Role Of Liver Biopsy Research Articles

Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder

BACKGROUND AND AIMPorto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension (PH). Liver biopsy (LB) is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyl transferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. METHODSThe study included all patients who underwent LB for persistent and unexplained GGT elevation in five Italian Hepatology Units between March 2015 and December 2021. RESULTS144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only twelve (8.3%) had liver stiffness measurements (LSM) >10 kPa, 7 (4.8%) had ultrasound PH evidence. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%). Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio, OR = 2.60, 95% confidence interval, CI: 1.13-5.99), LSM < 10 kPa (OR = 11.05, 95% CI: 2.16-56.66) and GGT < 200 U/L (OR = 2.69, 95% CI: 1.22-5.98). CONCLUSIONSPSVD was the main cause of persistent and unexplained elevation of GGT. Male sex, LSM < 10kPa and GGT < 200U/l were associated with PSVD. These findings highlight the role of LB in elucidating the underlying pathology and aiding in the diagnosis of patients with persistent and unexplained GGT elevation. IMPACT AND IMPLICATIONSIn outpatient settings, it is common to encounter subjects with persistent and unexplained GGT elevation. This study reveals, for the first time, a non-negligible prevalence of porto-sinusoidal vascular disorder (PSVD) among these subjects when they undergo liver biopsy. Male sex, liver stiffness measurement (LSM) < 10 kPa, and GGT < 200 IU/L predict this histological finding.These results may raise awareness of clinically relevant conditions that may be present in patients with persistent liver enzyme changes, even in the absence of signs of advanced chronic liver disease or portal hypertension (PH). Additionally, the data may encourage further studies in the field of PSVD, particularly to define its clinical evolution in patients without signs of PH at diagnosis.

Recent advances in the diagnosis of drug-induced liver injury.

Drug-induced liver injury (DILI) is a major problem in the United States, commonly leading to hospital admission. Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes. In addition, DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease. Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems. This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.

Liver biopsy for assessment of suspected drug-induced liver injury in metabolic dysfunction-associated steatohepatitis clinical trials: Expert consensus from the Liver Forum.

Causality assessment of suspected drug-induced liver injury (DILI) during metabolic dysfunction-associated steatohepatitis (MASH) clinical trials can be challenging, and liver biopsies are not routinely performed as part of this evaluation. While the field is moving away from liver biopsy as a diagnostic and prognostic tool, information not identified by non-invasive testing may be provided on histology. To address the appropriate utilisation of liver biopsy as part of DILI causality assessment in this setting. From 2020 to 2022, the Liver Forum convened a series of webinars on issues pertaining to liver biopsy during MASH trials. The Histology Working Group was formed to generate a series of consensus documents addressing these challenges. This manuscript focuses on liver biopsy as part of DILI causality assessment. Expert opinion, guidance and recommendations on the role of liver biopsy as part of causality assessment of suspected DILI occurring during clinical trials for a drug(s) being developed for MASH are provided. Lessons learned from prior MASH programs are reviewed and gaps identified. Although there are no pathognomonic features, histologic evaluation of suspected DILI during MASH clinical trials may alter patient management, define the pattern and severity of injury, detect findings that favour a diagnosis of DILI versus MASH progression, identify prognostic features, characterise the clinicopathological phenotype of DILI, and/or define lesions that influence decisions about trial discontinuation and further development of the drug.

Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives.

In recent years, cancer immunotherapy has made remarkable achievements. Immune checkpoint inhibitors (ICIs) have been used successfully in several types of cancer in the past decade. However, expanded indication and increased use of Immune checkpoint inhibitors have resulted in increased reports of toxicity called immune-related adverse events (irAEs). Due to the unique immunological characteristics of the liver, a hepatic immune-related adverse events has also been reported, which is usually termed Immune-mediated hepatitis (IMH). So far, it is generally considered that the mechanism of IMH induced by Immune checkpoint inhibitors is mainly the overactivation of T cells. It has been reported that the incidence of IMH ranges from 1% to 15%. Because of the lack of specific markers, a diagnosis of exclusion of IMH is critical. Although most IMH is mild and recoverable, several death cases have been reported, which has been increasingly concerned. This review summarizes the current understanding of the pathophysiology, epidemiology, diagnosis, management and prognosis of IMH caused by Immune checkpoint inhibitors. It also discusses the controversial issues in IMH, such as the role of liver biopsy, grading criteria, risk factors, rational treatment strategies with steroids, and the timing of Immune checkpoint inhibitors rechallenging, which may provide helpful information for IMH in future clinical practice.

Role of Liver Biopsy in Evaluation of Fibrosis: Review Article

Role of Liver Biopsy in Evaluation of Fibrosis: Review Article

S3080 Metastatic Merkel Cell Carcinoma Presenting as Silent Infiltrative Liver Disease: A Lesson Emphasizing the Utility of Liver Biopsy in the Exclusion of Immune Checkpoint Inhibitor-Mediated Hepatotoxicity

Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor that arises on skin exposed to the sun and occurs in patients who are Caucasian, elderly, and immunocompromised. The mortality of MCC is about 33% and disseminated disease suggests poor prognosis. Metastasis to the liver is exceedingly rare, with only few reported cases presenting as infiltrative liver disease. We present a case of MCC with “silent” infiltration in the liver effectively differentiated from suspected immune checkpoint inhibitor-mediated hepatotoxicity (IMH) by liver biopsy Case Description/Methods: A 76-year-old man with a history of metastatic MCC of the left distal thigh status-post stem cell transplant presented to a cancer care center for evaluation of fatigue, nausea, and dyspnea. He reported consuming 10 alcoholic drinks a week for many years until 2 years ago. He was started on a treatment regimen of pembrolizumab and plinabulin (a phase I microtubule inhibitor) with radiation to the liver 2 months ago. On admission, serum transaminases were elevated from baseline as indicated in Table 1. After an initial period of observation, the patient was started on oral budesonide 9 mg/d and ursodiol 1000 mg/d for empiric treatment of IMH without subsequent improvement in liver enzymes. Liver imaging was unrevealing for liver lesions. A diagnostic parenchymal liver biopsy was performed to clarify the underlying diagnosis, including possible IMH, drug-induced liver injury from plinabulin toxicity, radiation-induced liver injury, or metastatic disease. Histology showed that the tumor cells were strongly positive for synaptophysin, chromogranin, and extensive metastatic MCC. The steroids were discontinued, and the worsening hepatitis was attributed to Merkel cell liver infiltration. The patient subsequently passed away 3 months later from cancer. (Figure) Discussion: Traditionally when there is high suspicion, IMH is clinically diagnosed without expectation for liver biopsy, and steroids are often prescribed upfront. One critique regarding the role of liver biopsy may be that histological features associated with IMH are nonspecific, with features of lobular to pan-lobular hepatitis. However, the absence of an alternative findings on the biopsy confers additional confidence towards the diagnosis of IMH. This case highlights the importance of the diagnostic liver biopsy prior to immunosuppressive treatment for suspected IMH to exclude other differentials and guide the decision for empiric steroids.Figure 1.: Solid nests and lobules of poorly differentiated neuroendocrine cells are seen in this liver biopsy A) Merkel cell chromogranin - Tumor cells are strongly and diffusely positive for chromogranin. B) Merkel cell CK20- Tumor cells show perinuclear dot-like reactivity to Cytokeratin20 C) Merkel cell synaptophysin- Tumor cells are strongly and diffusely positive for neuroendocrine marker Synaptophysin. Table 1. - Prior to initiating immunotherapy, serum transaminases rose slowly but remained within 3x upper limits of normal (ULN) Laboratory Value Prior to Admission On Immunotherapy Day 1 Of Admission After Initiating Steroids Aspartate Aminotransferase (AST) 41 U/L 269 U/L 281 U/L Alanine Aminotransferase (ALT) 46 U/L 315 U/L 240 U/L Alkaline Phosphatase (ALP) 87 U/L 226 U/L 227 U/L Total Bilirubin 0.3 mg/dL 0.7 mg/dL 1.1 mg/dL International Normalized Ratio (INR) 1.06 1.15 1.18 At the end of treatment, transaminases reached >5 times ULN. No improvement was seen in liver enzymes after initiating empiric steroid therapy for suspected IMH.

FRI005 - Role of liver biopsy in management of immune checkpoint inhibitors hepatitis: a single-center retrospective study

FRI005 - Role of liver biopsy in management of immune checkpoint inhibitors hepatitis: a single-center retrospective study

Role of Liver Biopsy in the Diagnosis of Liver Diseases in Children

Role of Liver Biopsy in the Diagnosis of Liver Diseases in Children

Role of liver biopsy in management of liver diseases without hepatic nodules following end of the interferon era: experience of a tertiary referral center

Liver biopsy (LB) is the cornerstone in the management of patients with liver diseases. However, a lot of queries had emerged about its role following the end of the interferon era. The aim of this study was to re-evaluate the current role of LB in the diagnosis of liver diseases. All patients who had underwent LB at the Department of Hepatology, National Liver Institute, from January 2015 through December 2018 were recruited. Indications for LB, pathology reports and medical records of all cases were retrieved, reviewed and statistically analyzed. A total of 275 liver biopsies were collected, 191 males and 84 females with mean age 41.22 ± 13.36 years. Etiological diagnosis made by histopathological evaluation was 48 drug-induced liver injury (DILI), 42 nonalcoholic fatty liver disease (NAFLD), 34 chronic hepatitis B, or C with cholestasis, 29 autoimmune hepatitis, 34 primary sclerosing cholangitis, 13 primary biliary cholangitis, 7 autoimmune overlap syndrome, 13 active bilharziasis and 10 Wilson’s disease. Minor number of cases was diagnosed by different other etiologies. Initial diagnosis was made by liver biopsy and confirmed by clinical response and laboratory findings. Liver biopsy is still considered as the gold standard diagnostic measure of different liver diseases representing an integral component of management decisions in hepatology.

Role of Liver Biopsy in the Diagnosis of Liver Diseases in Children

Role of Liver Biopsy in the Diagnosis of Liver Diseases in Children

Role of liver biopsy versus non-invasive biomarkers for diagnosis of significant fibrosis and cirrhosis: a web-based survey

BackgroundLiver biopsy is the standard reference for staging hepatic fibrosis. Non-invasive methods for assessment of hepatic fibrosis and cirrhosis are becoming increasingly popular.ObjectiveWe aimed at exploring the change in practice regarding the use of liver biopsy and non-invasive methods for staging hepatic fibrosis and cirrhosis among hepatologists.MethodsWe performed a survey-based study that recruited hepatologists from various Egyptian institutions. Physicians were deemed eligible if they had a degree in internal medicine with hepatology as a subspecialty. We utilized an online-based survey that assessed the acceptability and reliability of liver biopsy, serum biomarkers, and radiological tools for evaluating liver fibrosis and cirrhosis.ResultsA total of 573 responses were retrieved (response rate = 80.3%). Out of them, 58% were having more than 15 years of experience as a hepatologist.Liver biopsy is still considered the gold standard for assessment of hepatic fibrosis and cirrhosis by 61% of participants. Liver biopsy was accepted by 44% of their patients. 84% reported the need for a more practical alternative to liver biopsy to assess disease progression or response to treatment. 78.34% of participants know serum biomarkers, 84.08% reported that they were acceptable by their patients, 37.79% thought they are reliable. 95.4% were familiar with radiological methods of non-invasive assessment of hepatic fibrosis, 89.1% reported that radiological methods were acceptable by their patients, 62% think that they are reliable and 78% reported they were applicable in clinical practice. Sixty-five percent think that combining non-invasive methods is better than using a single method. Forty percent of participants thought that radiological methods are easier to use for assessment of hepatic fibrosis followed by a combination of non-invasive methods, serum biomarkers, and liver biopsy respectively.ConclusionIn conclusion, liver biopsy is still considered the most reliable method for evaluation and staging of liver cirrhosis by hepatologists in Egyptian institutions, despite the modest acceptance by the patients. Nonetheless, non-invasive methods are gaining acceptance by Egyptian physicians and patients, and most of them consider these methods as reliable and applicable tools for predicting the course of liver cirrhosis.

Diagnosing Small Duct Primary Sclerosing Cholangitis—A Rarer Variant of a Rare Disease: Challenges and Role of Liver Biopsy

Diagnosing Small Duct Primary Sclerosing Cholangitis—A Rarer Variant of a Rare Disease: Challenges and Role of Liver Biopsy

Review of Clinical Guidelines in the Diagnosis of Pediatric Nonalcoholic Fatty Liver Disease.

Review of Clinical Guidelines in the Diagnosis of Pediatric Nonalcoholic Fatty Liver Disease.

NAFLD: Reporting Histologic Findings in Clinical Practice.

The role of liver biopsy in NASH has evolved along with the increased recognition of the significance of this disease, and the unmet medical need it presents. Drug development and clinical trials are rapidly growing, as are noninvasive tests for markers of steatosis, inflammation, injury, and fibrosis. Liver biopsy evaluation remains necessary for both drug development and clinical trials as the most specific means of diagnosis and patient identification for appropriate intervention. This White Paper, sponsored by the American Association for the Study of Liver Disease NASH Task Force, is a focused review of liver biopsy evaluation in fatty liver disease in subjects with presumed NAFLD for practicing clinical hepatologists and pathologists. The goal is to provide succinct and specific means for reporting the histopathologic elements of NASH, distinguishing NASH from nonalcoholic fatty liver without steatohepatitis, and from alcohol-associated steatohepatitis when possible. The discussion includes the special situations of NASH in advanced fibrosis or cirrhosis, and in the pediatric population. Finally, there is discussion of semiquantitative methods of evaluation of lesions of "disease activity" and fibrosis. Tables are presented for scoring and a suggested model for final reporting. Figures are presented to highlight the histopathologic elements of NASH.

Role of percutaneous liver biopsy in infantile cholestasis: cohort from Arabs

BackgroundInvestigators from different parts of the world are calling for a re-evaluation of the role of liver biopsy (LB) in the evaluation of infantile cholestasis (IC), especially in the light of emerging non-invasive diagnostic technologies. Therefore, this retrospective single-center study was conducted to determine the impact of LB on the diagnosis and management of IC in a cohort from Arabs.MethodsFrom 2007 until 2019, 533 cases of IC were referred for evaluation. All infants who underwent LB were included in the study. We categorized the yield of LB into: (1) defined specific diagnosis; (2) excluded an important diagnosis. A single pathologist reviewed and made the histology report.Results122 LB specimens met the inclusion criteria. The main indication for LB was a high suspicion of biliary atresia (BA) [high gamma-glutamyl transferase (GGT) cholestasis and pale stool] in 46 cases (37.8%). Liver biopsy had sensitivity of 86.4%, specificity (66.7%), PPV (70.4%), NPV (84.2%) in diagnosing BA. LB had a direct impact on clinical management in 52 cases (42.6%): (1) The true diagnosis was suggested by LB in 36 cases; (2) LB excluded BA and avoided intraoperative cholangiogram in 16 cases with high suspicion of BA. Among the 76 cases with low suspicion of BA, LB suggested the true diagnosis or helped to initiate specific management in 8 cases only (10.5%). In contrast, molecular testing confirmed the diagnosis in 48 (63%).ConclusionLB continues to be an important tool in the workup of cases with a high suspicion of BA. The low yield of LB in cases with low suspicion of BA calls for a re-evaluation of its role in these cases in whom early incorporation of cholestasis sequencing gene panels can have a better diagnostic yield.

Role of Liver Biopsy in Assessment of Radiologically Identified Liver Masses.

Despite improvements in imaging techniques that have enhanced the ability to diagnose hepatocellular carcinoma (HCC), histopathological evaluation of many other types of liver masses is critical. To evaluate the utility of liver biopsy in patients with radiologically undiagnosed liver masses. We retrospectively analyzed 293 consecutive patients who had a liver biopsy for evaluation of an undiagnosed liver mass between January 2014 and January 2018. Out of 293 biopsies, 246 patients were found to have malignancy (84%), including 210 (72%) patients with metastatic malignancy and 36 with primary hepatic malignancies (20 HCC and 16 others). In the 47 patients without malignancy, 17 patients had necrotic abscess/granuloma, 16 patients had normal histology, eight patients had hepatic fibrosis/cirrhosis without malignant foci, and six patients had benign tumors. The most common primary lesion in patients with liver metastasis was breast carcinoma (32/293, 11%), followed by colon and pancreas (31 (each)/293, 11%), and lung (9%) adenocarcinomas. Histopathological analysis confirmed the presence of metastasis in 165/200 (83%) patients with a history of oncological malignancy and in 45/93 (48%) patients who had no malignancy history. In patients with a radiologically identified liver mass of unclear etiology, liver biopsy/histology made a diagnosis in 95% (277/293) of patients, including 84% (246/293) found to have an oncological malignancy. Liver biopsy/histology also identified malignancy in a high proportion of patients without known underlying cancer. We conclude that liver biopsy is valuable for evaluation of radiologically identified liver masses of unclear etiology.

Hepatic magnetic resonance elastography: can it be an alternative to invasive biopsy preceding living donor liver transplantation?

BackgroundRecently, the living donor liver transplantation (LDLT) surgery is employed as the treatment of choice for end-stage chronic liver disease and hepatocellular carcinoma. The role of liver biopsy in donor’s selection protocol for adult living liver donors (LLDs) candidates is a point of controversy. Hepatic magnetic resonance elastography (MRE) is a promising technique particularly in grading of liver fibrosis that can be used for pre-transplantation evaluation of the LLDs candidates. The aim of the current study was to evaluate the diagnostic performance of hepatic MRE as a pre-transplantation imaging tool for LLDs candidates, prior to LDLT surgery.ResultsThirty-seven eligible healthy LLDs candidates (28 males and 9 females; their ages ranged from 24 to 45 years) were the subject of the current study. A cut-off value ≥ 2.24 kilo Pascal (kPa) was assumed for discrimination between normal and abnormal hepatic tissues with high accuracy (99.24%). Also, a cut-off value ≥ 2.38 kPa for grading steatosis gave 98.44% accuracy, while a cut-off value ≥ 2.57 kPa for discriminating fibrosis stages yielded 98.80% accuracy.ConclusionMRE can be considered as a reliable non-invasive pre-transplant screening technique that has the potential to alternate the invasive liver biopsy technique in selection and validation of LLDs candidates for LDLT surgery.

Rolul biopsiei hepatice în ficatul gras nonalcoolic

Rolul biopsiei hepatice în ficatul gras nonalcoolic

Role of liver biopsy in the era of clinical prediction scores for “drug-induced liver injury” (DILI): experience of a tertiary referral hospital

The clinical implications of the biopsy findings in cases of drug-induced liver injury (DILI) are not fully elucidated. The aim of this study was to evaluate the histopathological findings of cases diagnosed as DILI and to correlate them with clinical and biochemical findings (such as causality assessment algorithms). We searched our department database for all cases of liver biopsy with findings consistent with toxic liver disease and selected those with a clinical diagnosis of DILI. The causative relationships were established according to Roussel Uclaf Causality Assessment Method (RUCAM). A total of 53 cases of DILI were reviewed, most of them diagnosed in hospitalized patients (83%). The analytical toxicity profile was hepatocellular (R > 5) in 60% of the cases and cholestatic (R < 2) in 26.4% of cases. The group of drugs most implicated was the anti-microbials (18, 34%). The predominant histological patterns were "necroinflammation" (67.9%) and "cholestasis" (28.3%). The hepatocellular biochemical pattern was not associated with the presence of predominantly necroinflammatory findings in the biopsy (p = 0.44), and the biochemical cholestatic pattern was not associated with the presence of predominantly cholestatic findings in the biopsy (p = 0.51). This study supports that a better insight into the pathologic mechanisms associated with DILI should be based on liver biopsy due to the lack of a uniform correlation between clinical and biochemical patterns. Also, a liver biopsy may be used in those cases where clinical suspicion of DILI persists despite a low score on current causality assessment algorithms.

Safety and Role of Liver Biopsy in Diagnosing Liver Diseases Using a 5-Point Diagnostic Scale among Infants and Children

Introduction: Histological diagnosis is gold standard in many of the pediatric onset liver diseases. The safety and efficacy of the liver biopsy is less studied in infants and children, even though it is more often performed than in adult. We retrospectively reviewed the patients who had undergone percutaneous liver biopsy (LB) to assess the safety and role in the diagnosis of liver diseases.