Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome

The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.
Acute Kidney Injury/complications/*diagnosis/drug therapy/pathology ; Biomarkers/blood ; Creatinine/blood ; Humans ; Liver Cirrhosis/*complications ; Prognosis ; Serum Albumin/therapeutic use ; Severity of Illness Index

INTRODUCTIONMinimally invasive hepatectomy (MIH) for patients with hepatocellular carcinoma (HCC) is technically challenging, especially with large posteriorly located tumours or background of liver cirrhosis. This is a case-control study comparing the long-term oncological safety of HCC patients who underwent MIH and open hepatectomy (OH). Most of these patients have liver cirrhosis compared to other studies.

MATERIALS AND METHODSSixty patients were divided into 2 groups, 30 underwent MIH and 30 underwent OH for HCC resection. The patients in both groups were matched for extent of tumour resection, age and cirrhosis status. Patient characteristics, risk factors of HCC and all oncological data were studied.

RESULTSNegative resection margins were achieved in 97% of patients in both groups. The mean blood loss during surgery was significantly lower in the MIH group compared to the OH group (361 mL vs 740 mL; 95% CI, 222.2, 734.9; P = 0.04). Hospitalisation is significantly shorter in MIH group (7 days vs 11 days; 95% CI, 6.9, 12.2,; P = 0.04). Eight patients (27%) in the MIH group and 13 patients (43%) in the OH group developed HCC recurrence (P = 0.17). One, 3 and 5 years disease-free survival between MIH and OH groups are 76% vs 55%, 58% vs 47%, and 58% vs 39% respectively (P = 0.18). One, 3 and 5 years overall survival between MIH and OH groups are 93% vs 78%, 89% vs 70%, and 59% vs 65% respectively (P = 0.41).

CONCLUSIONMIH is a safe and feasible curative treatment option for HCC with similar oncological outcomes compared to OH. MIH can be safely performed to remove tumours larger than 5 cm, in cirrhotic liver, as well as centrally and posterior located tumours. In addition, MIH patients have significant shorter hospitalisation and intraoperative blood loss.

Blood Loss, Surgical ; Carcinoma, Hepatocellular ; complications ; pathology ; surgery ; Case-Control Studies ; Disease-Free Survival ; Hepatectomy ; methods ; Humans ; Laparoscopy ; Length of Stay ; Liver Cirrhosis ; complications ; Liver Neoplasms ; complications ; pathology ; surgery ; Margins of Excision ; Minimally Invasive Surgical Procedures ; methods ; Neoplasm Recurrence, Local ; epidemiology ; Tumor Burden

BACKGROUND/AIMS: Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). METHODS: From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality. RESULTS: A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001). CONCLUSIONS: s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak.
Adult ; Biomarkers/blood ; Biopsy ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Hypertension, Portal/*blood/complications/mortality ; Intercellular Signaling Peptides and Proteins/*blood ; Liver/blood supply/pathology ; Liver Cirrhosis/*blood/etiology/mortality/pathology ; Male ; Middle Aged ; Portal Pressure ; Prognosis ; Proportional Hazards Models ; Prospective Studies

BACKGROUND/AIMS: To screen for serum protein/peptide biomarkers of hepatitis B virus (HBV)-associated chronic hepatic lesions in an attempt to profile the progression of HBV-associated chronic hepatic lesions using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) techniques. METHODS: Using SELDI-TOF MS, serum protein/peptide profiles on the CM10 ProteinChip arrays were obtained from a training group including 26 HBV-associated hepatocellular carcinoma patients with liver cirrhosis (LC), 30 HBV-associated LC patients, 85 patients at different stages of liver fibrosis, and 30 asymptomatic HBV carriers. The most valuable SELDI peak for predicting the progression to LC in HBV-infected patients was identified. RESULTS: A SELDI peak of M/Z 5805 with value for predicting LC in HBV-infected patients was found and was identified as a peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1. CONCLUSIONS: The peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1 with M/Z 5805, may be a serological biomarker for progression to LC in HBV-infected patients.
Adult ; Aged ; Biomarkers/*blood ; Carcinoma, Hepatocellular/*virology ; Disease Progression ; Female ; Hepatitis B virus ; Hepatitis B, Chronic/*blood/complications ; Humans ; Liver Cirrhosis/*blood/pathology/virology ; Liver Neoplasms/*virology ; Male ; Middle Aged ; Protein Array Analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Young Adult

OBJECTIVETo determine serum pepsinogen levels in patients with liver cirrhosis and investigate the functions of the gastric mucosa in these patients with concurrent portal hypertensive gastropathy (PHG).

METHODSFifty-one patients with liver cirrhosis and 22 healthy controls were studied by gastroscopy. The hepatic function of the patients with or without PHG were evaluated with Child-Pugh grade. Helicobacter pylori infection was detected using rapid urease test or exhalation of carbon 13. The serum pepsinogen I and II levels were tested by latex-enhanced immunoturbidimetry to calculate the PGI/PGII ratio (PGR).

RESULTSIn cirrhotic patients, the levels of serum PGI and PGR were lower than those in the healthy controls. The patients without PHG had a serum PGI level of 49.48+23.86 µg/L, significantly lower than that in PHG patients (74.85+30.27 µg/L, P=0.000). The levels of serum PG II in patients with H.pylori infection was significantly higher that in patients free of H.pylori infection (P=0.003).

CONCLUSIONThe serum level of PGI decreases obviously in patients with hepatic cirrhosis and PHG, who can have damages of the gastric mucosa lamina propria and reduced secretory function of the gastric mucosa. H.pylori infection may affect the level of PGII. There is no significant correlation between serum PG level and liver function, but to a certain extent, serum PG level especially PGI can reflect the function of gastric mucosa in patients of liver cirrhosis.

Adult ; Case-Control Studies ; Female ; Gastric Mucosa ; pathology ; Helicobacter Infections ; Humans ; Hypertension, Portal ; complications ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Pepsinogen A ; blood ; Stomach Diseases ; blood ; etiology ; microbiology

BACKGROUND/AIMS: Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B. METHODS: The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared. RESULTS: Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B. CONCLUSIONS: Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.
Adolescent ; Adult ; Aged ; Area Under Curve ; Biological Markers/blood ; Female ; Hepatitis B, Chronic/complications/*diagnosis/pathology ; Humans ; Liver Cirrhosis/complications/*diagnosis ; Male ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Retrospective Studies ; Transferrins/*blood ; Young Adult ; alpha 1-Antitrypsin/blood

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.
Aged ; Creatinine/blood ; Foot/pathology ; Gangrene/*etiology ; Hepatitis C, Chronic/complications ; Humans ; Liver Cirrhosis/complications/diagnosis ; Liver Diseases/*diagnosis/drug therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Osteomyelitis/*etiology ; Severity of Illness Index ; Toe Phalanges/radiography ; Vasoconstrictor Agents/*adverse effects/therapeutic use

BACKGROUND/AIMS: Chronic hepatitis C patients with advanced fibrosis have unsatisfactory sustained virological response (SVR) rates. Few data demonstrating the efficacy of combination therapy in chronic hepatitis C patients with advanced fibrosis in South Korea are available. The purpose of this study was to assess whether the stage of fibrosis impacts the efficacy of combination therapy for chronic hepatitis C. METHODS: We retrospectively reviewed data for a total of 109 patients with chronic hepatitis C, treated with peginterferon alfa and ribavirin. SVR according to the stage of liver fibrosis assessed by pretreatment liver biopsy and genotype results were analyzed. RESULTS: Data from 66 genotype 1 patients (60.6%) and 43 genotype 2 or 3 patients (39.4%) among the 109 patients were analyzed. SVR rates for the genotype 1 patients were significantly lower for the stage 3-4 group (32.1%) than the stage 0-2 group (78.9%; P<0.001). SVR rates (92.0% for stage 0-2, 77.8% for stage 3-4, P=0.184) of genotype 2 or 3 patients were not significantly different according to fibrosis stage. Likewise, the frequency of adverse events was not significantly different according to fibrosis stage. CONCLUSIONS: Compared to patients without advanced fibrosis, we can anticipate good SVR rates for genotype 2 or 3 patients with advanced fibrosis and they did not show an inferior tolerability for peginterferon and ribavirin combination therpy. Our results suggest that active treatment is needed for genotype 2 or 3 patients with advanced fibrosis.
Adult ; Age Factors ; Antiviral Agents/therapeutic use ; Blood Platelets/cytology ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/genetics ; Humans ; Interferon-alpha/therapeutic use ; Liver Cirrhosis/complications/*pathology ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Polyethylene Glycols/therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/therapeutic use ; Retrospective Studies ; Ribavirin/therapeutic use ; Severity of Illness Index ; Treatment Outcome

OBJECTIVETo investigate the efficacy and safety of the Fuzheng Huayu Tablet FZHYT), which is used to reinforce qi and resolve stasis in patients with posthepatitic cirrhosis (PHC).

METHODSA multicenter, randomized, controlled clinical trial was conducted in 180 patients with PHC. The patients were randomly assigned using random numbers to a treatment group treated with FZHYT and a placebo group; the treatment course was 6 months for both groups. Overall response, adverse events (AEs), and the 2-year survival rate were assessed after treatment. Evaluations were made on changes in liver function, liver fibrosis, coagulation, hemodynamics, degrees of esophagogastric varices, ascites, quality of life (QOL), and scores of main symptoms.

RESULTSThe overall response was significantly higher in the treatment group than the placebo group (86.7% vs. 62.2%, P<0.01). Patients in both groups had significant improvements in liver function [total bilirubin (TBIL), albumin (ALB)], liver fibrosis [hyaluronic acid (HA), type IV collagen (CIV)], coagulation [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT)], hemodynamics portal venous flow (PVF), and splenic vein flow (SVF) after treatment. Between-group comparisons showed that compared with the placebo group patients in the treatment group achieved significantly greater improvements in TBIL, ALB, HA, C IV, PT, APTT, PVF, SVF, time to ascites resolution, 2-year survival, QOL, and symptom scores (P<0.05 or P<0.01). There were no significant AEs during the treatment.

CONCLUSIONFZHYT is effective and safe for the treatment of hepatic cirrhosis as it is associated with improved liver function, liver fibrosis, coagulation, portal hypertension state, QOL, 2-year survival rate, and fewer AEs.

Adult ; Aged ; Ascites ; complications ; pathology ; Blood Coagulation ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Esophageal and Gastric Varices ; drug therapy ; pathology ; Female ; Hemodynamics ; drug effects ; Humans ; Liver Cirrhosis ; complications ; drug therapy ; physiopathology ; Liver Function Tests ; Male ; Middle Aged ; Qi ; Quality of Life ; Survival Analysis ; Tablets ; Treatment Outcome ; Young Adult