The Adjunctive Efficacy of Fuzheng Huayu Tablet on Portal Hypertension with HBV Related Cirrhosis: A Protocol for a Multicenter Randomized Controlled Trial

When the Spleen Gets Tough, the Varices Get Going

Screening and Surveillance of Varices in Patients With Cirrhosis

Evolving Consensus in Portal Hypertension Report of the Baveno IV Consensus Workshop on methodology of diagnosis and therapy in portal hypertension

To study ability of FibroScan (FS) in diagnosing the size of oesophageal varices (OV) in patients with HBV-related cirrhosis. A total of 158 patients with HBV-related liver cirrhosis were enrolled in the study. The relation between the presence of OV assessed by endoscopy, and liver stiffness measurement by Fibroscan was studied, and ROC curves were drawn to assess the diagnostic ability of FS value. For the patients without OV, mild OV, moderate OV, and severe OV, their corresponding FS values were (21.7 +/- 9.9) kPa, (32.1 +/- 13.6) kPa, (42.3 +/- 20.0) kPa and (54.5 +/- 16.2) kPa, respectively. Significant difference was found among the groups (P < 0.001) and also between any two groups (P < 0.05). ROC curve for the diagnosis of with vs. without OV, <moderate vs. > moderate OV, and < severe vs. severe OV were 0.798 (95% CI: 73.1%-86.5%), 0.823 (95% CI: 74.5%-90.0%) and 0.879 (95% CI: 80.8%-95.0%), respectively, with corresponding FS cut-off value of 23.3 kPa, 31.5 kPa and 34.6 kPa. Liver stiffness measurement allows to predict the sizes of oesophageal varices in patients with HBV-related cirrhosis.

Reply to: “Small esophageal varices in compensated cirrhosis patients: To treat or not to treat?”

See the Original "The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data" on page 370.

Efficacy and safety of long-term therapy with Entecavir (ETV) or Tenofovir (TDF) in patients with HBV-related cirrhosis

Small esophageal varices in compensated cirrhosis patients: to treat or not to treat?

Portal hypertension and its complications are the leading causes of morbidity and mortality in patients with liver cirrhosis. Noninvasive assessment of liver stiffness had been an effective tool for assessment of fibrosis progression in chronic liver disease. It was intended to assess liver stiffness measurement (LSM), portal vein diameter (PVD), splenic bipolar diameter (SD), and the platelet count/spleen diameter (PC/SD) ratio in patients who test positive for the hepatitis C virus (HCV) and to study the impact of non-selective beta blockers (NSBB) on the grade of esophageal varices (EVs) and liver elasticity. Subjects were 80 patients with Child-Pugh grade A or B compensated cirrhosis who tested positive for HCV. All of the patients underwent a laboratory workup including AFP, HCV antibodies, HCV RNA, HBsAg, LSM according to real-time elastography, upper gastrointestinal endoscopy (UGIE) to detect and grade EVs, calculation of the PC/SD ratio, and measurement of the PVD and SD according to real-time abdominal ultrasonography. All patients were given the maximum tolerated dose of NSBB for three months, and UGIE, LSM, PC/SD, PVD, and SD were subsequently reassessed and reported. LSM and the PC/SD ratio were exceptional noninvasive tools for prediction of significant EVs (grade ≥ II, p < 0.001) with a sensitivity 82.4% and a specificity 82.6% at a cutoff point 18 kPa for LSM, and a sensitivity 94.1% and specificity 69.6% at a cutoff point 880 for the PC/SD ratio. LSM is highly correlated with PVD, the PC/SD ratio, SD, and the Child-Pugh score. NSBB significantly decreased PVD. The percent change in PVD significantly correlated with LSM, the grade of EVs, and SD. Findings indicated that LSM is a noninvasive, rapid, and reproducible tool with which to detect portal hypertension and EVs. NSBB therapy can effectively decrease PVD and may consequently improve the EV grade with no significant impact on LSM in patients with liver cirrhosis.

Multicenter timolol study: The value of timolol and hemodynamic monitoring in the management of portal hypertensive cirrhotics with no esophageal varices

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.

Background/Aims: Portal hypertension (PH) is a common complication of chronic liver disease and results in esophageal and gastric variceal bleeding, which is associated with a high mortality rate. Measurement of the hepatic venous pressure gradient (HVPG) is considered the gold standard for diagnosing PH and estimating the risk of varices and bleeding. In contrast, upper gastrointestinal (GI) endoscopy (UGE) can reliably demonstrate the presence of varices and bleeding. Both measures are invasive, and HVPG is mainly restricted to tertiary centers. Therefore, the development of noninvasive methods of assessing the severity of PH and the risk of variceal bleeding is warranted. Methods: We retrospectively examined the correlation of spleen stiffness (SSM) and liver stiffness measurements (LSM) with the incidence of variceal bleeding among 143 patients who underwent combined liver and spleen elastography between 2013 and 2015. Results: For 19 of 103 patients (16.8%), upper GI variceal bleeding was diagnosed and treated endoscopically. The median SSM of all patients was 35.3 kilopascals (kPa); the median LSM, 11.7 kPa. Patients with previous bleeding episodes had significantly higher SSM (75.0 kPa) and LSM (37.3 kPa) than those without a history of bleeding (SSM, 30.6 kPa; LSM, 8.2 kPa; p < 0.0001). Seventy-five patients (66.4%) underwent UGE in addition to SSM and LSM: 25 with no esophageal varices (EVs; SSM, 29.5 kPa; LSM, 11.4 kPa), 16 with EV grade 1 (SSM, 35.9 kPa; LSM, 33.4 kPa), 21 with EV grade 2 (SSM, 67.8 kPa; LSM, 27.0 kPa) and 13 with EV grade 3 (SSM, 75.0 kPa; LSM, 26.3 kPa). No statistically significant differences were found between respective grades of EV but were found between the presence and absence of varices. At a calculated cutoff level of 42.6 kPa (with application of 95% CI), SSM had sensitivity of 89% and specificity of 64% in determining the risk of bleeding, with a negative predictive value (NPV) of 0.97 (LSM sensitivity, 84%; LSM specificity, 80%; LSM NPV, 0.96 at LSM cutoff level of 20.8 kPa). When LSM (cutoff level, 20.8 kPa) and SSM (cutoff level, 42.6 kPa) were combined, the NPV was 1 (sensitivity, 100%; specificity, 55%). Conclusion: SSM and LSM as determined by FibroScan (a noninvasive method of detecting PH) is positively correlated with upper GI variceal bleeding (optimal SSM cutoff level, 42.6 kPa; optimal LSM cutoff level, 20.8 kPa). No patients with both SSM and LSM below cutoff levels had a history of bleeding complications.

Bleeding Stomal Varices: Case Series and Systematic Review of the Literature

Incidental esophageal varices

The Editor, Sir, Hepatitis B virus (HBV)-related decompensated cirrhosis is an end-stage liver disease; antiviral therapy can improve the prognosis in these patients (1). Entecavir (ETV) is considered an ideal drug for nucleotide and nucleoside-naive patients with decompensated cirrhosis due to its rapid and potent antiviral effects and low risk of resistance, but clinical data on the safety in these patients with severely impaired liver function are limited. A 58-year old Chinese male was diagnosed with chronic HBV in 2009, but he had not received any treatment for HBV at that time. He presented with HBV-related decompensated cirrhosis, including ascites and splenomegaly. The initial laboratory tests showed elevated liver tests and the serum HBV DNA level was 4.15 × 107 copies/mL. He was diagnosed with HBeAg-positive chronic HBV-related decompensated cirrhosis and his model for end-stage liver disease (MELD) score was 18. He was treated with 0.5 mg ETV daily and was evaluated for liver transplantation. After one month of therapy with ETV, he had a significant reduction in serum HBV DNA (9.70 × 103 copies/mL) and the MELD score remained stable. After receiving two months of ETV therapy, he was admitted to hospital with diarrhoea, abdominal pain, vomiting and fever. His body temperature was 37.2 °C, his pulse 120 beats per minute, respiratory rate 20 breaths per minute and blood pressure 110/70 mmHg. The physical examination revealed yellow sclera, abdominal tenderness and rebound pain, shifting dullness and active bowel sounds. The white blood cell count was 4.15 × 109/L, the neutrophil ratio 85.1%, haemoglobin 104 g/L, and the platelet count 71 × 109/L. The arterial pH value was 7.17, the oxygen pressure 23.3 kPa, the carbon dioxide pressure 3.2 kPa, the oxygen saturation 99%, the base excess −18.1 mmol/L, and the lactate level > 15 mmol/L. Empiric medical treatment for infection, prevention of further insult to the liver, and maintaining water, electrolyte and acid base balance was initiated, but the patient's condition rapidly deteriorated, and he eventually died 15 hours after admission. Two days later, the blood culture showed the presence of Escherichia coli. All of the approved oral nucleotide and nucleoside analogues for HBV carry a ‘black box’ warning in their labelling regarding potential mitochondrial toxicity that can manifest itself as lactic acidosis, myopathy, neuropathy, or even hepatotoxicity (1). The MELD score has been reported in association with lactic acidosis during ETV treatment (2). However, some recent studies observed only one adverse event of lactic acidosis in an ETV treated patient, and the event was resolved without interruption of drug. It is worth noting that two of these studies included patients with a worse liver function (median MELD score 17.1 and 15.3, respectively in the study by Liaw et al (3); 16.1 ± 4.3 and 16.7 ± 4.1, respectively in the report by Hyun et al (4)). Moreover, a small study found that the risk of lactic acidosis was not increased in patients with HBV decompensated cirrhosis with high MELD score who received ETV, compared with patients with non-HBV decompensated cirrhosis (5). The report from Germany also showed that the white blood counts of the patients with MELD scores ≥ 20 were significantly higher than those with MELD scores ≤ 17 (9.28 ± 3.06/nL vs 5.87 ± 2.43/nL, t = 2.41, p < 0.05, using SPSS version 13.0). Thus the patients with high MELD scores could have some unrevealed infections. In conclusion, even if more high-quality and well-designed studies are needed to confirm the correlation between ETV and lactic acidosis, prevention of infection in patients with HBV-related decompensated cirrhosis and severely impaired liver function should be more emphasized. Once these patients develop lactic acidosis, infection must be first excluded or controlled in a timely manner.