• Biliary atresia
• Biomarkers
• Diagnosis
• Liver fibrosis
• Native liver survival

Chronic Hepatitis C (CHC) affects 71 million people globally and leads to liver issues such as fibrosis, cirrhosis, cancer, and death. A better understanding and prognosis of liver involvement are vital to reduce morbidity and mortality. The accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting outcomes. Tests used to grade fibrosis include histological analysis and imaging but have limitations. Blood markers such as molecular biomarkers can offer valuable insights into fibrosis.

To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the disease.

Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1 (n = 13), F2 (n = 12), F3 (n = 6), and F4 (n = 15). To ensure that the identified biomarkers were exclusive to liver lesions (CHC fibrosis), healthy volunteer participants (n = 50) were also included. An untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database verification. Statistical analyses were performed to identify differential biomarkers among groups.

Six differential metabolites were identified in each grade of fibrosis. This six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis; thus, they showed greater efficiency in discriminating grades.

This study suggests that some of the observed biomarkers, once validated, have the potential to be applied as prognostic biomarkers. Furthermore, it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

• Chronic Hepatitis C
• Fibrosis
• Metabolome
• Biomarkers
• Plasma
• Liquid biopsy

• Elastography
• Endoscopic ultrasonography
• Fine needle aspiration
• Fine needle biopsy
• Hepatic focal lesions

• Biopsy
• Children
• Cirrhosis
• Embolization
• Interventional radiology
• Liver
• Portal hypertension
• Transjugular intrahepatic portosystemic shunt

• Endoscopic ultrasound guided liver biopsy
• Liver biopsy
• Liver parenchymal disease
• Percutaneous liver biopsy
• Portal pressure gradient
• Transjugular liver biopsy

• Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods
• Endosonography/methods
• Humans
• Image-Guided Biopsy/adverse effects
• Image-Guided Biopsy/methods
• Liver Diseases/pathology

• Computers
• Endosonography/methods
• Humans
• Neoplasm Staging
• Neoplasms
• Tomography, X-Ray Computed

• Elastography
• Endoscopic ultrasound
• Liver biopsy
• Liver disease
• Liver tumor
• Varices

• biomarkers
• complications
• liver fibrosis
• primary biliary cholangitis
• prognosis

• Aged
• Biomarkers/blood
• Biopsy
• Disease Progression
• Female
• Humans
• Liver Cirrhosis, Biliary/blood
• Liver Cirrhosis, Biliary/mortality
• Liver Cirrhosis, Biliary/pathology
• Male
• Middle Aged
• Retrospective Studies
• Severity of Illness Index

• Acoustic radiation force impulse
• Laparoscopy
• Liver biopsy
• Liver fibrosis

Accurate needle placement in deep-seated liver tumours can be difficult. In this work, we disclose two new manually controlled steerable needles for 17G radio-frequency ablation probe placement. The needles contain stylets with embedded compliant joints for active tip articulations, and concentric tubes for (curved-path) guidance. Needle steering was evaluated sequentially by intended users and in intended-use tissue types. Six interventional radiologists evaluated the needle in repeated ultrasound-guided steering tasks in liver-mimicking phantoms. Targets were located at a 100 mm depth and 20 mm lateral offset from the initial insertion line. The resulting mean absolute tip placement error was 1.0 ± 1.0 mm. Subsequently, steering-induced tissue damage was evaluated in fresh cirrhotic human liver explants. The surface area of puncture holes was estimated in scanned histology slides, using a connected-components analysis. The mean surface area was 0.26 ± 0.16 mm² after steering with a median radius of curvature of 0.7 × 10³ mm, versus 0.35 ± 0.15 mm² after straight-path insertions with the steerable needle and 0.15 ± 0.09 mm² after straight-path RFA probe insertions. The steering mechanisms proposed enable clinically relevant path corrections for 17G needles. Radiologists were quickly adept in curved-path RFA probe placement and the evaluation of histological tissue damage demonstrated a potentially safe use during liver interventions.

• ESPL1
• biomarker
• hepatitis B virus
• hepatocellular carcinoma
• integration

Percutaneous liver biopsy (PCLB) or transjugular liver biopsy (TJLB) have traditionally been performed to obtain a sample of hepatic tissue; however, endoscopic ultrasound-guided liver biopsy (EUSLB) has become an attractive alternative. The aim of this study was to compare the efficacy and safety of EUSLB, PCLB, and TJLB.

Search strategies were developed in accordance with PRISMA and MOOSE guidelines. Major outcomes included the following: adequacy of biopsy specimens (i.e., complete portal triads [CPT], total specimen length [TSL] in mm, and length of longest piece [LLP]) in mm), and rate of adverse events. Only studies comparing all biopsy approaches (i.e., EUSLB, PCLB, and TJLB) were included.

Five studies (EUSLB [n=301]; PCLB [n=176]; and TJLB [n=179]) were included. Biopsy cumulative adequacy rates for EUSLB, PCLB, and TJLB were 93.51%, 98.27%, and 97.61%, respectively. Based on the subgroup analysis limited to EUS biopsy needles in current clinical practice, there was no difference in biopsy adequacy or adverse events for EUSLB compared to PCLB and TJLB (all p>0.050). A comparison of EUSLB and PCLB revealed no difference between specimens regarding both CPT (p=0.079) and LLP (p=0.085); however, a longer TSL (p<0.001) was observed. Compared to TJLB, EUSLB showed no difference in LLP (p=0.351), fewer CPT (p=0.042), and longer TSL (p=0.005).

EUSLB appears to be a safe, minimally invasive procedure that is comparable to PCLB and TJLB regarding biopsy specimens obtained and rate of adverse events associated with each method.

• Endoscopic ultrasound (EUS)
• Interventional endoscopy
• Liver biopsy

Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists. Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People’s Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions. Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases. Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials.

• NAFLD
• NASH fibrosis
• qFibrosis

More than five years ago, the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral (DAA) drugs. They proved highly efficient in curing patients with chronic hepatitis C (CHC), including patients with cirrhosis. The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis, but the exact cause of the expected benefit was unclear. Further, little was known about how the underlying liver disease would be affected during and after viral clearance. In this review, we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects, such as macrophage activation, and the time-dependent effects of therapy, with specific emphasis on inflammation, structural liver changes, and liver function, as these factors are all related to morbidity and mortality in CHC patients. It seems clear that antiviral therapy, especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis. There seems to be a time-dependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions. These improvements lead to favorable effects on liver function, followed by an improvement in cognitive dysfunction and portal hypertension. Overall, the data provide knowledge on the several beneficial effects of DAA therapy on liver-related parameters in CHC patients suggesting short- and long-term improvements in the underlying disease with the promise of an improved long-term prognosis.

• Chronic hepatitis C
• Antiviral treatment
• Inflammation
• Liver fibrosis
• Liver cirrhosis
• Metabolic liver function
• Galactose elimination capacity
• Urea synthesis capacity
• Portal hypertension
• Hepatic encephalopathy

• Antiviral Agents/therapeutic use
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Humans
• Liver Cirrhosis/drug therapy
• Sustained Virologic Response
• Treatment Outcome

• Core biopsy
• Endoscopic ultrasound guided liver biopsy
• Fine-needle aspiration
• Fine-needle biopsy
• Liver biopsy
• Percutaneous liver biopsy
• Transjugular liver biopsy

• AGA, American Gastroenterology Association
• ALT, alanine aminotransferase
• APRI, AST-platelet ratio index
• AST, aspartate aminotransferase
• AUC, area under the curve
• BMI, body mass index
• Biomarkers
• CAP, controlled attenuation parameter
• CHB, chronic hepatitis B
• CHC, chronic hepatitis C
• CLD, chronic liver disease
• CPA, collagen proportionate area
• DAA, direct-acting antiviral
• ELF, enhanced liver fibrosis
• Elastography
• FIB-4, fibrosis-4
• FLIP, fatty liver inhibition of progression
• HCC, hepatocellular carcinoma
• IFN, interferon
• LSM, liver stiffness measure
• Liver biopsy
• MR, magnetic resonance
• MRE, magnetic resonance elastography
• NAFLD, non-alcoholic fatty liver disease
• NFS, NAFLD fibrosis score
• NITs, non-invasive tests
• Non-alcoholic fatty liver disease
• SVR, sustained virologic response
• US, ultrasound
• VCTE, vibration-controlled transient elastography
• Viral hepatitis

• Hepatocellular carcinoma
• Liquid biopsy
• Liver biopsy
• Liver cancer
• Prognostic factors
• Recurrence

• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/genetics
• Biopsy/adverse effects
• Biopsy/methods
• Biopsy/standards
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/genetics
• Clinical Decision-Making/methods
• Diagnostic Errors
• Humans
• Liver/diagnostic imaging
• Liver/pathology
• Liver Cirrhosis/complications
• Liver Cirrhosis/pathology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/drug therapy
• Liver Neoplasms/genetics
• Molecular Targeted Therapy/methods
• Neoplasm Seeding
• Patient Selection
• Practice Guidelines as Topic
• Precision Medicine/methods
• Prognosis

Liver biopsy is the main method for grading and staging liver disorders, but the effects of clinical information and optimal biopsy specimen size on interpretation remain contentious. The aim of the study was to evaluate the impact of clinical information and quality of liver specimen on inter-observer agreement for liver disease.

A total of 289 consecutive biopsy specimens from 2010 to 2017 were re-evaluated by five pathologists using the modified Ishak and non-alcoholic fatty liver diseases (NAFLD) activity score (NAS) systems. Detailed clinical information was extracted from medical records of patients and the size of all liver biopsy samples was recorded.

Full agreement between primary diagnosis and final diagnosis was obtained in 214 cases (74%). The remaining cases, namely 22 (7.6%) and 53 (18.3%) biopsies had minor and major diagnostic discrepancies, respectively. The results showed that the overall agreement was significantly higher in cases with complete clinical information than patients without any clinical information and even with partial clinical information (P<0.001). Interestingly, no significant difference in inter-observer agreement was achieved with a length over 20 mm (P=0.181). However, the inter-observer variation significantly decreased when the number of portal tract was more than 10 (P=0.001).

This study identified the impact of clinical information and the number of portal tracts as the key factors to diagnosis. Therefore, request forms for liver biopsies should always be accompanied with the clinical history. Moreover, adequacy of biopsy specimens is very useful for accurate evaluation of samples by pathologists.

• Grading
• Inter-observer
• Liver biopsy
• Pathology
• Staging

Sampling size variability of liver biopsy remains a major limitation in the assessment of liver fibrosis. We aimed to evaluate the diagnostic value of a fully quantitative method (second harmonic generation/two-photon excitation fluorescence, SHG/TPEF based) in “short” liver biopsy samples.

Liver biopsy samples from chronic hepatitis B (CHB) patients were constructed into “virtual” biopsies with different lengths. The original and “virtual” samples were measured by SHG/TPEF-based technology to obtain qFibrosis score, respectively. Here, ΔqFibrosis was defined as difference of qFibrosis between original biopsy and “virtual” biopsy. Equivalence test was used to compare ΔqFibrosis with the clinically acceptable error (deviation of 0.50) in each group.

In real-world practice, qFibrosis score increased significantly with fibrosis progression in ≥ 1.5-cm-, 1.0–1.5-cm-, and 0.5–1.0-cm-long specimens (p < 0.05), compared with ≤ 0.5-cm-long specimens (p > 0.05). In virtual biopsy samples with specified length, the equivalence was confirmed in 0.5–1.0-cm- and 1.0–1.5-cm-long specimens (0.27 vs. 0.22, p < 0.001), whereas not in ≤ 0.5-cm-long specimens (0.53, p > 0.05). The number of cross-linked collagen fibers, the total and aggregated collagen proportionate area, and the collagen strings in number, length, width and perimeter showed excellent consistency with original biopsy samples in 0.5–1.0-cm- and 1.0–1.5-cm-long specimens (ICC > 0.90).

The use of SHG/TPEF-based image technology may give useful suggestive information in evaluation of CHB-related liver fibrosis for the short sample (biopsy length > 0.5 cm).

The online version of this article (10.1007/s12072-019-09955-2) contains supplementary material, which is available to authorized users.

• Liver biopsy
• Liver fibrosis
• Quantification
• Sampling error

• Child
• Contrast Media
• Elasticity Imaging Techniques/methods
• Elasticity Imaging Techniques/trends
• Hemangioma/diagnostic imaging
• Humans
• Imaging, Three-Dimensional/methods
• Imaging, Three-Dimensional/trends
• Ultrasonography, Doppler, Color/methods
• Ultrasonography, Doppler, Color/trends

• Endoscopic ultrasound
• Fine needle biopsy
• Liver biopsy
• Non-alcoholic steatohepatitis

To investigate the value of ultrasound elastography combined with serological indexes in diagnosing liver fibrosis and assessing its severity.

A total of 338 chronic hepatitis B (CHB) patients were divided into a disease group (patients with hepatic fibrosis) and control group (subjects without hepatic fibrosis). The disease group was further divided into S1-S4 according to the degree of fibrosis. Independent risk factors for hepatic fibrosis were analyzed using multivariate logistic regression. The diagnostic values of hepatic fibrosis from different indicators were compared using receiver operating characteristic (ROC) curves. The combination of elastography and serological indexes was explored to assess the severity of hepatic fibrosis.

The multivariate logistic regression analysis results revealed that shear wave velocity (SWV), hyaluronic acid (HA), type IV collagen (CIV) and aspartate aminotransferase-to-platelet ratio index (APRI) significantly affected the occurrence of hepatic fibrosis. The ROC curve revealed that the accuracy of the diagnosis of hepatic fibrosis for SWV and HA were 87.3% and 84.8%, respectively. The accuracy of SWV combined with HA was 88.9%. The multiple linear regression analysis revealed that SWV, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), HA, CIV, APRI and fibrosis index based on the 4 factor (FIB-4) were screened as statistically significant independent factors. The established regression equation was: Fibrosis level = -4.046 + 1.024 × SWV + 1.170 × AST/ALT + 0.011 × HA + 0.020 × CIV + 0.719 × APRI + 0.379 × FIB-4.

SWV combined with serological indexes can improve the accuracy of diagnosis for CHB hepatic fibrosis. Serum indexes can help diagnose the degree of hepatic fibrosis.

• Elastography
• Serology
• Hepatic fibrosis
• Non-invasive diagnosis

• Acoustics
• Adult
• Alanine Transaminase/blood
• Area Under Curve
• Aspartate Aminotransferases/blood
• Biopsy
• Collagen Type IV/metabolism
• Elasticity Imaging Techniques
• Female
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/diagnosis
• Humans
• Hyaluronic Acid/blood
• Linear Models
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Male
• Middle Aged
• Multivariate Analysis
• Platelet Count
• ROC Curve
• Regression Analysis
• Reproducibility of Results
• Risk Factors

• Hepatocarcinogenesis
• Liver fibrosis
• M2BPGi

In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly interfere with elastography-based techniques, and longitudinal follow-up strategies must be tailored in light of these findings. Knowledge of different test modalities and diagnostic performance indicators can allow for better clinical decision-making and resource allocation.

• biomarkers
• chronic hepatitis C
• elastography
• fibrosis
• staging

Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic hepatitis (CH). The development of fibrosis is a crucial event in the progression of hepatic disease that is of prognostic value. The pathophysiology of hepatic fibrosis in human patients and rodent models has been studied extensively. Although less is known about this process in dogs, evidence suggests that fibrogenic mechanisms are similar between species and that activation of hepatic stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs requires histopathological examination of a liver biopsy specimen. However, performing a liver biopsy is invasive and assessment of fibrotic stage is complicated by the absence of a universally accepted staging scheme in veterinary medicine. Serum biomarkers that can discriminate among different fibrosis stages are used in human patients, but such markers must be more completely evaluated in dogs before clinical use. When successful treatment of its underlying cause is feasible, reversal of hepatic fibrosis has been shown to be possible in rodent models and human patients. Reversal of fibrosis has not been well documented in dogs, but successful treatment of CH is possible. In human medicine, better understanding of the pathomechanisms of hepatic fibrosis is leading to the development of novel treatment strategies. In time, these may be applied to dogs. This article comparatively reviews the pathogenesis of hepatic fibrosis, its diagnosis, and its treatment in dogs.

• Antifibrotic
• Chronic hepatitis
• Fibrogenesis
• Hepatic stellate cell

• Adult
• Aged
• Area Under Curve
• Case-Control Studies
• Chronic Disease
• Elasticity Imaging Techniques/methods
• Female
• Humans
• Liver/diagnostic imaging
• Liver Diseases/diagnostic imaging
• Liver Diseases/pathology
• Male
• Middle Aged
• Prospective Studies
• ROC Curve
• Reproducibility of Results
• Severity of Illness Index
• Young Adult

• Italian Minister of Health

• Fib-4
• Fibrofast (FIB-5)
• Hepatitis C genotype 4
• Liver biopsy
• Liver fibrosis

• Adult
• Alanine Transaminase/blood
• Alkaline Phosphatase/blood
• Aspartate Aminotransferases/blood
• Biomarkers/blood
• Biopsy
• Cross-Sectional Studies
• Egypt/epidemiology
• Genotype
• Hepacivirus/genetics
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/pathology
• Hepatitis C, Chronic/virology
• Humans
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/complications
• Liver Cirrhosis/pathology
• Middle Aged
• Platelet Count/methods
• Point-of-Care Testing
• RNA Viruses/genetics
• Serum Albumin/analysis

Changes in liver structure are an important issue in chronic hepatopathies. Until the end of the 20^th century, these changes could only be determined by histological analyses of a liver specimen obtained via biopsy. The well-known limitations of this technique (i.e., pain, bleeding and the need for sedation) have precluded its routine use in follow-up of patients with liver diseases. However, the introduction of non-invasive technologies, such as ultrasound and magnetic resonance imaging, for measurement of liver stiffness as an indirect marker of fibroses has changed this situation. Today, several non-invasive tools are available to physicians to estimate the degree of liver fibrosis by analysing liver stiffness. This review describes the currently available tools for liver stiffness determination that are applicable to follow-up of liver fibrosis/cirrhosis with established clinical use in children, and discusses their features in comparison to the “historical” tools.

• Children
• Transient elastography
• Liver fibrosis
• Liver biopsy

• Fibrosis regression
• Hepatitis C cure
• Liver-related outcomes
• Non-invasive markers of fibrosis
• Sustained virologic response

• Chronic liver disease
• Cirrhosis
• Graft fibrosis
• Hepatitis B
• Hepatitis C
• Invasive assessment, non-invasive assessment
• Liver fibrosis
• Non-alcoholic steatohepatitis

• Biopsy
• Consensus
• Cost-Benefit Analysis
• Elasticity Imaging Techniques/economics
• Elasticity Imaging Techniques/methods
• Humans
• Liver Cirrhosis/diagnosis
• Observer Variation
• Practice Guidelines as Topic

• Diagnosis, Differential
• Diagnostic Errors/prevention & control
• Elasticity Imaging Techniques/methods
• Elasticity Imaging Techniques/trends
• End Stage Liver Disease/complications
• End Stage Liver Disease/diagnostic imaging
• Evidence-Based Medicine
• Humans
• Image Enhancement/methods
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnostic imaging

• R37 EB001981 NIBIB NIH HHS

• Adult
• Elasticity Imaging Techniques/methods
• Fatty Liver/diagnostic imaging
• Female
• Humans
• Liver/diagnostic imaging
• Liver Cirrhosis/diagnostic imaging
• Male
• Middle Aged
• Multivariate Analysis
• Non-alcoholic Fatty Liver Disease/diagnostic imaging
• Odds Ratio
• Predictive Value of Tests

• Korea Healthcare Technology R&D project, the Ministry of Health and Welfare

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis.

• Cirrhosis
• Elastography
• Portal hypertension
• Ultrasound
• Viral hepatitis

• Interventional radiology
• ablation
• drug-eluting beads
• embolization
• hepatocellular carcinoma
• liver biopsy

• Cytology
• Peritoneal lavage
• Stomach neoplasms
• Variation

Natural killer (NK) cells are considered to play a critical role in liver disease. However, the available numbers of intrahepatic lymphocytes (IHL) derived from liver biopsies (LB) for ex vivo analysis of intrahepatic NK cells is very limited; and the isolation method may hamper not only yields and viability, but also phenotype and function of IHL. The aim of the present study was therefore to (1) refine and evaluate the cell yields and viability of a modified isolation protocol from standard size needle LB; and (2) to test the effects of mechanical dissociation and enzymatic tissue digestion, as well as the analysis of very low cell numbers, on the phenotype and function of intrahepatic NK cells. Peripheral blood mononuclear cells (PBMC) and IHL, freshly isolated from the peripheral blood, LB (n = 11) or partial liver resections (n = 5), were used for phenotypic analysis by flow cytometry. NK cell function, i.e., degranulation and cytokine production, was determined by staining of CD107a and intracellular IFN-γ following in vitro stimulation. The mean weight of the LB specimens was 9.1 mg, and a mean number of 7,364 IHL/mg were obtained with a viability of >90%. Exposure of IHL and PBMC to 0.5 mg/ml collagenase IV and 0.02 mg/ml DNase I for 30 min did affect neither the viability, NK cell function, nor the percentages of CD56⁺, NKp46⁺, and CD16⁺ NK cells, whereas the level of CD56 surface expression was reduced. The phenotype of LB-derived NK cells was reliably characterized by acquiring as few as 2,500 IHL per tube for flow cytometry. The functional assay of intrahepatic NK cells was miniaturized by culturing as few as 25,000 IHL in 25 μl (10⁶/ml) using 96-well V-bottom plates with IL-2 and IL-12 overnight, followed by a 4 h stimulation with K562 cells at a NK:K562 ratio of 1:1. In summary, we report reliable phenotypic and functional analyses of small numbers of intrahepatic NK cells isolated from LB specimens providing us with a tool to better address the emerging role of human NK cell immunobiology in liver diseases.

• CD107a
• IFN-γ
• collagenase
• flow cytometry
• human NK cells
• intrahepatic lymphocytes
• liver biopsy

AIM: To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus (HDV) and to identify the factors that would be predictive of the sustained viral response (SVR).

METHODS: This prospective study was conducted in Medical Unit IV of the Liaquat University of Medical and Health Sciences Hospital Jamshoro from June 2008 to September 2011. This study cohort included all patients of either sex who presented during this time with hepatitis B surface antigen positivity, hepatitis B virus DNA > 20 000 IU/mL, serum glutamic pyruvic transaminase (SGPT) > 2(upper limit of normal), HDV-RNA positivity with fibrosis stage ≥ 2. Informed consent was obtained from each of these individuals. Patients were diagnosed with hepatitis D on the basis of detectable viral antibodies and the presence of HDV-RNA in their serum. A liver biopsy was performed in all cases and fibrosis staging was performed in accordance with the METAVIR scoring system. All eligible patients were administered peg-interferon at a weekly dosage of 1.5 μg/kg body weight for 48 wk. HDV-RNA was assayed at the end of this treatment period and again at 24 wk later. A biochemical response was determined by a normalization of SGPT at the end of the treatment or during follow up. The end of treatment response was defined by a HDV-RNA negative status. A sustained virological response was defined by undetectable serum HDV-RNA at six months after the end of treatment.

RESULTS: Among the 277 patients enrolled in our present study, 238 completed a course of peg-interferon therapy of which 180 (75.6%) were male and 58 (24.4%) female. Biochemical responses were achieved in 122/238 (51.3%) patients. End of treatment responses were achieved in 71/238 (29.8%) cases. A SVR was achieved in 70 of these patients (29.4%). A strong association was found between the SVR and the end of treatment responses (P = 0.001), biochemical responses (P = 0.001) and the degree of fibrosis (P = 0.002).

CONCLUSION: Peg-interferon therapy can induce remission in nearly one third of patients harboring HDV.

• Hepatitis D
• Peg-interferon
• Biochemical response

Primary malignant liver mesenchymal tumor is a rare condition defined as a tumor with vascular, fibrous, adipose, and other mesenchymal tissue differentiation. We report a case of primary malignant liver mesenchymal tumor in a 51-year-old male with anemia, weight loss and hepatomegaly. Finally unconventional liver biopsy and histological manifestation led to the definitive diagnosis.

• Hepatic mesenchymal tumor
• Liver biopsy
• Hepatic leiomyosarcoma
• Hepatic schwannoma

AIM: To analyze whether computer-enhanced dynamic analysis of elastography movies is able to better characterize and differentiate between different degrees of liver fibrosis.

METHODS: The study design was prospective. A total of 132 consecutive patients with chronic liver diseases and healthy volunteers were examined by transabdominal ultrasound elastography. All examinations were done by two doctors.

RESULTS: Due to the limitations of the method, we obtained high-quality elastography information in only 73.48% of the patients. The κ-means clustering method was applied to assess the inter-observer diagnosis variability, which showed good variability values in accordance with the experience of ultrasound examination of every observer. Cohen’s κ test indicated a moderate agreement between the study observers (κ = 0.4728). Furthermore, we compared the way the two observers clustered the patients, using the test for comparing two proportions (t value, two-sided test). There was no statistically significant difference between the two physicians, regardless of the patients’ real status.

CONCLUSION: Transabdominal real-time elastography is certainly a very useful method in depicting liver hardness, although it is incompletely tested in large multicenter studies.

• Elastography
• Ultrasonography
• Liver steatosis
• Viral hepatitis
• Liver cirrhosis

• biomarkers
• fibroscan
• fibrotest
• histology
• liver biopsy
• noninvasive assessment

Assessment of hepatic fibrosis is important for determining prognosis, guiding management decisions, and monitoring disease. Histological evaluation of liver biopsy specimens is currently considered the reference test for staging hepatic fibrosis. Since liver biopsy carries a small but significant risk, noninvasive tests to assess hepatic fibrosis are desirable. This editorial gives an overview on noninvasive methods currently available to determine hepatic fibrosis and their diagnostic accuracy for predicting significant fibrosis and cirrhosis in chronic hepatitis C. Based on available data, the performance of simple tests derived from routine laboratory parameters appears to be similar to that of more complex and expensive fibrosis panels. Transient elastography seems more accurate than blood tests for diagnosing cirrhosis.

• Noninvasive fibrosis tests
• Significant fibrosis
• Cirrhosis
• Biomarkers
• Transient elastography

• Biomarkers/metabolism
• Biopsy
• Elasticity
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/pathology
• Humans
• Liver/enzymology
• Liver/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Liver Cirrhosis/pathology
• Predictive Value of Tests