Elasticity Imaging Techniques ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Liver Diseases/pathology* ; Ultrasonography

BACKGROUND/AIMS: The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined . The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naive chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy. METHODS: This study included 364 treatment-naive CHB patients treated with ETV for > or =48 weeks and who received continuous ETV monotherapy for > or =96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log10 IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48. RESULTS: Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for > or =96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up. CONCLUSIONS: Long-term ETV monotherapy is effective for achieving a VR in treatment-naive CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Administration Schedule ; Female ; Genotype ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy/pathology/virology ; Humans ; Liver Cirrhosis/etiology/radiography/ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome

We report on a case of a 57-year-old male who underwent a curative resection for hepatocellular carcinoma (HCC) with histological confirmation of a spontaneously necrotized tumor. Initial serum AFP level was 4,778 ng/mL. A 3.7 cm hyperechoic mass in segment 6 of the liver was observed on ultrasonography and dynamic contrast-enhanced liver MRI showed a 3.7x3.1 cm sized HCC. He was scheduled to undergo curative surgical resection under the clinical diagnosis of an early stage HCC (Barcelona Clinic Liver Cancer stage A). Without treatment, the serum AFP level declined rapidly to 50 ng/mL over five weeks. He underwent curative wedge resection of segment 6 of the liver. Histology revealed complete necrosis of the mass rimmed by inflamed fibrous capsule on a background of HBV-related cirrhosis with infiltration of lymphoplasma cells. Exact pathophysiology underlying this event is unknown. Among the proposed mechanisms of spontaneous neoplastic remission of HCC, circulatory disturbance and activation of host immune response offer the most scientific explanation for the complete histologic necrosis of HCC in the resected mass seen in our patient.
Carcinoma, Hepatocellular/*diagnosis/diagnostic imaging/pathology ; Hepatitis B/complications/diagnosis ; Humans ; Liver/diagnostic imaging/pathology ; Liver Cirrhosis/etiology ; Liver Neoplasms/*diagnosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Necrosis ; Radiography ; Remission, Spontaneous ; Ultrasonography ; alpha-Fetoproteins/analysis

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.
Adult ; Aged ; Biopterin/*analogs & derivatives/analysis ; *Chromatography, High Pressure Liquid ; Chronic Disease ; Elasticity Imaging Techniques ; Female ; Hepatic Veins/physiology ; Humans ; Hypertension, Portal/complications/*diagnosis/metabolism ; Liver/pathology ; Liver Cirrhosis/ultrasonography ; Liver Diseases/complications/*diagnosis/metabolism ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Portal Pressure ; Regression Analysis ; Severity of Illness Index

Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.
Age Factors ; Antiviral Agents/therapeutic use ; Biological Markers/blood ; Hepatitis, Chronic/drug therapy/*pathology ; Hepatitis, Viral, Human/drug therapy/*pathology ; Humans ; Liver/ultrasonography ; Liver Cirrhosis/*pathology ; Orthohepadnavirus/genetics ; Risk Factors

BACKGROUND/AIMS: The red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores. METHODS: This study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively. RESULTS: After adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61+/-0.41% (mean+/-SD), 12.70+/-0.70%, 12.77+/-0.62%, 12.87+/-0.82%, and 13.25+/-0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71+/-0.72%, 12.79+/-0.66%, and 13.23+/-1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and > or =2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of > or =1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score. CONCLUSIONS: Elevated RDW is independently associated with advanced fibrosis in NAFLD.
Adult ; Alcohol Drinking ; C-Reactive Protein/analysis ; Diabetes Mellitus/pathology ; Erythrocyte Indices ; Fatty Liver/complications/*diagnosis/ultrasonography ; Female ; Humans ; Hypertension/pathology ; Liver Cirrhosis/*diagnosis/epidemiology/etiology ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Questionnaires ; Severity of Illness Index

BACKGROUND/AIMS: We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis. METHODS: Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4+/-9.5 y, mean+/-SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated. RESULTS: The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS > or =6: LSM > or =17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4. CONCLUSIONS: The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.
Adult ; Area Under Curve ; *Elasticity Imaging Techniques ; Female ; Hepatic Veins/physiopathology ; Humans ; Liver Cirrhosis/pathology/*ultrasonography ; Male ; Middle Aged ; Odds Ratio ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Severity of Illness Index ; Spleen/anatomy & histology ; Splenic Vein/physiology

OBJECTIVEThe purpose of this study was to investigate the clinical and genetic characteristics of autosomal recessive polycystic kidney disease.

METHODTargeted sequencing was used on a children who was accurately diagnosed as autosomal recessive polycystic kidney disease in Peking Union Medical College Hospital to analyze the major clinical manifestations of the disease. An analysis of the PKHD1 genes was made on the patient, and then verified by polymerase chain reaction (PCR). And the related literature was reviewed also.

RESULTThe patient was a boy, 2 years and 3 months old, and had abdominal distention for about one year. The abdominal ultrasound suggested diffuse liver lesions, mild intrahepatic bile duct dilatation, structure disturbance of both kidneys, appearance of multiple strong echo. The child was clinically highly suspected of polycystic kidney disease. Targeted sequencing showed two mutations in exon 32 and exon 50 of PKHD1 gene, respectively, c.4274T > G, leading to p.Leu1425Arg, c.7973T > A, leading to p.Leu2658Ter. Verified by PCR, the father has one mutation of c.4274T > G.

CONCLUSIONThe clinical manifestations of autosomal recessive polycystic kidney disease are multiple renal cyst, cyst of liver and liver fibrosis, intrahepatic bile duct dilatation. Two mutations (c.4274T > G, c.7973T > A) in PKHD1 gene may be pathogenic.

Child, Preschool ; DNA Mutational Analysis ; Exons ; genetics ; Humans ; Kidney ; diagnostic imaging ; pathology ; Liver ; diagnostic imaging ; pathology ; Liver Cirrhosis ; pathology ; Male ; Mutation ; Polycystic Kidney, Autosomal Recessive ; diagnosis ; genetics ; pathology ; Polymerase Chain Reaction ; Receptors, Cell Surface ; genetics ; Sequence Homology, Amino Acid ; Ultrasonography

Breast cancer is a rare disease in men. We report a case of 53-year-old obese male, with known cryptogenic cirrhosis and hepatocellular carcinoma, presenting a tender mass on left breast. He was diagnosed with invasive intraductal carcinoma, which was consistent with a sporadic lesion. On the basis of previous literatures, obesity can be regarded as a cause for breast cancer even in men. However, there has been inconsistent data about link between liver cirrhosis and male breast cancer, which can be due to heterogenity in the etiology of cirrhosis. Through this case, it can be postulated that the risk for male breast cancer may vary according to the etiology of cirrhosis.
Breast Neoplasms, Male/*etiology/secondary/ultrasonography ; Carcinoma, Hepatocellular/diagnosis/pathology ; Humans ; Immunohistochemistry ; Liver Cirrhosis/complications/*diagnosis/pathology ; Liver Neoplasms/diagnosis/pathology ; Male ; Middle Aged ; Receptors, Estrogen/metabolism ; Tomography, X-Ray Computed

BACKGROUNDHepatocellular carcinoma (HCC) often occurs in association with liver cirrhosis. A stepwise carcinogenesis for HCC has been proposed. The purpose of this study was to observe the enhancement pattern of hepatocellular nodules in cirrhotic patients using contrast-enhanced ultrasound (CEUS) and to correlate patterns of enhancement at CEUS with the diagnosis of hepatocellular nodules using pathologic correlation as the gold standard.

METHODSNinety-three cirrhotic patients with indeterminate hepatocellular nodules at ultrasound, underwent biopsy of each indeterminate nodule. Patients with nodules found to have pathologic diagnoses of regenerative nodules (RNs), dysplastic nodules (DNs), or DNs with focus of HCC (DN-HCC), were enrolled in this study. Enhancement patterns of all nodules were examined throughout the various vascular phases of CEUS and classified into five enhancement patterns: type I, isoenhancement to hepatic parenchyma at all phases; type II, hypoenhancement in the arterial phase, and isoenhancement in the portal venous phase and late phase; type III, iso-to-hypoenhancement in arterial and portal venous phase, and hypoenhancement in the late phase (washout); type IV, slight hyperenhancement in the arterial and portal venous phase and hypoenhancement in the late phase (washout); and type V, partial hyperenhancement in the arterial phase and hypoenhancement in the late phase; and another partial iso-to-hypoenhancement in the arterial and portal venous phase and hypoenhancement in the late phase (washout). The correlation between the contrast enhancement patterns and the pathological diagnoses was analyzed by the chi-squared test.

RESULTSTotally 132 lesions were examined with CEUS in 93 patients. Pathologic diagnoses included 45 DN, 68 RN, and 19 DN-HCC. The enhancement patterns observed were as follows: type I, 49 (37.1%); type II, 27 (20.5%); type III, 28 (21.2%); type IV, 9 (6.8%); type V, 19 (14.4%). Nodules with type I enhancement showed dysplasia in 5 (10.2%) cases; nodules with type II were dysplastic in 11 (40.7%) of cases; nodules with type III enhancement pattern were dysplastic in 22 (78.6%), and those with type IV enhancement contained dysplasia in 7 (77.8%) of cases. Type V enhancement corresponded to DN-HCC in 19 (100%) of cases. CEUS enhancement pattern was correlated with likelihood of dysplasia at pathologic analysis (Trend chi-square test, P < 0.001). Pathological diagnosis was HCC in the enhanced area and hepatocyte dysplasia in the un-enhanced area in the 19 DN-HCC.

CONCLUSIONPattern of enhancement at CEUS correlates with the pathologic diagnosis of hepatocellular nodules in liver cirrhosis, and may be helpful in predicting the progress from RN to HCC nodules.

Adult ; Aged ; Carcinoma, Hepatocellular ; diagnostic imaging ; pathology ; Contrast Media ; Female ; Humans ; Image Enhancement ; Liver Cirrhosis ; complications ; Liver Neoplasms ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Ultrasonography