BACKGROUNDThe etiological spectrum of cirrhosis has changed over the years, but our knowledge of it is limited. The present study aimed to investigate the etiological features of cirrhosis inpatients and their variation in the past 18 years in Beijing.

METHODSA retrospective analysis was performed on all patients with cirrhosis diagnosed for the first time in Peking University People's Hospital from January 1, 1993, to October 25, 2010. Data were analyzed using SPSS 20.0.

RESULTSA total of 2119 cirrhosis inpatients were included in this study: 1412 (66.6%) male and 707 (33.4%) female. Chronic hepatitis B accounted for 58.7%; chronic hepatitis C for 7.6%; chronic hepatitis B and hepatitis C virus co-infection for 0.8% (16 cases); alcoholic liver disease for 9.4% (200 cases); and autoimmune diseases for 9.4% (199 cases). In the past 18 years, the percentage of chronic hepatitis B has decreased from 75.2% to 48.7%; alcoholic liver disease has increased from 5.1% to 10.6%; and autoimmune disease has increased from 2.2% to 12.9%. The percentages of chronic hepatitis B and alcoholic liver disease were higher among men, whereas the percentages of chronic hepatitis C, autoimmune diseases and cryptogenic cirrhosis were higher among women.

CONCLUSIONSChronic hepatitis B was still the most common etiology of cirrhosis in China, but the percentage has been decreasing. The percentages of alcoholic liver disease and autoimmune diseases have been increasing. The etiological spectrum of cirrhosis inpatients differed significantly according to sex.

Adult ; Aged ; Female ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Liver Cirrhosis ; etiology ; Liver Diseases, Alcoholic ; complications ; Male ; Middle Aged ; Retrospective Studies ; Sex Characteristics

BACKGROUND/AIMS: To determine the treatment modalities and the prognosis of a patient with liver cirrhosis, quantitative estimation of liver function is important. We assessed the Child-Pugh score (CPS), the common method as a severity index for the cirrhosis, the Promthombin, gamma GT, and Apolipoprotein A1 (PGA) index and model for end-stage liver disease (MELD) score. The purpose of this study was to evaluate the correlation between these indices in the patients with cirrhosis only and hepatocellular carcinoma (PHC), according to underlying causes (HBV and alcohol). METHODS: We reviewed medical records of 339 cirrhotic patients with/without hepatocellular carcinoma and divided patient groups by disease and underlying cause: cirrhosis caused by alcohol; LC-Al, cirrhosis caused by HBV; LC-B, hepatocellular carcinoma with cirrhosis caused by alcohol; HCC-Al, hepatocellular carcinoma with cirrhosis caused by HBV; HCC-B. We assessed the CPS, PGA index and MELD score and calculated the correlation coefficient between these scores. RESULTS: Among the total of 339 patients, 201 patients were diagnosed on the liver cirrhosis only, and 138 patients on the hepatocellular carcinoma with cirrhosis. In each groups, mean score values were not significantly different in CPS, PGA index and MELD score. The correlation of CPS, PGA index and MELD score in all groups, except for the correlation of PGA index and MELD score in HCC-Al group, was significantly positive (p<0.05). Compared to correlation coefficients between three indices, the patients with cirrhosis only had higher tendencies than the patients with hepatocellular carcinoma. The patients by HBV had higher tendencies than by alcohol. CONCLUSIONS: The correlations between CPS, PGA index and MELD score showed significantly positive correlations in the patients with liver cirrhosis only and hepatocellular carcinoma with cirrhosis (except in HCC-Al group). The patients with cirrhosis only had higher correlation coefficients than the patients with PHC and the patients by HBV had higher than by alcohol.
Adult ; Aged ; Carcinoma, Hepatocellular/*complications ; Female ; Hepatitis B/*complications ; Humans ; Liver Cirrhosis/*complications ; Liver Cirrhosis, Alcoholic/complications ; Liver Neoplasms/*complications ; Male ; Middle Aged ; Prognosis ; *Severity of Illness Index

Many studies have suggested that occult HBV infection has a substantial clinical relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important risk factor for the development of cirrhosis and HCC in patients without HBsAg. As a matter of fact, occult HBV infection is one of the most common causes of crytogenic HCC in endemic areas of HBV. However, there still are controversial issues about the association between occult HBV infection and HCC according to the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may exert synergistic effect on the development of HCC. However, there is insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may play a direct role in the development of HCC. In order to elucidate the assocciation between occult HBV infection and HCC, underlying liver disease must be specified and larger number of cases must be included in future studies.
Carcinoma, Hepatocellular/*complications/*diagnosis/epidemiology ; DNA, Viral/analysis ; Hepatitis/complications ; Hepatitis B/*complications/*diagnosis/epidemiology ; Hepatitis B virus/genetics ; Humans ; Liver Cirrhosis, Alcoholic/complications ; Liver Neoplasms/*complications/*diagnosis/epidemiology ; Risk Factors

Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome.
Acute-On-Chronic Liver Failure/complications/mortality/*pathology ; Age Factors ; Cytokines/metabolism ; Hepatitis, Alcoholic/complications ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Sepsis/complications ; Severity of Illness Index ; Survival Rate

OBJECTIVETo establish and identify an animal model of non-alcoholic fatty liver disease in chronic HBV infected mice.

METHODSTransgenic mice with sustaining HBV production were established by microinjection of ocyte. Then they were randomly assigned into 4 groups (male control, male NAFLD model, female control and female NAFLD model) and treated with high fat diet (2% cholesterol, 10% lard, 88% forage) and common forage, respectively. NAFLD-related physical indexes, liver and kidney function, glucose and lipid metabolism were investigated at the time points of 8 weeks, 16 weeks and 24 weeks. Meanwhile, HBV type, serum levels of HBV DNA and HBeAg, immunohistochemical staining of hepatic HBsAg were detected. The establishment of NAFLD was evaluated by serum levels of total cholesterol (TC), triglycerides, glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), etc. Histological changes were also analyzed by HE, oil red O and Masson's trichrome staining. The status of CHB was assessed on the basis of immunohistochemistry and real-time PCR.

RESULTSThe body and liver weights, liver index in HBV transgenic mice were significantly increased in regardless of the gender of HFD feeding, and the levels of serum ALT, AST, ALP, GGT, TBIL, TBA, TC, TG, HDL-C, LDL and FBG were higher in HFD groups as compared with the control mice. Lipid droplets, cytologic ballooning and liver steatosis could be observed in most lobules of HFD groups after 8-week administration, fatty degeneration of hepatocytes, patch necrosis, mild to moderate chronic inflammatory infiltration were also observed in some of HFD feeding, reflecting the emerge of steatohepatitis. At the time point of 24-week perisinusoidal fibrosis and local fibrosis occurred in HFD groups. Immunohistochemical staining and real-time PCR analysis of the liver tissues showed positive signal of HBsAg in all groups of mice, although no significant difference was documented.

CONCLUSIONOur study suggests that animal model of NAFLD can be established in HBV transgenic mice and provide a nice animal model for further studies on NAFLD with chronic hepatitis B infection.

Animals ; Disease Models, Animal ; Fatty Liver ; virology ; Female ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Male ; Mice ; Mice, Transgenic ; Non-alcoholic Fatty Liver Disease

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.
Humans ; Child ; Hepatitis B, Chronic/pathology* ; Retrospective Studies ; Case-Control Studies ; Hepatitis B virus/genetics* ; Liver Cirrhosis/pathology* ; Non-alcoholic Fatty Liver Disease/complications* ; Risk Factors

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) has been characterized by a wide spectrum of liver damages that span from steatosis to cryptogenic liver cirrhosis and even to hepatocellular carcinoma (HCC). The aims of this study were to determine whether the prevalence of HCC arising from cryptogenic cirrhosis has increased during the last ten years and to characterize the clinical features of cryptogenic HCC in Korea. METHODS: A retrospective and hospital-based analysis of the clinical data was done in 1,145 HCC patients; group A (Jan. 1993-Dec. 1995), group B (Jan. 2000-Dec. 2002). The etiologies of HCC with liver cirrhosis in group A and group B were analyzed. The risk factors of NAFLD such as obesity, type 2 diabetes mellitus, hypertriglyceridemia and hypertension between cryptogenic HCC and HCC with well-defined etiologies were compared. RESULTS: The major leading causes of HCC in each group were hepatitis B virus infection, followed by alcohol, hepatitis C virus and cryptogenic. There was a significant increase in the proportion of cryptogenic HCC in group B (A: 2.3%, B: 5.4%, p<0.05). In the case of HCV, it was 5.3% in group A and 9.9% in group B (p<0.05). Although the prevalence of cyptogenic HCC was significantly increased at an interval of seven years apart, there was no significant difference in the proportions of risk factors of NAFLD between cryptogenic HCC group and well-defined etiology group. CONCLUSIONS: The prevalence of cryptogenic HCC was significantly increased in Korea during the last decade. Although statistically insignifcant, there was a trend toward the higher proportion of risk factors with NAFLD in patients with cryptogenic HCC. This suggests that increased proportion of risk factors associated for NAFLD may have contributed to the development of cryptogenic HCC.
Aged ; Carcinoma, Hepatocellular/*epidemiology/etiology ; English Abstract ; Fatty Liver/complications ; Female ; Hepatitis B/complications ; Hepatitis C/complications ; Humans ; Incidence ; Korea/epidemiology ; Liver Diseases, Alcoholic/complications ; Liver Neoplasms/*epidemiology/etiology ; Male ; Middle Aged

Adult ; Age Factors ; Aged ; Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Aspartate Aminotransferases ; blood ; China ; Female ; Hepatitis B ; complications ; Hepatitis C ; complications ; Hospitalization ; statistics & numerical data ; Humans ; Liver Cirrhosis, Alcoholic ; complications ; mortality ; pathology ; Male ; Middle Aged ; Survival Rate ; gamma-Glutamyltransferase ; blood

BACKGROUND/AIMS: Alcohol may be a cocarcinogen in patients with chronic viral hepatitis. We investigated the effect of alcohol on the development of hepatocellular carcinoma (HCC) in liver cirrhosis (LC) caused by hepatitis B virus (HBV). METHODS: All patients with LC or HCC associated with HBV or alcohol, admitted between March 2001 and June 2005, were included. Patients were divided into three groups according to the etiology of LC: Alcohol (AL), HBV, or HBV+alcohol (HBV+AL). Age and laboratory data at the enrollment of study were analyzed. The logistic regression coefficiency for the prevalence of HCC was calculated by using variables such as age, gender, serologic markers, and etiology of LC. RESULTS: In LC patients (n=342), the proportions of AL, HBV, and HBV+AL groups were 44%, 39%, and 17%, respectively. The proportions of HCC in AL, HBV and HBV+AL groups were 17%, 55%, and 76%, respectively. Age at the diagnosis of HCC was younger in HBV+AL than in AL group (p=0.036). In logistic regression analysis for the risk factor of HCC, odds ratio of age was 1.056 (p<0.001). Odds ratios of HBV and HBV+AL group comparing AL were 8.449 (p<0.001) and 17.609 (p<0.001), respectively. Therefore, old age and chronic alcohol intake in patients with HBsAg were the risk factors of HCC. CONCLUSIONS: Chronic alcohol intake may be an additive factor for the development of HCC in patient with LC caused by HBV. However, a prospective cohort study is needed to confirm these findings.
Adult ; Aged ; Carcinoma, Hepatocellular/*epidemiology/etiology ; Cross-Sectional Studies ; Female ; Hepatitis B, Chronic/*complications/epidemiology ; Hepatitis, Alcoholic/complications/epidemiology ; Humans ; Liver Cirrhosis/*complications/virology ; Liver Cirrhosis, Alcoholic/*complications/epidemiology/virology ; Liver Neoplasms/*epidemiology/etiology ; Male ; Middle Aged ; Odds Ratio ; Regression Analysis ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: Alcohol and the hepatitis B virus (HBV) exert synergistic effects in hepatocelluar carcinogenesis. We aimed to elucidate the clinical significance of the antibody to hepatitis B core antigen (anti-HBc) and occult HBV infection on the development of hepatocellular carcinoma (HCC) in patients with alcoholic liver cirrhosis (LC). METHODS: Patients with alcoholic LC alone (n=193) or combined with HCC (n=36), who did not have HBsAg or antibody to hepatitis C virus were enrolled. Clinical data and laboratory data including anti-HBc were investigated at enrollment. The polymerase chain reaction was applied to HBV DNA using sera of patients with HCC or LC after age and sex matching. RESULTS: Patients with HCC were older (60+/-11 years vs. 53+/-10 years, mean+/-SD, P<0.001), more likely to be male (100% vs. 89%, P=0.03), and had a higher positive rate of anti-HBc (91.2% vs. 77.3%, P=0.067), and a higher alcohol intake (739+/-448 kg vs. 603+/-409 kg, P=0.076) than those with LC. Age was the only significant risk factor for HCC revealed by multiple logistic regression analysis (odds ratio, 1.056; P=0.003). The positive rate of anti-HBc and alcohol intake did not differ in age- and sex-matched subjects between the LC (n=32) and HCC (n=31) groups. However, the detection rate of serum HBV DNA was higher in the HCC group (48.4%) than in the LC group (0%, P<0.001). CONCLUSIONS: Anti-HBc positivity is not a risk factor for HCC. However, occult HBV infection may be a risk factor for HCC in patients with alcoholic LC.
Adult ; Aged ; Antibodies, Viral/blood ; Carcinoma, Hepatocellular/diagnosis/epidemiology/*etiology ; DNA, Viral/analysis ; Female ; Hepatitis B/*complications/diagnosis ; Hepatitis B Core Antigens/*immunology ; Hepatitis B Surface Antigens/immunology ; Hepatitis B virus/genetics/immunology/isolation & purification ; Hepatitis C/complications/diagnosis ; Humans ; Liver Cirrhosis, Alcoholic/*complications/diagnosis/epidemiology ; Liver Neoplasms/diagnosis/epidemiology/*etiology ; Male ; Middle Aged ; Risk Factors