Synchronous presentation of tuberculosis and hepatocellular carcinoma in a cirrhotic patient: a case report

Background

Tuberculosis (TB) is endemic in India and therefore exists as a virtually universal differential diagnosis. The reactivation of TB is a well-known phenomenon, occurring mostly in the setting of an immunocompromised state. ¹ TB reactivation is difficult to treat and requires more aggressive management. TB reactivation is frequently seen in haematological malignancies, immunocompromised patients, and after TACE and TARE for hepatocellular carcinoma (HCC).^2–4 Cirrhosis from any aetiology puts a patient at increased risk of HCC. With the availability of newer and potent antiviral drugs for hepatitis C, the natural history of these infections may be favourably altered and further progression to cirrhosis, end-stage liver disease and HCC may be halted. The simultaneous occurrence of TB with HCC on the background of hepatitis C virus (HCV) has been rarely reported owing to potent anti-tubercular treatment nowadays.^5–7 We hereby report such a case.

Case report

A 70-year-old man, known to have diabetes mellitus and systemic hypertension, was diagnosed as having hepatitis C genotype 3 related chronic liver disease in April 2018 with a HCV RNA load of 715,600 IU/mL. After 12 weeks of sofosbuvir + velpatasvir treatment, repeat HCV RNA in August 2018 was undetectable. On regular follow-up, he was progressing well until September 2018.

One month later, he presented with chief complaints of decreased appetite and weight loss of approximately 5 kg. There was no history of abdominal pain, fullness, jaundice, altered sleep, fever, decreased urine output, pedal oedema or altered bowel habits. Considering the background of cirrhosis, HCC was our consideration. His general and systemic examination was unremarkable. Investigations are listed in Table 1. A chest radiograph was deemed normal, but an abdominal ultrasound scan showed a hypoechoic lesion (1.2 × 1.2 cm) with surface nodularity in the left hepatic lobe associated with mild splenomegaly.

OPEN IN VIEWER

Table 1.

Laboratory investigation on patient.

Investigated parameter	Value
Haematological investigations
Haemoglobin	123 g/L
White cell counts	5800/mm3
Platelets	1.63/mm3
Biochemical investigations
Blood urea	3.2 mmol/L (normal 2.5–10.7)
Creatinine	61 µmol/L (normal 50–95)
Serum sodium	132 mmol/L
Serum potassium	4.5 mmol/L
Aspartate aminotransferase (AST)	1.17 µkat/L (normal < 0.92)
Alanine aminotransferase (ALT)	0.90 µkat/L (normal < 0.84)
Alkaline phosphatase (ALP)	2.24 µkat/L (normal < 2.51)
Serum total protein	75 g/L
Serum albumin	32 g/L
Total bilirubin	19.7 µmol/L (normal < 22.2)
Microbiological investigations
Anti-hepatitis C virus	Positive
Hepatitis B virus surface antigen	Negative
Serum alpha fetoprotein	7.61 ng/mL (normal < 9.0)

The normal serum alpha fetoprotein warranted further evaluation; so triple phase CT scan was done which showed a well-defined heterogeneous lesion of 2.0 × 1.6 cm in size in liver segment III then with arterial hyper-enhancement and heterogenous enhancement in the venous phase. (Figures 1 and 2), also a well-defined suspicious heterogeneous non-enhancing lesion, 2.0 × 1.6 cm in size, was noted in segment V with caudate lobe hypertrophy of a hypertrophied liver; para-aortic, aortocaval, bilateral external iliac and common iliac lymphadenopathy were seen (Figure 3). Core needle biopsy of segment 3 nodule showed periportal to intralobular chronic inflammation with cores of a tumour arranged as nests, with surrounding necrosis, trabeculae and closely packed pseudoglandular structures lined by polygonal cells with enlarged, vesicular nuclei, prominent nucleoli and abundant granular cytoplasm, with paucity of reticulin within atypical cell foci, all suggestive of well-differentiated HCC on a background of cirrhosis (Figure 4a and 4b). OPEN IN VIEWER

OPEN IN VIEWER

Figure 2.

Left-nodule in segment 3 with hyper-enhancement on arterial phase. Right- a heterogenous non enhancing lesion in segment V with hypertrophy of caudate lobe.

OPEN IN VIEWER

Figure 3.

Right-enlarged para aortic lymph node. Left-non enhancing lesion in segment V.

OPEN IN VIEWER

Figure 4.

(a) Cirrhotic background surrounding areas of infiltrating tumor cells. (b) HCC in the background of cirrhosis. (c) caseous granuloma of segment V of liver. (d, e) caseous granuloma of para aortic LN.

Biopsy from the segment V liver nodule showed multiple granulomas, coalesced into a conglomerate tubercle, with central caseation of epithelioid and Langerhans giant cells, suggestive of TB (Figure 4c). Core left para-aortic needle biopsy showed necrotising granulomatous inflammation with multinucleated giant cells of Langhans type and moderate lymphocytic infiltrate with few histiocytes with no evidence of malignancy (Figure 4d and 4f).

Treatment with radiofrequency ablation of the segment 3 nodule was carried out. Subsequent first line anti-tubercular treatment with isoniazid (300 mg), rifampicin (450 mg), pyrazinamide (750 mg) and ethambutol (800 mg) was continued for two months with consolidation treatment using the first two drugs for a further four months. After the treatment was initiated, the patient’s appetite improved and weight loss was reduced. Blood parameters in February 2019 returned to normal.

Discussion

The moral of our case is that clinicians should not refrain from taking biopsies whenever the clinical, imaging and laboratory investigations do not match. Aggressive treatment of both diseases simultaneously provides a good outcome. Even in the presence of cirrhosis, provided normal baseline liver function pertains, routine first-line anti-tubercular treatment can be safely administered.