ABNORMAL LFT AND HEPATITIS

UKM FAMILY MEDICINE TELECONFERENCE 21 JAN 2014

BY DR NURUL NADIASUPERVISOR: DR NADIAH, PHYSICIAN HOSPITAL

TUANKU JAAFAR SEREMBAN

The aim of this teleconference is to enable the postgraduate trainees to elaborate on the clinical approach to a patient with abnormal liver function test and discuss on the latest development in management of Viral Hepatitis, particularly chronic Hepatitis B and C.

General objectives

1. Know how to approach patients with abnormal liver function test 

2. Be able to discuss the diagnostic tools/methods available for patients with abnormal liver function test (especially for viral hepatitis A, B and C and fatty liver)

3. Be able to identify the various viruses that could cause hepatitis and their peculiar course and prognosis of disease.

4. Be able to outline on the management of patients with fatty liver and hepatitis especially A,B and C.

Specific objectives

Normal values

Liver function test (LFT)

Formed from lysis of red cell Unconjugated bilirubin: bound to albumin,

water insoluble Conjugated bilirubin: water soluble, appears

in urine Parenchymal liver disease, biliary obstruction

LFT- bilirubin

Causes of isolated hyperbilirubinemia

Unconjugated

Increased bilirubin production- Hemolysis- Ineffective erythropoiesis- Blood transfusion- Resorption of hematoma Decreased hepatic uptake- Gilbert’s syndrome- Drugs- rifanpicin Decreased conjugation- Criggler-Najlar syndrome- Physiological jaundice of newborn

Conjugated

Dubin-Johnson Syndrome Rotor’s syndrome

Low level with progressive liver disease reflecting decrease synthesis

Level dependent on nutritional status, catabolism, hormonal factors, urinary/GI losses

Albumin concentration does correlate with prognosis in chronic liver disease

LFT- albumin

LFT- aminotranferases

Aspartate transaminase (AST)

- Found in liver, cardiac muscle, kidneys, brain, pancreas, lungs, leucocytes, red cells

- Less sensitive/specific

Alanine transaminase (ALT)

- Highest concentration in liver

- More specific

Common causes of raised transaminases

Suggested algorithm for evaluating raised transaminases (ALT, alanine transaminase; HAV, hepatitis A virus; HCV, hepatitis C virus; PT, prothrombin time).

Limdi J K , and Hyde G M Postgrad Med J 2003;79:307-312

Copyright © The Fellowship of Postgraduate Medicine. All rights reserved.

LFT- alkaline phosphatase

Mainly from liver and bone Also present in intestine, kidney, placenta,

leucocyte Elevation maybe physiological or

pathological GGT is a good discriminator to identify

source of ↑ALP, rise in liver but not bone disease

Causes of ↑ALP

Physiological

Women in 3rd trimester Adolescent Benign, familial (d/t

↑intestinal ALP)

Pathological

Bile duct obstruction Primary biliary cirrhosis Primary sclerosis

cholangitis Drug induced cholestasis Adult bile ductopenia Metastatic liver disease Bone disease

Suggested algorithm for evaluating a raised ALP (ALP, alkaline phosphatase; ERCP, endoscopic retrograde cholangiopancreatography; GGT, gammaglutamyl transferase; PT,

prothrombin time; MRCP, magnetic resonance cholangiopancreatography).

Limdi J K , and Hyde G M Postgrad Med J 2003;79:307-312

Copyright © The Fellowship of Postgraduate Medicine. All rights reserved.

LFT- gammaglutamyl transferase

Found in hepatocytes and biliary epithelial cells

Sensitive test of hepatobiliary disease Usefulness is limited by lack of specificity Isolated ↑ GGT need to be followed up at

few months interval If still persistent with abnormal AST/ALT

further USS abd/ CT ± liver biopsy may be considered

Causes of raised GGT

LFT- PT / INR

Prothrombin Time

Measures rate of conversion of prothrombin to thrombin

Prolonged in vit K deficiency, warfarin therapy, liver disease, consumptive coagulapathy

Administration of vit K will reduce prolonged PT due to fat malabsorption but not due to intrinsic liver disease

International Normalised Ratio

Recent travel Transfusion Drugs history including herbal Tattoos Unprotected sex Alcohol Occupation Medical hx: DM, obesity, dyslipidemia FHx

History

Stigmata of chronic liver disease: icteric skin/ mucuos membrane, palmar erythema, bruising, spider naevi, gynecomastia

Hepatomegaly Splenomegaly Ascites Obesity Any clues to the underlying cause e.g.

lymphadenopathy Features suggestive of hepatic encephalopathy

Examination

1. Unexplained liver abnormalities >1.5 time normal on 2 occasions, minimum of 6months apart

2. Unexplained liver disease with evidence of hepatic dysfunction

3. Known liver disease where treatment beyond withdrawal of the implicating agent is required

Abnormal LFT- when to refer

1. Viral hepatitis screening2. Antinuclear antibody3. Ceruloplasmin in <40y4. Iron studies5. Ultrasound of the liver especially suspected

fatty liver

Tests to do before referal

Acute liver infection caused by a hepatovirus of the Picornavirus family hepatitis A virus

2nd most common vaccine preventable infection Most common form of viral hepatitis Associated with poor hygiene and overcrowding HAV is shed in stool of infected persons, can survive

for weeks, can persist on hands for several hours and longer in food kept in room temperature, resistant to heat/freezing

Transmission is via fecal/oral route, and can occur through direct person-person contact, occasional transmission through sexual contact and blood transfusion

Hepatitis A

Incubation period: 15-50 days Childhood infection is usually asymptomatic

but in adult 75% develop icteric disease 4-10days of prodromal symptoms: fever,

malaise, nausea, vomiting, weakness, anorexia

Acute infection manifest as dark urine, followed by jaundice and pale stool 1-2 days later with gradual resolution of other symptoms

Malaise and anorexia may persist, hepatic discomfort and pruritus

LFT usually normalise within a month Complications are unusual but rarely include

fulminant hepatitis Chronic infection doesn’t occur but 10%

have prolonged or relapsing symptoms over6-9 months

Detection of anti HAV IgM in acute phase May from 3-6months after acute illness Anti HAV IgG indicates past infection or

immunisation and likely to persist for life

Hepatitis A - diagnosis

No specific Rx Supportive measures Usually with complete recovery

Hepatitis A - treatment

Vaccine is recommended especially for travelers in endemic area

Education on hygiene and food and water precaution

Hepatitis A - prevention

Globally estimated 350mil persons chronically infected by hepatitis B virus

Prevalence decrease with vaccination HBV is transmitted in blood and secretions

infectious outside the body >7days Commonly acquired from infected mother

(vertical transmission) or from family members (horizontal transmission)

Hepatitis B

Double stranded DNA hepadnavirus HBV genome produces nucleocapsid

contains hepatitis B core antigen (HBcAg) Has outer envelope called hepatitis B surface

antigen (HBsAg) *for screening A segment of HBcAg results in production of

hepatitis B e antigen (HBeAg) associated with viral replication and high infectivity

HBV

Hepatitis B- diagnosis

Evaluation of patient’s blood

1. HBcAg2. HBsAg3. HBeAg4. HBV DNA5. General liver

investigations

Liver biopsy- measure inflammation (current activity) and fibrosis (more chronic scarring)

Acute infection may cause nonspecific symptoms: fatigue, poor appetite, nausea, vomiting, abdominal pain, low grade fever, jaundice, dark urine

Physical exam: hepatomegaly, splenomegaly, liver tenderness

Typically last 2-4 months Infants, child <5y, immunosuppressed adults usually

asymptomatic In adult with healthy immune system, 95% of acute

infection is self-limited and developed immunity <5% progress to chronic infection

Acute hepatitis B

Chronic necroinflammatory disease persists longer than 6 months

Can be divided into HBeAg positive or negative

Risk inversely related to age Occult HBV infection maybe reactivated by

chemotherapy or immunosupressant Coinfection with HIV and HCV

Chronic hepatitis B

Inactive HBsAg carrier state= persistent HBV infection of the liver without significant ongoing necroinflammatory disease

Treatment

To reduce inflammation of the liver Prevent liver failure and cirrhosis Reduce risk of hepatocellular carcinoma by

suppressing HBV replication Treatment is based on phase of infection Finite course of interferon therapy or long

term viral suppression with neucloside/nucleotide analogue

Hepatitis C

Leading cause for chronic liver disease Principal cause of death from liver disease

and leading indication for liver transplant in the US

Caused by hepatitis C virus single-stranded RNA virus

Transmitted through percutaneous exposure of infected blood

No vaccine

Most patients are asymptomatic Nonspecific symptoms: fatigue, nausea,

anorexia, myalgia, arthralgia, weakness, weight loss

Chronic infection leads to cirrhosis, increased risk of complication of liver disease: portal hypertension, ascites, hemorrhage, hepatocellular carcinoma

Factors associated with disease progression to cirrhosis

1. Male2. Age >403. HIV or HBV coinfection4. Immunosupression5. Alcohol intake6. Hepatotoxic drugs

 Natural history of hepatitis C virus infection.

Lo Re V , and Kostman J R Postgrad Med J 2005;81:376-382

Copyright © The Fellowship of Postgraduate Medicine. All rights reserved.

HCV antibody enzyme immunoassay Recombinant immunoblot assay

(confirmatory test) Quantitative HCV RNA PCR Liver biopsy

Diagnosis

Treatment

To slow or stop progression of fibrosis prevent complications and death recommended treatment: combination of

pegylated interferon alfa and ribavirin Sustained virologic response used to

evaluate effectiveness of therapy

Non alcoholic fatty liver disease (NAFLD)

Definition1. evidence of hepatic steatosis by imaging or

histology2. No causes for secondary hepatic fat

accumulation3. Lack of alcohol consumption- <21 drinks per week in men- <14 in women

NAFLD

Histologically can be divided into 1. Nonalcoholic fatty liver (NAFL) = presence

of hepatic steatosis with no evidence of hepatocellular injury

2. Nonalcoholic steatohepatitis (NASH)= presence of hepatic steatosis and inflammation with hepatocyte injury with/without fibrosis

Treating liver disease and associated co-morbidities mainly for NASH

To reduce aminotranferases and improve hepatic steatosis

Lifestyle modification 1. Diet - hypocaloric2. Exercise 3. Weight loss

NAFLD - Management

Metformin Thiazolidinediones Vitamin E- Decrease in aminotransferases- Improve in steatosis, inflammation,

ballooning and resolution of steatohepatitis- No effect on hepatic fibrosis

Ursodeoxycholic acid (UCDA), omega-3 fatty acids

Bariartric surgery Statins are safe in patients with liver disease

to treat dyslipidemia Reduce alcohol consumption

 Treatment algorithm for NAFLD.

Adams L A , and Angulo P Postgrad Med J 2006;82:315-322

Copyright © The Fellowship of Postgraduate Medicine. All rights reserved.

A 45 year-old lady comes for follow up for her Diabetes, Dyslipidaemia and Hypertension. She is asymptomatic. She is on Diamicron 80mg bd , Enalapril 10mg bd and Lovastatin 20mg ON, which she was on since 1 year ago. Her latest blood result shows HbA1c is 7%, FSL: TG is 2.1mmol/l , HDL is 1.0 mmol/l, LDL 4.1 mmol/l. Her liver function test shows ALT 66 iU/L (previously was 74). Other parameters in the liver function test are normal. How would you manage her?

Case scenario 1

A 30 year old man presents to the casualty with nausea, vomiting and general malaise for the past 4 days. Clinically he is jaundice with tender right upper quadrant. Proceed with your management.

Case scenario 2

Thank you!