A INTERESTING CASE OF

HEPATOMEGALY

A. KARTHICK RAMALINGAM

PROF. P. VIJAYARAGHAVAN’S UNIT

37 Year old Mrs. Lakshmi was admitted with

C/o Abdomen distension - 3 months

Abdomen Pain - 3 months

HOPI:

Patient was apparently normal till 3 months ago after which she developed abdomen distension insidious onset , increasing in size , uniform abdomen distension

Abdomen distension not associated with Oliguria , pedal edema , facial puffiness, chest pain ,palpitation.

Dyspnoea – insidious onset , progressive , grade II was present.

Abdomen pain – right hypochondrium, dull aching type pain, continuous, aggravated by lying on right side & deep inspiration .

H/O jaundice -3 months, yellow coloured urine , no clay coloured stools , no pruritis

No LOW LOA+ No fever, bleeding tendencies, altered sleep Past H/o

Hypothyroid – 8 months—on thyroxine -75 mcg

No other co morbid illness

Personal H/O

No Habituations Menstrual and marital H/O

amennorhea-8 months

3 Children Treatment H/o

No H/o chronic drug intake other than thyroxine

General Examination Conscoius Oriented obesity Afebrile

Icteric pale Facial puffiness Dry skin Hoarse voice

BP:110/70 mmHg PR:86/min JVP not Raised BMI 26.93kg/sq m

P/A uniform distension Skin normal Hepatomegaly present

17 cm below right costal margin

tender , nodular surface, firm in consistency , no bruit

No splenomegaly. No Free fluid Other systems normal

Differential Diagnosis

Infective cause HCC Haematological malignancy Amyloidosis

InvestigationsCBC

Hb 6 gm%

TC 9600cells/dl

DC P68 L29 E3

ESR 28/60

MCV 79.5 fl

MCHC 28.3

RBS 101 mg/dl

UREA 22 mg/dl

Creatinine 0.7 mg /dl

Na 147

K 2.9

HCO3 21

Cl 100

LFT

T.Bilirubin 2.5

SGOT 48

SGPT 22

ALP 148

T.Protein 6.5

Globulin 3.2

albumin 3.3

PT 19 sec

INR 1.9

Peripheral smear:

Normocytic Normochromic anemia

Free T4 0.3 ng/dl

TSH 72.5mic IU/ml

Urine

Alb Nil

Sug Nil

Dep 0-2 Pus cell/hpf

USG Abdomen: Hepatomegaly with fatty infiltration. Portal Vein 15 mm. normal flow Splenomegaly 14 cm

CECT Abdomen Liver enlarged – 24 cm. Diffusely

hypodense area of altered density seen in segment 5/8

GB contracted Spleen 15 cm enlarged IMP: Fatty liver with hepatomegaly.

Areas of altered density noted in segments 5/8 of right of liver

P.V Doppler

Liver increased in echoes ,enlarged.

portal vein 1 cm at the hilum .(Flow +)

Portal vein 1.4 cm at the confluence of splenic and SM vein

Velocity 18.87 cm/s

Hepatopedal flow+

Hepatic veins flow + Spleen 14.4 cm enlarged .

Splenic Vein 17 cm at the hilum

IMPRESSION Hepatosplenomegaly with Fatty liver

Blood for QBC – Negative HBsAg -- Negative Anti HCV – Negative HIV I & II – Negative AFP – not elevated

T. Cholesterol 174 mg/dl

HDL 32 mg/dl

LDL 120 mg/dl

VLDL 22 mg/dl

TGL 109 mg/dl

OGD: Lax OGJ . Otherwise normal

ECHO- Normal

NAFLD score Age, BMI, hyperglycemia, AST/ALT ratio,

platelet count, and serum albumin level Score =0.915

< -1.455: predictor of absence of significant fibrosis (F0-F2 fibrosis)(negative predictive value of 93%)≤ -1.455 to ≤ 0.675: indeterminate score> 0.675: predictor of presence of significant fibrosis (F3-F4 fibrosis)(positive predictive value of 90% )

Formula : -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 ×

IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio – 0.013 × platelet (×109/l) – 0.66 × albumin (g/dl)

ANA -- Negative S.Ceruloplasmin 20.5mg/dl(18-35mg/dl) S . Iron 23.8 mcg/dl(50-150 mcg/dl) TIBC 283 mcg/dl(300-360mcg/dl) Ferritin 21.04 ng/dl (50-200mcg/dl)

Final diagnosis

Non alcoholic steatohepatitis Pre -Obesity Hypothyroidism Nutritional anemia

Treatment given

Thyroxine dose increased to 125 mcg/day

T.vitamin E 400mg twice a day FST 100 mg twice a day

At dischargeCBC

Hb 11.8 gm%

TC 8000

DC P80 L20

ESR 4/10

Platelet 2.5 lakh

TSH 39.98mIU/ml

Patient is now on thyroxine 150 mcg/day

DISCUSSION

NAFLD

a) There is evidence of hepatic steatosis , either by imaging or by histology.

b)There is no causes for secondary hepatic fat accumulation such as alcohol consumption , use of steatogenic drugs or hereditary disorders.

NAFL

The presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes

NASH

The presence of hepatic steatosis and inflammation with hepatocyte injury(ballooning) with or without fibrosis

Prevalence : NAFLD 6.3 to 33%(median -20%) NASH 3 to 5 %

High risk groups Type 2 Diabetes Mellitus Obesity Dyslipedemia Metabolic syndrome

Emerging Risk factors

PCOD Hypothyroidism Obstructive sleep apnea Hypopituitarism Hypogonadism Pancreatoduodenal resection

What is significant alcohol consumption for eligibility for NASH in clinical practice

>21 drinks per week in men >14 drinks per week in women

over a period of 2 years before baseline histology

When to evaluate incidentally discovered hepatic steatosis

Unsuspected hepatic steatosis detected on imaging have symptoms or signs attributable to liver disease or have abnormal liver biochemistries – should be evaluated as for NAFLD

Screening for high risk groups ?

Not recommended

Non invasive methods to assess steatohepatitis S.Aminotransferase, USG ,CT,MR donot

reliably assess steatohepatitis and fibrosis in patients with NAFLD.

Liver biopsy is the most reliable approach

Non invaisve approaches include

a) NAFLD fibrosis score

b)Enhanced fibrosis score

c)Transient elastography

When to do biposy ?

Those who are increased risk to have steatohepaitis and advanced fibrosis.

( NAFLD score , metabolic syndrome can be used to predict risk)

Competing etiologies for hepatic steatosis and co existing chronic liver disease cannot be excluded without a liver biopsy

Management

Loss of 3 to 5 % weight loss improves steatosis ,loss of 5 to 10 % improves necroinflammtion

Metformin is not recommended as a specific treatment for liver disease in adults with NASH

Vitamin E 800IU/day improves liver histology in biopsy proven NASH. Considered as first line therapy in this population

Statins should not be used specifically to treat NASH. Can be used in dyslipedemia.

UDCA is not recommended

Hypothyroidism and NASH Journal of Clinical Gastroenterology: October 2003 - Volume 37 - Issue 4 - pp 340-343 Liver, Pancreas, and Biliary Tract: Clinical Research

Is Hypothyroidism a Risk Factor for Non-Alcoholic Steatohepatitis?

Liangpunsakul, Suthat MD; Chalasani, Naga MD Abstract Purpose: Thyroid hormones play an important role in the regulation of lipid and

carbohydrate metabolism, both of which are affected in patients with non-alcoholic steatohepatitis (NASH). Anecdotally, we have observed that a number of patients with NASH carried a diagnosis of hypothyroidism. However, it is unknown if thyroid dysfunction plays any role in the pathogenesis of NASH. To further investigate this observation, we conducted a case-control study to determine the association between hypothyroidism and NASH

Conclusion: These data suggest that hypothyroidism is associated with human NASH. Further research is needed to confirm this finding and to understand its implications.

Dig Dis Sci. 2012 Feb;57(2):528-34. doi: 10.1007/s10620-011-2006-2. Epub 2011 Dec 20.

Prevalence of hypothyroidism in nonalcoholic fatty liver disease.

Pagadala MR, Zein CO, Dasarathy S, Yerian LM, Lopez R, McCullough AJ. Source Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, USA.

Abstract BACKGROUND: A possible association between nonalcoholic fatty liver disease (NAFLD) and hypothyroidism has

been suggested. The recognized link between hypothyroidism and elements of the metabolic syndrome may explain this association.

AIM: The purpose of this study was to determine the prevalence of hypothyroidism in a cohort of

patients with NAFLD and analyze the potential factors associated with hypothyroidism in this patient population.

CONCLUSIONS: A higher prevalence of hypothyroidism was demonstrated in patients with NAFLD

compared to controls. Among subjects with NALFD, female gender, increased BMI and history of abstinence from alcohol were associated with hypothyroidism. Patients with hypothyroidism were also more likely to have NASH

Hypothyroidism and NASH

Hypothyroidism and anaemia Anaemia is seen in 1/3 to ½ patients with

hypothyroidism Usually mild to moderate , lower levels do occur Anaemia can be microcytic , normocytic ,

macrocytic. Aneamia of chronic disease is the most common(normocytc normochromic) .

Microcytosis occurs in the setting of mennorhagia

Macrocytosis can be seen even without anaemia . Overt macrocytosis suggest perinicious anaemia or folate deficiency

Thank you