Non-invasive diagnosis of alcoholic liver disease

Abstract

Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.

Keywords: Alcoholic hepatitis; Alcoholic liver disease; Alcoholic steatohepatitis; Liver stiffness; Non-invasive; Serum marker; Steatosis.

Figure 1

Natural course of alcoholic liver disease and major end points. HCC: Hepatocellular carcinoma.

Figure 2

General non-invasive approaches for patients with suspected alcoholic liver disease. Combination of different tests will help to establish alcohol as underlying reason and to assess the stage of liver disease. ALD: Alcoholic liver disease; HCC: Hepatocellular carcinoma; CDT: Carbohydrate deficient transferrin; MCV: Mean corpuscular volume; CT: Computed tomography; MRI: Magnetic resonance imaging; TE: Transient elastography; ARFI: Acoustic radiation force impulse imaging elastography (Siemens); CAP: Controlled attenuation parameter (Echosens); MRE: Magnetic resonance elastography; SWE: Shear wave elastography (Supersonic imaging); GGT: γ-glutamyl transpeptadase; GOT: Glutamic-oxal(o)acetic transaminase; GPT: Glutamate pyruvate transaminase; AFP: α-fetoprotein.

Figure 3

Liver stiffness scale with cut-off values for various fibrosis stages in alcoholic liver disease patients without pronounced inflammation, congestion, tumors or mechanic cholestasis.

Figure 4

Complete non-invasive diagnostic work plan for patients with alcoholic liver disease at Salem Medical Center Heidelberg with follow up. Flow scheme allowed diagnosis of fibrosis in 95% of patients. In the remaining 5% of patients without valid LS measurements, the role of serum markers need to be settled but single hyaluronic acid looks promising. In patients with LS > 30 kPa, cirrhosis is established despite increased transaminase levels. MCV: Mean corpuscular volume; HCC: Hepatocellular carcinoma; LS: Liver stiffness; US: Ultrasonography; GGT: γ-glutamyl transpeptadase; GOT: Glutamic-oxal(o)acetic transaminase; GPT: Glutamate pyruvate transaminase; AFP: α-fetoprotein.

Figure 5

Clinical significance of synthesis impairment and portal hypertension in cirrhotics. Both factors are independently and individually occurring in cirrhotic patients and determine the individual risk of severe complications (framed). While synthesis is easily assessed by lab tests, elastographic techniques are the future highly sensitive method of choice to identify patients with portal hypertension. HCC: Hepatocellular carcinoma; SBP: Systolic blood pressure.