Liver biopsy is the gold standard for diagnosis of many liver diseases and is a useful tool for follow-up. Despite the many advantages it has also drawbacks. It is an invasive maneuver that causes pain and liability for bleeding that may be life threatening. Organ perforation is one of the reported complications. Sometimes it may miss or underestimate the diagnosis as some diseases do not affect all parts of the liver evenly requiring both right and left lobe biopsy. Besides, there is inter-observer variation [13].
In the context of liver transplantation liver biopsy may be done early or late. The early indications are worsening or non-decreasing liver functions, re-rise of the liver functions after improvement and protocol biopsy. The late indications are rise of the liver enzymes from baseline, failed normalization after treated event, imaging abnormalities, and protocol biopsies [3].
The common histopathology depends on the time of the liver biopsy. Early, the diagnosis is usually small for size, acute cellular rejection, confirmation of vascular event, or severe recurrent of diseases as fibrosing cholestatic hepatitis. In the late one, it is common to find recurrent diseases as viral hepatitis, acute, or chronic rejection and sometimes recurrent malignancies [3, 4].
The need of liver biopsy till now is mandatory for diagnosis and assessment of some diseases as acute, chronic rejection, steatohepatitis, and de novo autoimmune hepatitis. Liver biopsy is needed for confirmation of uncertain laboratory or radiology diagnosis as with CMV or liver tumors. The enthusiasm of liver biopsy has faded away in many aspects and supplanted nowadays by noninvasive parameters as seen with recurrent viral hepatitis where laboratory and radiological parameters are sufficient to commence antiviral therapy.
On reviewing the studies on the utility of liver biopsy post-transplant; Yu et al. [14] analyzed 50 biopsies out of 27 patients (2002-2003). The time till biopsy ranged from 5 h to 330 days. The main histological diagnosis was acute rejection (48.2%), preservation-reperfusion injury (25.9%), chronic rejection (14.8%), hepatic artery thrombosis (11.1%), drug induced hepatitis (11.1%), CMV (3.7%), and recurrent hepatitis (3.7%).
An Iranian study [15] analyzed 382 post LT biopsies from 287 patients. The average age was 28 (1-64 years). The main indication of liver transplantation was HBV (20.2%) followed by AIH (17.7%). The time till biopsy varied from few hours till 261 days post-transplant. Acute cellular rejection was the most common finding (47%) followed by hepatic artery related ischemic changes. Some patients had normal liver histopathology (17.7%).
In another study, Kanodia et al. [16] studied 57 biopsies from 35 patients (January 2010 to July 2014). Some patients underwent repeated biopsies. The average age was 53 years and most of them were males. The mean bilirubin was 5.54 mg/dL, AST (197 U/L), ALT (298 U/L), and ALP (256 U/L). The most common indication for LT was alcoholic cirrhosis (25.71%), cryptogenic (17.14%), HBV related (17.14%), and Wilson’s disease (11.42%). Few cases with HCV, AIH, and PSC were present. The time till biopsy ranged from 1 to 980 days. The most common histological diagnosis was acute rejection (55.36%), preservation-reperfusion injury (17.86%), drug toxicity (14.29%), and recurrent HCV infection (5.36%).
Voigtlander et al. [17] reported 496 liver biopsies obtained from 312 liver transplant patients. The main indications of LT were mainly viral hepatitis (28%), PSC (19%), and acute liver cell failure (8%). The main indications for doing liver biopsy were suspected rejection (66%) and protocol biopsies (22%). Other indications were disease recurrence (7%) and unclear cholestasis (3%). The average time till liver biopsy was 27 months. The histological findings were acute cellular rejection (36%), chronic hepatitis (28%), obstructive cholangiopathy (7%), and fatty liver disease (6%).
In another report, Fonseca et al. [18] analyzed liver biopsies in Indian liver transplant center. He analyzed the explants, donor liver histopathology, and biopsies done after liver transplantation for pediatric and adult cases. About 58 biopsies were done for 42 patients (adult and pediatric). Some patients underwent repeated biopsies. In adults, the most common histopathology was acute cellular rejection.
In the current study, 89 patients were followed up where 38.2% underwent liver biopsy mainly for suspecting acute rejection or recurrent diseases especially viral ones. Some patients underwent single biopsy and some patients underwent repeated biopsies consistent with other studies [14,15,16, 18]. The average age was 44 years that is lower than Kanodia et al. [16], and higher than Geramizadeh et al. [15] as he enrolled pediatric cases. Most patients were males in agreement with Kanodia et al. [16]. In comparison to biopsy free patients, most patients had more liver dysfunction that was assessed by the ALBI score
Most of the liver functions are elevated more than 2-3 folds and the wide fluctuations were with AST, ALT, GGT, and ALP. In our center, 91.2% of cases were positive for HCV. Regarding indications of liver transplantation, the first one was HCV related decompensated liver disease followed by HCC on top of HCV related liver disease. In the other studies, the indication was different according to the geographical distribution, so in the Iranian study HBV was the main one [15], whereas alcohol in the Indian study [16].
The average time till the 1st liver biopsy was 19.88 (10-93) months. Some centers did very early liver biopsy within hours postoperatively as with Geramizadeh et al. [15], Kanodia et al. [16], and some center earlier time as with Voigtlander et al. [17]. The different histopathological diagnosis was not affected by the time till biopsy.
The first histopathological diagnosis was recurrent viral hepatitis in 50% of cases followed by acute cellular rejection, steatohepatitis, and chronic rejection. In fact, the incidence of acute cellular rejection is low (20.6%) in our study compared to 48.2% [14], 36% [17], 47% [15], and 55.36% [16]. The most probable explanation that some studies applied protocol biopsies [18] and they began earlier postoperative biopsies [15,16,17]. Acute cellular rejection is very common in the early 3 months post-transplant. Maybe the application of induction therapy with basiliximab in some cases and the triple regimen has decreased the occurrence of acute rejection in our center.
Since three studies did early biopsies, so it was common to report preservation-reperfusion injury [14, 16] and hepatic artery thrombosis [14, 15].
The incidence of recurrent viral hepatitis especially HCV was high (50%) compared to 3.7% [14], 5.36% [16], and 28% [17]. The explanation that Egypt is one of the countries of high prevalence of chronic hepatitis C [19].
Regarding liver fibrosis and histological activity, most cases were free of F4 fibrosis where most of them were F1 (38.2%) and A1 (35.3%). This was due to regular follow-up and early management of the complications.
None of the patients who underwent biopsy were free of positive diagnostic findings in contrast to Geramizadeh et al. [15], who reported that 17.7% of the patients had normal histopathology.
On correlation of the indication of liver transplant and the found histopathology, it was found that 50% of the patients with pre-transplant chronic hepatitis C had recurrent viral hepatitis.
The varied immunosuppressive drug regimen did not affect that pattern of histopathology. Few patients needed on demand second (n = 9) and third biopsy (n = 5). Sometimes the diagnosis was the same as acute rejection and some proceeded to chronic rejection. Patients with viral hepatitis proceeded to other events as rejection in the other biopsies.
The limitations of the study were small number, single centered experienced, and absence of protocol biopsies.