A reappraisal. Dig Liver Dis 2010;42:341-7.
Balogh J, Victor D 3rd
, Asham EH, Burroughs SG, Boktour M, Saharia A, et al.
Hepatocellular carcinoma: A review. J Hepatocell Carcinoma 2016;3:41-53.
Centers for Disease Control and Prevention (CDC). Hepatocellular carcinoma – United States, 2001-2006. MMWR Morb Mortal Wkly Rep 2010;59:517-20.
Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529-38.
Batey RG, Burns T, Benson RJ, Byth K. Alcohol consumption and the risk of cirrhosis. Med J Aust 1992;156:413-6.
Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology 2014;59:2188-95.
Wang C, Wang X, Gong G, Ben Q, Qiu W, Chen Y, et al.
Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: A systematic review and meta-analysis of cohort studies. Int J Cancer 2012;130:1639-48.
Gao C, Fang L, Zhao HC, Li JT, Yao SK. Potential role of diabetes mellitus in the progression of cirrhosis to hepatocellular carcinoma: A cross-sectional case-control study from Chinese patients with HBV infection. Hepatobiliary Pancreat Dis Int 2013;12:385-93.
Alkofer B, Lepennec V, Chiche L. Hepatocellular cancer in the non-cirrhotic liver. J Visc Surg 2011;148:3-11.
Kabbage L, El Kouhen M, Taghy A, Znati K, Kabbaj N. A rare presentation of hepatocellular carcinoma in non-cirrhotic liver. Pan Afr Med J 2017;28:69.
Russell P, Sanjay P, Dirkzwager I, Chau K, Johnston P. Hepatocellular carcinoma during pregnancy: Case report and review of the literature. N Z Med J 2012;125:141-5.
Newman NB, Jabbour SK, Hon JD, Berman JJ, Malik D, Carpizo D, et al.
Hepatocellular carcinoma without cirrhosis presenting with hypercalcemia: Case report and literature review. J Clin Exp Hepatol 2015;5:163-6.
Hadjittofi C, Athanasopoulos PG, Koti RS, Konstantinidou SK, Davidson BR. Long-term survival with repeated resections of recurrent hepatocellular carcinoma in a non-cirrhotic liver: Case report and brief review of the literature. Ann Transl Med 2016;4:112.
Murakami A, Tanaka Y, Ueda M, Nagano Y, Kunisaki R, Morimoto M, et al.
Hepatocellular carcinoma occurring in a young Crohn's disease patient. Pathol Int 2009;59:492-6.
Parikh N, Martel-Laferriere V, Zhang X, Dieterich D, Fiel MI, Perumalswami P. Hepatocellular carcinoma in a noncirrhotic patient with HIV: A case report and review of the literature. Semin Liver Dis 2012;32:186-92.
Komiyama S, Okazaki H, Nakao S, Nishigori S, Terada M, Hamanaka J, et al.
Diffuse fatty metamorphosis of a large, well-differentiated hepatocellular carcinoma originating in the normal liver: A case report and literature review. Clin J Gastroenterol 2015;8:345-50.
Saeian K, Franco J, Komorowski RA, Adams MB. Hepatocellular carcinoma after renal transplantation in the absence of cirrhosis or viral hepatitis: A case series. Liver Transpl Surg 1999;5:46-9.
Téllez-Zenteno JF, Hernández-Ronquillo L, Tapia-Rangel B, Garduño-Espinosa J. A fibrolamellar variety of hepatocarcinoma in a young woman 17 years old. Gac Med Mex 1999;135:83-7.
Lubrano J, Huet E, Tsilividis B, François A, Goria O, Riachi G, et al.
Long-term outcome of liver resection for hepatocellular carcinoma in noncirrhotic nonfibrotic liver with no viral hepatitis or alcohol abuse. World J Surg 2008;32:104-9.
Young AL, Adair R, Prasad KR, Toogood GJ, Lodge JP. Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, seronegative liver: Surgical approaches and outcomes. J Am Coll Surg 2012;214:174-83.
Sacco R, Tapete G, Simonetti N, Sellitri R, Natali V, Melissari S, et al.
Transarterial chemoembolization for the treatment of hepatocellular carcinoma: A review. J Hepatocell Carcinoma 2017;4:105-10.
Zhou Y, Lei X, Wu L, Wu X, Xu D, Li B. Outcomes of hepatectomy for noncirrhotic hepatocellular carcinoma: A systematic review. Surg Oncol 2014;23:236-42.
Amato B, Aprea G, De Rosa D, Milone M, di Domenico L, Amato M, et al.
Laparoscopic hepatectomy for HCC in elderly patients: Risks and feasibility. Aging Clin Exp Res 2017;29:179-83.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]