A liver SGOT of 30 is good
When is it harmless, when is it critical?
Elevated liver values are also a common problem in the family doctor's practice - be it as a chance finding or as a result of a clarification of complaints. Even a slight increase in classic liver values such as ALT, AP, γ-GT or bilirubin can conceal a serious liver disease, which sometimes leads to cirrhosis. Less serious but easily treatable liver diseases should also be recognized as early as possible.
The unclear increase in liver values is a relevant problem in the routine of general practitioners (see case study) [1, 2]. According to the Gutenberg Heart Study, around every fifth person in Germany has elevated liver values (γ-GT, ALT) . During routine checks, people who are symptom-free are often noticed. Further clarification is essential here in order to detect serious or life-threatening diseases early and to prevent long-term effects such as cirrhosis of the liver. In addition to the most common causes such as non-alcoholic fatty liver disease (NAFLD) (75% of all chronic liver diseases) and damage caused by ethyl and drug toxicity , typical liver diseases should always be considered. These include viral hepatitis, autoimmune hepatitis (AIH), hemochromatosis, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) or Wilson disease. Although these diseases are much rarer, some - such as autoimmune hepatitis - are very treatable. In view of the different framework conditions - general practitioner practice / emergency room / intensive care unit / liver outpatient department - it makes sense to develop a situation-related algorithm for further clarification of elevated liver values with regional and individual risk factors. The serological diagnosis of hepatitis should be carried out early on in patients from a risk group - possibly also in the case of "highly normal" transaminases. The following describes the possible procedure in a family doctor's practice.
Initially, it is important to differentiate in which case it is better to wait and when an immediate clarification is indicated. For this you should first determine the basic parameters: ALT, AST, alkaline phosphatase, γ-GT, bilirubin, INR, blood count. On the basis of the results, it is usually possible to roughly differentiate between toxic, hepatic and cholestatic damage patterns (Table 1). If the damage pattern is toxic, the γ-GT in particular is increased - in connection with a lower increase in AST and ALT. In the case of a cholestatic damage pattern, however, AP, γ-GT and bilirubin elevations are found. Depending on the genesis, the transaminases are also higher .
Significantly increased transaminases are found in hepatic damage patterns, with ALT usually being higher than AST. The so-called DeRitis quotient (AST / ALT) indicates a more inflammatory (<1), necrotizing (> 1) or ethyl-toxic genesis (> 2). A normal value by no means excludes cirrhosis of the liver . If the ALT / AST is elevated and liver disease has been ruled out, it is important to also consider a chronic muscle disease. A sustained isolated increase in γ-GT is considered a cardiovascular risk factor, even if there is no evidence of liver pathology . The genesis of the increase is diverse and mostly exogenously toxic (diabetes, thyroid dysfunction, medication, etc.).
In addition to the laboratory values and the physical examination, the detailed medical history with travel and medication history including phytotherapeutics and dietary supplements as well as alcohol and drug consumption is another important component for clarification (Table 2). In principle, if the liver values are elevated, an ultrasound of the abdomen is always recommended. If an acute clinical picture - such as liver failure, painless jaundice or choledocholithiasis - shows up in the first phase of the check-up, a quick diagnosis and, if necessary, immediate hospitalization is indicated.
Significant increase in liver values
In stable patients with a significant increase in liver values (> 3-fold Upper Limit of Normal, or ULN for short), a short-term check-up should be carried out within one week. If the dynamics are relevant, immediate and, if necessary, inpatient clarification is indicated. Otherwise, direct further chemical laboratory diagnostics using aHCV, aHBc, aHEV, aHAV, HBsAg, IgG, IgA, IgM and ferritin is recommended (Fig. 1 and 3). In the case of acute viral hepatitis, close-knit ambulatory laboratory checks are sufficient as long as the liver synthesis is completely intact. If the liver values do not normalize promptly, you should also think about a clarification with a hepatologist, if necessary inpatient. This is especially true for the antiviral treatment of acute HBV, HCV and HEV infections. Even with persistently elevated liver values, it is advisable to see a hepatologist for further clarification (Fig. 1).
Slight increase in liver function
In the case of a slight increase in liver values (<2-fold ULN), a check of the "basic parameters" and sonography within three months is usually sufficient to rule out a harmless reaction. There are always transient increases and individual fluctuations without disease value [9, 10].
If the slight increase persists, aHCV, aHBc, HBsAg, IgG, IgA, IgM and ferritin are important for clarifying chronic liver disease. If these parameters are pathological or if there are no groundbreaking findings, you should also refer to the hepatologist. If the liver values are normal, it is important to wait for another check in three months (Fig. 1), because even with chronic liver disease there is a transient normalization of the liver values. Diseases that are easily treatable and can be diagnosed with relatively little effort should be recognized and treated at an early stage in order to prevent long-term effects. These include, among others. hepatitis B and C, autoimmune hepatitis, hemochromatosis and PBC. Referral to a hepatologist is usually helpful if there is a diagnosis or strong evidence of chronic liver disease. A slight persistent increase in liver values should also be further clarified in order to prevent subclinical liver damage from being diagnosed only when the damage is hardly reversible.
Common causes of elevated liver values
5 to 20% of patients with NAFLD develop non-alcoholic steatohepatitis (NASH) over the course of the day. In around 10 - 20% this turns into a higher grade fibrosis and in <5% into cirrhosis . The symptoms are mostly non-specific and the transaminases are typically increased . Often it is not the actual liver damage that is more important, but the cardiovascular risk. Keeping this as low as possible is essential. Normal liver values do not rule out the disease or even cirrhosis. The biopsy remains the gold standard for diagnosing NASH. In order to assess the risk of fibrosis non-invasively early on, there are simple scores, such as the NAFLD Fibrosis Score (NFS), which is made up of age, BMI, diabetes, GOT, GPT, platelets and albumin. The extent of the fibrosis can in turn be estimated using the APRI (AST to Platelet Ratio Index).
At around 0.5%, hepatitis B has a prevalence similar to that of hepatitis C (0.3%) [15, 16].
Both are significantly higher depending on the risk group (drug abuse, origin (Africa, countries of the former Soviet Union, East Asia, Middle East), blood transfusion (before 1992)). Only 30% of patients with acute hepatitis B show acute symptoms such as fatigue, jaundice, vomiting or diarrhea. The HBsAg determination is considered a search test. To further differentiate between acute and chronic infection, HBV-DNA, HBeAg, anti-HBe and anti-HBs are determined (Table 3). The acute infection heals in about 95% without specific therapy. The doctor should decide on antiviral treatment of acute HBV infection in consultation with the local liver center and if liver synthesis decreases (increase in INR). In the case of a chronic infection, this depends on the level of transaminases, the viral load and damage to the parenchyma.
Acute hepatitis C is usually asymptomatic or unspecific. About 80% of acute infections go undiagnosed . The anti-HCV IgG determination is considered a search test. The viral load is then determined using HCV RNA (Table 3). In 50 - 85% of the cases, acute hepatitis C turns into a chronic infection (> 6 months) and after 20 years leads to cirrhosis in around 20%. The risk of hepatocellular carcinoma is very high at around 4% per year. Treatment has improved dramatically thanks to the new, direct antiviral substances. Today, the cure rates for chronic hepatitis C are over 90%.
With a prevalence of 10-30 / 100,000 inhabitants, AIH is much rarer than NASH, chronic hepatitis B and C, but due to its high risk of cirrhosis (if left untreated, about half of the patients develop liver cirrhosis in 15 years) and it is relatively easy to treat a high diagnostic value . AIH can occur at any age. Women get sick about three times more often than men. In almost 30% of patients, the diagnosis is only made in the cirrhosis stage . If the liver values are elevated, IgG,
IgA and IgM level determinations recommended, since a selective IgG increase can strongly indicate an AIH. If there is any suspicion, an autoantibody test is indicated (Table 3). The diagnosis can only be made by looking at the findings and specific scores (IAHG score for autoimmune hepatitis or simplified AIH score according to Hennes). Confirmation of the diagnosis requires a biopsy and should be done before therapy. The primary therapy of choice is a combination of glucocorticoid and azathioprine.
- Diseases with little diagnostic effort and good treatability should not be overlooked - especially hepatitis B, hepatitis C, autoimmune hepatitis and hemochromatosis, PBC
- After six months of unclear increase in liver values: Referral to the hepatologist
- Even a small increase in liver values should be taken seriously and pursued in order to prevent possible long-term effects
Conflicts of Interest: MS: Lecture and consulting fees from AbbVie, Gilead, Intercept, Norgine
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