Risk Factor For Liver Cirrhosis Research Articles

Global burden of liver cirrhosis 1990–2019 and 20 years forecast: results from the global burden of disease study 2019

Background Cirrhosis is a disease that imposes a heavy burden worldwide, but its incidence varies widely by region. Therefore, we analysed data on the incidence and mortality of cirrhosis in 204 countries and territories from 1990–2019 and projected the disease development from 2019–2039. Methods Data on the incidence and mortality of liver cirrhosis from 1990 to 2019 were acquired from the public Global Burden of Disease (GBD) study. In addition, the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) of the age-standardized rate (ASR) of cirrhosis in different regions were calculated. The estimates of risk factor exposure were summarized, and the proportion of causes and risk factors of liver cirrhosis and their relationship with the human development index (HDI) and socio–demographic index (SDI) were analysed. Trends in the incidence of cirrhosis in 2019–2039 were predicted using Nordpred and BAPC models. Results Globally, the ASR of cirrhosis incidence decreased by 0.05% per year from 25.7/100,000 in 1990 to 25.3/100,000 in 2019. The mortality risk associated with cirrhosis is notably lower in females than in males (13 per 100,000 vs 25 per 100,000). The leading cause of cirrhosis shifted from hepatitis B to C. Globally, alcohol use increased by 14%. In line, alcohol use contributed to 49.3% of disability-adjusted life years (DALYs) and 48.4% of global deaths from liver cirrhosis. Countries with a low ASR in 1990 experienced a faster increase in cirrhosis, whereas in 2019, the opposite was observed. In countries with high SDI, the ASR of cirrhosis is generally lower. Finally, projections indicate that the number and incidence of cirrhosis will persistently rise from 2019–2039. Conclusions Cirrhosis poses an increasing health burden. Given the changing etiology, there is an imperative to strengthen the prevention of hepatitis C and alcohol consumption, to achieve early reduce the incidence of cirrhosis.

Important Risk Factors of Liver Cirrhosis in HIV and Hepatitis C Coinfected Patients: A Systematic Review

Important Risk Factors of Liver Cirrhosis in HIV and Hepatitis C Coinfected Patients: A Systematic Review

Hepatocyte CHRNA4 mediates the MASH-promotive effects of immune cell-produced acetylcholine and smoking exposure in mice and humans

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading risk factor for liver cirrhosis and hepatocellular carcinoma. Here, we report that CHRNA4, a subunit of nicotinic acetylcholine receptors (nAChRs), is an accelerator of MASH progression. CHRNA4 also mediates the MASH-promotive effects induced by smoking. Chrna4 was expressed specifically in hepatocytes and exhibited increased levels in mice and patients with MASH. Elevated CHRNA4 levels were positively correlated with MASH severity. We further revealed that during MASH development, acetylcholine released from immune cells or nicotine derived from smoking functioned as an agonist to activate hepatocyte-intrinsic CHRNA4, inducing calcium influx and activation of inflammatory signaling. The communication between immune cells and hepatocytes via the acetylcholine-CHRNA4 axis led to the production of a variety of cytokines, eliciting inflammation in liver and promoting the pathogenesis of MASH. Genetic and pharmacological inhibition of CHRNA4 protected mice from diet-induced MASH. Targeting CHRNA4 might be a promising strategy for MASH therapeutics.

Risk of Hepatitis C Virus Transmission through Acupuncture: A Systematic Review and Meta-Analysis.

Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission. Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models. Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively. In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46-2.32]; p<0.001; I2 =80%). In the subgroup analysis, both cross-sectional case-control (n=14; OR, 1.96 [1.47-2.61]; p<0.001; I2 =88%) and cross-sectional studies (n=12; OR, 1.85 [1.32-2.61]; p<0.001; I2 =0%) showed significantly higher HCV infection rates in the acupuncture group than in the control group. Both Asian and non-Asian acupuncture users showed a higher HCV transmission risk than the controls (all Ps<0.001). No significant publication bias was observed. Our findings indicate that acupuncture increases the risk of HCV transmission. Due to HCV's contagiousness, unsafe medical and social practices (including acupuncture) should be performed with caution.

Deficiency of SCAP inhibits HBV pathogenesis via activation of the interferon signaling pathway

Hepatitis B virus (HBV) infects the liver and is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Approaches for an effective cure are thwarted by limited knowledge of virus-host interactions. Herein, we identified SCAP as a novel host factor that regulates HBV gene expression. SCAP, sterol regulatory element-binding protein (SREBP) cleavage-activating protein, is an integral membrane protein located in the endoplasmic reticulum. The protein plays a central role in controlling lipid synthesis and uptake by cells. We found that gene silencing of SCAP significantly inhibited HBV replication; furthermore, knockdown of SREBP2 but not SREBP1, the downstream effectors of SCAP, reduced HBs antigen production from HBV infected primary hepatocytes. We also demonstrated that knockdown of SCAP resulted in activation of interferons (IFNs) and IFN stimulated genes (ISGs). Conversely, ectopic expression of SREBP2 in SCAP-deficient cells restored expression of IFNs and ISGs. Importantly, expression of SREBP2 restored HBV production in SCAP knockdown cells, suggesting that SCAP participates in HBV replication through an effect on IFN production via its downstream effector SREBP2. This observation was further confirmed by blocking IFN signaling by an anti-IFN antibody, which restored HBV infection in SCAP-deficient cells. This led to the conclusion that SCAP regulates the IFN pathway through SREBP, thereby affecting the HBV lifecycle. This is the first study to reveal the involvement of SCAP in regulation of HBV infection. These results may facilitate development of new antiviral strategies against HBV.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease.

Although many studies have investigated the impact of chronic hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) on liver disease, few have investigated the relationship between nonalcoholic steatohepatitis (NASH) defined by liver pathology and the prognosis of chronic HBV infection. Most patients were followed up for a short time. This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection. To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events [cirrhosis, hepatocellular carcinoma (HCC), and death] in patients with chronic hepatitis B (CHB) virus infection. We enrolled patients with chronic hepatitis B virus (HBV) infection who underwent liver biopsy at the Third People's Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020. Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected. Propensity score matching (PSM) was used to balance baseline parameters, Kaplan-Meier (K-M) survival analysis was used to evaluate the risk of clinical events, and Cox regression was used to analyze the risk factors of events. Overall, 456 patients with chronic HBV infection were included in the study, of whom 152 (33.3%) had histologically confirmed NAFLD. The median follow-up time of the entire cohort was 70.5 mo. Thirty-four patients developed cirrhosis, which was diagnosed using ultrasound during the follow-up period. K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis (log-rank test, P > 0.05). Patients with CHB with fibrosis at baseline were more prone to cirrhosis (log-rank test, P = 0.046). After PSM, multivariate analysis showed that diabetes mellitus, ballooning deformation (BD), and platelet (PLT) were independent risk factors for cirrhosis diagnosed using ultrasound (P < 0.05). A total of 10 patients (2.2%) developed HCC, and six of these patients were in the combined NAFLD group. K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher (log-rank test, P < 0.05). Hepatocyte ballooning, and severe liver fibrosis were also associated with an increased risk of HCC (log-rank test, all P < 0.05). Cox multivariate analysis revealed that hepatocyte ballooning, liver fibrosis, and diabetes mellitus were independent risk factors for HCC. There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD. Diabetes mellitus, BD, and PLT were independent risk factors for liver cirrhosis. Patients with chronic HBV infection and NASH have an increased risk of HCC. BD, liver fibrosis, and diabetes mellitus are independent risk factors for HCC.

A Meta-Analysis of Risk Factors for Liver Cirrhosis Combined with Upper Gastrointestinal Bleeding in China

In order to systematically evaluate the risk factors for liver cirrhosis complicated with upper gastrointestinal bleeding in China, we searched CNKI, Wanfang Digital Journals Full-text Database (Wanfang), Weipu Journal Resource Integration Service Platform(VIP) and PubMed database on risk factors for liver cirrhosis combined with upper gastrointestinal bleeding in China, Newcastle-Ottawa Scale(NOS) used the most comprehensive data collection based on relevant case-control trials to evaluate the quality of the extracted literature combined with inclusion and exclusion criteria. Studies with a score of ≥ 7 were included and meta-analysed using RevMan 5.4. Finally, twenty-one articles met the inclusion criteria, the cumulative number of cases and controls were 2222 and 2785 cases. We can come to the conclusion that Spleen, gastric varices, esophageal varices, PT (prothrombin time), ascites, left gastric vein diameter, liver function child grade C, esophageal varices, liver cirrhosis, portal vein diameter, and alcohol consumptionIt is an independent risk factor for liver cirrhosis combined with upper gastrointestinal bleeding in China, and the control of the above factors can effectively improve the risk of patients with liver cirrhosis and upper gastrointestinal bleeding in China.

Risk Factors of Liver Cirrhosis in Chad: Large Proportion of Cases without Clear Etiology

Risk Factors of Liver Cirrhosis in Chad: Large Proportion of Cases without Clear Etiology

Extracellular Vesicles and Fatty Liver.

Fatty liver is a complex pathological process caused by multiple etiologies. In recent years, the incidence of fatty liver has been increasing year by year, and it has developed into a common chronic disease that seriously affects people's health around the world. It is an important risk factor for liver cirrhosis, liver cancer, and a variety of extrahepatic chronic diseases. Therefore, the early diagnosis and early therapy of fatty liver are important. Except for invasive liver biopsy, there is still a lack of reliable diagnosis and staging methods. Extracellular vesicles are small double-layer lipid membrane vesicles derived from most types of cells. They play an important role in intercellular communication and participate in the occurrence and development of many diseases. Since extracellular vesicles can carry a variety of biologically active substances after they are released by cells, they have received widespread attention. The occurrence and development of fatty liver are also closely related to extracellular vesicles. In addition, extracellular vesicles are expected to provide a new direction for the diagnosis of fatty liver. This article reviews the relationship between extracellular vesicles and fatty liver, laying a theoretical foundation for the development of new strategies for the diagnosis and therapy of fatty liver.

Genetic Polymorphism in Toll-Like Receptor 3 and Interferon Regulatory Factor 3 in Hepatitis C Virus-Infected Patients: Correlation with Liver Cirrhosis.

Host genetic factors could play a primary role in determining the risk for cirrhosis development in chronic hepatitis C virus (HCV)-infected patients. We designed this work to study the effect of single-nucleotide polymorphism (SNP) in Toll-like receptor 3 (TLR3) and interferon regulatory factor (IRF) on the risk of HCV-related cirrhosis. This study enrolled 139 Egyptian HCV-infected patients. They were divided into patients with cirrhotic (56) and noncirrhotic (83) liver. Genotyping of rs3775291 F459F (+1234C/T) and rs3775290 L412F (+1377C/T) in TLR3 and IRF3 rs2304204 (-925A/G) was performed by restriction fragment length polymorphism-polymerase chain reaction. Although there is no significant difference in genotype and allele distribution of +1377C/T of TLR3 gene between cirrhotic and noncirrhotic subjects, CC (odds ratio [OR] = 1.572, 95% confidence interval [CI]: 0.781-3.164); TT (OR = 1.463, 95% CI: 0.351-6.104) genotypes might be considered as risk factors for liver cirrhosis. On the contrary, the analysis revealed that only one genotype (CC) and one allele (C) were detected in +1234C/T SNP, with the total disappearance of CT/TT genotypes and T allele in all subjects. On the contrary, lower frequency has been found for the AG genotype of the IRF3 (-925A/G) gene in cirrhotic patients compared with noncirrhotic ones, indicating that AG is a protective genotype (OR = 0.509, 95% CI: 0.256-1.012). Our data stressed the association of AG genotype SNP in IRF3 (-925A/G) in protection against the worth outcome of HCV infection.

The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis

Alpha-1-antitrypsin (AAT) has different phenotypes. Evidence suggests that the abundance of each of these phenotypes may be associated with a disease. The purpose of this study was to evaluate the frequency of AAT phenotypes in patients with liver cirrhosis as well as in healthy individuals. In this study, 42 patients with liver cirrhosis were selected. The results of the previous research done by the researcher on healthy individuals were used to construct the control group. After obtaining informed consent, 5mL of fasting venous blood sample was taken, and phenotypes were analyzed by isoelectric focusing. Data were analyzed using Chi-square and Fisher's exact tests at a significant level of 0.05. The results of this study indicated that all 42 healthy subjects had an MM allele (100%). However, among 42 patients, 35 (83.3%) had an MM allele, 5 (11.9%) had an MS allele, and 2 (4.8%) had MZ allele. The difference between the two groups was significant (p=0.02). There was no difference between men and women in the allele type (p=0.557). This study revealed that MS and MZ alleles were observed only in patients with liver cirrhosis, and none of these alleles were found in healthy subjects. Therefore, MS and MZ alleles can be further investigated as risk factors for liver cirrhosis.

To investigate the link between serum prolactin levels and the severity of liver cirrhosis

Aim: To investigate the link between serum prolactin levels and the severity of liver cirrhosis. Methods: This cross-sectional research covers 60 chronic liver disease patients (CLD). There are 25 female patients and 35 male patients. Their ages vary from 35 to 58 years, with a mean standard deviation of 52.94±6.99. According to the Modified Child's Pugh score, the cases studied are divided into three groups: Group 1: Consists of 20 individuals with mild liver cirrhosis. Group 2: Consists of 20 individuals with mild liver cirrhosis. Group 3: Consists of 20 individuals with severe liver cirrhosis. Results: This research included 60 patients ranging in age from 35 to 60 years old, with a mean SD of 52.94±6.99 years; there were 35 male patients (58.33 percent) and 25 female patients (41.67 percent). PRL levels range from (5.6-39) ng/ml with a mean S.D of (19.76±10.14 ng/dl). The albumin level ranges from (1.3-4.2) mgdl, with a mean S.D of (3.18±0.95) gdl. Total bilirubin levels range from (1.3-6.8) mg/dl, with a mean standard deviation of (2.71.4 mg/dl). The prothrombin time ranges from (2.8-8.5) sec, with a mean S.D of (8.85.44 sec). Creatinine levels range from (0.7-6) mg/dl, with a mean S.D. of (2.35±1.31 mg/dl). The ultrasonic diameter of the portal vein (PV) varies from (10-19) cm with a mean S.D (13.19±1.84 cm). The child Pugh score ranges from (5 to 14) with a mean S.D of (10.16±4.16). The Roc curve for blood prolactin level as a predictor of severe/moderate liver cirrhosis reveals that at the cutoff point of 19.8 ng/ml, the sensitivity is 68.94%, the specificity is 80.15%, the PPV is 85.5%, and the NPV is 62%. Conclusion: Prolactin levels rise considerably in individuals with severe liver illness, especially those with ascites and hepatic encephalopathy. A high prolactin level might therefore be regarded as a risk factor for liver cirrhosis.

Comparative Analysis of Risk Factors for Liver Cirrhosis in the World

Comparative Analysis of Risk Factors for Liver Cirrhosis in the World

Risk factors for liver cirrhosis in acute-on-chronic liver failure patients without liver cirrhosis in the convalescence stage

Risk factors for liver cirrhosis in acute-on-chronic liver failure patients without liver cirrhosis in the convalescence stage

IL-35: A Novel Immunomodulator in Hepatitis B Virus-Related Liver Diseases.

Chronic hepatitis B virus (HBV) infection is a risk factor for liver cirrhosis (LC) and hepatocellular carcinoma (HCC), however, little is known about the mechanisms involved in the progression of HBV-related diseases. It has been well acknowledged that host immune response was closely related to the clinical outcomes of patients with HBV infection. As the factors closely related to the immunomodulatory process, cytokines are crucial in the cell-cell communication and the host responses to HBV infection. Recently, a newly discovered cytokine, designated as interleukin-35 (IL-35), has been proved to be essential for the progression of chronic HBV infection, the development of cirrhosis, the transformation of cirrhosis to HCC, and the metastasis of HCC. Specifically, it showed various biological activities such as inhibiting the HBV-specific cytotoxic T lymphocyte (CTL) proliferation and cytotoxicity, deactivating the immature effector T-cells (Teffs), as well as delaying the proliferation of dendritic cells. It regulated the immune responses by acting as a “brake” on the activation of Teffs, which subsequently played important roles in the pathogenesis of various inflammatory diseases and malignancies. In this review, we focused on the most recent data on the relationship between IL-35 and chronic HBV infection, LC and HCC.

Retrospective analysis of risk factors of liver cirrhosis combined with overt hepatic encephalopathy: a single -center case-control study

Objective: To explore the risk factors of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis. Methods: A retrospective study was designed. Patients with liver cirrhosis combined with /without OHE who were hospitalized to our hospital during the same period were selected as the case/control group. Clinical and laboratory data of both groups of patients were compared to analyze the risk factors affecting the occurrence of OHE. SPSS software was used for statistical analysis. A t-test or rank-sum test was used to compare the measurement data. Chi-square test or Fisher's exact probability method was used to compare the count data. Logistic regression was used for multivariate analysis. Results: A total of 500 patients with liver cirrhosis diagnosed in our hospital from August 2017 to December 2018 were selected as the case group, and 40 cases with cirrhosis without OHE who were hospitalized during the same period were randomly selected as the control group. The gender composition and age of the case and control group were comparable. Viral hepatitis (mainly hepatitis B) was the main etiology of liver cirrhosis in both groups. There were 52.5% patients in the case group and 57.5% patients in the control group, respectively. Alcoholic liver disease, autoimmune liver disease and so on were the other included causes. With regard to blood biochemical indicators, the serum creatinine levels of both groups were comparable, but in the case group, the serum total bilirubin level was higher (34.30 μmol / L vs. 18.65 μ mol/L, Z = -3.185, P < 0.05), while the serum sodium level was lower (137.00 mmol/L vs. 140.08 mmol/L, Z = -2.348, P < 0.05), and the prothrombin time was longer (14.60 s vs. 12.20 s) s. 078, P < 0.05), and international normalized ratio (1.33 vs. 1.07, Z = - 5.632, P < 0.05), and serum albumin level (30.6 g/L vs. 35.6 g/L, t = 3.386, P < 0.05) was lower. In terms of complications, patients in the case group had a higher proportion of combined gastrointestinal bleeding (30.0% vs. 10.0%, χ(2) = 5.000, P < 0.05), ascites (87.5% vs. 30.0%, χ(2) = 27.286, P < 0.05) and secondary infection (32.5% vs. 10.0%, χ(2) = 7.813, P < 0.05). In terms of severity classification, the proportion of Child-Pugh C in the case group was higher (62.5% vs. 10.0%, χ(2) =26.593, P < 0.05). In terms of outcome, there were 3 deaths in the case group and no deaths in the control group. Multivariate analysis showed that Child-Pugh class C (OR = 12.696), and combined ascites (OR = 10.655) were an independent risk factor for OHE in patients with liver cirrhosis. Conclusion: Our single-center retrospective clinical study shows that patients with cirrhosis combined with OHE are more critical and have more complications. In order to promptly diagnose and treat OHE, more attention should be paid to patients with combined ascites and Child-Pugh class C.

Prevalence of liver cirrhosis in individuals with hepatitis B virus infection in sub-Saharan Africa: Systematic review and meta-analysis.

Background & AimsChronic hepatitis B virus (HBV) infection accounts for 30%‐50% of cirrhosis related deaths in sub‐Saharan Africa (SSA). Since HBV‐related cirrhosis is an indication for immediate antiviral therapy and cancer surveillance, we aimed to estimate the prevalence of cirrhosis among treatment‐naïve patients with chronic HBV infection in SSA.MethodsWe performed a systematic review of published articles which evaluated liver fibrosis stage among treatment‐naïve HBV‐infected individuals who presented to care in SSA. Our primary outcome was the prevalence of cirrhosis in HBsAg‐positive persons, which was estimated using random‐effects meta‐analysis. Risk factors for cirrhosis were explored using subgroup‐analyses and multivariable meta‐regression.ResultsOf 2129 articles identified, 17 met our eligibility criteria. The studies described 22 cohorts from 13 countries, including 13 cohorts (3204 patients) with chronic HBV mono‐infection and nine cohorts (688 patients) with HIV/HBV‐coinfection. Liver fibrosis was assessed using transient elastography (10 cohorts), APRI score (11 cohorts), and Fibrotest (one cohort). The pooled prevalence of cirrhosis was 4.1% (95% confidence interval [CI] 2.6‐6.4) among studies from primary care facilities or general population, compared to 12.7% (95% CI 8.6‐18.3) in studies performed in referral or tertiary care facilities (adjusted odds ratio 0.29, 95% CI 0.15‐0.56). We found no association between cirrhosis and age, gender, fibrosis test used or HIV‐coinfection.ConclusionsDepending on the setting, between 4% and 13% of HBV‐infected individuals in SSA have cirrhosis and need immediate antiviral therapy. These estimates should be considered when planning HBV treatment strategies and resource allocation.

Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma-A Review.

Liver cancer is the fourth leading cause of cancer deaths globally, of which hepatocellular carcinoma (HCC) is the major subtype. Viral hepatitis B and C infections, alcohol abuse, and metabolic disorders are multiple risk factors for liver cirrhosis and HCC development. Although great therapeutic advances have been made in recent decades, the prognosis for HCC patients remains poor due to late diagnosis, chemotherapy failure, and frequent recurrence. MicroRNAs (miRNAs) are endogenous, non-coding RNAs that regulate various molecular biological phenomena by suppressing the translation of target messenger RNAs (mRNAs). miRNAs, which often become dysregulated in malignancy, control cell proliferation, migration, invasion, and development in HCC by promoting or suppressing tumors. Exploring the detailed mechanisms underlying miRNA-mediated HCC development and progression can likely improve the outcomes of patients with HCC. This review summarizes the molecular and functional roles of miRNAs in the pathogenesis of HCC. Further, it elucidates the utility of miRNAs as novel biomarkers and therapeutic targets.

S2745 Thinking Outside the Box: Is This Really NASH?

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is a diagnosis of exclusion and an alternative diagnosis should always be sought. We present a patient with features of portal hypertension and possible sepsis, concerning for decompensated NASH cirrhosis. He was eventually diagnosed with a hemophagocytic syndrome-associated variant of intravascular large B-cell lymphoma on autopsy. CASE DESCRIPTION/METHODS: A 64-year-old Caucasian male with metabolic syndrome presented with a 2-month history of fatigue, fevers, and 20-pound weight loss. Initial work-up was notable for an elevated AST (65 IU/L) and high total bilirubin (2 mg/mL; direct 1.3 mg/mL). Albumin was 3.2 g/dL, INR was 1.0 and platelets were 48,000 cells/mL. CT imaging showed mild hepatosplenomegaly with no ascites. He had no known history of liver disease or alcohol use. He was referred to the liver clinic for possible chronic liver disease and portal hypertension, thought to be from NASH. At the time of presentation, he was febrile (101.8 °F), tachycardic (105 bpm), and hypotensive. Besides hepatosplenomegaly, there were no other stigmata of chronic liver disease on exam. Admission labs were unchanged except an increase in total bilirubin (4 mg/mL) and a high ferritin (2400 ng/ml). Work-up for infectious etiologies, autoimmune liver serologies and drug toxin screen were unrevealing. He met 5 out of 8 criteria to diagnose hemophagocytic lymphohistiocytosis (HLH) including fever, splenomegaly, cytopenia, increased ferritin, and absent NK cell function. A PET scan showed uptake in the bone marrow, liver, spleen and lymph nodes. The patient rapidly declined clinically and died from respiratory failure. Autopsy showed diffuse involvement of the liver, spleen, bone marrow, lymph nodes and several other organs by intravascular large B-cell lymphoma (IVBCL). DISCUSSION: Our case emphasizes the importance of considering a broad differential in patients with thrombocytopenia and hepatosplenomegaly, even if typical risk factors for liver cirrhosis are present. Hematological malignancies should be strongly considered in the differential especially if patients present with B symptoms. Hemophagocytic syndrome-associated variant of IVBCL, the so-called ‘Asian variant’, is a rare and aggressive form of diffuse large B cell lymphoma. A prompt diagnosis is crucial, given its life-threatening potential and possibility of recovery with institution of therapy early in the course of the disease.Figure 1.: The cut sections of the liver looked relatively normal and did not show any gross evidence of cirrhosis.Figure 2.: Histology of the liver, which shows intravascular infiltration of tumor cells.

Decrease in Chitinase 3-Like Protein 1 Levels Reflects Improvement in Liver Fibrosis after HCV Eradication.

Aim The success of direct-acting antivirals (DAAs) against hepatitis C virus is a major breakthrough in hepatology. Previous studies have shown that chitinase 3-like protein 1 (CHI3L1) was a marker for staging of liver fibrosis caused by HCV. In this investigation, we used CHI3L1 as a surrogate marker to compare dynamic hepatic fibrosis variations following the elimination of HCV among cases receiving sofosbuvir (SOF)-based regimens and pegylated interferon/ribavirin (PR) treatments. Methods The study enrolled 105 patients, including 46 SOF-based regimens treated patients, 34 PR-experienced patients, and 25 untreated patients. Serum samples and clinical data were obtained at the baseline, the end of treatment, and at weeks 24 and 48 after treatments. Results First, we found that serum level of CHI3L1 correlated moderately but significantly with LSM (r = 0.615, P < 0.001) at the baseline, and diagnosed liver cirrhosis at baseline with high accuracy (AUC = 0.939) by ROC analysis. So we explored CHI3L1 as a sensitive biomarker to monitor the regression of liver fibrosis after HCV eradication. We found that the serum CHI3L1 level of CHC cases receiving SOF-based regimen treatments was markedly reduced immediately after treatment compared with that at the baseline (123.79 (118.55) vs. 118.20 (103.68), P = 0.001). For cases undergoing PR treatment, the serum CHI3L1 decreased significantly at week 24 posttreatment compared with that at the baseline (69.98 (51.44) vs 89.15 (110.59), P = 0.016). For the untreated cirrhotic patients, CHI3L1 levels increased at week 96 follow-up compared with that at the baseline (194.73 (172.46) vs. 89.50 (242.97), P = 0.048), reflecting continued worsening of liver fibrosis. Conclusion CHI3L1 is suggested to be the sensitive marker to monitor fibrosis variations in weeks during treatments and after achieving SVR. It has the potential to allow the identification of early treatment failure for a timely switch to alternative treatment and to allow monitoring progression of fibrosis as a risk factor for liver cirrhosis.