Hepatocellular carcinoma in eastern India, a detail analytical report from a tertiary care hospital

INTRODUCTION

Hepatocellular carcinoma is the commonest primary malignant tumor of the liver. It is the fifth most common cancer in men and the eighth most common in women, and it ranks fourth in annual cancer mortality rates.^1,2

The annual global incidence is approximately 1 million cases, with male preponderance. The incidence rates varies from low-incident countries (like US) to intermediate (like Austria, South Africa) to high areas in the orient (China and Korea). In India, the mean incidence of HCC in four population-based registries is 2.77% for males and 1.38% for females. The prevalence of HCC in India varies from 0.2% to 1.6%.^3,4 However, there is paucity of published literature on profile of HCC patients in eastern India. Therefore we studied these patients for detail analysis of their demographic characteristics.

METHODS

It is a cross sectional, observational, hospital based study. Total 90 HCC patients who were admitted in department of medicine and gastroenterology, R.G.K.M.C.H, Kolkata, from 2007-2013 were retrospectively analyzed. The diagnosis of HCC was based on EASL diagnostic criterias.⁵ All clinical, biochemical, serological, radiological and endoscopical details were noted from the case records and analysed accordingly. Other space occupying lesions in liver like metastasis or primary benign tumors were excluded from the study.

RESULTS

Demographic: Out of the 90 (n=90) HCC patients 81 are male (90%), only 9 patients are female (10%). There is definite male preponderance. Male:Female = 81:9 = 9:1. Out of 90 (n=90) patients 75 are Hindu (83.4%) & 15 are Muslim (16.6%). Maximum patients are in the age group of 40-59 years. That is, HCC is occurring maximally in the middle age (43.3%). Next common age group is above 60 years (33.4%).

Clinical: (clinical profile shown in Table 1 & 2) most common symptom is anorexia (96.6%). But it is a nonspecific one. Other nonspecific symptoms are weight loss (83.3%), swelling of face (26.6%). Among gastrointestinal tract related symptoms most common is pain abdomen (80%) and then abdominal swelling (66.6%), jaundice (60%). Impaired consciousness due to metastasis to brain or due to hepatic failure present in 13.3% of patients. 83.3% have poor nutrition, due to cancer cachexia or anorexia. 53% have hepatic facies, predominantly due to previous chronic liver disease. 70% have pallor, due to poor nutrition, hematemasis and/or melaea. 60% have jaundice, quite a common feature. Only 26.6% have clubbing and edema, not a common feature. Lymphadenopathy is not a feature of HCC. Hypotension is due to poor general condition. Hypertension is most probably part of nonalcoholic fatty liver disease. Respiratory distress may be due to pleural effusion - may be due to metastasis. Hepatomegaly is present in all patients (100%). 43.3% have splenomegaly and it is mostly due to portal hypertension. Ascites present in 73.3% of patients. It may be due to chronic liver disease or metastases. In 66.6% cases liver enlarged more than 5 cm and mostly hard and nodular (96.6%). 80% livers are tender. In 73.3% cases Rt lobe enlargement is more than left lobe. In 20% cases hepatic bruit are present.

Most commonly involved system other than gastrointestinal system is respiratory system (6%) in the form of pleural effusion. Lung parenchymal metastasis is not present in our study population. Pleural effusion may be due to chronic liver disease or pleural metastasis. Central nervous system involvement occurred in the form of impaired consciousness - may be due to hepatic failure or brain metastasis (Table 1 & 2).

Etiological: 56.5% HCC patients are alcoholic - 26.6% had ingested alcohol in the cirrhotic risk range & 23.3% had ingested in the fatty liver risk range. 56.6% of patients are addicted to alcohol, 70% of them are addicted to tobacco (including one patient who is addicted to gurakhu). 46.4 % of them are addicted to both tobacco and alcohol. Only 20% of them have no addiction. Majority of patients have no significant past history related to gastrointestinal tract. 40% give definite past history of chronic liver disease which is a predisposing factor for HCC. 30% give history of fatty liver which was detected by ultrasonography and it is associated with alcohol intake. Only 16.6% give history of jaundice but the cause was not known to them. Only 16.6% of HCC patients have other risk factors. Even if they are predisposing factors for HCC, they are not prevalent at all. 33.3% of HCC patients are HbsAg +ve. 3.3% has Ab against HCV (Table 3 & 4).

Biochemical: (Table 5 & 6) 80% have hyperbilirubinemia and 70% have conjugated hyperbilirubinemia. SGOT & ALP levels are increased in 56.6% cases but SGPT levels are increased in only 26.65% cases. In 30% cases albumin levels are less than 3 gm%. 53.3% cases have altered albumin- globulin ratio - may be due to chronic liver disease. Altered liver function in the form of increased prothrombin time - in 30% cases, which may increase risk of bleeding. 76.7% (40% ± 36.7%) of HCC patients have AFP level more than 500unit and practically diagnostic of HCC. But 23.3% have AFP level less than 500 units. All HCC patients have AFP level above the normal range of 10 ng/ml. 20% have increased leukocyte count - may be due to secondary infection or reactionary. 26.6% have decreased hemoglobin and in 40% of them have increased ESR. Azotemia - probably due to other causes unrelated to HCC. Electrolyte imbalance is not common in this study group.

Radiological: 66.6% have chronic liver disease, portal hypertension and splenomegaly-cirrhosis is a definite possibility. Most SOLs are single (53.3%) and mostly hyper echoic (83.3%). Either the SOLs are large and single or small and multiple-affecting mostly right lobe (53.3%). Abdominal lymphadenopathy is rare. Lung or brain parenchymal metastasis is rare - only3.3%. Pleural effusion is also not common and left sided pleural effusion is not present in this study group (Table 7).

Endoscopy: 43.4% of HCC patients have esophageal varices, 3.3% have gastric erosion and 33.3% have normal esophageal findings. Although only 3.3% manifested hematemasis and 16.6% have melaena.

DISCUSSION

This is the first study from eastern India revealing detailed analysis of epidemiological clinical biochemical etiological and radiological features.

The pattern of HCC incidence by age is sometimes dependent on the geographic pattern or on etiologic factors.⁶ The male preponderance is somewhat more in our study (Male:Female - 9:1). The incidence of HCC peaks during fifth and sixth decade as in other studies. The population-based data shows a male to female ratio of 3:1-2:1.1.⁷

However, high preponderance of HCC in males reported in hospital-based data could suggest a gender bias in seeking medical treatment

The clinical presentation of HCC patients in our study was similar to other studies. The paraneoplastic syndrome was very rare in this series. Only one patient developed troublesome hypoglycemia. The rarity of paraneoplastic syndrome has been seen in other Indian series as well.^8-10 The symptom duration at diagnosis was mainly 1-3 months like other study from India.^9,10

Chronic viral hepatitis due to either HBV or HCV is the main cause of HCC in most area worldwide.^11,12 One study from India showed that HBV is the predominant factor for the development of HCC, often related to mutant form of HBV.¹³

Our study showed similar etiological profile with Hepatitis B being the most common cause, followed by alcohol ingestion (cirrhotic range), unknown cause and Hepatitis C only in 3.3 %. 50% of patients ingested alcohol for >10 years and in amount which can cause chronic liver disease. 16.6% of patients have history of other risk factor like diabetes and hypertension, indicating nonalcoholic fatty liver disease, which is probably a risk factor for HCC. 33.3% 0f HCC patients are sero-positive for HBV and 3.3% are sero-positive for HCV. Only 4 patients presented with HCC without any alarming features (de novo).

No patient is positive for both and 63.3% of HCC patients are sero-negative for both. Therefore in our study alcoholic chronic liver disease is the main cause of HCC, next come chronic HBV infection, nonalcoholic fatty liver disease and chronic HCV infection.

In HCC the sensitivity of serum AFP ranges from 39% to 64%, specificity 76–91% and positive predictive value 9-32%.^14,15

In another study from India, the prevalence of detectable AFP in patients with HCC was 51%.¹⁶ however in our study 76.7% of HCC patients have AFP level more than 500 unit and practically diagnostic of HCC, suggesting a good role of AFP as diagnostic purpose.

CONCLUSION

The characteristics of HCC in eastern India are somewhat different from the rest of worlds. Alcohol and HBV infection are the two most important etiology prevailing here. Lifestyle modification is very much needed to curtail the intake of alcohol to reduce the burden of HCC in this part of world. On the other hand Mandatory vaccination against Hepatitis B will very much reduce the incidence of HCC.

ACKNOWLEDGEMENTS

We acknowledge the contribution from all patients.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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