2015年 · 第35卷第02期

The pathological basis of drug-induced liver injury that clinicians are familiar with is the damage of hepatocytes and bile duct cells. Patients can show fatigue, anorexia and jaundice, and laboratory tests show elevated ALT, AST or bilirubin, etc. However, an excellent clinician's knowledge and understanding of drug-induced liver injury cannot be limited to this, but also recognize another type of drug-induced liver injury, that is, the injury of liver blood vessels (hepatic sinuses) by drugs-hepatic sinusoidal obstruction syndrome (SOS). This is a disease with endothelial injury of the hepatic sinus as the main pathological basis. Intrahepatic post-sinus portal hypertension is the main pathophysiological basis leading to clinical manifestations similar to Budd-Chiari syndrome, hepatitis or cirrhosis. It has been reported abroad that SOS is mostly related to high-dose pretreatment of cytotoxic drugs and immunosuppressive agents before bone marrow transplantation^[1]In China, oral administration of Chinese herbal medicines containing pyrrolidine alkaloids such as Tu Panax notoginseng is the most common report of this disease.

In the United States, the prevalence of non-alcoholic fatty liver disease (NAFLD) in adults is as high as 40%, non-alcoholic steato hepatitis (NASH) is 12.2%, and NASH liver fibrosis is 2.7%^[1]。 From simple fatty liver to NASH liver fibrosis, there are five important links: insulin resistance (IR), oxidative stress, chronic mild inflammatory reaction, angiogenesis and fibrogenesis, leptin, hepatic stellate cell (HSC) activation and liver fibrosis^[2]Among them, IR, leptin and adiponectin are the most important. Hepatocellular carcinoma can occur in both NASH combined with liver fibrosis (non-cirrhosis) and liver cirrhosis, and the former is less common.

According to the 2006 National Population Seroepidemiological Survey of Hepatitis B (hereinafter referred to as Hepatitis B), there are 93 million HBV carriers in China^[1]About 1/4 of them will develop chronic liver disease, and some patients can develop cirrhosis or even hepatocellular carcinoma. Studies have shown that HBV DNA replication is the root cause of disease progression in hepatitis B patients^[2,3]。 Therefore, antiviral treatment is particularly important for patients with chronic hepatitis B. Entecavir is the first choice of oral antiviral drugs for hepatitis B due to its strong and high resistance barrier^[4]。 Thymosin α is a commonly used immune enhancer, which has been widely used in the treatment of severe infections, allergies, neuroendocrine diseases, various tumors, and chemotherapy^[5,6]。 In this study, thymosin alpha combined with entecavir was used to treat patients with chronic hepatitis B, and follow-up and analysis were performed.

The level of serum resistin in cirrhotic patients was significantly higher than that in healthy patients, and it was positively correlated with the degree of liver inflammatory reaction and fibrosis^[1]。 Telmisartan is a novel angiotensin Ⅱ receptor blocker (ARB) with peroxisome proliferator-activated receptor gamma (PPAR γ) agonism. Telmisartan can protect non-alcoholic fatty liver disease (NAFLD) by regulating the expression of various factors.

A 56-year-old male was admitted to the Department of Gastroenterology of Shanghai Public Health Clinical Center on December 1, 2013 after hematemesis due to eating peanuts one week ago, followed by melena. The patient had a history of hepatitis B cirrhosis for 20 years. He underwent gastroscopic rubber band ligation for hematemesis 10 years ago, cholecystectomy and splenectomy for gallstones and hypersplenism 5 years ago, and was treated with entecavir for anti-HBV treatment for 2 years. In the family history, his father, one sister and one brother all suffered from hepatitis B. Physical examination at admission: temperature 36.4 ℃, heart rate 76 beats/min, breathing 19 beats/min, blood pressure 115/75 mmHg (1 mmHg =0.133 kPa). Chronic liver disease face, clear mind, spirit is acceptable, physical examination cooperation. There was no yellowing stain on the skin and mucosa of the whole body, no petechia, ecchymosis, liver palm, spider nevus, pigmentation, and no facial telangiectasia. There was no yellowing stain on the sclera. Heart and lungs are not special. There were no abnormalities in the peripheral vascular signs. The abdomen was flat, with a surgical scar located in the middle and upper abdomen, healed well, without abdominal varices, no gastrointestinal type, no peristaltic waves, and no abdominal wall hernia. The abdominal wall is soft, without tenderness and rebound pain. The upper boundary of the liver is located in the 5th intercostal area of the midline of the right clavicle. The subcostal area of the liver is untouched, the subxiphoid process is untouched, and the spleen is untouched. There was no edema in both lower limbs, normal knee tendon reflex, normal Achilles tendon reflex, negative Babinski sign, negative Kernig sign, and negative flapping tremor. Laboratory test: WBC count 3.57×10⁹/L, RBC count 2.80×10¹²/L, Hb 85.00 g/L, blood ammonia 244.00 μ mol/L, ALT 21.00 U/L, AST 32.00 U/L, ALP 78.00 U/L, GGT 21.00 U/L, LDH 184.00 U/L, cholinesterase 3 859 U/L, TBil 23.20 μ mol/L, DBil 9.90 μ mol/L, Total protein 57.50 g/L, albumin 26.40 g/L and total bile acids 70.40 μ mol/L. HBsAg>25×10⁴U/mL, anti-HBs 0.380 U/L, S/CO value of HBeAg 0.552, anti-HBe 1.560, anti-HBc 9.70, CEA 7.95 μ g/L; Hyaluronic acid 1 055.50 ng/mL, glycolic acid 23.88 μ g/mL, type III procollagen 56.80 ng/mL, type IV collagen 54.52 ng/mL. HBV DNA<500 U/mL. PTA 62.00%, PT 16.80 s, activated partial thromboplastin time 42.70 s, fibrinogen 1.45 g/L, thrombin time 19.10 s.

Not only the prognosis of viral hepatitis varies greatly among individuals, but also the antiviral efficacy varies among individuals. Besides the biological characteristics of the infected virus and the factors of the host itself, it has recently been found that it is closely related to whether the infected person has fatty liver. The incidence of HBV and HCV associated fatty liver varies greatly among different regions in the world, accounting for 14% ~70% and 22% ~76% of HBV and HCV infected patients, respectively. Among them, hepatitis C combined with fatty liver is more common^[1]。 The coexistence of fatty liver and viral hepatitis can promote the occurrence of liver fibrosis and increase the risk of liver cirrhosis and liver cancer^[2,3]。 In recent years, studies have shown that the presence of hepatic steatosis also affects the antiviral efficacy^[3,4]。 Therefore, international antiviral guidelines have clearly identified fatty liver as one of the factors affecting the virological response of HCV^[5]However, whether combined fatty liver has an impact on the antiviral efficacy of HBV needs further exploration. In addition, fatty liver is also the cause of elevated ALT in patients with chronic HBV infection, and sometimes it has a certain influence on the selection of indications for antiviral therapy. Therefore, it is very important to improve people's understanding of the clinical characteristics of patients with chronic HBV or HCV infection and fatty liver.

Variceal bleeding is a common serious complication of cirrhosis. Gastroesophageal varices are present in about 50% of cirrhotic patients, and about 7% of cirrhotic patients develop varices every year, and about 7% of cirrhotic patients develop from small varices to large varices every year. The annual incidence of venous bleeding is 12%, and the annual incidence of rebleeding is nearly 60%^[1]。 In recent years, due to the rapid development of diagnostic and therapeutic techniques, the prognosis of acute variceal hemorrhage has improved, but the 6-week mortality rate of an acute hemorrhage event is still as high as 20%^[2]。

Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. Its clinical manifestations range from mild disturbance of consciousness to severe coma, and it is one of the common complications of decompensated cirrhosis. It is reported that more than 70% of patients with liver cirrhosis have different degrees of hepatic encephalopathy, and the one-year mortality rate of alcoholic cirrhosis patients with hepatic encephalopathy is over 60%^[1]。 In recent years, more and more studies have proved that rifaximin can not only treat dominant hepatic encephalopathy and minimal hepatic encephalopathy (MHE), but also effectively prevent the recurrence of hepatic encephalopathy in patients with decompensated cirrhosis, and has high cost performance and safety. This study reviewed the application status of rifaximin in the prevention and treatment of hepatic encephalopathy.

The intestinal microecology has a symbiotic relationship with human body, which is an indispensable and important part of human body^[1]。 It affects human health in many aspects, such as digestion and absorption of food, vitamin synthesis, immune response, metabolic level, resistance to colonization of pathogenic bacteria^[2]。 The imbalance of intestinal microecology can promote the occurrence and development of many diseases, including liver diseases^[2]。 The liver has a close anatomical and functional relationship with the intestine. Intestinal microorganisms interact with the host in the intestine, and play an important role in the occurrence and development of liver inflammatory response, liver injury, chronic liver fibrosis, liver cirrhosis and liver tumors through the hepatointestinal circulation and the micro-ecology-liver axis^[3,4]。 Hepatic inflammatory reactions and diseases [including alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), viral liver disease and cirrhosis, etc.] are often accompanied by intestinal permeability and microecological changes; In disease states, intestinal microecological disturbances can promote chronic inflammatory responses in the liver, leading to chronic fibrosis and promoting tumor formation^[3,4]。 Therefore, it is a scientific and cutting-edge topic to study the intestinal micro-ecological changes during liver disease, explore the interaction between liver disease progression and intestinal micro-ecological changes, and find the potential microbial treatment methods for liver disease.