Daw-Shyong Perng

Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis

BACKGROUND & AIMS Taiwan has a high prevalence of hepatitis B viral (HBV) infection and hepatocellular carcinoma (HCC) with increasing consumption of alcohol. We investigated the impact of heavy alcohol consumption and HBV infection on HCC in cirrhotic patients. METHODS 966 cirrhotic patients (132 with HBV infection and alcoholism, 632 with HBV infection, and 202 patients with alcoholism) were enrolled between 2000 and 2009 and followed until 2011. The primary end point was newly developed HCC. RESULTS Within the three patient groups (cirrhotic patients with HBV infection and alcoholism, HBV infection alone, and alcoholism alone) 38 (28.8%), 100 (15.8%), and 21 (10.4%) showed newly developed HCC, respectively. The 10-year cumulative (52.8% vs. 39.8% vs. 25.6%, p <0.001) and annual incidences (9.9%, 4.1%, and 2.1%) of HCC were significantly higher in cirrhotic patients with HBV infection and alcoholism than those in patients with HBV infection or alcoholism alone. For patients with HBV infection and alcoholism, baseline serum HBV DNA (OR=16.8, p=0.025), antiviral nucleos(t)ides analogues (NUCs) therapy (OR=0.01, p=0.035), and serum α-fetoprotein (OR=1.18, p=0.045) were risk predictors of HCC by multivariate logistic regression models. The cumulative incidence of HCC was higher in patients with higher baseline serum HBV DNA. Antiviral NUCs therapy reduced the incidence of HCC. CONCLUSIONS Heavy alcohol consumption significantly increased the risk of HCC in HBV-related cirrhotic patients. Elevated baseline serum HBV DNA was a strong risk predictor of HCC and antiviral NUCs therapy reduced the incidence of HCC in cirrhotic patients with HBV infection and alcoholism.

Controlled trial of ligation plus vasoconstrictor versus proton pump inhibitor in the control of acute esophageal variceal bleeding.

Endoscopic therapy combined with vasoconstrictor was generally recommended to treat acute variceal bleeding. However, up to 30% of patients may still encounter treatment failure.

Complete activation of autophagic process attenuates liver injury and improves survival in septic mice.

ABSTRACT The accumulation of autophagosomes in the terminal step of the autophagic process has recently emerged as a potentially maladaptive process in the septic heart and lung. However, the role of autophagy in the septic liver has not been ascertained. This study was investigated by first examining the entire sequence of the autophagic process in the liver of septic mice. Second, a novel pharmacotherapeutic approach was utilized to treat sepsis with autophagy enhancer/inhibitor. Sepsis was induced by cecal ligation and puncture (CLP). C57BL/6 mice received autophagy enhancer carbamazepine (CBZ), autophagy inhibitor 3-methyladenine (inhibition of autophagosomal formation), or chloroquine (impairment of autophagosomal clearance). We found that the whole autophagic process was activated at 4 h after CLP; however, it did not proceed to completion during the 4- to 24-h time period, as indicated by accumulated autophagosomes and decreased autophagic flux. Carbamazepine, which induced complete activation of the autophagic process, improved CLP survival. This protective effect was also associated with decreased cell death, inflammatory responses, and hepatic injury. However, disruption of autophagosomal clearance with chloroquine abolished the above protective effects in CBZ-treated CLP mice. 3-Methyladenine, which resulted in inhibition of the autophagosomal formation, did not show any above beneficial effects in CLP mice. Impaired autophagosome-lysome fusion resulting in incomplete activation of autophagy may contribute to sepsis-induced liver injury. Treatment with CBZ may serve a protective role in the septic liver, possibly through the effect of complete activation of autophagic process.

Dengue hemorrhagic fever complicated with acute pancreatitis and seizure.

Dengue fever is an acute febrile viral disease, which frequently presents with high fever, headache, bone pain and skin rash. Acute pancreatitis and seizure are rare manifestations of dengue virus infection. A 66-year-old woman with diabetes mellitus presented with epigastralgia, nausea, vomiting, diarrhea and fever. Acute pancreatitis, abnormal liver function and thrombocytopenia were diagnosed at a local hospital. After persistent fever, thrombocytopenia and seizure developed she was transferred to our medical center. Dengue virus infection was confirmed by serology study and dengue hemorrhagic fever grade II was diagnosed. No further neurological symptoms occurred and pancreatitis improved gradually after supportive care. She recovered and had no sequelae at 1 year follow-up. Acute pancreatitis and seizure may be manifestations of dengue virus infection, especially in patients with delayed diagnosis, prolonged fever and thrombocytopenia.

Diabetic nephropathy and risk factors for peripheral artery disease in Chinese with type 2 diabetes mellitus.

The risk for peripheral arterial disease (PAD) is increased in patients with chronic kidney disease. We investigated the effects of renal function on PAD in Chinese with type 2 diabetes mellitus. This study enrolled a total of 2983 (1342 men and 1641 women) Chinese adults with diabetes. The mean age was 63.2 +/- 11.9 years. Peripheral arterial disease was diagnosed by an ankle-brachial index less than 0.9. Renal function was evaluated by serum creatinine (SCr), estimated glomerular filtration rate, and urinary albumin-creatinine ratio (ACR). Risk factors for PAD were evaluated using multiple logistic regression analysis. Age, cholesterol, and high-density lipoprotein cholesterol (HDL-C) (inverse association) were significant risk factors in men, whereas age, body mass index (inverse association), low-density lipoprotein cholesterol, and HDL-C (inverse association) were significant risk factors for diabetic women. After adjustment for age, body mass index, blood pressure, glycosylated hemoglobin, cholesterol, HDL-C, low-density lipoprotein cholesterol, and triglyceride levels, we found that SCr levels greater than 1.5 mg/dL, estimated glomerular filtration rate less than 60 mL/min, and urinary ACR greater than 30 mg/g were independent risk factors for PAD in diabetic men and that SCr levels greater than 1.4 mg/dL and urinary ACR greater than 30 mg/g were independently associated with PAD in diabetic women. The risk factors for PAD are somewhat different between men and women with diabetes in Chinese population in Taiwan. Diabetic nephropathy is significantly associated with PAD in this patient population.

Entecavir versus lamivudine in the treatment of chronic hepatitis B patients with hepatic decompensation.

BACKGROUND Lamivudine has been widely used in chronic hepatitis B patients with hepatic decompensation, but its use is limited by drug resistance. This outcome research aimed to investigate the comparative efficacy and safety of entecavir versus lamivudine in decompensated patients. METHODS Between November 2004 and February 2010, 126 consecutive treatment-naive patients received either entecavir (n=53) or lamivudine (n=73) for decompensated chronic hepatitis B. All patients presented with both hyperbilirubinaemia and coagulopathy. Primary outcome was mortality within 1 year; secondary outcomes included liver-related mortality, biochemical and virological response, and improvement of hepatic dysfunction. RESULTS Both treatment groups were comparable in baseline characteristics. A total of 19 (35.8%) entecavir and 33 (45.2%) lamivudine receivers expired within 1 year, respectively (P=0.29, log rank test). Age (hazard ratio [HR] 1.04 per year, 95% CI 1.01, 1.06), cirrhosis (HR 2.07, 95% CI 1.02, 4.23), and international normalized ratio for prothrombin time (HR 1.44, 95% CI 1.20, 1.74) were independent baseline predictors for all-cause mortality. Antiviral therapy was also unrelated to liver-specific death. However, more patients taking entecavir tended to attain aminotransferase normalization (76.5% versus 52.5%; P=0.05) and viral DNA undetectability (100% versus 58.3%; P=0.06). Moreover, entecavir was associated with significantly greater reduction of the model for end-stage liver disease scores (median 10.0 versus 4.3; P=0.02). Overall, 3 (7.5%) lamivudine but no entecavir users acquired drug resistance in 1 year (P=0.25). CONCLUSIONS Entecavir as compared with lamivudine is similar in the effect on short-term mortality but is associated with greater clinical improvement among chronic hepatitis survivors who recovered from hepatic decompensation.

Determinants of hepatocellular carcinoma in cirrhotic patients treated with nucleos(t)ide analogues for chronic hepatitis B

OBJECTIVES We aimed to identify determinants of hepatocellular carcinoma (HCC) in cirrhotic patients who received nucleos(t)ide analogues for chronic hepatitis B (CHB). PATIENTS AND METHODS This retrospective-prospective study screened all patients (n = 1630) who received antiviral therapy for CHB between 1 September 2007 and 31 March 2013 at the E-Da Hospital and enrolled 210 consecutive cirrhotic patients with pretreatment viral DNA >2000 IU/mL. Those who developed HCC within 3 months of treatment were excluded. All participants were observed until occurrence of HCC, death or 1 January 2014. The incidence and determinants of HCC were estimated using competing risk analyses adjusted for mortality. RESULTS Thirty-five (16.7%) patients developed HCC during a median follow-up of 25.2 months (IQR, 16.3-37.3 months), with a cumulative incidence of 24.1% (95% CI, 16.3%-32.0%) at 5 years. Multivariate-adjusted analyses identified age >55 years [adjusted hazard ratio (HR), 2.19; 95% CI, 1.03-4.66], male gender (adjusted HR, 3.07; 95% CI, 1.05-9.02), model for end-stage liver disease (MELD) score >12 points (adjusted HR, 2.16; 95% CI, 1.10-4.23) and diabetes mellitus (DM; adjusted HR, 3.49; 95% CI, 1.54-7.91) as independent risk factors after adjusting for multiple covariates, including antidiabetes medication. A scoring formula that used information on age, gender, MELD score, DM and antidiabetes regimen significantly discriminated patients at high or low risk of HCC, with sensitivity and specificity of 82.9% and 62.3%, respectively. CONCLUSIONS Age, gender, hepatic dysfunction, DM and medication for DM are baseline factors that stratify the risk of HCC in cirrhotic patients who receive nucleos(t)ide analogues for CHB.

High-sensitivity C-reactive protein and silent myocardial ischemia in Chinese with type 2 diabetes mellitus

Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. When diabetes exists in patients with established CAD, absolute risk for future events is very high. Diabetic patients often have severe, yet asymptomatic, CAD. Although high-sensitivity C-reactive protein (hsCRP) is a strong independent risk factor for cardiovascular events, there is an unclear association between it and silent myocardial ischemia in diabetic patients. In this study, we assess the relationship between hsCRP and silent myocardial ischemia in Chinese with type 2 diabetes mellitus. We designed a cross-sectional study with 225 asymptomatic diabetic patients having no known CAD. Ischemia was assessed by myocardial perfusion imaging. A total of 109 patients (48.4%) was found to have silent myocardial ischemia. Logistic regression analysis revealed age (odds ratio = 4.01, P = .002) (95% confidence interval, 1.98-7.44) and hsCRP (odds ratio = 2.58, P = .005) (95% confidence interval, 1.33-5.01) to be associated with greater risk of silent myocardial ischemia. Using the American Diabetes Association screening guidelines to evaluate risk, we found silent myocardial ischemia to be equally distributed between diabetic patients with 2 or more cardiac risk factors and those with less than 2 risk factors. Twenty-seven (24.8%) patients with silent myocardial ischemia were missed when the American Diabetes Association guidelines were used alone. High-sensitivity C-reactive protein was associated with silent myocardial ischemia in our study. High-sensitivity C-reactive protein might help detect silent myocardial ischemia in diabetic Chinese who may need aggressive treatment to reduce future CAD morbidity and mortality in Taiwan.

Diallyl sulfide protects against ultraviolet B-induced skin cancers in SKH-1 hairless mouse: analysis of early molecular events in carcinogenesis

Background: Diallyl sulfide (DAS) has been shown to have a preventive effect against various cancers.

Spontaneous regression of advanced hepatocellular carcinoma: a case report

Spontaneous regression of advanced hepatocellular carcinoma is extremely rare. A 66-year-old Taiwanese male patient with liver cirrhosis related to chronic hepatitis C presented with hepatocellular carcinoma with portal vein thrombosis. At first, he refused curative therapy, except for silymarin medicine. Spontaneous regression of hepatocellular carcinoma occurred with a decline in tumour size and tumour marker in imaging studies. The patient agreed to undergo surgery approximately 14 months after presentation because of no further decrease in tumour size and an increase in tumour marker in the imaging studies. The resected tumour was hepatocellular carcinoma with portal vein thromboses. Presently, the patient is alive and in good condition without any symptoms or tumour recurrence. We concluded that this was a rare case of spontaneous regression of advanced hepatocellular carcinoma.