GP beware – hepatology
Hepatologists Dr Shahid Khan and Dr Tiong Yeng Lim advise on three primary care presentations where the initial diagnosis was more serious than initially appeared.
Mrs P is a 45-year-old lady with a background of hypothyroidism, for which she has been taking levothyroxine for many years. She had been experiencing fatigue, which had worsened over the last six months, and had also started to complain of occasional skin itching. She denied any weight loss, fevers or rigors. Routine blood tests revealed normal TFTs, FBC, renal function and clotting screen. Her LFTs were mildly impaired:
- Bilirubin – 29 umol/l (normal <21)
- Alkaline phosphatase (ALP) – 163IU/l (normal range <130)
- Alanine transferase (ALT) – 30IU/l (normal range <40)
- Albumin 36 (normal >35)
She had also recently been treated for a lower respiratory chest infection with a five-day course of amoxicillin, which she completed two weeks ago. She had not started any other new medications or herbal preparations recently and had no known drug allergies. There was no evidence of chronic liver disease on physical examination.
Initially, the deranged LFTs were attributed to an antibiotic usage. However, her symptoms persisted and her LFTs did not improve when checked two months later. An ultrasound of the abdomen was unremarkable. A non-invasive liver screen found positive anti-mitochondrial antibody and raised immunoglobulins (IgG). Mrs P was then referred to a hepatologist and started on ursodeoxycholic acid. Her liver biochemistry improved, although her symptoms persisted. She was found to have primary biliary cirrhosis on biopsy and is on six-monthly ultrasound surveillance for hepatocellular carcinoma (HCC).
Deranged LFTs secondary to antibiotics.
Primary biliary cirrhosis (PBC).
The patient is in the right age and sex group, with a past medical history of an autoimmune condition. Her pruritus, although non-specific, is also a clue towards PBC.
If symptoms precede a presumed precipitant, such as drugs, be suspicious of other aetiologies. Have a low threshold for performing a non-invasive liver screen.
Mr D is a 50-year-old man with a history of hypertension and diet-controlled diabetes. At a routine check-up, he was found to have deranged LFTs, with an ALT at 59IU/l. His only routine mediation is atenolol 50mg od. He was asymptomatic and drinks a minimal amount of alcohol (less than 10 units a week).
Physical examination was unremarkable, except that Mr D had a BMI of 32kg/m2. His hypertension and diabetes were both well controlled. Non-invasive liver screen was negative for auto-antibodies and viral hepatitis. A fatty liver was confirmed on ultrasound, but the patient was not referred onwards, and instead was kept on annual GP follow-up with monitoring of his LFTs.
Four years later he was reviewed by a different GP, who decided to refer to an outpatient hepatology clinic as the LFTs had never settled. Initially the patient had a scan, which suggested fibrosis, so a liver biopsy was recommended. The biopsy showed high-grade inflammation, or steatohepatitis (NASH), and marked fibrosis. Compared to hepatic steatosis, non-alcoholic steatohepatitis (NASH) has a much higher risk of developing fibrosis and eventual cirrhosis (around 25%), as well as HCC. He was kept under regular hepatology follow-up.
The patient was advised about the importance of managing a tight control of his metabolic syndrome features, as well as losing weight. He was advised to lose about 5% of his body weight over six months, as this often improves not only liver biochemistry and risk of developing severe liver disease, but also the risk of CVD.
Simple fatty liver/hepatic steatosis.
Non-alcoholic steatohepatitis (NASH) with liver fibrosis.
Transaminitis indicates inflammation and this can lead to fibrosis or cirrhosis of the liver.
The diagnosis of NASH, within the context of NAFLD, may necessitate a more aggressive approach in the management of the metabolic risk factors and lifestyle measures to reduce the risk of progression to cirrhosis and HCC.
Mr S is a 55-year-old who complained of mild right upper quadrant (RUQ) pain for the last four weeks. This was dull in nature and not related to meals. He went to see his GP and examination was unremarkable. Routine blood tests, including FBC, renal function and LFTs were normal. An ultrasound picked up a 6mm gall bladder polyp, but no gallstones or features of cholecystitis. The patient’s symptoms spontaneously resolved and no further scans or follow-up were instituted.
Three years later, the patient came back with worsening abdominal pain, weight loss and jaundice. He was admitted to hospital and on further imaging was found to have a gall bladder cancer.
Gall bladder polyp requiring no follow-up.
Pre-malignant gall bladder polyp.
Presence and size of the polyp.
Polyps of the gallbladder are typically incidental findings detected on abdominal ultrasound. Their significance is in their potential for malignant change. A stable-sized gall bladder polyp in sequential ultrasound is reassuring. We recommend follow-up ultrasounds of 5-10mm diameter polyps at six months, and then yearly. Certainly polyps of 6mm and above may be simple cholesterol polyps, adenomas, or even carcinomas. Polyps more than 10mm in diameter should be regarded as potentially malignant and referral for cholecystectomy is generally recommended.
Dr Shahid Khan is a consultant hepatologist and Dr Tiong Yeng Lim is a specialist registrar, both based at Imperial College Healthcare NHS Trust.