Alcohol Drinking ; Clinical Trials as Topic ; Diet Therapy ; trends ; Disease Management ; Drug Therapy ; trends ; Hepatitis, Alcoholic ; therapy ; Humans

China ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; Liver Diseases, Alcoholic ; drug therapy ; Phytotherapy

Severe alcoholic hepatitis has very high short term mortality and corticosteroids have been the mainstay of treatment for decades. Patients with Lille score >0.45 are considered non-responders to steroids and have poor outcome. Recently Orthotopic Liver Transplantation (OLT) is being increasingly used as rescue treatment for these patients, without waiting for 6 months of abstinence. Liver transplant is the only rescue treatment which can potentially provide long term benefit for patients who are steroid non-responders. However, with scarcity of organs being a concern, all patients of severe alcoholic hepatitis cannot be chosen for transplantation in an arbitrary way. There is a need for development of predictive tools and objective protocols to select patients who can justify the use of precious liver grafts. With a stringent criteria for selection of patients receiving the graft, liver transplantation in severe alcoholic hepatitis can become a viable rescue therapeutic option conferring significant survival advantage of both short- and long-term basis. The optimal criteria for selection will also prevent misuse of the liver donor pool as well as to prevent mortality in salvageable patients. Further research needs to be done to identify subset of patients which are at low risk of recidivism and also cannot be managed with pharmacotherapy alone. We reviewed the current knowledge on role of OLT in patient with acute severe alcoholic hepatitis in the present review.
Adrenal Cortex Hormones ; Alcoholics* ; Drug Therapy ; Fibrosis ; Hepatitis, Alcoholic* ; Humans ; Liver Diseases, Alcoholic ; Liver Transplantation* ; Liver* ; Mortality ; Steroids ; Tissue Donors ; Transplants

No abstract available.
Antiviral Agents/therapeutic use ; Ascites/diagnosis/prevention & control/therapy ; Cholagogues and Choleretics/therapeutic use ; Fatty Liver/diagnosis/diet therapy ; Fatty Liver, Alcoholic/diagnosis/drug therapy ; Hemorrhage/prevention & control/therapy ; Hepatic Encephalopathy/diagnosis/prevention & control/therapy ; Hepatitis B, Chronic/diagnosis/drug therapy ; Hepatitis C, Chronic/diagnosis/drug therapy ; Humans ; Liver Cirrhosis/*diagnosis/drug therapy/pathology/*therapy ; Liver Cirrhosis, Biliary/drug therapy ; Vasodilator Agents/therapeutic use

BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events. RESULTS: A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period. CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.
Adolescent ; Adult ; Aged ; Alanine Transaminase/*blood ; Cholagogues and Choleretics/*therapeutic use ; Dioxoles/*therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Hepatitis, Alcoholic/*drug therapy ; Hepatitis, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*drug therapy ; Tertiary Care Centers ; Treatment Outcome ; Ursodeoxycholic Acid/*therapeutic use ; Young Adult

Objective: To explore the efficacy of entecavir antiviral therapy on the degree of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with chronic hepatitis B (CHB) in Tibet region. Methods: HBeAg-positive CHB patients who were treated with entecavir in the outpatient and inpatient Department of Infectious Diseases of the Tibet Autonomous Region people's Hospital between January 2018 to December 2019 were retrospectively analyzed. Among the 140 subjects with CHB, 95 cases were CHB alone, and the other 45 cases were diagnosed as CHB combined with NAFLD by ultrasound. All patients were given entecavir 0.5 mg orally once daily on an empty stomach for 48 weeks. HBeAg negative conversion rate, blood glucose, blood lipid, liver function and the degree of liver fibrosis were compared between the two groups at the 12th, 24th and 48th weeks of treatment to evaluate the virological response. SPSS 19.0 statistical software was used to process the data. Measurement data were expressed as mean ± standard deviation (x¯±s). Descriptive statistical analysis was used for t-test, and the categorical variables were expressed as percentage (%) and χ² test. A p-value < 0.05 was considered as statistically significant. Results: After 48 weeks of treatment, the HBeAg and HBV DNA negative conversion rate were significantly better in patients with CHB alone (group B) than CHB combined with NAFLD (group A), that is to say, HBeAg negative conversion rate in group A and B patients were 28.90% and 40%, respectively, and group B was better than group A. HBV DNA negative conversion rate was significantly elevated in group B (83.2%) than group A (64.4%), with statistical significance (P<0.05), and the difference between the both groups was statistically significant. Alanine aminotransferase level was significantly decreased in patients with CHB alone than patients with CHB combined with NAFLD. Aspartate aminotransferase/platelet ratio index was significantly decreased after treatment than before treatment in both group of patients, and the depletion was more pronounced in CHB alone group. Liver stiffness values were significantly decreased in patients with CHB combined with NAFLD than CHB alone group. Moreover, liver stiffness values was higher in group A than group B before treatment under the influence of fat attenuation factors, and the differences before treatment and after treatment were 3.50±4.66 and 2.05±2.53, respectively; however, group B was not affected by fat attenuation factors, so LSM value reduction in group A was more obvious, and the differences were statistically significant. There was no statistically significant difference in blood glucose and blood lipids levels before and after treatment between the two groups. Conclusion: NAFLD has a certain effect on antiviral therapy and liver fibrosis in patients with CHB, i.e., the effect of antiviral therapy in patients with CHB alone is better than patients with CHB combined with NAFLD. Patients with CHB combined with NAFLD when treated with antiviral therapy had a significantly greater degree of liver stiffness reduction than patients with CHB alone. Therefore, it is necessary to actively intervene the risk factors associated with NAFLD according to the actual situation of different individuals to improve clinical efficacy of antiviral therapy.
Antiviral Agents/therapeutic use* ; DNA, Viral ; Guanine/analogs & derivatives* ; Hepatitis B e Antigens ; Hepatitis B, Chronic/drug therapy* ; Humans ; Liver Cirrhosis/complications* ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Retrospective Studies ; Tibet ; Treatment Outcome

Alcoholic hepatitis (AH) is defined as an acute hepatic manifestation resulting from heavy alcohol intake. Histologically, alcoholic steatohepatitis (ASH) is characterized by hepatocellular steatosis, inflammation, and fibrosis. Alcohol abstinence is the sine qua non of therapy for AH and, in the milder forms, is prerequisite to clinical recovery. Severe ASH may lead to multi-organ failure such as acute kidney injury and infection, which has a major impact on survival and thus should be closely monitored. Patients with severe ASH have a drastic short-term mortality of up to 40-50%. Specific therapies should be considered for patients with severe ASH at risk of early death. Corticosteroids are the standard of care for patients with severe ASH. When corticosteroids are contraindicated, pentoxifylline may be an alternative option. Steroid responsiveness should be evaluated on the basis of Lille score. Tactically, we should explore novel therapeutic targets to suppress inflammation based on cytokine profiles, promote hepatic regeneration, limit innate immune responses, and restore altered gut mucosal integrity in severe ASH.
Adrenal Cortex Hormones/therapeutic use ; Free Radical Scavengers/therapeutic use ; Hepatitis, Alcoholic/*diagnosis/drug therapy/pathology ; Humans ; Liver Transplantation ; Pentoxifylline/therapeutic use ; Prognosis ; Severity of Illness Index

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.
Cholangitis, Sclerosing ; Cholelithiasis ; Colitis, Ulcerative ; Crohn Disease ; Drug Therapy ; Drug-Induced Liver Injury ; Hand ; Hepatitis ; Hepatitis Viruses ; Humans ; Inflammatory Bowel Diseases ; Liver Failure ; Non-alcoholic Fatty Liver Disease ; Prevalence

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.
Cholangitis, Sclerosing ; Cholelithiasis ; Colitis, Ulcerative ; Crohn Disease ; Drug Therapy ; Drug-Induced Liver Injury ; Hand ; Hepatitis ; Hepatitis Viruses ; Humans ; Inflammatory Bowel Diseases ; Liver Failure ; Non-alcoholic Fatty Liver Disease ; Prevalence

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.
Antiviral Agents ; Apoptosis ; Carcinoma, Hepatocellular ; Cytokines ; Diet ; Drug Therapy ; Dyslipidemias ; Fibrosis ; Hepatitis B ; Humans ; Insulin Resistance ; Korea ; Liver Cirrhosis ; Liver Diseases ; Liver Transplantation ; Non-alcoholic Fatty Liver Disease ; Obesity ; United States ; Weight Loss