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Introduction 

A space occupying lesion (SOL) by definition is a discrete abnormality arising within the liver¹. SOLs of the liver can be classified into developmental, neoplastic, inflammatory and miscellaneous. Although in some cases, it is difficult to distinguish these entities with imaging criteria alone, certain focal liver lesionshave classic ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) features. Mass lesions of the liver occur quite frequently, thus clinicians interested in liver diseases should have a thorough understanding of their presentations, diagnosis and treatment. Hepatic mass lesions include tumors, tumor-like lesions, abscesses, cysts, hemartomas and confluent granulomas. The frequency with which each is seen varies in different geographic regions and different populations. 

Liver neoplasms are one of the most common tumours worldwide, especially in developing countries². Rapid developments in liver surgery and liver pathology have led to many new types of primary hepatic space-occupying lesions (PHSOLs) being surgically resected and pathologically diagnosed. Liver masses are increasingly being identified due to the widespread use of imaging modalities. 

Amoebic liver abscess (ALA) is a significant leading cause of morbidity in the developing countries³. Cystic diseases of liver constitute a large percentage of the space occupying lesions in liver out of which hydatid disease is quite common. Hemangiomas are small, asymptomatic lesions seen in all age groups that are most often discovered incidentally on routine cross-sectional imaging studies. Malignant and various benign focal liver lesions can occur in patients. 

In this regard, only few studies have been conducted from India and data from Sub-Himalayanregion is not available. This study was conducted to evaluate the magnitude, spectrum and clinical profile of various types of SOLs in liver in this region

It was a cross-sectional observational study conducted at Indira Gandhi Medical College, Shimla, in the sub Himalayan region of Himachal Pradeshfrom July 2014 to June 2015. Total 109 consecutive patients withSOL in liver, on ultrasound of abdomen, were included in the study after taking informed written consent. All patients aged 18 years or more and having evidence of SOL in liver on imaging were included in the study. 

A detailed history, clinical examination and laboratory profile of the patients were recorded on a predesigned proforma. All patients were subjected to complete haemogram, liver function tests, kidney function tests and coagulation profile. Reference ranges of these investigations were defined by the reference ranges of hospital laboratory. Blood and urine cultures were also performed. Serologies for Entamoebahistolytica, HIV, Echinococcusgranulosus(IgG antibodies to Echinococcus by ELISA) and hepatitis B and hepatitis C viruses were also done. Contrast enhanced CT of abdomen was done wherever indicated.

After taking informed consent, USG guided fine needle aspiration cytology of the SOL in liver was performed wherever indicated. Interventions were done after correction of international normalized ratio (INR) below 1.4 to those who presented with coagulopathy. 

The median (range) age of the patients (n=109) was 51 (20 to 90) years. Male to female ratio was 2.3:1. About 80% of the patients were from the rural background and 20% from the urban background.

Benign SOLswere more common (n=62, 57%) than the tumour or tumour like SOLs(n=47, 43%) (Table 1). Liver metastases comprised the maximum number of cases (n=36, 33%) followed by amoebic liver abscess (n=27, 25%). Benign cysts (n=12, 11%), hepatic hemangioma (n=11, 10%), hepatocellular carcinoma (HCC) (n=7, 6%),pyogenic liver abscess and hydatid cyst (each 6,5%), focal nodular hyperplasia (n=2, 2%), granuloma liver (n=1, 1%) and cholangiocarcinoma liver (n=1, 1%) were other lesions noted in the study. 

Among 36 cases of liver metastases, FNAC was performed in 33 patients and remaining 3 were already diagnosed cases of malignancy at presentation. FNAC from suspected primary site of malignancy was performed in 29 patients and in 4 patients FNAC was done from SOL in liver. Lung cancer was the most common primary malignancy present (22%). Adenocarcinoma of stomach, pancreas, gall bladder and colon,esophagus, tongueandovarywere main sites for primary tumours.Klatskin Tumour, Non Hodgkin lymphoma, malignant melanoma, retroperitoneal mass with liver metastasis, periampullary carcinoma and squamous cell carcinoma pyriform Sinus were other malignancies associated with metastasis in liver. Two patients (5%) had liver metastasis with unknown primary site of malignancy. (Figure 1)

Liver abscess was diagnosed in 33 cases, which included 27 cases of amoebic liver abscess (82%) and 6 cases of pyogenic liver abscess (18%). Among the 27 cases of amoebic liver abscess, 20 cases presented with isolated liver abscess (74%) and 7 patients had complicated amoebic liver abscess with features of sepsis in 5 patients (18%) and 2 patients (7.4%) had rupture into right pleural cavity. Secondary infection (1), Multi Organ Dysfunction Syndrome (1), right-sided pleural effusion (2) and portal vein thrombosis (1) were few of complications noted. There was monthly variation in the cases of liver abscess. Maximum number of cases of liver abscess occurred in summer months of May (5) and least number in winter months of January. Pain abdomen (97%) and fever (94%) were most common presenting complaints. Abdominal tenderness (96%) and tender hepatomegaly (36.4%) were the most common findings on per-abdominal examination. Jaundice was seen in 30% patients in this study. Trophozoites of Entamoeba could be visualised on microscopy of pus only in 3 patients however serology for Entamoebahistolytica was positive in 26 cases. Twenty six (96%) patients of amoebic liver abscess required therapeutic drainage in addition to metronidazole for management. 

Among 6 cases of pyogenic liver abscess, 3 patients (50%) presented with isolated liver abscess and 3 patients (50%) had complicated liver abscess. One patient with intra-peritoneal rupture died due to multi organ failure. Causative organisms were grown from pus of all cases. Therapeutic drainage of abscess was done in all patients of pyogenic liver abscess in addition to antibiotics. Consistent with the latest management strategy of minimally invasive drainage techniques, percutaneous needle aspiration was used in most of patients (97%).

Hydatid cyst in liver was diagnosed in 6 patients. Three patients  had isolated liver cysts, 2 had disseminated disease and 1 had ruptured hydatid cyst with multiple cholangiolar abscesses with sepsis. All were treated with albendazole,one patient required surgery in addition to medical management. 

Hepatocellular carcinoma (HCC) accounted for 7 cases in our study. Of these, 4 cases had single lesion, 2 had multifocal HCCwhereas 1 patient had HCC with liver metastasis.  Three patients had underlying chronic hepatitis B infection and oneof them had underlying liver cirrhosis. Two patients had history of chronic alcohol intake. Triple phase CT scan of abdomen was diagnostic of hepatocellular carcinoma in all the cases. 

Hepatic haemangioma were detected as incidental finding in 11 cases, and it constituted 18% of the total cases of benign space occupying lesions in liver. 

Our study found thatamong 109 consecutive patients, benign SOLs were noticed in 57% cases where as tumours and tumour like SOLsconstituted 43%. Liver metastases constituted the highest proportion (33%) followed by amoebic liver abscess (25%). This pattern of occurrence of space occupying lesions in liver has also been reported in the previous Indian series by Mallick et al⁴ and Rizvi et al⁵. However, in the Eastern Hepato-billiary Surgery Hospital series⁶, malignant space occupying lesions accounted for 84% cases. In our study, there is high percentage of cases of liver abscess because most of the patients in our study were having low socioeconomic status along with rural background where the prevalence of liver abscess is high. In a study conducted by Karhunen PJ et al⁷, benign hepatic tumours and tumour like conditions occurred in 52% of the 95 men aged 35-69 years. These results indicate that benign hepatic tumours and tumour like conditions are not rare in men but may remain undetected because of their small size.

Liver metastases were most common in elderly patients in the age group of 5th and 7th decade. Solid organ malignancies were the most common cause of liver metastases (75%) with primary sites including lung cancer (22%), gastric cancer (14%), pancreatic cancer (11%), were commonest. Only 6% patients had liver metastases from an unknown primary site. Mallick et a^l4 reported liver metastases only in 3% of their patients. 

Among 109 patients with SOLs in liver, 33(25%) patients had liver abscess. Among 33 cases, amoebic liver abscess accounted for 27 cases (82%) andpyogenic liver abscess (PLA) accounted for 6 cases (18%).  Liver abscess was most common in the age group of 30-39 years along with mean age 40±8.5 years. Males were more commonly affected than females. The incidence of liver abscess was higher in rural areas because of the paucity of safe drinking water, hygiene and sanitation in rural areas. Smoking (70%) and alcohol (30%) werecommon risk factors for development of liver abscess in our study. In a study by Mukhopadhyay et al⁸ 61% patients gave history of alcohol consumption. In this study jaundice was present in 30% patients. In earlier studies from India, jaundicehas been reported in 45-50% of patients⁹. But after advent of good antimicrobial therapy, it has become less common. Sharma et al¹⁰ reported jaundice in only 13% of patients. Yoo et al¹¹ reported a fall in incidence of jaundice from 25% to 7% from 1970s to 1980s. 

HCC was the cause of liver SOL in 7(6.4%) patients. Mean age of the patients harbouring  HCC in our study was 50±15 years. Many of our patients (57%) were smokers and infection due to HBV (3, 43%) emerged as the single most important factor associated with HCC. This is consistent with other studies from the Indian Subcontinent^12-14. The carrier rate of HBV reported from India is 2-4%15. In 29% of our patients, alcohol has been found as either the sole etiologic agent or in combination with viral hepatitis. Thus, HBV is a much more important carcinogen in Indian patients than in the West, where alcohol and HCV are the leading etiological agents. Serum alphafeto-protein was elevated in 3 patients (43%). Paul SB12 reported elevated alpha fetoprotein above the diagnostic range in 36% of patients of HCC.

Hydatid cyst was found in 6 patients constituting 10% of the total cases of benign space occupying lesions in liver. Most of the cases were in the age group of 40-49 years with mean age of 49±15 years. Hydatid cyst was more common in males (4, 66.6%) than females (2, 33.3%) with male: female ratio of 2:1. Palanivelu et al¹⁶ reported mean age of 38.5 years with male: female ratio of 5:1. Of total 6 patients with hydatid disease in our study, lump abdomen (4), pain abdomen (3%) and jaundice (3%) were main presenting clinical presentations which weresimilar to the other Indian studies on hydatid cyst like by Palanivelu et al¹⁶ and Kayal et al¹⁷. One patient in our study had intra-peritoneal rupture with sepsis and required operative management whereas remaining 5 patients were managed with anthelminthic therapy.

The risk factors for hydatid disease identified in our study were rural inhabitation and smoking, which were identical to findings of previous studies. Most of the population of Himachal Pradesh living in rural areas is indulged in farming for their daily living. A study done in Xinjiang province of People’s Republic of China, found that maximum numbers of cases in farm labourers in rural areas¹¹.  Farming in rural areas of India involves physical labour and working with hands in the soil and contact with livestock. Numerous stray dogs are found here, and hence contamination of soil with dog faeces is a common occurrence¹⁸.

Hepatic hemangiomas were detected in 11 cases, admitted for other reasons, constituting 18% of the total cases of benign space occupying lesions in liver. Most of the hepatic hemangiomas were found in 30-50 years age group with mean age of 51±16 years. Hepatic hemangiomas were found almost equally in males (6, 54.5%) and females (5, 45.4%) with no sex predilection in our study. Schumaker et al²⁰ and Henson et al²⁰ reported higher incidence in females. Our study was conducted only on admitted patients thus many cases of hepatic haemangioma coming in the outpatient department were not included in this study. This may be responsible for the sex differences reported in this study as compared to the other studies conducted on hepatic haemangioma. All patients with hepatic haemangioma were asymptomatic were picked up as an incidental finding on radiological investigations. Tait N et al²¹, studied 61 patients of hepatic haemangioma over a 10-year period. Only 7 patients had symptoms attributable to haemangioma.

In conclusion, ours is the first study of its kind from the Sub-Himalayanregion of India which provides a comprehensive spectrum of liver SOLs and clinical profiles of such patients. 

Abbreviations: SOL (Space Occupying Lesions), ALA ( Amoebic Liver Abscess), HCC (Hepato cellular Carcinoma) ,FNAC (Fine needle aspiration cytology) USG (Ultrasonography)