This case presentation describes a 60-year-old male with hepatitis C and hypertension who presented with fever, weight loss, and right upper quadrant pain. Imaging revealed a large liver lesion consistent with hepatocellular carcinoma. The patient underwent transarterial chemoembolization (TACE) and was discharged with medications. TACE involves selectively delivering chemotherapy to the tumor along with arterial embolization. The patient will follow up in one week.

1. Case Presentation
By: Dr. Noshirwan P. Gazder
FCPS TRAINEE YEAR 1

2. History
60 year old male known case of Hypertension for the last 8 years, Pan
Consumer , H/o Hepatitis C came via ER with complaints of:
• Fever for 1 month
• Right Upper Quadrant Pain for around 2 weeks
• History of 4 kg weight loss in the last 3 months

3. History of Presenting Complains
• As per my patient he was in his usual state of health when he developed Fever
for 1 month. The fever was documented at 100 F which was intermittent,
gradual in onset, occasionally associated with chills. He also gave complaints
that he would break out into sweats at night. Fever was relieved by taking
paracetamol. He gave complaints of on and off nausea with decreased appetite
for the last one month and gave history of 4 kgs weight loss within a period of 3
months. He had no ear discharge, cough, diarrhea or urinary complaints.
• For about 2 weeks however, he had developed Right upper quadrant pain, pain
was sudden in onset, gnawing in character, non-radiating, associated with no
aggravating factors. It was usually limited for about 6 to 8 hours and would then
improve eventually on its own.
• He had shown himself in a local clinic 1 week back, where the doctor assumed
he was having typhoid and was started on oral ciprofloxacin. That showed no
improvement.

4. • Past Medical History:
- Hypertensive for the last 8 years, Compliant to meds.
- Chronic Hepatitis C Treated with DAA (Direct Acting AntiVirals: Sofosbuvir / Velpatasvir) in 2018 for
3 months- ETR was achieved then lost to follow up.
- No H/o previous hospital admissions.
• Past Surgical History:
• H/o blood transfusion around 30 years ago, as he underwent an RTA and had fractured his Left Femur
and was operated on the same leg as well. Name of Procedure was unknown; No record was
available.
• Family history:
No history of Ischemic heart disease, tuberculosis, asthma, thyroid disorders, autoimmune diseases or cancers
in the family
• Travel history: No recent travel from Karachi

5. Drug History:
• Tab. Amlodipine 5 mg 1+0+0
• Tab. Rosuvastatin 10 mg 0+0+1
• Cap. Omeprazole 40 mg 1+0+0 (30 mins before breakfast)
• Started on Ciprofloxacin 500 mg 1+0+1 by local clinic doctor 1 week
back.

6. Personal History:
- Regular Tobacco Pan Consumer; No h/o drug use, smoking or alcohol consumption.
- Appetite: Decreased
- 4 kgs weight loss within a period of 3months
- Sleep: Normal
- Micturition: Normal
Social History:
He is a resident of North Nazimabad. Office worker by profession. He Lives in a 2 room house with his
wife and sons. Drinks boiled water and eats mostly meals cooked at home. No contact history of tuberculosis.
No pets or birds in his house.

7. System Review
Respiratory System
•SOB/Dyspnoea
•Sputum
•Haemoptysis
•Chest pain
•Hoarseness
•Wheezing
Cardiovascular
•Chest pain
•Paroxysmal Nocturnal Dyspnoea
•Orthopnoea
•Short Of Breath(SOB)
•Palpitations
•Cyanosis
Gastrointestinal/Alimentary
•Nausea/vomiting
•Abdominal pain
•Oral ulcers
•Regurgitation/heart burn
•Haematemesis, melaena,
haematochagia
•Jaundice
Nervous System
•Speech problem
•Head ache
•Seizures
•Visual/Smell/Taste/Hearing
problem
•Abnormal sensation
•Change of behaviour
-ve
-ve
-ve
-ve

8. System Review
Urinary System
•Back Loin Pain
•Urgency
•Hesitancy
•Terminal dribbling
•Nocturia
•Incontinence
•Character of urine
Musculoskeletal System
•Back plus neck pain
Radiating from occiput
•Swelling
•Red eyes
•Deformities
•Skin rash
•Painful/ cold fingers
Endocrine System
•Swelling in neck
•Fatigue
•Thirst
•Sweating
-ve
-ve
-ve
HEMATALOGICAL System
•Bruises
•Epistaxis
•Lumps
•Gum bleeding
-ve

9. Examination:
• General Impression:
A 60 year old male, lying on bed comfortably, oriented to time, place and
person.
Vitals:
• Blood Pressure:110/80 mm/Hg
• Pulse: 98/min, regular
• Temperature: 100 F
• Respiratory Rate: 19 breaths/min
• Oxygen saturation: 98 % on room air
-Weight 54kg , Height: 170cm BMI: 18.6 kg/m2

10. Examination:
HEENT:
Normocephalic, atraumatic, no bruises
Nose, mouth,pharynx,ears WNL
EYE: No Anemia/ Jaundice , VA:6/6, reactive to light, EOMI
NECK:
Supple, no lymphadenopathy, No JVD, swelling in neck or carotid bruit
HEART:
Normal S1 and S2, no murmurs, rubs or gallops.
CHEST:
No tenderness, clear breath sounds bilaterally, no rales, wheezes or ronchi, trachea central, tactile fremitus
normal.
ABDOMEN:
No scar marks, Tender in Right hypogastrium upto epigastrium, Tip of spleen palpable, No other organomegaly, -ve Murphys
sign, -ve for Renal punch, -ve fluid thrill , bowel sounds were audible.
NEURO:
Mental status: alert, Cranial nerves:Intact, Motor: 5/5 upper and lower extremities. Sensory: intact to touch
and pinprick. DTRs: 2+ symmetric in upper and lower extremities, - babinski. Cerebellar: Intact
EXTREMITIES:
No clubbing, cyanosis or edema. Pulses 2+ and symmetric. No tremors.
MUSCLOSKELETAL:
No warmth or erythema, no tenderness, normal range of motion, motor/sensory/reflexes, pulsations
LYMPHNODES:
Axillary, Groin were not palpable.

11. Differential Diagnosis
• Liver Abscess
• Cholecystitis / Cholangitis
• Viral Fever
• Pancreatitis
• Typhoid
• Malignancy
• Viral Hepatitis

12. INVESTIGATIONS:

13. CXR

14. U/S Abdomen

15. Patient was admitted under Gastroenterology services who started the
patient on:
• Inj. Drotaverine 40 mg IV 12 hrly
• Inj. Paracetemol 1 gm IV SOS
• Tab. Mebeverine 135 mg 1+1+1
• Tab. Amlodipine 5 mg 1+0+0
• Tab. Rosuvastatin 10 mg 0+0+1
• Cap. Omeprazole 40 mg 1+0+0 (30 mins before breakfast)
• CT Triphasic was advised, along with Alpha Feto Protein and PT/INR

16. CT TRIPHASIC

17. • PT / INR: 13.6/1.33
• Alpha Feto Protein: 7199.14 ng/ml ( <15 ng/ml)
• HCV RNA PCR QUALITATIVE: Negative For SVR-1
• CHILD CLASS: Class A

18. • Review was given to Interventional Radiologist, who after reviewing
CT report advised patient to undergo TACE.
• TACE was performed using Epirubicin(Anthracyclines) and Lipiodol
(selective uptake and retention in hyperarterialyzed liver tumors)
• No Post-Procedure complications were noted.

19. The Patient was subsequently discharged on
• Tab. Amoxicillin / Clavulanic acid 625 mg 1+1+1 for 7 days
• Tab. Amlodipine 5 mg 1+0+0
• Tab. Rosuvastatin 10 mg 0+0+1
• Tab. Mebeverine 135 mg 1+1+1
• Tab. Domperidone 10 mg 1+1+1
• Syp. Lactulose 30 ml 0+0+1
• Tab. Paracetomol 2 Tabs SOS
• Cap. Omeprazole 40 mg 1+0+0 (30 mins before breakfast)
• Was advised OPD F/U in one week

20. Hepatocellular Carcinoma

21. • Hepatocellular carcinoma (HCC) is a primary tumor of the liver that usually
develops in the setting of chronic liver disease, particularly in patients with
cirrhosis due to alcohol use, chronic hepatitis B or C virus infections, or
nonalcohol-associated steatohepatitis (NASH).
• HCC is the fourth leading cause of cancer-related deaths in the world according to
the World Health Organization, and the most rapidly growing cause of cancer
deaths in the United States.
• The prognosis of patients with this tumor remains poor, with a five-year survival
rate of 18 percent.

22. Sequence of cellular lesions in liver leading to the
development of hepatocellular carcinoma

23. CLINICAL FEATURES
• Most patients are asymptomatic until late stages of the disease.
• The majority of HCC cases occur in the setting of chronic liver disease.
• Among patients with more advanced liver disease, symptoms and physical findings are
often due to underlying cirrhosis rather than the tumor itself. Such as features of liver
decompensation (eg, variceal bleeding or ascites) due to the extension of HCC into the
hepatic or portal veins as the initial manifestation of the tumor.

24. Symptomatic Patients
Patients with advanced lesions may present with mild to moderate upper abdominal
pain, weight loss, early satiety, or a palpable mass in the upper abdomen.
• Hypoglycemia: usually occurs in advanced HCC, is thought to result from the
tumor's high metabolic needs. Less than 5 percent of tumors secrete insulin-like
growth factor-II, which can cause severe, symptomatic hypoglycemia sometimes
early in the course of the disease.
• Erythrocytosis: tumor secretion of erythropoietin (EPO).
• Hypercalcemia: Seen in association with osteolytic metastases, but it may also be
seen in the absence of bony metastasis due to secretion of parathyroid hormone.
• Diarrhea: Patients with HCC may infrequently present with intractable diarrhea and
associated electrolyte disturbances (eg, hyponatremia, hypokalemia, metabolic
alkalosis). Its related to secretion of peptides that cause intestinal secretion. These
include vasoactive intestinal polypeptide, gastrin, and peptides with prostaglandin-
like immunoreactivity

25. • Intraperitoneal bleeding: Can occur due to tumor rupture, Tumor rupture is often
associated with sudden onset of severe abdominal pain with distension, an acute drop in
the hemoglobin and hypotension, and is most commonly diagnosed by abdominal
imaging.
• Tumor rupture is a life-threatening complication, and control of bleeding may require
emergent angiography and embolization of the bleeding vessel, or surgery.
• Extrahepatic metastases: For patients who do not undergo surveillance, extrahepatic
metastases are present at the time of diagnosis in approximately 10 to 15 percent of
cases. Extrahepatic metastases are more common in patients with advanced stage
primary tumors (>5 cm, large vessel vascular invasion).
• The most common sites of extrahepatic metastases are lung, intra-abdominal lymph
nodes, bone, and adrenal gland, in that order. Brain metastases are rare overall (0.2 to 2
percent).

26. Serum Markers
• Alpha-fetoprotein: The most commonly used serum marker for HCC is
serum alpha-fetoprotein (AFP) concentration. AFP is a glycoprotein that is
normally produced during gestation by the fetal liver and yolk sac, and the
serum concentration can be elevated in patients with HCC.
• When elevated, the AFP is 75-91% specific, and values greater than 400
ng/mL are generally considered diagnostic of HCC in the proper clinical
context, including appropriate radiologic findings.
• Serum levels of AFP are typically higher for advanced HCC compared to
early HCC, but overall, AFP levels do not correlate well with the clinical
features of the tumor.
The differential diagnosis of an elevated AFP includes the following:
• Elevated serum AFP may be seen in patients with chronic liver disease such as acute or
chronic viral hepatitis, but without HCC.
• Elevated serum AFP also occurs in pregnancy, with tumors of gonadal origin (both germ cell
and non-germ cell) and in a variety of other malignancies, of which gastric cancer is the most
common.

27. • For patients at high risk for developing HCC, the diagnosis can be
made with dynamic contrast-enhanced computed tomography (CT) or
magnetic resonance imaging (MRI) tailored for liver lesion evaluation.
• If the lesion demonstrates specific imaging characteristics, a diagnosis
of HCC can be made radiographically, avoiding the need for a biopsy.
• High-risk patients are candidates for surveillance. This includes most
patients with cirrhosis and subsets of those with chronic hepatitis B
virus infection.
• Diagnostic approach to a solid liver lesion in a high-risk patient is
determined initially by the size of the lesion, as detected on
surveillance US.
DIAGNOSTIC APPROACH

29. IMAGING
• HCC can be diagnosed on contrast-enhanced computed tomography (CT),
magnetic resonance imaging (MRI), or ultrasound (US).
• In most high-risk patients, HCC can frequently be diagnosed on imaging
alone, avoiding the need for biopsy. These are categorized as LR-5 in
the Liver Imaging Reporting and Data System (LI-RADS) for high risk
patients.
• The choice of modality should be individualized based on available scanner
technology, imaging expertise, and patient contraindications and
preferences. Contrast-enhanced CT, MRI, or US are all sufficiently accurate
to diagnose HCC. Very few false positive diagnoses are observed with any
of these modalities if the diagnostic criteria are rigorously applied.

30. Diagnosis on CT or MRI — For a lesion to be considered suspicious for HCC (in a
non-high risk patient) or definitely HCC or LR-5 (in a high-risk patient), it should be
≥1 cm and demonstrate non-rim arterial phase hyperenhancement relative to the
liver parenchyma. In addition, the following features are assessed:
• Non-peripheral washout appearance – Hypoenhancement when compared to
liver in portal venous or delayed phase of contrast administration
• Enhancing capsule appearance – Smooth border around most or all of the lesion
that enhances visibly in the portal venous or delayed phase of contrast
administration
• Growth – ≥50 percent increase in size in ≤6 months (a threshold of ≥5 mm
increase in size is recommended to ensure that the change represents biological
growth and not measurement error). Assessment of growth cannot be made
comparing the CT or MRI to a prior US or CEUS.

33. Treatment
• Using tumor stage to select treatment is complicated by the fact that
many of the staging systems (including the Tumor, Node, Metastasis
[TNM] staging system of the combined American Joint Committee on
Cancer [AJCC]/Union for International Cancer Control [UICC]) are
based upon surgical findings and do not incorporate other important
factors, such as underlying liver dysfunction and performance status.
• The Barcelona Clinic Liver Cancer (BCLC) staging system has been a
dominant approach to HCC, particularly outside of the United States.
The BCLC classifies patients with HCC into four categories: early,
intermediate, advanced, and terminal.

37. Radiofrequency ablation (RFA)
• In this method, heat is generated by passing electrical current
through the tumor and surrounding tissues.
• The technique is limited in large lesions because of difficulty passing
electrical current through desiccated tissue that has high impedance.
• The 5-year survival is 70%.
• RFA is generally avoided in subcapsular lesions, as there is an
increased risk of peritoneal seeding.Outcomes in patients with
solitary HCC <2 cm treated with RFA are similar to surgical resection.

40. Transarterial chemoembolization (TACE)
• Selective arterial embolization combined with selective injection of a
chemotherapeutic agent (doxorubicin, cisplatin) mixed with a contrast
agent.
• Improves survival in patients with intermediate stage HCC. 1-year
survival: 80%; 2-year survival: 60%.
• Contraindications: portal vein thrombosis, extrahepatic spread.
• Complications: Nausea, vomiting, abdominal pain.Post-embolization
syndrome (fever, abdominal pain, and ileus) Treatment is supportive.

42. Chemotherapy agents used in TACE:
• Doxorubicin: Slows or stops the growth of cancer cells by blocking an
enzyme called topo isomerase 2 (which is needed for cancer cells to
divide and grow)
• Cisplatin: Binds to the N7 reactive center on purine residues and can
cause DNA damage in cancer cells, blocking cell division and resulting
in apoptotic cell death.

43. • TACE is a treatment, not a cure. Approximately 70 percent of the
patients will see improvement in the liver and, depending on the type
of liver cancer, it may improve survival rates and quality of life.

44. • Atezolizumab-Bevacizumab: Atezolizumab, a Programmed Death
Ligand ( PD-L1) monoclonal antibody, plus bevacizumab, an anti-VEGF
monoclonal antibody, (atezo/bev) has become a new standard-of-care
as the first-line therapy for patients with advanced hepatocellular
carcinoma (HCC).
• Durvalumab-Tremelimumab: Durvalumab (blocks the interaction of
PD-L1 with PD-1), Tremelimumab (stimulates immune system to attack
tumor cells by inhibiting a protein molecule called cytotoxic T
lymphocyte associated 4 (CTLA-4) on immune cells).
• Sorafenib: Exerts its action through inhibition of several kinases
involved in both tumour cell proliferation and angiogenesis.

48. Thank You