Non-Alcoholic Liver Disease Flashcards
Non Alcoholic Fatty Liver Disease
NAFLD and NASH
Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of liver disease in the developed world. It is largely caused by obesity and describes a spectrum of disease ranging from:
steatosis - fat in the liver
steatohepatitis - fat with inflammation, non-alcoholic steatohepatitis (NASH), see below
progressive disease may cause fibrosis and liver cirrhosis
NAFLD is thought to represent the hepatic manifestation of the metabolic syndrome and hence insulin resistance is thought to be the key mechanism leading to steatosis
Non-alcoholic steatohepatitis (NASH) is a term used to describe liver changes similar to those seen in alcoholic hepatitis in the absence of a history of alcohol abuse. It is relatively common and thought to affect around 3-4% of the general population. The progression of disease in patients with NASH may be responsible for a proportion of patients previously labelled as cryptogenic cirrhosis
NAFLD - Associations
Associated factors obesity hyperlipidaemia type 2 diabetes mellitus jejunoileal bypass sudden weight loss/starvation
NAFLD - Features
Features usually asymptomatic hepatomegaly ALT is typically greater than AST (other way round to Alcoholic hepatitis) increased echogenicity on ultrasound
NAFLD - Mx
Management
the mainstay of treatment is lifestyle changes (particularly weight loss) and monitoring
there is ongoing research into the role of gastric banding and insulin-sensitising drugs (e.g. Metformin)
NAFLD - Example Question
A 54-year-old man is referred to gastroenterology clinic by his GP for review following an incidental finding of hepatic steatosis on a recent abdominal ultrasound. The patient had previously presented to the emergency department complaining of recurrent abdominal pain and had been diagnosed with biliary colic following the demonstration of gallstones on ultrasound scan. An elective laparoscopic cholecystectomy was planned in the coming months.
At the clinic, the patient stated that he had researched the details of his ultrasound scan report online and then became concerned about the risk of developing serious liver disease secondary to hepatic steatosis. Between occasional attacks of biliary colic, the patient reported feeling well in himself. Aside from a lifelong tendency to overweight, the patient had no other significant medical history and took no regular medications. In particular, there was no personal or family history of liver disease. The patient consumed only small amounts of alcohol on special occasions and denied having any risk factors for blood-borne viruses.
Physical examination indicated a moderately overweight middle-aged man who appeared generally well. No signs of chronic liver disease were evident on abdominal examination and the patient’s liver was not palpable. Please see below for the results of basic blood tests arranged by the patient’s GP prior to attendance at the clinic.
Haemoglobin 158 g / dL Mean cell volume 95.0 fl White cell count 6.5 x 10>3 / microlitre Platelets 167 x 10>3 / microlitre Urea 5.4 mmol / L Creatinine 98 micromol / L Albumin 48 g / L (reference 35-50) Alkaline phosphatase 93 U / L (reference 35-100) ALT 30 U / L (reference 3-36) Bilirubin 19 micromol / L (reference < 26) Ferritin 185 microgram / L (30-300) International normalised ratio 1.1 (reference 0.8-1.2)
What is the appropriate next investigation to assess the patient’s risk of developing a serious liver disease as a consequence of hepatic steatosis?
MRI liver Liver biopsy > Enhanced liver fibrosis blood test Hepatitis virus antibodies Gamma-GT blood test
The patient has an incidental finding of non-alcoholic fatty liver disease (NAFLD). In a minority of cases, NAFLD progresses to serious liver diseases such as non-alcoholic steatohepatitis, fibrosis or cirrhosis.
NAFLD is known to have a poor prognosis when associated with severe liver fibrosis. Therefore, recent guidelines suggest that individuals with an incidental finding of NAFLD should be offered an enhanced liver fibrosis (ELF) blood test. If the ELF result indicates advanced liver fibrosis ( 10.51) then the individual should receive specialist monitoring and intervention. If the ELF result is negative (< 10.51) then the individual is likely to have a benign prognosis from their NAFLD and can be monitored in primary care. For these individuals, a repeat ELF blood test is recommended every 3 years.
NICE recommends that individuals with NAFLD are encouraged to undertake lifestyle modifications in order to lose weight and to remain within the recommended limits for alcohol consumption. Individuals with NAFLD who are taking statins should be encouraged to continue to do so.
Non Alcoholic Fatty Liver Disease - Ix: Example Question
A 43 year-old man is referred to the outpatient clinic by his GP due to the abnormal results of his liver function tests.
The blood test results are as follows:
Bilirubin 18 µmol/l ALP 95 u/l ALT 124 u/l γGT 54 u/l Albumin 45 g/l
His only other reported symptom is that he has been feeling tired over the last six months. He denies having any pain or weight loss. His past medical history includes hypercholesterolaemia for which he is taking simvastatin. He is on no other regular medication. He drinks 5-10 units of alcohol per day and has a 20 pack-year history. There is no relevant family history.
Examination reveals a BMI of 34 and non-tender hepatomegaly of 1cm below the right costal margin. There are no other significant findings. An abdominal ultrasound scan does not show up any obvious abnormality and liver autoantibody screen is normal.
What is the most appropriate next step in this case?
> Liver biopsy Magnetic Resonance Cholangiopancreatography (MRCP) Computed tomography of the abdomen Percutaneous transhepatic cholangiography (PTC) Endoscopic retrograde cholangiopancreatography (ERCP)
This patient has likely got non-alcoholic fatty liver disease, now present in 20-30% of the general population. Patients often present due to the coincidental findings of abnormal liver function tests and upon more direct questioning can report tiredness and right upper quadrant pain. Ultrasound scan is an appropriate first-line investigation along with autoantibody screen, however, the most specific is liver biopsy which with exclude other causes and assess the stage and prognosis of the disease. In this case, as the liver screen and ultrasound scan have been reported as normal, a liver biopsy would be an appropriate next step, especially as the patient has got a raised Alanine transferase.
NASH - Example Question
A 58-year-old female was referred to the gastroenterology clinic. Her GP had detected on routine blood investigations deranged liver function testing which despite repeated testing was found to be persistent. Her past medical history comprised diabetes mellitus type 2 diagnosed twelve years ago. Unfortunately, this was poorly controlled, despite the use of metformin 500mg TDS, glitazone 160mg OD, pioglitazone 15mg OD, aspirin 75mg OD and Lantus 42 units OD. She also suffered from diabetic nephropathy for which she was using ramipril 10mg OD as well as diabetic retinopathy requiring laser treatment. No other past medical history was noted. She strongly denied consuming alcohol and did not smoke. She admitted to a brief period of intravenous drug use many years ago lasting a few months but as far as she was aware of did not suffer from any sequelae arising from this.
On examination, she was noted to be obese but otherwise systemically well. Blood pressure was recorded as 138/86 mmHg. The cardiovascular and respiratory examination was otherwise normal. Gastrointestinal examination revealed a palpable mass in the right upper quadrant with a smooth border, 3 fingerbreadths from the lower costal margin. There were no other palpable masses and no other stigmata of chronic liver disease. Neurological examination was unremarkable.
Investigations revealed the following:
Hb 141g/l Platelets 212 * 109/l WBC 6.4 * 109/l Na+ 144 mmol/l K+ 3.9 mmol/l Urea 5.8 mmol/l Creatinine 81 µmol/l
Bilirubin 18 µmol/l ALP 74 u/l ALT 162 u/l AST 28 u/l Albumin 34 g/l Calcium 2.12 mmol/l Adjusted calcium 2.38 mmol/l Total protein 76 g/l HbA1c 66 mmol/mol Fasting cholesterol 3.8 mmol/l
HBsAg negative Anti-HBs antibody positive Anti-HBc antibody negative HBeAG negative Anti-HBe antibody negative Anti Hep C antibody negative HIV serology negative
Iron studies normal Copper studies normal ANA positive AMA negative SMA negative
Ultrasound: bright hyper-echogenic image
What is the single most likely diagnosis?
Autoimmune hepatitis > Nonalcoholic steatohepatitis Chronic hepatitis B infection Alcoholic hepatitis Drug induced hepatitis
This lady has developed non-alcoholic steatohepatitis (NASH). She has features of metabolic syndrome with type 2 diabetes, obesity, hypertension and dyslipidaemia. The absence of alcohol consumption would point against the diagnosis of alcoholic hepatitis, and in the presence of a raised ALT relative to AST and a hyperechogenic ultrasound appearance is strongly in keeping with NASH. The hepatitis serology is a red herring; the presence of anti-HBs antibody with otherwise normal serology is in keeping with previous hepatitis B vaccination.
Enhanced Liver Fibrosis Blood Test
Usually an incidental finding of non-alcoholic fatty liver disease (NAFLD), in a minority of cases, NAFLD progresses to serious liver diseases such as non-alcoholic steatohepatitis, fibrosis or cirrhosis.
NAFLD is known to have a poor prognosis when associated with severe liver fibrosis. Therefore, recent guidelines suggest that individuals with an incidental finding of NAFLD should be offered an enhanced liver fibrosis (ELF) blood test. If the ELF result indicates advanced liver fibrosis ( 10.51) then the individual should receive specialist monitoring and intervention. If the ELF result is negative (< 10.51) then the individual is likely to have a benign prognosis from their NAFLD and can be monitored in primary care. For these individuals, a repeat ELF blood test is recommended every 3 years.
NICE recommends that individuals with NAFLD are encouraged to undertake lifestyle modifications in order to lose weight and to remain within the recommended limits for alcohol consumption. Individuals with NAFLD who are taking statins should be encouraged to continue to do so.
NASH
Non-alcoholic steatohepatitis (NASH):
- Features of metabolic syndrome with type 2 diabetes, obesity, hypertension and dyslipidaemia.
Absence of alcohol consumption in the presence of a raised ALT relative to AST and a hyperechogenic ultrasound appearance is strongly in keeping with NASH.
