Patients Underwent Liver Biopsy Research Articles

Fecal Fungi Dysbiosis in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) can systematically harm more aspects of human health than just the liver. In addition to the potential roles of the gut microbiota in NAFLD, commensal fungi can functionally replace intestinal bacteria in maintaining the host immune response in the gut by reversing disease susceptibility. Therefore, gut commensal fungi should be studied to help understand NAFLD. The fungal compositions of 79 patients with NAFLD and 34 matched healthy subjects were studied via internal transcribed spacer sequencing. In the NAFLD group, 32 patients underwent liver biopsies to evaluate the associations between gut fungi and NAFLD development. The fungal microbiota distribution was skewed in the patients with NAFLD. The relative abundances of Talaromyces, Paraphaeosphaeria, Lycoperdon, Curvularia, Phialemoniopsis, Paraboeremia, Sarcinomyces, Cladophialophora, and Sordaria were higher in patients with NAFLD, whereas the abundances of Leptosphaeria, Pseudopithomyces, and Fusicolla were decreased. Patients with NAFLD exhibited more co-occurring fungal intrakingdom correlations. Several fungi were found to be associated with liver injury, lipid metabolism, and the development of NAFLD. This study found that gut fungi may play some roles in NAFLD development. Research on gut fungi may be of great value in diagnosing and monitoring NAFLD.

Feasibility and Safety of Transjugular Liver Biopsy for Japanese Patients with Chronic Liver Diseases.

Background and study aim: Transjugular liver biopsy (TJLB) can be used in patients who are ineligible for percutaneous liver biopsy (PLB) with acute and chronic hepatic disease. This study aimed to evaluate the usefulness and safety of TJLB in patients who were not indicated for PLB. Methods: Between July 2014 and February 2019, a total of 134 patients underwent liver biopsies at our institution. Among these, PLB was performed in 110 patients and TJLB in 24 patients. A retrospective comparison of clinical results in these patients was then performed. The primary endpoints of this study were the utility and safety of TJLB in patients who were not indicated for PLB. Results: The procedural success rate was 100% in both groups. The clinical response rate and the effective tissue sampling rate were 100% in the TJLB group and 97% in the PLB group (p = 0.55). There was no difference in the number of portal fields examined retrospectively between the two groups. No serious adverse events were observed in either group. Conclusions: It is suggested that TJLB is useful because it can be safely performed in patients with poor general condition who are not indicated for PLB.

Clinical features of 35 Down syndrome patients with transient abnormal myelopoiesis at a single institution

Transient abnormal myelopoiesis (TAM) is a unique clonal myeloproliferation characterized by immature megakaryoblasts that occurs in 5-10% of neonates with Down syndrome (DS). Although TAM regresses spontaneously in most patients, approximately 20% of TAM cases result in early death, and approximately 20% of survivors develop acute megakaryoblastic leukemia (AMKL). We retrospectively reviewed records of 35 DS patients with TAM to determine the correlation between clinical characteristics and blast percentage. Thirteen of the 35 patients were classified as low blast percentage TAM (LBP-TAM), defined as TAM with a peak peripheral blast percentage ≤ 10%. Although no patient with LBP-TAM experienced systemic edema, disseminated intravascular coagulation, or early death, eight patients had elevated direct bilirubin levels (> 2mg/dl) and one developed AMKL. All patients with LBP-TAM had serum markers of liver fibrosis that exceeded the normal limits, and two patients underwent liver biopsy to clarify the etiology of pathological jaundice. Taken together, our results suggest that patients with LBP-TAM may be at risk of liver fibrosis and liver failure, similarly to patients with classical TAM. Although these patients generally have a good prognosis, they should be carefully monitored for potential development of liver disease and leukemia.

Are noninvasive biochemical parameters an alternative to liver biopsy in patients with chronic hepatitis B?

Aim: Although there is a gold standard liver biopsy in showing the histological activity of the disease, there are contradictory results in the studies conducted for using some non-invasive methods that are alternatively biochemically calculated due to being an invasive procedure. We aimed to investigate the relationship of FIB-4, APRI, API and AAR values with histopathology in patients undergoing liver biopsy due to chronic hepatitis B virus (HBV) infection.Materials and Method: Patients with follow-up between November/2016-October/2019 with the diagnosis of chronic HBV were included. Demographic data and histopathological data were documented. Accompanying comorbid diseases, medications and previous operations were questioned. Patients were grouped as mild, moderate and advanced fibrosis according to fibrosis scoring. Sensitivity, specificity, cutt-of, AUC values of biochemical parameters were calculated between the groups.Results: A total of 151 patients, 64(42.3%) women, were included in the study. As a result of the liver biopsy; mild fibrosis was found in 73(48.3%) patients, moderate fibrosis in 33(21.8%) patients and advanced fibrosis in 45(29.9%) patients. There was a significant correlation between fibrosis level and age, liver function tests, bilirubin and albumin (p<0.05). While there was no relationship between fibrosis stage and HBV-DNA, there was a significant relationship between groups with AAR, API, APRI and FIB4 (p<0.05).Conclusions: Although FIB-4, APRI, AAR and API values are important in determining the level of hepatic fibrosis, the effect of biochemical parameters on various factors negatively affects the specificity and sensitivity of these tests. For this reason, liver biopsy is still seen as the gold standard.

Factors Influencing Transient Elastography in Detecting Liver Stiffness

Transient elastography (TEE) is a method used for estimating liver fibrosis by measuring the liver stiffness (LSM). Aim of this study was to investigate whether TEE fibrosis scores and liver biopsy fibrosis scores are comparable. It was a Cross sectional study of patients undergoing liver biopsy because of high TEE with persistent transaminitis/normal TEE with persistent transaminitis/high TEE with normal transaminases. TEE fibrosis score of study population was compared to liver biopsy fibrosis scores, which is considered as gold standard, and patients with discordance of more than one fibrosis stage was analyzed with above mentioned variables which can affect TEE. Characteristics of the discordant population was analysed. After applying spearmanˊs correlation it was found that albumin, Total bilirubin and INR had a strong correlation with TEE values. Multiple regression analysis showed albumin and SGOT were independent predictors of Liver stiffness measurement. The discordant population was again analysed after classifying it into two groups i.e F 0-2 (minimal fibrosis) and F 3 (significant fibrosis based on biopsy). After analysis it was found that in F 0-2 group there were certain variables like SGPT, Albumin and INR which had strong correlation with TEE values. Total bilirubin and platelets had moderate correlation with TEE values. After analysing F3 group, age had strong positive correlation with TEE values. TEE was found to be better in detecting liver stiffness than liver biopsy in clinically suspected cirrhosis in this study.

The Predictive Value of Mean Platelet Volume for Liver Fibrosis in Children With Chronic Liver Diseases

Introduction: Almost all causes of chronic liver damage can culminate in liver fibrosis and ultimately cirrhosis. Studies have suggested a relationship between mean platelet volume (MPV) and liver fibrosis; however, this needs confirmation by further studies. We here assessed the predictive value of MPV for liver fibrosis in children with chronic liver diseases. Methods: In this study, children &lt;18 years old with chronic liver diseases referred to the Nemazee Hospital of Shiraz during 2013-2016 were studied. The patients underwent liver biopsy for assessing liver fibrosis. Statistical analyses were conducted in SPSS 23. Results: From 368 studied children, 52.2% were boys. The patients’ mean age was 4.5±3.9 years old. Most patients had grade 6 fibrosis (36.7%). Cryptogenic (42.7%) was the most common cause of chronic liver disease, and jaundice was the most prevalent clinical presentation (53%). There was a significant association between the liver fibrosis and MPV (P=0.025). Conclusion: MPV was significantly different between patients with different severities of liver fibrosis. However, assigning an appropriate cut off value to distinguish different degrees of fibrosis requires more studies.

Non-invasive testing for liver pathology in alpha-1 antitrypsin deficiency

BackgroundMany patients with alpha-1 antitrypsin deficiency (A1ATD) receive care in respiratory clinics without access to specialist hepatology expertise. Liver disease can develop asymptomatically, and non-invasive markers of fibrosis may help...

Non-alcoholic fatty liver disease does not increase dementia risk although histology data might improve risk prediction

Background & AimsNon-alcoholic fatty liver disease (NAFLD) is common in the general population, but its association with dementia is unclear. We aimed to assess the risk of dementia related to NAFLD, and to determine whether histological parameters could improve the predictive capacity of a conventional risk model for dementia in patients with biopsy-proven NAFLD.MethodsA retrospective matched cohort study of 656 NAFLD patients underwent liver biopsy at 2 hospitals between 1971 and 2009. Up to 10 individuals (controls) from the general population (n = 6,436) were matched for age, sex, and municipality to each patient. Dementia was ascertained from National registers until 2014. Using Cox regression, we estimated hazard ratios for dementia with 95% confidence intervals. In the biopsy cohort, the discriminative power of adding histological markers to a conventional risk model was assessed by Harrell’s C-index and compared with a likelihood-ratio test.ResultsDuring a mean follow-up of 19.7 ± 8.7 years, 3.3% of the NAFLD patients and 4.9% of the controls developed dementia (p = 0.07). Overall, NAFLD was not significantly associated with incident dementia. In the biopsy cohort, the model of conventional risk factors (age, sex, hypertension, and cardiovascular diseases) had a C-index of 0.912 to predict incident dementia. Adding individual histological parameters significantly increased the prediction of dementia, with the most pronounced improvement for fibrosis stage (C-index = 0.938, p <0.05).ConclusionsAlthough NAFLD was not associated with the risk of dementia, we found that adding histological markers to a conventional risk model for dementia enhanced the predictive capacity, indicating a shared metabolic origin.Lay summaryBoth non-alcoholic fatty liver disease (NAFLD) and dementia are increasing in prevalence because of a more sedentary lifestyle, increased prevalence of obesity and population ageing. However, the link between these 2 diseases is not well studied. We investigated the association between NAFLD and the risk of dementia and found no association. However, liver histology parameters, especially fibrosis, could significantly improve the prediction of dementia risk.

PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease.

BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide, with significant morbidity associated with nonalcoholic steatohepatitis (NASH). Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD progression.AIMTo investigate PNPLA3 and TM6SF2 genotype frequency and their association with NAFLD development and progression in Brazilian patients.METHODSThis cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in Brazil. The case patients (n = 148) were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver disease. According to the clinical protocol, patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis (n = 65). Steatohepatitis was confirmed in 54 patients. Individuals who did not have biopsy indication or NASH on histology were considered to have simple steatosis (n = 94). The control group (n = 137) was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical tests. All individuals underwent PNPLA3 and TM6SF2 genotype analysis. RESULTSPNPLA3 CC, CG and GG genotype frequencies were 37%, 44% and 19%, respectively, in NAFLD patients and were 58%, 31% and 10% in controls (P < 0.001). In a model adjusted for gender, age, body mass index and type 2 diabetes mellitus, the G allele increased the chance of NAFLD (OR = 1.69, 95%CI: 1.21-2.36, P = 0.002) and NASH (OR = 3.50, 95%CI: 1.84-6.64, P < 0.001). The chance of NASH was even higher with GG homozygosis (OR = 5.53, 95%CI: 2.04-14.92, P = 0.001). No association was found between G allele and the features of metabolic syndrome. In histological assessment, PNPLA3 genotype was not associated with steatosis grade, although GG homozygosis increased the chance of significant NASH activity (OR = 17.11, 95%CI: 1.87-156.25, P = 0.01) and fibrosis (OR = 7.42, 95%CI: 1.55-34.47, P = 0.01) in the same adjusted model. TM6SF2 CC, CT and TT genotype frequencies were 83%, 15% and 0.7%, respectively, in NAFLD patients and were 84%, 16% and 0.7% in controls (P = 0.78). The T allele presence was not associated with NAFLD or NASH, and was not associated with histological features.CONCLUSIONPNPLA3 may be involved in susceptibility and progression of NAFLD and NASH in the Brazilian population. More advanced histological liver disease was associated with the G allele. The TM6SF2 genetic variants were not associated with NAFLD susceptibility and progressive histological forms in the population studied, but further studies are required to confirm these findings.

S2670 Wilson Disease Presenting With Autoimmune Hepatitis Features: A Clinical Enigma

INTRODUCTION: Wilson disease (WD) is a genetic disorder that commonly presents with neuropsychiatric and hepatic symptoms due to an inherited defect in the metabolism of copper. In some cases, the presence of autoimmune hepatitis (AIH) markers despite features of WD can result in diagnostic delays. We present the case of a 25 year old woman presenting with decompensated liver cirrhosis attributed to WD with confounding factors of AIH. CASE DESCRIPTION/METHODS: A 25 year old woman presented to the emergency department with abdominal distension and bilateral lower extremity edema. Her physical exam was remarkable for abdominal ascites and bilateral pitting leg edema. Laboratory analysis demonstrated an elevated alkaline phosphatase at 211 U/L, as well as aspartate aminotransferase and alanine aminotransferase at 97 IU/L and 62 IU/L respectively. CT abdomen demonstrated small sclerotic liver with evidence for portal hypertension. Further studies were significant for a low ceruloplasmin level, positive antinuclear antibody (ANA) and low titer positive anti-smooth muscle antibodies (ASMA). She underwent upper endoscopy that revealed Grade 2 esophageal varices (Figure 1). Patient underwent liver biopsy and pathology revealed extensive bands of bridging fibrosis consistent with cirrhosis (Figure 2). Glycogenated nuclei, iron stain and alpha-1 antitrypsin test were negative with copper stain positive for occasional deposits in hepatocytes (Figure 3). After discharge, a 24 hour urinary copper level was elevated at 595μg/and dry weight copper level was 910.3 mcg/mg confirming WD. DISCUSSION: WD is a rare genetic condition that involves hepatic and neurological dysfunctions occurring in 1 to 30,000 of the worldwide population. Intriguingly, our patient did not have any neurological or psychiatric symptoms at the moment of presentation. Of note, the patient did not undergo slit lamp examination so the presence or absence of Kayser-Fleischer rings that are present in almost every patient with neurologic disease could not be determined. We report a case of a diagnosis of WD presenting with a positive ANA and ASMA initially misdiagnosed as AIH. The confounding factor of this case was the early detection of a positive ANA and ASMA suggesting AIH as the culprit for the decompensated cirrhosis. The correct identification of the etiology for this patient’s cirrhosis is critical as treatment and prognosis differ greatly between these two entities and can prevent delays in effective interventions.Figure 1.: EGD demonstrating grade II esophageal varices.Figure 2.: Liver biopsy slide with extensive thick bands of bridging fibrosis consistent with cirrhosis.Figure 3.: Liver biopsy slide showing copper deposits in hepatocytes.

Liver Metastasis of Malignant Pilomatrixoma: Devastating Outcome from A Possibly Under-Treated Case

Malignant of pilomatrixoma, known as pilomatrix carcinoma, is a rare cutaneous adnexal tumor that derives from hair matrix cells.The tumor usually occurs in male, with the predominant age range between 40 to 60 years old, located in the head and neck area. The tumor consisted of atypical basaloid cells aggregation, ghost cells, and keratinous material. We report a case of 54 years old male patient referred to Cipto Mangunkusumo Hospital Jakarta with a mass in his right upper quadrant abdomen and a lump in the axilla. The magnitude resonance imaging (MRI) and positron emission tomography (PET)-scan revealed metastatic lesions in several lymph nodes and internal organs. The patient underwent liver biopsy which showed that tumor was composed of atypical basaloid cells, amyloid-like material, keratin mass, and was diagnosed as pilomatrix carcinoma. This case is being reported due to its rarity, potential pitfalls due to histologic similarity with several other entities, and to show the importance of histopathology examination in patient’s treatment to prevent a devastating outcome.

Modest alcohol intake not associated with significant hepatic steatosis or more severe liver disease among patients with diabetes mellitus.

The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear. This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤21units/week in men and ≤14units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter>263dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement≥9.6kPa using M probe or ≥9.3kPa using XL probe. Patients with liver stiffness measurement≥8.0kPa were offered liver biopsy. Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease. Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.

Serum miR-17 levels in patients with hepatitis B virus induced liver fibrosis.

To investigate the clinical significance of detecting serum level of miR-17 in patients with hepatitis B virus (HBV) induced liver fibrosis. A total of 200 HBV patients undergoing liver biopsy in Henan Provincial People's Hospital from June 2016 to December 2018, and 200 healthy subjects during the same period were included. Serum miR-17 level was detected by qRT-PCR. Multivariate Logistic regression analysis was conducted to evaluate independent risk factors of liver fibrosis in HBV patients. Meanwhile, ROC curves were used to assess the value of miR-17 in determining liver fibrosis severity of HBV patients. 200 HBV patients were classified into 4 groups based on the severity of liver fibrosis, including 52 cases in S0-1, 47 cases in S2, 53 cases in S3, and 48 cases in S4. Serum level of miR-17 was lower in healthy subjects than that in HBV patients. In addition, the serum level of miR-17 was negatively correlated with liver fibrosis severity. The relative levels of aspartate aminotransferase (AST), HBV-DNA, albumin (ALB), platelets (PLT), aspartate aminotransferase-to-platelet ratio index (APRI) and miR-17 were the independent factors of advanced liver fibrosis in HBV patients. Serum level of miR-17 exerted a predictive potential in diagnosis of the severity of HBV-induced liver fibrosis. Serum miR-17 level is highly expressed in HBV patients, and negatively correlated with liver fibrosis severity, which could be utilized as a non-invasive hallmark assessing liver fibrosis severity in HBV patients.

To biopsy or to not biopsy, that is the question: A single-center retrospective analysis of outcomes of liver biopsy with hepatocellular carcinoma and other liver diseases.

e16606 Background: Unlike other malignancies, hepatocellular carcinoma (HCC) is most often diagnosed radiologically, based on previous studies suggesting complication rates of 1.4%-3.4% (e.g., bleeding) and concerns regarding “tumor seeding.” Lack of tissue for analysis has led to a lag in understanding the molecular biology of HCC. Molecular characterization of biopsies may allow HCC subtyping in order to personalize medicine, thus the potential of liver biopsy’s safety and utility needs to be reassessed. Methods: We performed a retrospective review of patients who underwent biopsy for suspected HCC or other liver diseases between Jan 1, 2010 and Jan 1, 2020. Demographics and clinical data including comorbidities, renal function, ascites, hepatic encephalopathy, varices, and labs including hemoglobin, WBC, platelets, sodium, creatinine, liver function test and coagulation studies were collected. Child Pugh (CP) and MELD-Na scores were calculated. Adherent medications at the time of biopsy and type of biopsy with any complications were included. Results: A total of 427 patients underwent liver biopsy. Patient characteristics are given in the table. Most patients (97%) underwent core needle biopsy. Biopsy complication rate was 1.23% (n = 5); these included bleeding (80%, n = 4), hospitalization (60%, n = 3), infection (20%, n = 1), and death (20%, n = 1). In the 5 patients, increased creatinine was associated with bleeding complications; however, one patient was on dialysis (Cr = 11.20), and this should be interpreted with caution. Existing comorbidities, concurrent medication use (including anticoagulants), CP and MELD-NA score, and lab findings were not associated with biopsy complications. Conclusions: To our knowledge, this review is first to demonstrate a low complication rate of 1.23% in suspected HCC patients who underwent liver biopsy in the current era of improved radiological techniques. This is consistent with historical data in liver disease patients. Comorbidities, being on anticoagulants, CP and MELD scores do not predict for biopsy complications. Higher creatinine was associated with more complications, but this needs to be examined in a larger study. Biopsy should be considered a valuable tool in understanding the molecular profiles of HCC, which could lead to more novel treatment. [Table: see text]

The Utility of Assessing Liver Allograft Fibrosis and Steatosis Post–Liver Transplantation Using Transient Elastography With Controlled Attenuation Parameter

AimAllograft steatosis is an emerging concern after liver transplantation (LT). The use of transient elastography (TE) with controlled attenuation parameter (CAP) may facilitate early detection of and intervention for allograft steatosis. This study aimed to evaluate the prevalence and risk factors of allograft steatosis using TE and CAP. MethodsThe presence of steatosis and severe steatosis were defined by CAP ≥222 and ≥290 dB/m, respectively. Demographics and clinical characteristics were compared between patients with and without severe steatosis. Regression analyses were performed to determine factors associated with severe steatosis. ResultsOf 150 patients, 105 (70%) had steatosis while 40% of these had severe steatosis. Thirty-four (81.0%) patients with severe steatosis had normal alanine transaminase at the time of TE. In multivariable analyses, age at LT (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.08), post-LT obesity (OR 5.34, 95% CI 1.53-18.65), and alcoholic liver disease (OR 12.86, 95% CI 2.24-73.74) were significant predictors of severe steatosis. Five patients underwent liver biopsies as a result of advance fibrosis seen on TE and were later diagnosed with chronic allograft rejection. Two of these patients had normal liver chemistries, and the remaining 3 had mild elevation of alkaline phosphatase. ConclusionSteatosis was present in 70% of patients who underwent TE after LT. Advanced age at LT, post-LT obesity, and alcoholic liver disease were significant predictors for severe steatosis. The majority of patients with severe steatosis had normal liver enzymes. TE should be considered as a screening modality for allograft steatosis and fibrosis even when liver chemistries are normal.

Platelet count is closely associated with the severity of liver injury in patients with chronic hepatitis B virus infection: A cross-sectional study.

Although the platelet count may provide clues regarding the severity of liver disease, there are currently no available data supporting the utility of the platelet count to evaluate the degree of liver injury in patients with chronic hepatitis B virus (HBV) infection. The present study aimed to determine the association between the platelet count and the severity of liver injury in patients with chronic HBV infection. A total of 941 patients were included and were stratified into a Child-Turcotte-Pugh (CTP) class A group and a CTP class B/C group using the CTP scoring system. A total of 53 patients underwent liver biopsy. The pathological stage F4 was defined as cirrhosis based on the METAVIR scoring system. Compared with that in patients with CTP class A, the platelet count in patients with CTP class B/C was lower (P<0.001). Similarly, for patients with normal alanine aminotransferase (ALT) levels, the platelet count was significantly different between the CTP class B/C and A groups (P<0.001). The platelet count was inversely correlated with the CTP score (r=-0.420, P<0.001) and independently associated with CTP grade B/C [odds ratio (OR), 0.994; 95% CI, 0.990-0.999; P=0.009]. The area under the receiver operating characteristic curve (AUC) of the platelet count to distinguish CTP grade B/C from A was 0.712 and 0.791, respectively, in all patients with HBV infection and the subset with normal ALT levels. In addition, compared to patients with chronic hepatitis B, patients with cirrhosis had a lower platelet count and higher aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) (P<0.001). The platelet count was inversely correlated with FIB-4 (r=-0.855, P<0.001) and APRI (r=-0.741, P<0.001). The AUC for the platelet count to distinguish cirrhosis from chronic hepatitis B was 0.927 (sensitivity, 78.76%; specificity, 92.22%). Among patients who underwent liver biopsy, the platelet count in those with F4 was lower compared with that in patients with ≤F3 (P=0.013). The platelet count was inversely correlated with the pathological stage (r=-0.295, P=0.032) and was independently associated with F4 (OR, 0.978; 95% CI, 0.960-0.997; P=0.026). The AUC of the platelet count to distinguish F4 from patients with ≤F3 was 0.761. In conclusion, the platelet count may be used as a non-invasive marker to assess the severity of liver injury and of liver fibrosis in patients with chronic HBV infection.

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy.

Obesity is associated withnon-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients withchronic liver diseaseof different aetiologies (egHCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery. Two-hundred and twenty-six subjects (160 females; mean age 42.9years ±10.8SD) without evidence of any further cause of liver disease consecutively underwent bariatric surgery in two Italian liver centers. During surgery, all patients underwent liver biopsy for histological evaluation and molecular studies. Liver DNA extracts were tested for PNPLA3, TM6SF2, MBOAT7, IRGM polymorphisms and for OBI. Univariate and multivariate analyses were used to identify predictors of NASH. Histology showed NASH in 115 (50.9%) and NAFL in 111 cases (49.1%). Twenty-nine/226 (12.8%) cases had OBI, 24 (82.8%) of whom had NASH and 5 (17.2%) NAFL, whereas among the 197 OBI-negative cases, 91 (46.2%) had NASH and 106 (53.8%) NAFL (P=.0002). Multivariate analysis showed that older age (P=.03, OR 1.034), alanine aminotransferase values (P=.005, OR 1.023), insulin resistance/diabetes (P=.02, OR 2.257), TM6SF2 polymorphism (P=.04, OR 3.168) and OBI (P=.004, OR 5.503) were independent predictors of NASH. NASH is highly prevalent in obese individuals undergoing bariatric surgery. OBI is one of the strongest risk factors of NASH in these patients.

Long-Term Follow-up of Liver Transplant Recipients Treated With Direct-Acting Antiviral Agents for Hepatitis C Recurrence After Transplantation

BackgroundTreatment of hepatitis C virus (HCV) recurrence after liver transplantation (LTX) with direct-acting antiviral agents (DAA) is effective and leads to sustained viral response (SVR) in most cases. Long-term effect of HCV elimination on LTX function is not clear. The aim of the study was to evaluate the long-term influence of DAA with HCV on the liver function in LTX recipients. MethodsThe study included 120 LTX patients with HCV recurrence. Before starting DAA therapy, all patients underwent liver biopsy and elastography. Biochemical tests and HCV viremia were assessed at baseline, 4, 12, and 24 weeks and 24 months after the end of treatment (EOT). The study protocol conformed with the Declaration of Helsinki. ResultsIn the HCV genotype 1 (G1) group, 106 patients were treated with ledipasvir/sofosbuvir with ribavirin (RBV), and 3 patients received paritaprevir/ritonavir/ombitasvir/dasabuvir/RBV. All HCV genotype 3 (G3) patients were treated with sofosbuvir/RBV; all HCV genotype 4 (G4) patients were treated with paritaprevir/ombitasvir/RBV. The efficacy of the treatment defined as SVR at week 12 after EOT (SVR12) was 97.3% in G1 group, 75% in G3, and 100% in G4 group. Median alanine (ALT) and aspartate (AST) transaminase before therapy were 44.0 IU/mL and 42.5 IU/mL, respectively. Median ALT and AST at 24 months after EOT were 17 IU/mL and 22 IU/mL, respectively. The lack of transaminases normalization was observed in 10 patients 24 months after EOT. ConclusionThe efficacy of DAA therapy of HCV recurrence after LTX is as high as that reported in randomized clinical trials. It is also associated with the improvement of liver function tests during long-term follow-up.

The performance of M and XL probes of FibroScan for the diagnosis of steatosis and fibrosis on a Brazilian nonalcoholic fatty liver disease cohort.

Recently, controlled attenuation parameter (CAP) was incorporated for XL probe. However, its performance through M and XL probes has been scarcely evaluated in nonalcoholic fatty liver disease (NAFLD). The performance of probes regarding transient elastography by Fibroscan is still under debate. Compare the performance of CAP and transient elastography in NAFLD patients obtained through XL with M probes using histological analysis as gold standard. NAFLD patients underwent liver biopsy and FibroScan/CAP with M and XL probes the same day. C-statistic evaluated CAP performance in the identification of moderate/severe (≥33%) and severe (≥66%) steatosis by both probes and transient elastography performance for identification of significant fibrosis (≥F2). Eighty-one patients (74% female; age 54.2 ± 9.9 years; BMI 32.8 ± 5.2/ BMI ≥ 25 92.6%; 96% metabolic syndrome; 60% diabetes mellitus) were included. Mean CAP with M and XL probes was 314 ± 39 and 325 ± 47 dB/m, respectively. The areas under receiver operating characteristic curves (AUROCs) of the M and XL probes for steatosis detection ≥33% were 0.75 (0.64-0.84) and 0.76 (0.65-0.84) (P = 0.95) and for steatosis ≥66% 0.83 (0.73-0.90) and 0.82 (0.71-0.89) (P = 0.73), respectively, with similar performances for both degrees of steatosis. Regarding transient elastography, AUROCs of M and XL probes for ≥F2 were 0.82 (0.71-0.93) and 0.80 (0.69-0.92) (P = 0.66). Performance of M and XL probes is similar for the diagnosis of moderate and severe steatosis and significant fibrosis even on a overweight population with NAFLD.

Diagnostic Accuracy of Shear Wave Elastography as a Non-invasive Biomarker of High-Risk Non-alcoholic Steatohepatitis in Patients with Non-alcoholic Fatty Liver Disease

In this study, we evaluated the diagnostic accuracy of shear wave elastography (SWE) for differentiating high-risk non-alcoholic steatohepatitis (hrNASH) from non-alcoholic fatty liver and low-risk non-alcoholic steatohepatitis (NASH). Patients with non-alcoholic fatty liver disease scheduled for liver biopsy underwent pre-biopsy SWE. Ten SWE measurements were obtained. Biopsy samples were reviewed using the NASH Clinical Research Network Scoring System and patients with hrNASH were identified. Receiver operating characteristic curves for SWE-based hrNASH diagnosis were charted. One hundred sixteen adult patients underwent liver biopsy at our institution for the evaluation of non-alcoholic fatty liver disease. The area under the receiver operating characteristic curve of SWE for hrNASH diagnosis was 0.73 (95% confidence interval: 0.61–0.84, p < 0.001). The Youden index-based optimal stiffness cutoff value for hrNASH diagnosis was calculated as 8.4 kPa (1.67 m/s), with a sensitivity of 77% and specificity of 66%. SWE may be useful for the detection of NASH patients at risk of long-term liver-specific morbidity and mortality.