New Diagnostic Technology in Liver Disease

Hepatology, as almost no other discipline in medicine, is an example of how results deriving from basic science influence our everyday clinical practice. This involves diagnostic procedures as well as therapeutic developments. Examples are the discovery of the hepatitis viruses and the development of laboratory tests for the diagnosis of viral hepatitis as well as the newly developed real-time polymerase chain reaction (PCR) methodology to determine hepatitis virus DNA or RNA levels quantitatively. This quantitative viral nucleic acid testing (NAT) is helpful with regard both to the indications for treatment and monitoring of antiviral therapy. The successful development of prophylactic vaccines for hepatitis B and hepatitis A would not have been possible without the application of the modern technology of molecular and cell biology. The new era of drug development in hepatitis B and hepatitis C is also a direct consequence of the application of molecular and cell biology to clinical hepatology.

This issue of Seminars in Liver Disease concentrates on new diagnostic technology in liver disease. This includes the discussion of the new quantatitive assays for the hepatitis viruses. Nucleic acid testing (NAT) for hepatitis viruses has become more important than the serological assays for the detection of viral antigens and antibodies. The new assays based on real-time PCR have a direct impact on the development of novel treatment paradigms for the new generation of antiviral drugs.

A controversial issue in hepatology is the present and future role of liver biopsy. On the one hand, liver biopsy is no longer necessary as an endpoint for antiviral therapy against hepatitis C. Here, sustained virological response (SVR = negative hepatitis C virus RNA in serum 24 weeks after the end of therapy) has become the gold standard. On the other hand, novel technologies open new possibilities to analyze biopsy material. Now in the age of gene profiling we need to carefully explore the diagnostic possibilities that novel techniques like gene array assays may offer to the clinical management of our patients. Different approaches are available to obtain liver tissue, including trans-jugular biopsy, mini-laparoscopy, and ultrasound-guided biopsy. It is very important that liver centers are experienced in these techniques and use them to obtain tissue material appropriately. At the same time, noninvasive tests for liver fibrosis are being developed either based on a combination of serum makers or on techniques to measure the elasticity of liver tissue. It will be interesting to see in the future whether these noninvasive assays will be able to substitute for staging of liver tissue by liver biopsy.

Once cirrhosis has developed, it is very important to prevent its complications. Therefore, early diagnosis of such complications is necessary. New techniques are urgently needed to identify or foresee complications of liver cirrhosis, such as portal hypertension, to start appropriate treatment as early as it is indicated. Once portal hypertension becomes a threat to the patient, medical therapy must be monitored to allow effective dosing. Therefore, we urgently need noninvasive techniques to measure portal hypertension for monitoring therapy. The main and most prominent complication of liver cirrhosis today, however, is hepatocellular carcinoma. This is due to the increase of hepatitis C-associated end stage liver disease as well as due to the success in the management of other complications of cirrhosis, such as portal hypertension and ascites. Therefore, effective surveillance of cirrhotic patients for the development of hepatocellular carcinoma is mandatory to allow early detection of hepatocellular carcinoma. Today, more than 50% of hepatocellular carcinomas are being diagnosed at an advanced stage when efficient therapies are no longer possible, such as resection, transplantation, and locoregional therapies, including radiofrequency ablation, percutaneous ethanol injection, or transarterial chemoembolization. Unfortunately, we cannot offer effective chemotherapy for advanced stages of liver cellular carcinoma at the moment; hence, the detection of early stages of hepatocellular carcinoma is a critical clinical problem. New serum markers are urgently needed.

The articles that follow address these important issues. Nevertheless, the guest editors of this issue of Seminars in Liver Disease are well aware that this is an unusual issue for Seminars, but are also aware that the number of topics is not complete in this important area for clinical hepatology. We hope, however, that we can highlight some of the areas of hepatology where new diagnostic technology is appearing at the horizon for the management of our patients with liver disease.