A listless 45-year-old man

Published on 10/04/2015 by admin

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Last modified 22/04/2025

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Problem 54 A listless 45-year-old man

You arrange some further blood tests. The results are as follows:

Investigation 54.1 Summary of results

White cell count 7.3 × 109/L  
Haemoglobin 13.5 g/dL  
Platelets 100 × 109/L  
INR 1.3  
Sodium 138 mmol/L  
Potassium 4.3 mmol/L  
Bicarbonate 24 mmol/L  
Urea 4.6 mmol/L  
Creatinine 67 mmol/L  
Glucose 5.6 mmol/L  
Cholesterol 3.1 mmol/L  
Calcium 2.23 mmol/L  
Phosphate 0.88 mmol/L  
Total protein 65 g/L  
Albumin 43 g/L  
Globulin 22 g/L  
ALP 172 U/L  
Bilirubin 20 mmol/L  
AST 148 U/L  
ALT 136 U/L  
GGT 132 U/L  
Autoimmune profile Negative  
IgG 16.8  
IgA 3.9  
IgM 1.3  
Thyroid function Free T4: 18.1 TSH: 3.5

The following tests are now available:

Investigation 54.2 Summary of results

Hepatitis B surface antigen Negative
Hepatitis C IgG Positive
Hepatitis C PCR Positive with a viral load of 1 324 000 IU/mL

You review him in the outpatient clinic to discuss the results with him.

This patient underwent an ultrasound scan which shows a slightly fatty looking liver and normal sized spleen. Doppler studies of his portal vein shows normal flow. He went on to have a liver biopsy which confirms moderate inflammation and established cirrhosis.

He is found to be genotype 1 and commences a course of interferon and ribavirin. After 3 months, unfortunately, the treatment is stopped as his viral load has failed to fall and the side-effects of the treatment have become intolerable.

Six months later he attends his planned outpatient appointment and complains of feeling more unwell. He has become increasingly fatigued and has developed some swelling of his ankles. His partner thinks that his eyes look a little yellow.

On examination, he is mildly jaundiced. There is mild ankle oedema and some shifting dullness on abdominal examination. His weight has increased by 3 kg since his last clinic visit.

Blood tests are as follows:

Investigation 54.3 Summary of results

White cell count 2.9 × 109/L
Haemoglobin 10.3 g/dL
Platelets 67 × 109/L
INR 1.9
Albumin 28 g/L
Globulin 22 g/L
ALP 312 U/L
Bilirubin 87 µmol/L
AST 111 U/L
ALT 165 U/L
GGT 278 U/L
Alphafetoprotein 1885 kiu/L (0–5)  

The following investigation is performed:

Answers

A.1 A complete history for risk factors for hepatitis should be taken. This includes enquiring about alcohol consumption, a family history of liver disease, blood transfusions (especially transfusions prior to September 1991), intravenous drug use and sharing of needles, a sexual history and significant foreign travel. It is also important to ask about close contacts with anyone with hepatitis.

Blood products used prior to 1991 were not always tested for hepatitis C, although the introduction of widespread treating varied from country to country.

A.2 The blood tests show a modest rise in his transaminases (ALT and AST) implying hepatic inflammation/mild hepatitis. His liver synthetic function (as demonstrated by normal albumin, normal clotting and a normal bilirubin) is well preserved at present. His platelet count is slightly low. This may reflect portal hypertension and hypersplenism. In this scenario, blood flow through the portal venous system and therefore through the splenic vein is impaired. The spleen becomes engorged and has more opportunity to remove platelets from the circulation. This raises the possibility of an established cirrhosis.

In view of his history of intravenous drug use, viral hepatitis is high on the list of possibilities. Serology for viral hepatitis should be done. However, the net should be thrown wide and other forms of liver disease should be screened for. A ferritin and alpha-1 antitrypsin are important in ruling out inherited liver diseases.

A.3

A.4 He will need an ultrasound of his abdomen and Doppler studies of his portal vein to investigate the possibility of portal hypertension.

He also needs a blood test to check his genotype. This shows him to be genotype 1.

Liver biopsy can be an important way of assessing the degree of inflammation and fibrosis. The presence of cirrhosis reduces the chance of successful treatment.

However, recent advances in the use of non-invasive markers of fibrosis have reduced the number of liver biopsies performed. Consideration should be give to the use of these techniques including transient elastography or serum markers of fibrosis.

A.5 Hepatitis C is currently treated with a combination of interferon and ribavirin. There are two different preparations of interferon available: interferon alfa-2a and interferon alfa-2b. There is no current evidence to suggest that one product is significantly superior to the other.

Interferon works by enhancing the immune response to the hepatitis C virus rather than being directed specifically at the virus, while ribavirin is a non-specific antiviral agent that disrupts replication.

The duration of treatment is dependent on the genotype of hepatitis C. The current standard treatment is 48 weeks for genotypes 1, 4 and 5 and 24 weeks for genotypes 2 and 3. There is ongoing work being performed with regard to short course treatment in genotype 1, 2 and 3 patients.

Both interferon and ribavirin have significant side-effects that need to be discussed with the patient prior to starting them on treatment. These include:

Ribavirin

Significant anaemia may require a reduction of the ribavirin dose or support with erythropoietin (EPO). It is important to counsel the patient about the risks of birth defects prior to starting treatment and that any planned conception should be postponed until treatment has been completed.

The aim of treatment is to achieve a sustained viral response (SVR) – undetectable virus 6 months after completing treatment. The chance of achieving this differs depending on the genotype. Patients with genotype 1 have a 40–44% of achieving SVR, while patients with genotype 2 or 3 have an 80–85% of achieving SVR. Factors such as duration of infection, viral load, age and grade of inflammation and fibrosis also play an important role in determining the response to treatment. There are many new drugs currently in development and on the verge of commercial availability that may improve these outcomes. As yet these new drugs are expected to be used in combination with interferon and ribavirin but the landscape is rapidly evolving.

A.6 He has established cirrhosis and is therefore at increased risk of both hepatic decompensation and hepatocellular carcinoma (HCC). He should be reviewed regularly and entered into an HCC screening programme with 6-monthly ultrasound examinations and alphafetoprotein measurement.

Patients who have failed to clear the virus should always be considered for entry into clinical trials as soon as promising alternative therapies become available.

A.7 He now has evidence of significant synthetic dysfunction evidenced by a raised INR, depressed albumin and elevated bilirubin. He has a pancytopenia which is likely to be due to worsening hypersplenism and, by inference, increasing portal hypertension. This is further supported by the new development of fluid retention including possible ascites.

His alphafetoprotein is grossly elevated which, in the context of a patient with hepatitis C-related liver cirrhosis, is almost diagnostic of hepatocellular carcinoma.

He should have urgent cross-sectional imaging of his liver in the form of either a contrast enhanced CT or a contrast enhanced MRI.

A.8 This is a CT scan of the liver. You can tell that it is an arterial phase as bright contrast is seen within the aorta. A 4.5 cm enhancing lesion is seen in segment four of the liver. This is an arterialized hepatocellular carcinoma. The liver outline, in addition, appears irregular, consistent with the known cirrhosis.

In a patient with hepatitis C and HCC, the only curative option is liver transplantation. The tumour appears to be single and is less than 5 cm in diameter meaning he remains eligible. Surgical resection is not an option as his liver disease is advanced. Pending transplantation, his tumour could be treated with transarterial chemoembolization to allow ‘bridging’ to the curative procedure.

Revision Points

Hepatocellular Carcinoma

Further Information

www www.hepctrust.co.uk. UK-based advocacy group for HCV patients

www www.hepatitisaustralia.com. Excellent web resource for all types of hepatitis