Hep C Discussion Forum

More tidbits, starting to trickle out, about the new ALT levels, "Liver Tests" and other destined changes to guidelines:

Medscape Medical News

Liver Test Guidelines Updated by ACG

Veronica Hackethal, MD

January 12, 2017

The American College of Gastroenterology (ACG) has released updated guidelines on liver chemistry tests. The revised recommendations are the first to include specific ranges for normal alanine aminotransferase (ALT) levels and provide stepwise algorithms for evaluating abnormal ALT, aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin levels.

The guidelines, published online December 20, 2016, in the American Journal of Gastroenterology, include 19 recommendations and are geared toward both primary care providers and specialists.

To develop the guidelines, the authors conducted a formal literature review and consulted past ACG guideline policies. When rigid scientific evidence did not exist, they based their recommendations on consensus opinion.

In a major change, the new guidelines define no rmal ALT levels. Past guidelines were based on the upper limit of normal (ULN), which can vary between institutions and can range from 30 to 40 international units per liter in some hospitals to as high as 70 or 80 IU/L in others. The new guidelines state that the normal ALT range is 19 to 25 IU/L for women and 29 to 33 IU/L for men.

"We recognize that by lowering the levels, many people will now have liver tests that will be considered abnormal. There are concerns raised in multiple journals that we're going to go chasing a ton of elevated liver tests," first author Paul Kwo, MD, from Stanford University Medical School in California, told Medscape Medical News.

However, he emphasized the importance of the lower cutoffs: "Multiple studies have demonstrated that if your ALT is even seemingly innocuously elevated, your risk of liver-related death is significantly higher," he stressed.

Elevated ALT can identify people with chronic liver disease, such as nonalcoholic fatty liver disease, as well as chronic hepatitis C and B. Curative therapy now exists for hepatitis C, and other therapies exist that can improve liver health for people with certain other liver diseases, according to Dr Kwo.

"It's important that we recognize that an ALT level that is even slightly elevated and that does not normalize over time warrants an investigation," he said, "We hope that over time, clinicians will adjust to these new levels, and that liver health as well as overall health will improve for everybody."

The guideline includes algorithms for elevated AST and ALT that provide a graded approach to evaluation by categorizing elevations as borderline, mild, moderate, severe, or massive. It also provides specific recommendations for when immediate evaluation is warranted in cases of markedly elevated tests.

Algorithms for evaluation of abnormalities in alkaline phosphatase and bilirubin levels are also included, although these have not changed much over time, according to Dr Kwo.

The guidelines also include appropriate history questions and important physical exam findings, as well as recommendations for laboratory and radiologic tests and for when liver biopsy should be considered.

Other recommendations address diagnostic testing for specific liver diseases, including viral hepatitis A, B, and C; nonalcoholic fatty liver disease; alcoholic liver disease; autoimmune liver disease; metabolic and genetic disorders (eg, hereditary hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency); and liver injury caused by prescription drugs, over-the-counter medications, and herbal supplements.

Rare diseases such as primary biliary cholangitis and primary sclerosing cholangitis are covered, as is screening for celiac disease. Disorders of striated muscle, liver disorders of pregnancy, and uncommon reasons for abnormal live tests, such as Lyme disease, are also included.

Finally, the guidelines emphasize using the term "liver chemistry tests" or "liver tests," rather than "liver function tests," because the tests normally included in basic metabolic panels are indirect, not direct, markers of liver function.

"We are now recognizing that liver tests are an important window into somebody's overall health. As we enter an era when we have good therapies for some liver diseases and we're rapidly exploring options for other chronic liver diseases, it's important to be able to identify these people," Dr Kwo concluded.

The article received no financial support. The authors have disclosed no relevant financial relationships.

Am J Gastroenterol. Published online December 20, 2016. Abstract

The American Journal of Gastroenterology 112, 18-35 (January 2017) | doi:10.1038/ajg.2016.517

ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries

Paul Y Kwo, Stanley M Cohen and Joseph K Lim

Abstract

Clinicians are required to assess abnormal liver chemistries on a daily basis. The most common liver chemistries ordered are serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin. These tests should be termed liver chemistries or liver tests. Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels. Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels. The majority of bilirubin circulates as unconjugated bilirubin and an elevated conjugated bilirubin implies hepatocellular disease or cholestasis. Multiple studies have demonstrated that the presence of an elevated ALT has been associated with increased liver-related mortality. A true healthy normal ALT level ranges from 29 to 33 IU/L for males, 19 to 25 IU/L for females and levels above this should be assessed. The degree of elevation of ALT and or AST in the clinical setting helps guide the evaluation. The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency. In addition, a history of prescribed and over-the-counter medicines should be sought. For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken. Total bilirubin elevation can occur in either cholestatic or hepatocellular diseases. Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible.