Abnormal Liver Functions - Essay Example

?Case Study on abnormal liver functions The given case is about a 62 year old man presented to his GP with complaints of abdominal pain, weight loss and general lethargy. He exercised regularly, had never smoked and only drank alcohol in moderation. He was a carrier of Hepatitis B. further investigation reveals that he has an abnormal liver functions. This paper intends to discuss the potential types of malignancies of the liver and their epidemiology, diagnosis that could explain the findings in the case of this patient, information that can be gained from the liver biopsy and imaging, aetiology and pathogenesis of primary liver cancer, and finally possible prognosis and treatment options for this patient. Malignancies of the liver are of two types; primary liver cancer and secondary liver cancer. The cancerous cells originate from the liver cells themselves. The different types of Primary Liver cancer includes Hepatocellular carcinoma, Cholangiocarcinoma, Angiosarcoma,and Hepatoblastoma. Hepatocellular Carcinoma (HCC) is the most common form of primary liver carcinoma. Cirrhosis is the most common association of HCC. Conditions like inborn errors of metabolism, alcohol abuse or chronic infection with diseases like hepatitis B or C, hemochromatosis leads to cirrhosis which ultimately results in Hepatocellular carcinoma (Understanding Liver Cancer -- the Basics, n.d.). As Bosch et al (2004) note, the incidence of hepatocellular carcinoma in developing nations is twice of that in developed countries. The male to female ratio was approximately 2.4 to 1. The highest incidence of HCC is in East Asia followed by Africa and the Pacific Islands. The prevalence of HCC in third world countries is due to presence of viral hepatitis reservoirs endemic in the population (Ibid ). Cancerous growth along the bile ducts is called cholangiocarcinoma. If cancer occurs in the sections of duct inside the liver it is called intraheptic cholangiocarcinoma. If the cancer develops in the sections of duct outside the bile ducts it is called extraheptic cholangiocarcinoma. Both are treated as bile duct cancer. As Singal et al (2011) report, incidence in most western countries ranges from 2 to 6 cases per 1000,000 people per year. The highest annual incidence in Japan is, at 5.5 cases per 100,000 people, Israel, at 7.3 cases per 100,000 people (Ibid). Angiosarcoma is also called haemangiocarcinoma. This type of cancer begins in the blood vessels of the liver. This is an extremely rare form of cancer. 4.1% of angiosarcomas were diagnosed in 26,758 cases of soft tissue sarcoma available for analysis from 1978-2001 (Toro et al 2006). The age adjusted incidence rate for soft tissue sarcoma was 3.1 per 1000,000 men and women per year in the 2000-2004 period; and the worldwide incidence is low (Ibid). Hepatoblastoma is a rare type of primary liver cancer affecting young children below the age of 3. The treatment is surgery and chemotherapy. Hepatoblastoma accounts for 79% of all liver tumours in children and almost two thirds of primary malignant liver tumors in the pediatric age group (Types of primary liver cancer, n.d.). Approximately 100 cases of Hepatoblastoma are reported per year in the US. In Japan, efforts to improve vaccination rates have led to decrease in hepatocellular carcinoma and to a lesser degree, in hepatoblastoma. Carcinogen exposure in some developing countries is linked to hepatoblastoma and HCC (Ibid). Secondary Liver Cancer occurs as the cancer cells break off from the original site and travel through the blood or lymph and lodges itself in another organ and grow there. Though their site of growth is different, the cells are the same as of the original organ. So the treatment is according to the original cell type. This 62 year old gentleman had a history of blood transfusion followed by hepatitis B viral infection (HBV). HBV can lead to acute hepatitis, chronic hepatitis B infection which can either be a chronic hepatitis or a cancer state. as this patient is diagnosed to have a mass in the right lobe of the liver with elevated abnormal liver function test (LFT) and elevated alpha feta protein (AFP) level he is likely to have the diagnosis of a primary liver cancer namely Hepatocellular carcinoma (HCC). This is because he has a risk factor of chronic hepatitis B viral infection which probably could have led to either chronic hepatitis or cirrhosis which was undetected. His moderate alcohol intake could have led to cirrhosis liver and later hepatocellular carcinoma. On histology, the hallmark of HCC is its resemblance to the normal liver both in its plate like growth and its cytology. Three patterns may be seen namely the trabercular pattern, the acinar pattern and the compact pattern. Tumour cells are polygonal with rounded nuclei and prominent nucleoli. Immunohistochemistry is used in routine practice to diagnose HCC (Vauthey & Brouquet 2013). The highly specific markers are Hep Par1, alpha 1 antitrypsin, alpha feta protein. Glypican -3 is seen in 80% of cases of poorly differentiated cases of HCC. HCC is divided in to four grades on the basis of histological differentiation (Ibid). Gross specimen of liver showing Cirrhosis and Hepatocellular carcinoma (Source: Kumar et al 2009, n.p. Image 4) Cut specimen of liver showing large tan mass of HCC with several satellite nodules (Source: Kumar et al 2009, n.p. Image 5). Microscopy (H& E) showing irregular trabeculae of malignant hepatocytes with enlarged nuclei containing nucleoli (Source: Kumar et al 2009, n.p. Image 6). Accurate diagnosis and surgical planning require adequate cross sectional imaging studies .While Ultrasound (US) is commonly used for screening it does not provide sufficient anatomic detail for planning surgical resection or ablation. US is only 60% sensitive in diagnosing HCC (Colli et al 2006). In general HCC appears to be a round or oval mass with sharp, smooth borders. Triple phase CT scanning is highly accurate and has a sensitivity of 68% and specificity of 93% in diagnosing HCC. Findings include hypervascular pattern with arterial enhancement and rapid wash out during portal venous phase and a necrotic centre (Ibid). (29) In contrast regenerative nodules appear isoattenuating or hypoattenuating. Small lesions are frequently missed on CT scan. CT is the currently preferred modality to diagnose HCC. MRI has the highest sensitivity (80%) and adequate specificity (85%) in diagnosing HCC (Colli et al 2006). Well differentiated tumours are usually hyper intense on T1 images and iso intense on T2 images while poorly differentiated tumors tend to be hyperintense on T2 images and iso intense on T1 images. A significant overlap may occur between tumour and regenerative nodules (Ibid). “Any agent or factor that contributes to chronic, low-grade liver cell damage and mitosis makes hepatocyte DNA more susceptible to genetic alterations.” (Kim & Kim 2013, p. 265). Chronic liver diseases of any type are a risk factor and predisposes to development of liver cell carcinoma. These conditions include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), alcoholic liver disease, alpha1 antitrypsin deficiency, hemochromatosis, type1 glycogen storage disease and tyrosinemia. Hepatocellular tumors may occur with long term androgenic steroid administration, with exposure to thorium dioxide or vinyl chloride and possibly with exposure to estrogen in the form of oral contraceptives (Fauci et al 2008). Various toxins including mushroom toxins and aflatoxin B1 are also implicated. The loss, inactivation, or mutation of p53 gene has been implicated in tumerogenesis and is most common genetic derangement present in human cancers (Ibid). The other genes appear to be mutated in HCC are PIKCA , ARID 2 and beta-catenin. It is speculated that HCC develops from hepatic stem cells that proliferate in response to chronic regeneration caused by viral injury. The cells in small dysplastic nodules appear to carry markers consistent with progenitor or stem cells (Ibid). Tumour size is the most important predictor of survival. As this tumour is more than 5 cm this patient has around 40% two year survival rate (Liovet & Bruix 2003). A post surgical histology of grade 1 suggests good prognosis and grade 4 suggest the worst prognosis. Nuclear atypia is also graded to suggest prognosis from good to poor. Presence of micro vascular invasion is a poor prognostic factor. Post surgical TNM staging is also highly correlated with outcomes with stage 1 five year survival of 38% and stage 3 five year survival of 17%. Multimodel therapy may lead to more than 50% survival at five years (Tanabe et al 2005). This patient appears to be in TNM stage 3A as his tumor size is more than 5 cms with no evidence of lymph node involvement or metastasis. Surgical resection should be done if he has reasonable residual liver function. The expected five year survival is 40% if he is non cirrhotic. Tumor recurrence chance is 70% at five years. Transcatheter arterial chemo embolization using doxorubicin, mitomycin C and cisplatin provides a survival benefit in focal HCC. This may not be a treatment option in this patient. This modality can be combined with radio frequency thermal ablation. Systemic chemotherapy can be tried as an adjuant after surgery or transplantation using cisplatin, interferon alpha, 5-flurouracil and doxorupicin. Sorafenib is a multikinase inhibitor which improves survival in HCC. Liver transplantation is an option with overall mortality of around 17% and 80% recurrence free survival at 4years. To conclude, hepatocellular carcinoma is usually at an adavanced stage when detected and the prognosis is uniformly bad. So screening at regular basis is a possible tool to detect early cancer with those with risk factors like HBV infection and cirrhosis. Ultrasound and AFP level determination are recommended screening techniques for hepatocellular carcinoma detection. Since HBV infection aggravate the risk of hepatocellular carcinoma prevention is the preferred strategy. Hepatitis B vaccine can prevent infection. So, universal vaccination is an attractive option to prevent the occurrence of the disease. References Bosch F., X, et al. 2004. “Primary liver cancer: worldwide incidence and trends”. Gastroenterology. Nov 127(5 suppl 1): 55-516. Colli, A et al. 2006 “Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha- fetoprotein in diagnosing hepatocellular carcinoma; a systemic review”. Am J Gastroenterol. Mar 101(3); 513-23. Crawford, J. M & Liu, C. “Liver and biliary tract”. In Robbins & Cotran Pathologic Basis of Disease. (Eds.) V. Kumar, et al. 2009. Elsevier Health Sciences, 2009. Fauci, A. S. et al. (Eds.). (2008). Harrison's principles of internal medicine. McGraw-Hill. Kim, B et al (Eds.). 2013 Clinical PET and PET/CT: Principles and Applications. Spring. Liovet, J. M, Bruix, B. A. 2003 “Hepatocellular carcinoma”. Lancet 362: 1907–1917. Singal, A. K et al. 2011 “Intra heptic cholangio carcinoma-frequency and demographic patterns: thirty year data from the M.D Anderson Cancer Center”. J cancer Res Clin Oncol. Jul 137(7):1071-8. Tanabe, K et al.2005.Case Record. NEJM 353 (4):401-410. Toro, J. R et al. 2006 “Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: An analysis of 26,758 cases”. Int J cancer. Dec 15, 119(12):2922-30. Types of primary liver cancer. Cancer Research UK. [online] available at [accessed 12 July 2013]. Understanding Liver Cancer -- the Basics. WebMd. [online] available at [accessed 12 July 2013]. Vauthey, J. N & Brouquet,A. 2013 Multidisciplinary treatment of HCC. Springer. Read More