Endoscopic Ultrasound(EUS)-Guided TRUCUT Biopsy (EUS-TCB) of Suspected Nonalcoholic Fatty Liver Disease(NAFLD.)
Condition: Non-alcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional

Summary: 
      Endoscopic Ultrasound involves the placement of a small flexible camera through the mouth and
      into the stomach to image various parts of the body. A small piece of tissue called a biopsy,
      of your liver nay be obtained by this method. the tissue (biopsy) would be obtained by
      inserting a small needle through the lining of the stomach into the liver. Consideration for
      this biopsy is because there may be extra fat stored within the liver. In some people who
      drink too much alcohol, extra fat may be stored in the liver, however, in some people who
      don't drink too much alcohol, this may also occur and is called :non-alcoholic fatty liver
      disease or NAFLD. Over time, this extra fat may lead to liver irritation and scar tissue
      called cirrhosis. If NAFLD is detected early enough, then treatment with medications, losing
      weight, or dietary changes may help avoid cirrhosis. the purpose of this study is to learn
      about whether doctors can obtain the biopsy from the liver by a new method. The biopsy of the
      liver allows the doctors to look for any signs of scar tissue or inflammation from any cause.
    

Detailed description: 
      Non-alcoholic Fatty Liver Disease (NAFLD) is an alcohol-like liver disease that occurs in
      individuals who do not consume excessive alcohol. Similar to alcohol-induced liver disease,
      NAFLD encompasses a spectrum of liver damage, ranging from non-alcoholic fatty liver (NAFL)
      on the most clinically benign end of the spectrum to cirrhosis on the opposite extreme where
      most liver-related morbidity and mortality occur. In NAFL, the liver is steatotic but
      generally healthy. Nonalcoholic steatohepatitis (NASH) is a more severe form of liver damage
      than NAFL because there is increased hepatocyte death in addition to steatosis. The liver
      injury in NASH triggers a repair response that sometimes leads to cirrhosis.1-3 The
      architecture of cirrhotic livers is distorted by regenerating nodules and fibrous tissue.
      Cirrhosis results when fibrosis disrupts the normal liver architecture, carving the
      parenchyma into nodules of hepatocytes that are separated from each other by bands of
      connective tissue. Some individuals with NAFLD develop cirrhosis. As in other types of liver
      disease, progression to this advanced stage of liver damage from NAFLD is generally thought
      to require many years, perhaps decades. Because most liver-related morbidity and mortality
      occur in cirrhotic individuals, researchers are trying to understand the basis for
      inter-individual differences in the tendency to develop cirrhosis. Exiting blood tests and
      imaging modalities have limited sensitivity for detecting liver steatosis, steatohepatitis
      and cirrhosis. In addition, there is no test that can distinguish NAFLD from other causes of
      fatty liver disease. Thus, at the present time, NAFLD is a diagnosis of exclusion.

      Results from two large population-based studies are extremely useful in defining the
      prevalence of NAFLD in the general US adult population.4,5 The Dallas Heart Study used liver
      imaging to assess the prevalence of fatty liver in over 2200 adults. The overall prevalence
      of fatty liver in that study was 31% with a range of 24-45% of the population demonstrating
      hepatic steatosis. Of note, most individuals with elevated liver fat content did not
      demonstrate aminotransferase elevations. The latter finding helps to explain why NHANES III,
      another large population-based study, suggested a much lower prevalence of NAFLD in the
      general US adult population. In NHANES III, serum aminotransferases were used to assess NAFLD
      prevalence in over 15,000 adults and that approach suggested that 5.5% of the population has
      NAFLD. Based on the results of the Dallas Heart Study it is likely that the approach used in
      NHANES III underestimated the true prevalence of NAFLD in US adults. In any case, the net
      results from these two studies suggest that between 5.5 to 31% of the adult US population has
      NAFLD. To appreciate the significance of this finding, it is useful to compare the prevalence
      of NAFLD to that of hepatitis C, which is thought to exist in 1.8% of the US population.6
      NAFLD is three to ten times more common than hepatitis C-related liver disease in the US.

      Population-based studies and case series demonstrate strong associations between NAFLD and
      several conditions, including obesity, type 2 diabetes, and dyslipidemia, that comprise the
      metabolic syndrome.4,5,7-13 This suggests that the prevalence of NAFLD is likely to be much
      greater in these high risk populations. Studies of morbidly obese patients undergoing gastric
      bypass surgery support this concept. In most of these individuals, liver disease was
      unsuspected pre-operatively. However, intraoperative liver biopsies consistently demonstrate
      NAFLD. In four recent series that included over 600 subjects, the prevalence of NAFL
      (steatosis) ranged from 30-90% and NASH (steatohepatitis) was documented in 33-42%. Thus,
      over two-thirds of morbidly obese patients undergoing gastric bypass surgery have NAFL/NASH.
      Although overt manifestations of portal hypertension likely excluded patients as candidates
      for elective abdominal surgery, these four surgical series consistently identified
      individuals with hepatic fibrosis. Well-established cirrhosis was relatively unusual,
      occurring in 1-2% of the group. However, advanced fibrosis was noted in 12% and a third had
      unexplained periportal fibrosis. There is also a high prevalence of NAFLD is high in
      populations of patients with type 2 diabetes mellitus. A recent survey of 100 non-alcoholic
      patients with type 2 diabetes used ultrasonography to screen for NAFLD and demonstrated fatty
      liver in half of the group. Subsequent liver biopsy revealed NAFL in 12% and NASH in 87% of
      those with ultrasonographic evidence of fatty liver. Fibrosis or cirrhosis were noted in
      20%.14 In patients with metabolic syndrome and hyperlipidemia, fatty liver was detected in
      50% of 95 adults using ultrasonography to screen for unsuspected hepatic steatosis.15

      Similar to other types of chronic liver disease, liver-related morbidity and mortality are
      dictated by the severity of liver damage. This concept explains observations that NAFL has a
      relatively benign prognosis, whereas NAFLD-related cirrhosis may be complicated by portal
      hypertension and hepatocellular carcinoma, eventuating in death from liver disease.2 Studies
      disease.2 Studies in the US and France independently demonstrated 3 easily-assessed clinical
      parameters that identify individuals with cryptogenic hepatitis who are likely to have
      advanced fibrosis on liver biopsy. These parameters are older age (greater than 45-50 years),
      overweight or obese body mass index, and type 2 diabetes. The probability of having bridging
      fibrosis or cirrhosis on liver biopsy is approximately 66% in individuals with cryptogenic
      hepatitis who are older and either overweight/obese or diabetic.16,17 Identification of
      individuals who have NASH with fibrosis has important prognostic implications. Follow-up of
      patients with NASH and fibrosis demonstrates that almost 30% of these individuals become
      cirrhotic within 5-10 years. In contrast, only about 3% of individuals with milder forms of
      non-alcoholic fatty liver disease develop cirrhosis after more than a decade of follow-up.
      Therefore, NASH with fibrosis progresses to cirrhosis both more consistently and more rapidly
      than simple NAFL.2,13

      In order to provide optimal therapy for individuals with NAFLD, their liver disease must be
      diagnosed. The diagnostic evaluation of an individual who is suspected of having NAFLD has 3
      goals. The first goal is to establish fatty liver disease as the etiology of the liver
      disease. Unfortunately, no specific serologic marker for NAFLD has been identified yet.
      Moreover, all of the current diagnostic tests for NAFLD have some limitation. Standard
      imaging tests such as ultrasonography and CT scan, may under- or over-estimate hepatic fat
      content.1,18 Moreover, detecting liver fat by abdominal imaging can neither distinguish
      alcoholic- from non-alcoholic-fatty liver disease, nor exclude other types of liver disease
      that might co-exist with hepatic steatosis. The second goal is to confirm the specific type
      of fatty liver disease, alcoholic fatty liver disease (AFLD) or non-alcoholic fatty liver
      disease (NAFLD). These two entities cannot be distinguished by histologic parameters but only
      by assessment of drinking habits of the patient. The third and arguably most important, goal
      of the diagnostic work-up is to establish the clinical severity and prognosis of the liver
      disease. Because NAFLD is common and often generates few manifestations of liver disease, it
      is necessary to have a high index of suspicion to identify individuals who might have NAFLD.
      This includes individuals with the metabolic syndrome (at least 2 of the following disorders:
      obesity, type 2 diabetes, hypertension and dyslipidemia) or detection of fatty liver on an
      imaging study of the abdomen. Imaging studies or laboratory tests may point to advanced liver
      disease but early cirrhosis and NAFLD without fibrosis cannot be reliably diagnosed without
      liver biopsy.

      At this time, liver biopsy remains the "gold standard" for staging the severity of liver
      damage in NAFLD and all other types of chronic liver disease.2 This biopsy is traditionally
      performed percutaneously with or without ultrasound guidance. Needle entry for biopsy is
      typically into the right lobe below the diaphragm between the ribs in the right mid-axillary
      line. Alternatively, this may be done by an anterior approach into the left lobe. However,
      there are potential limitations with percutaneous biopsy including sampling error19,20 (which
      may not be representative of the hepatic architecture) and complications (pain, bleeding and
      puncture of another organ, not obtaining liver tissue). Due to anatomical considerations,
      some patients are not even candidates for liver biopsy by the percutaneous approach. In this
      case, biopsy may be performed by the transjugular method. This technique involves use of
      conscious sedation followed by needle access of the jugular vein. A wire is then passed
      through the heart and into a branch of a hepatic vein to guide a needle biopsy of the liver.
      Similar to percutaneous biopsy, this procedure is safe when performed by experienced
      operators. However, complications including neck hematoma, hepatic arteriovenous fistula,
      liver capsular puncture, intraperitoneal hemorrhage and death have been reported by this
      technique.21,22 Regardless of the approach, liver biopsy incurs monetary cost, including fees
      for the facility, equipment, hepatologist and pathologist, as well as for processing the
      tissue sample itself. On the other hand, the expense of a liver biopsy is roughly equivalent
      to that of magnetic resonance imaging (MRI), which is the most sensitive radiologic test for
      quantifying liver fat,fat; an MRI is inferior to biopsy for detecting liver inflammation and
      fibrosis.23

      Alternative methods for acquisition of a core biopsy of the liver may be helpful in patients
      in whom percutaneous and transjugular liver biopsies would be difficult, risky or
      contraindicated. Endoscopic ultrasound (EUS)-guided fine needle aspiration (EUS-FNA) has been
      used for over 15 years at Indiana University Medical Center and other hospitals to sample
      lymph nodes and masses in the posterior mediastinum, upper abdomen and pelvis.24-29 In 2003,
      we published our experience of EUS-FNA of the liver using a 22-gauge needle in 77 patients
      without complications and to date this remains the largest series reported in the
      literature.30 Since that report, we have performed this procedure in over 100 patients also
      without a known complication (not published). In 2003, the FDA approved development of a
      19-gauge Trucut biopsy (TCB) device (Wilson-Cook Medical, Inc.; Winston-Salem, North
      Carolina) that provides a histologic tissue sample for use with EUS. The initial reported use
      of this device demonstrated its safety and utility for biopsy of major upper abdominal organs
      (including the liver) in a swine model.31 Its subsequent use for sampling of gastrointestinal
      stromal tumors (GISTs), pancreatic masses and mediastinal lymph nodes in humans has also been
      reported.312-35 We have also studied its use in the diagnosis of nonfocal chronic
      pancreatitis.36 At Indiana University, we our EUS group have used this device in over 30
      patients off protocol for various accepted indications without known complications (not
      published). The use of this EUS-TCBdevice for liver biopsy has been reported in abstract form
      in only two patients with suspected metastatic malignancy.37 No complications were reported
      in these two patients. Its use for suspected benign disease of the liver has not been
      reported to date.
    

Intervention name(s): Tru-cut biopsy; Tru-cut
Intervention type(s): Device; Procedure
Intervention description(s): Tru-cut biopsy may be an alternative to percutaneous and transjugular liver biopsy.; Tru-cut may be an alternative to percutaneous and transjugular liver biopsy.
Other intervention name(s): Wilson-Cook 19 Gauge Quick-Core EUS Biopsy Needle.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: EUS Biopsy for Non-alcoholic Fatty Liver Disease