Primary biliary cholangitis presenting with granulomatous lung disease misdiagnosed as lung cancer:A case report

BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE SUMMARY A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography.She underwent left lobectomy,and the pathology of the nodules showed granulomatous inflammation,which was then treated with antibiotics.However,a new nodule appeared.Further investigation with lung biopsy and liver serology led to the diagnosis of PBC,and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid.CONCLUSION Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.

Human umbilical cord blood-derived mononuclear cell transplantation for umbilical hernia and hepatic hydrothorax in primary biliary cirrhosis

Cell therapy was proposed as a potential treatment intervention for liver cirrhosis recently due to the fact that the therapeutic protocol for primary biliary cirrhosis (PBC)-associated refractory umbilical hernia and hepatic hydrothorax is not well defined currently. We report herein the case of a 58-year-old woman who received routine treatments for PBC, which developed into an incarcerated hernia and uncontrolled hydrothorax. This subject’s condition was significantly improved and maintained stable condition after receiving human umbilical cord blood-derived mononuclear cell (CBMC) transplantation. Consequently, this new strategy may be a potential treatment option for the refractory umbilical hernia and hydrothorax caused by PBC. However, sufficient data from large-scale controlled and double-blinded clinical trials are needed to further confirm the treatment efficacy and longterm safety before this cell transplantation can be used as a regular therapy for liver cirrhosis.

Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)].Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

Non-invasive diagnosis of advanced fibrosis and cirrhosis

Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.

A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis

Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease （AILD） remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry （UPLC-MS）, differed between autoimmune hepatitis （AIH） and primary biliary cir- rhosis （PBC）, to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS： Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS： The partial least squares discrimination analysis model （R2y=0.991, Q2=0.943） was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS： The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators

AIM: To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. METHODS: One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. RESULTS: LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%). CONCLUSION: The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value.

SIMULTANEOUS OVER-EXPRESSION OF INSULIN-LIKE GROWTH FACTOR- Ⅱ (IGF- Ⅱ ) AND IGF- Ⅱ RECEPTOR(IGF- Ⅱ R) GENES IN HUMAN PRIMARY CANCER-IMPLICATION OF AUTOCRINE AND PARACRINE MECHANISM IN AUTONOMOUS GROWTH OF HEPATIC CANCER

This is first report about the simultaneous over-expression of both Insulin-like growth factor (IGF- I ) and its receptor (IGF- I R) at mRNA level in human primary hepatic Cancer (PHC). In 10 PHC samples from China, IGF-I and IGF- I R were both over-expressed, whereas only a background signal was detected in normal liver. In 5 pairs of PHC and its non- tumorous adjacent liver tissues from South Africa, IGF- I and IGF- I R were also over-expressed in PHC. mRNA expression of IGF- I in all 5 cases and IGF- I R in 4 of 5 cases were higher in cancer than non- tumorous adjacent liver tissues. These results strongly implicate that an autocrine and/ or paracrine mechanism might be Involved in formation and progression of PHC.

Risk factors for hepatic decompensation in patients with primary biliary cirrhosis

AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were enrolled.Clinical signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during follow-up.Cox regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and survival.RESULTS:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were female.Two hundred and forty-five(93.5%) were seropositive for anti-mitochondrial antibodies.At presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune disease.During the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 died.The cumulative survival rate and median survival time were 83.9% and 181.7 mo,respectively.Cox regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P < 0.001;hazard risk(HR) 95%CI = 2.423-7.541],anti-centromere antibodies(ACA) positivity(P < 0.001;HR 95%CI = 2.516-7.137),alanine aminotransferase ratio(AAR) elevations(P < 0.001;HR 95%CI = 1.357-2.678),and histological advanced liver disease(P = 0.006;HR 95%CI = 1.481-10.847) were predictors of hepatic decompensation.The clinical features and survival of PBC in China are consistent with those described in Western countries.CONCLUSION:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histological stage are predictors of decompensation.

Spontaneous regression of hepatic inflammatory pseudotumor with primary biliary cirrhosis:Case report and literature review

Hepatic inflammatory pseudotumor （IPT） is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis （PBC）. To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.

Negative impact of hepatitis B surface seroclearance on prognosis of hepatitis B-related primary liver cancer

AIM To assess the impact of hepatitis B surface(HBs Ag) seroclearance on survival outcomes in hepatitis B-related primary liver cancer.METHODS Information from patients with hepatitis B-related liver cancer admitted in our hospital from 2008-2017 was retrieved. Cases diagnosed with HBs Ag(-) and HBc Ab(+) liver cancer were included in the HBs Ag seroclearance(SC) group. HBs Ag(+) liver cancer patients strictly matched for liver cancer stage(AJCC staging system, 8 th edition), Child-Pugh score, and first diagnosis/treatment method(surgery, ablation and TACE) were assigned to the HBsA g non-seroclearance(NSC) group. Then, clinical, pathological and survival data in both groups were assessed.RESULTS The SC and NSC groups comprised of 72 and 216 patients, respectively. Patient age(P < 0.001) and platelet count(P = 0.001) in the SC group were significantly higher than those of the NSC group. SC group patients who underwent surgery had more intrahepatic cholangiocarcinoma(ICC) and combined HCC-CC(CHC) cases than the NSC group, but no significant differences in tumor cell differentiation and history of liver cirrhosis were found between the two groups. The numbers of interventional treatments were similar in both groups(4.57 vs 5.07, P > 0.05). Overall survival was lower in the SC group than the NSC group(P = 0.019), with 1-,3-, and 5-year survival rates of 82.1% vs 85.1%, 43.2%vs 56.8%, and 27.0% vs 45.2%, respectively. Survival of patients with AJCC stage Ⅰ disease in the SC group was lower than that of the NSC group(P = 0.029).CONCLUSION Seroclearance in patients with hepatitis B-related primary liver cancer has protective effects with respect to tumorigenesis, cirrhosis, and portal hypertension but confers worse prognosis, which may be due to the frequent occurrence of highly malignant ICC and CHC.

Role of albumin-bilirubin score in non-malignant liver disease

The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

Hepatic reactive lymphoid hyperplasia in a patient with primary biliary cirrhosis

Reactive lymphoid hyperplasia(RLH) of the liver is an extremely rare lesion characterized by the proliferation of non-neoplastic lymphocytes forming follicles.Hepatic RLH is known to be associated with gastrointestinal carc inoma and autoimmune diseases including primary biliary cirrhosis(PBC).We report a case of hepatic RLH in a patient with PBC and gastric cancer.A 68 year old Japanese woman with a 10 year history of liver enzyme abnormality was admitted.Laboratory testing revealed that her anti-mitochondrial antibody was markedly elev ated.Five mo after the diagnosis of PBC,she was foun d to have gastric cancer.Abdominal computed tom og raphy disclosed a liver nodule in S8,suggesting metas tatic gastric carcinoma.Histopathologically,the resected liver lesion comprised of a nodular proliferation of small lym phocytes with lymphoid follicles.This is the first reported case of hepatic RLH in a patient with both PBC and gastric cancer.Pre-operative diagnosis of hepatic RLH by clinical imaging is extremely difficult.Therefore,a need le biopsy could be useful to make a diagnosis of hepat ic RLH,especially to differentiate from metastatic gastroin t estinal carcinoma.

Socioeconomics and attributable etiology of primary liver cancer,1990-2019

BACKGROUND Primary liver cancer(PLC)is a major contributor to cancer-related deaths.Data on global and country-specific levels and trends of PLC are essential for understanding the effects of this disease and helping policymakers to allocate resources.AIM To investigate the association between the burden of PLC and socioeconomic development status.METHODS Cancer mortality and incidence rates were obtained from the Global Burden of Disease(GBD)2019,and the data were stratified by country and territory,sex,and the Socio-demographic Index(SDI)level.The association between the attributable etiology of PLC and socioeconomic development status,represented using the SDI,was described.The attributable etiology of PLC included hepatitis B,hepatitis C,alcohol use,and nonalcoholic steatohepatitis.The association between the attributable etiology of PLC and SDI was further stratified by sex and geographical location.A confidence analysis was also performed based on bootstrap draw.RESULTS The age-standardized incidence rate of PLC was 6.5[95%confidence intervals(CI):5.9-7.2]per 100000 person-years,which decreased by-27.5%(-37.0 to-16.6)from 1990 to 2019.Several countries located in East Asia,South Asia,West Africa,and North Africa shouldered the heaviest burden of PLC in 2019.In terms of incidence rates,the first leading underlying cause of PLC identified was hepatitis B,followed by hepatitis C,alcohol use,and nonalcoholic steatohepatitis.Regarding stratification using the SDI,the incidence rate of PLC was the highest for high and middle SDI locations.Further,the leading attributable etiologies of PLC were hepatitis B for the middle and high middle SDI locations while hepatitis C and nonalcoholic steatohepatitis for the high SDI locations.CONCLUSION The pronounced association between socioeconomic development status and PLC burden indicates socioeconomic development status affects attributable etiologies for PLC.GBD 2019 data are valuable for policymakers implementing PLC cost-effective interventions.

Intra-hepatic and extra-hepatic cholangiocarcinoma:New insight into epidemiology and risk factors

Cholangiocarcinoma(CCA) is a malignant tumour that arises from biliary epithelium at any portion of the biliary tree.CCA is currently classified as intra-hepatic or extra-hepatic CCA(EH-CCA).Recent evidences suggest that intra-hepatic CCA(IH-CCA) and EH-CCA are biologically different cancers,giving further support to a number of recent epidemiological studies showing large differences in terms of incidence,mortality and risk factors.The purpose of this manuscript is to review recent literature dealing with the descriptive epidemiology and risk factors of CCA with a special effort to compare IH-with EH-CCA.

Patients with primary biliary cirrhosis have increased serum total antioxidant capacity measured with the crocin bleaching assay

AIM： The balance between oxidants and antioxidants can play an important role in the initiation and development of liver diseases. Recently, we have described a new automated method for the determination of total antioxidant capacity （TAC） in human serum and plasma.METHODS： We measured TAC and corrected TAC （CTACabstraction of interactions due to endogenous uric acid,bilirubin and albumin） in 52 patients with chronic liver diseases （41 patients with primary biliary cirrhosis （PBC）,10 patients with chronic hepatitis C and 13 patients with viral HCV cirrhosis） as well as in 10 healthy controls. In 23 PBC patients measurement were also done 6 mo after treatment with ursodeoxycholic acid （UDCA）. The TAC assay was based on a modification of the crocin bleaching assay. The results were correlated with routine laboratory measurements and the histological stage of PBC.RESULTS： There were no significant differences in TAC between the various groups. However, CTAC was considerably increased in the PBC group compared to controls and cirrhotics. Analysis of these patients according to disease stages showed that this increase was an early phenomenon observed only in stages I and II compared to controls, cirrhotics and patients with chronic hepatitis C）.After 6 mo of treatment with UDCA, levels of CTAC decreased to those similar to that of controls.CONCLUSION： Patients in the early stages of PBC present with high levels of corrected total antioxidant capacity and this maybe related to the pathophysiology of the disease. UDCA treatment restores the levels of CTAC to control levels.

Primary biliary cirrhosis in HBV and HCV patients:Clinical characteristics and outcome

AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.

Genetic association of cytokines polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese

AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls.METHODS: The study population consisted of 62 patients with AIH, and 77 patients with PBC. The genetic profile of four cytokines was analyzed by restriction fragmentlength polymorphism after specific PCR amplification (PCR-RFLP) or sequence-specific primers PCR (SSP-PCR). The analyzed gene polymorphism included interleukin-1 (IL-1) (at position +3 953 and IL-1RN intron 2), IL-6 (atposition -174), IL-10 promoter (at position -1 082, -819, and -592). The control group consisted of 160 healthyblood donors.RESULTS: The majority of Chinese people including patients and healthy controls exhibited IL-1B 1,1genotype, and there was no significant difference in AIH, PBC patients and controls. There were highly statistically significant differences in the distribution of the IL-1RN gene polymorphism between the patients with PBCcompared with controls. The frequency of IL-1RN 1,1was significantly higher (90.9% vs 79.4%, P = 0.03)and the frequency of IL-1RN 1,2 was significantly lower in PBC patients (6.5% vs 17.5%, P = 0.01). No statistical difference was observed between AIH patients and controls. All of the 160 healthy controls and 62 cases of AIH patients exhibited IL-6-174GG genotype, and there were four cases, which expressed IL-6-174GC genotype in 77 cases of PBC patients. The frequency of IL-6-174GC was markedly significantly higher in PBC patients compared with controls (5.2% vs 0%, P = 0.004). No statistically significant difference was found in the distribution of IL-10 promoter genotype in AIH and PBC patients compared with controls. CONCLUSION: The polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC in Chinese patients.

Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis

AIM:To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis(AIH)and primary biliary cirrhosis(PBC)with AIH features.METHODS:Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined.The activity of periportal and lobular inflammation was scored0(none or minimal activity)to 4(severe),and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3.The infiltration of mononuclear cells positive for CD20,CD38,CD3,CD4,and CD8 and positive for immunoglobulins(IgG,IgM,and IgA)at the periportal areas(interface hepatitis)and in the hepatic lobules(lobular hepatitis)were semiquantitatively scored in immunostained liver sections(score 0-6).Serum aspartate aminotransferase(AST),immunoglobulins,and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions.RESULTS:Lobular hepatitis,hepatitic rosette formation,and emperipolesis were more extensive and frequent in AIH than in PBC.CD3+,CD4+,and CD8+cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC.The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC,but to a lesser degree in AIH.CD20+cells were mainly found in the portal tracts and,occasionally,at the interface in both diseases.Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration,specifically CD38+cells in PBC.No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH.While most AIH cases were IgG-predominant at the interface,PBC cases were divided into IgM-predominant,IgM/IgGequal,and IgG-predominant types,with the latter sharing several features with AIH.CONCLUSION:These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.

Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations

AIM: To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mu-tations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis. METHODS: We investigated 264 liver cirrhosis pa-tients who were not treated with antiviral drugs, in-cluding 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe poly-merase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ2 test and unconditional logistic regression analysis. RESULTS: In the HCC group, genotype C strains, spon-taneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains,spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The dif-ferences in genotype C strains, spontaneous YMDD mu-tations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ2=15.441, P=0.000; χ2=11.983, P=0.001; P=0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC oc-curred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P=0.000). Unconditional logistic regres-sion analysis revealed that patients infected by geno-type C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P=0.013, 95%CI: 1.540-39.264). CONCLUSION: Genotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.