**3. Results**

of certain complications including pain, bleeding, pneumothorax, puncture of bile ducts or

Repeating samples in different time intervals are useful in monitoring the efficacy of treat‐ ments. Many patients are, however, reluctant to experience repeated biopsies, which limits

Due to the limitations of the procedure many non-invasive techniques were developed such as single serological markers, panels of different markers, imaging techniques and elastogra‐ phy [4]. None of the non-invasive methods is suitable and reliable enough to entirely substi‐ tute the liver biopsy. Non-invasive techniques are very helpful in the detection of severe lesions. However, results obtained from patients with intermediate lesions very often over‐ lap between different categories of staging. Nevertheless non-invasive methods are useful in situations where contraindications to liver biopsy do not allow to perform the procedure.

Liver biopsy can be percutaneous, transjugular or laparoscopic. Percutaneous liver biopsy can be blind, ultrasound- guided or ultrasound assisted. Various approaches differ in the number of potential complications and require various equipment. Ultrasound guidance al‐ lows safer intercostal approach and may be useful in the evaluation of relative position of the liver, gall bladder, kidneys and lungs. The technique reduces the risk of hemothorax and

The aim of this study was to evaluate safety and reliability of the liver biopsy in children in

Seventy five cases of percutaneous liver biopsies carried between 2005-2012 were analyzed. The biopsies were performed in children aged 4-17 years (mean 15.30±2.35 years). Study group included 26 girls, 49 boys. Procedures were done due to chronic hepatitis C (CHC) – 44 cases, chronic hepatitis B (CHB) – 16 cases, autoimmune hepatitis (AIH) – 3 cases, hepati‐ tis/hepatomegaly of unknown origin (HUO)– 12 cases, non-alcoholic fatty liver disease (NAFLD) – 2 cases. Number of the procedures performed in the following years has been

Written informed consent was obtained from the parents and patients aged 16 years and over according to Polish law regulations. Before the procedure children were clinically eval‐ uated and blood samples were taken for standard hematological and clinical chemistry anal‐

from the procedure. All children underwent abdominal ultrasound performed the day be‐ fore the procedure to exclude potential hemangiomas and malposition of the organs. All children were managed by Menghini procedure in sedation. Children aged less than 5 years received general anesthesia. 36 biopsies were ultrasound guided directly prior to the proce‐ dure (performed by the operator), 39 biopsies were blind. The ultrasound prior to the biopsy was performed to identify the intercostal space and to avoid accidental puncture of the gall

were excluded

ysis. Children with coagulopathies and thrombocytopenia below 80,000/mm3

the ability to monitor disease progression and treatment effects. [3].

pneumothorax and puncture of the gall bladder.

**2. Material and methods**

presented in Figure 1.

relation to obtained results and potential complications.

the gall bladder.

76 Liver Biopsy – Indications, Procedures, Results

Liver samples were obtained in all children. Adequate sample size was not obtained in the case of 5 children - 2 samples were to short and did not contain the adequate number of por‐ tal spaces, one sample was fragmented. Four inadequate samples resulted from the blind liver biopsy and 1 was obtained by the ultrasound guided procedure (p=0.21). No significant adverse events were observed. No clinical signs of hemorrhage, no cases of pneumothorax, puncture of the gallbladder nor severe infections were observed. Larger bile ducts were punctured in 4 cases – all undergoing blind procedure (p=0.07). 12 patient were complaining on pain in the right upper quadrant of the abdomen following the procedure that required more intensive analgesics – 3 undergoing ultrasound guided procedure, 9 having blind liver biopsy done (p=0.07). Pain was mild to moderate and resolved after analgesics. There were no deaths following the procedure in both groups of children.

**Indication for the biopsy Result Number of children**

Grading

Staging

Grading

Staging

AIH - 3 Autoimmune hepatitis 3

**Table 1.** Histological assessment of the liver biopsy specimens performed in 75 children. CHC- chronic hepatitis C, CHB – chronic hepatitis B, NAFLD – non-alcoholic fatty liver disease, HUO – hepatitis/hepatomegaly of unknown origin, AIH

Studies describing the safety of liver biopsy performed on larger cohorts of patients seem to prove that the procedure results in more complications in children than in adults [5]. Never‐ theless, Lebensztejn et al. described the group of 250 pediatric patients undergoing blind procedure with serious complications as internal hemorrhage and puncture of the gallblad‐

1 23 2 11 3 5 4 5

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79

Safety and Reliability Percutaneous Liver Biopsy Procedure in Children with Chronic Liver Diseases

0 1 1 19 2 17 3 5 4 2

1 3 2 8 3 3 4 2

1 3 2 7 3 5 4 1

Steatosis 1 Steatohepatitis 1

Metabolic disorders 3 Nonalcoholic steatohepatitis 6 Wilson disease 1 Normal liver histology 2

CHC - 44

CHB - 16

NAFLD - 2

HUO - 12

der occurring in 3 children [6].

– autoimmune hepatitis

**4. Discussion**

Results from pathological assessment were presented in Table 1. The majority of children underwent liver biopsy due to CHC. Remaining indications were CHB, AIH, NAFLD, HUO. In patients with viral hepatitis grading and staging assessed according to Ishak scoring sys‐ tem was usually mild to moderate. Nevertheless, severe lesions were also present in some patients. Figure 2 and Figure 3.show examples of inflammatory changes and portal fibrosis in various patients with CHC. In patients with AIH and NAFLD diagnosis was confirmed by pathological assessment. Ten of HUO patients gained diagnosis either of metabolic disor‐ ders or NAFLD thanks to pathological evaluation. Normal liver histology was described in 2 patients.

**Figure 2.** Liver biopsy specimen of the patient with CHC where inflammatory infiltrates cross lamina basalis of the lo‐ buli (thin arrows) and intralobular focus of inflammatory infiltrate (thick arrow).Staining: hematoxylin+eosine. Magni‐ fication 40x

Fifteen children with viral hepatitis underwent repeated procedures allowing to assess the progression of lesions in time. In 9 of them the progression of lesions was described, 6 had similar results in both biopsies.

Safety and Reliability Percutaneous Liver Biopsy Procedure in Children with Chronic Liver Diseases http://dx.doi.org/10.5772/52619 79


**Table 1.** Histological assessment of the liver biopsy specimens performed in 75 children. CHC- chronic hepatitis C, CHB – chronic hepatitis B, NAFLD – non-alcoholic fatty liver disease, HUO – hepatitis/hepatomegaly of unknown origin, AIH – autoimmune hepatitis

### **4. Discussion**

biopsy done (p=0.07). Pain was mild to moderate and resolved after analgesics. There were

Results from pathological assessment were presented in Table 1. The majority of children underwent liver biopsy due to CHC. Remaining indications were CHB, AIH, NAFLD, HUO. In patients with viral hepatitis grading and staging assessed according to Ishak scoring sys‐ tem was usually mild to moderate. Nevertheless, severe lesions were also present in some patients. Figure 2 and Figure 3.show examples of inflammatory changes and portal fibrosis in various patients with CHC. In patients with AIH and NAFLD diagnosis was confirmed by pathological assessment. Ten of HUO patients gained diagnosis either of metabolic disor‐ ders or NAFLD thanks to pathological evaluation. Normal liver histology was described in 2

**Figure 2.** Liver biopsy specimen of the patient with CHC where inflammatory infiltrates cross lamina basalis of the lo‐ buli (thin arrows) and intralobular focus of inflammatory infiltrate (thick arrow).Staining: hematoxylin+eosine. Magni‐

Fifteen children with viral hepatitis underwent repeated procedures allowing to assess the progression of lesions in time. In 9 of them the progression of lesions was described, 6 had

no deaths following the procedure in both groups of children.

78 Liver Biopsy – Indications, Procedures, Results

patients.

fication 40x

similar results in both biopsies.

Studies describing the safety of liver biopsy performed on larger cohorts of patients seem to prove that the procedure results in more complications in children than in adults [5]. Never‐ theless, Lebensztejn et al. described the group of 250 pediatric patients undergoing blind procedure with serious complications as internal hemorrhage and puncture of the gallblad‐ der occurring in 3 children [6].

The majority of children underwent the liver biopsy due to chronic viral hepatitis – mostly CHC. Histological assessment was not necessary to establish diagnosis since it is usually based on blood tests. However, information regarding grading and staging was essential for treatment decisions since the length of treatment may vary depending on the severity of le‐ sions. In patients with CHB decisions regarding the initiation of the treatment may depend on the presence of lesions in the liver tissue [8]. In both types of chronic viral hepatitis pa‐ tient with liver cirrhosis requires different approach than the child with mild lesions in the liver. In children with AIH the diagnosis was confirmed by the detection of specific inflam‐ matory cells in the liver tissue. Although the number of NAFLD was small, the procedure distinguished between simple steatosis and steatohepatitis. Patients who underwent the procedure due to HUO benefited from diagnosis in 10/12 children. Metabolic disorders were detected in 3 patients and steatosis was detected in 6 children, 1 child was found to have Wilson's disease. Normal liver histology found in the specimens from the following 2 chil‐ dren with HOU raises questions regarding indications to the liver biopsy. The decision con‐ cerning the procedure was always carefully made basing on clinical and laboratory findings. Obtained results may be a consequence of the limitations of the procedure regarding sample size and sample error related to the site of the biopsy. Diffuse liver diseases are hardly ever

Safety and Reliability Percutaneous Liver Biopsy Procedure in Children with Chronic Liver Diseases

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81

Another problem with pathological assessment is an intraobserver variety. Except for skill‐ ful operator, an experienced pathologist is essential for proper evaluation of the samples. However, differences in the assessment between to various pathologists are difficult to

In recent years many non-invasive methods of liver assessment were developed. Imaging techniques allow to describesteatosis, focal changes, malformations, inflammatory processes of bile ducts and advanced fibrosis. Mild changes are, however, still difficult to detect. Elas‐ tography has been developed to evaluate liver stiffness being a useful tool to assess liver fib‐ rosis [9]. Fibrosis is also evaluated by different serological markers and panels of direct and indirect markers or combination of both. Various cut-offs of the markers to detect advanced fibrosis and cirrhosis were validated in numerous studies [4]. Nevertheless, problem with intermediate stages of fibrosis still exist, since in such cases serological markers overlap.

Attempts to completely replace the biopsy with other non-invasive methods are not effec‐ tive as the collection of adequate liver sample and proper histological evaluation allows to

Percutaneous liver biopsy is safe even in small children. Although severe complications are rare, patients require frequent monitoring. Ultrasound guidance seem to reduce the number of complications. Remaining a golden standard, the liver biopsy has certain limitations and

determine the extent ofthe liver damage and helps to establish the diagnosis.

evenly distributed in the organ.

**5. Conclusions**

drawbacks that influence the results.

avoid even with the use of validated scoring systems.

**Figure 3.** Syrius red staining of the liver specimen of CHC patient with present fibrosis in dilated portal space (thick arrow) and porto-portal bridging. Magnification 40x.

Number of biopsies in the current study was lower, however even the number of mild com‐ plications was relatively low. Moreover, no serious adverse events were noted among chil‐ dren from the study group. Noted complications included puncture of larger bile ducts and pain after the procedure. Although the results were not statistically significant, both prob‐ lems were more frequent in children undergoing blind liver biopsy. Ultrasound assistance during the whole procedure was found to reduce the number of potential consequences [7]. Thus, ultrasound guidance even performed right before and after the biopsy makes the whole procedure safer. Since the majority of complications occur within first hours after the liver biopsy all children were monitored for 24 hours after the procedure as inpatients. Al‐ though hospitalization increases the costs of the procedure, monitoring enables quick re‐ sponse to encountered complications and prompt treatment, if necessary. Another issue is general anesthesia performed in small children in order to obtain liver sample. Although costly, general anesthesia decreases fear, pain and enables to perform the procedure in safe circumstances, reducing the risk of hemorrhage caused by lack of cooperation from the pa‐ tient side.

The majority of children underwent the liver biopsy due to chronic viral hepatitis – mostly CHC. Histological assessment was not necessary to establish diagnosis since it is usually based on blood tests. However, information regarding grading and staging was essential for treatment decisions since the length of treatment may vary depending on the severity of le‐ sions. In patients with CHB decisions regarding the initiation of the treatment may depend on the presence of lesions in the liver tissue [8]. In both types of chronic viral hepatitis pa‐ tient with liver cirrhosis requires different approach than the child with mild lesions in the liver. In children with AIH the diagnosis was confirmed by the detection of specific inflam‐ matory cells in the liver tissue. Although the number of NAFLD was small, the procedure distinguished between simple steatosis and steatohepatitis. Patients who underwent the procedure due to HUO benefited from diagnosis in 10/12 children. Metabolic disorders were detected in 3 patients and steatosis was detected in 6 children, 1 child was found to have Wilson's disease. Normal liver histology found in the specimens from the following 2 chil‐ dren with HOU raises questions regarding indications to the liver biopsy. The decision con‐ cerning the procedure was always carefully made basing on clinical and laboratory findings. Obtained results may be a consequence of the limitations of the procedure regarding sample size and sample error related to the site of the biopsy. Diffuse liver diseases are hardly ever evenly distributed in the organ.

Another problem with pathological assessment is an intraobserver variety. Except for skill‐ ful operator, an experienced pathologist is essential for proper evaluation of the samples. However, differences in the assessment between to various pathologists are difficult to avoid even with the use of validated scoring systems.

In recent years many non-invasive methods of liver assessment were developed. Imaging techniques allow to describesteatosis, focal changes, malformations, inflammatory processes of bile ducts and advanced fibrosis. Mild changes are, however, still difficult to detect. Elas‐ tography has been developed to evaluate liver stiffness being a useful tool to assess liver fib‐ rosis [9]. Fibrosis is also evaluated by different serological markers and panels of direct and indirect markers or combination of both. Various cut-offs of the markers to detect advanced fibrosis and cirrhosis were validated in numerous studies [4]. Nevertheless, problem with intermediate stages of fibrosis still exist, since in such cases serological markers overlap.

Attempts to completely replace the biopsy with other non-invasive methods are not effec‐ tive as the collection of adequate liver sample and proper histological evaluation allows to determine the extent ofthe liver damage and helps to establish the diagnosis.
