The clinical thinking of diagnosis and treatment of cryptogenic cirrhosis / 医学研究生学报

Cryptogenic cirrhosis (CC), cirrhosis of unknown cause, is common in clinic. With the improvement of the level of diagnosis and the diversification of the diagnosis and treatment, the incidence of CC is gradually declining. In the process of diagnosis and treatment, perfect clinical thinking can help clinicians to analyze and evaluate the existing clinical data, and it is expected to further improve the diagnostic rate of CC. In this paper, the clinical thinking of CC diagnosis and treatment is expounded from the aspects of disease spectrum thinking, anatomy thinking and macroscopic micro thinking.

Indian childhood cirrhosis (ICC) & ICC-like diseases: The changing scenario of facts versus notions.

Indian childhood cirrhosis (ICC), a disease considered to have been endemic in and unique to India has now been documented in children of non-Indian origin from other countries. More recently available findings from a large multicentre study sponsored by the Indian Council of Medical Research (ICMR) have dispelled some of the generally accepted notions and have established several new facts on different aspects of the disease. All relevant reports on ICC and ICC-like diseases, till date, were reviewed to obtain a proper perspective on the current state of our understanding on this non-Wilsonian copper overload liver disease. A primary role of exogenous copper in causing the disease was earlier debated on the basis of studies in India but investigators abroad studying some sporadic cases and a series of endemic ICC-like diseases supported a hepatotoxic injury by ingested copper in genetically susceptible infants and children in ICC- like disease and in ICC. Epidemiologic and morphologic findings in the well controlled ICMR study based on 225 cases of ICC and 426 controls, all confirmed on liver biopsy, have however, convincingly refuted this concept. Additionally, this study revealed that unlike what has been believed earlier, older children more than 3 yr age can get the disease and that in its natural course the hepatic histology can transform between the characteristic one considered diagnostic and some other patterns, any one of which can be the morphologic manifestation at first presentation of the patient. Older children and cases with milder morphologic changes at presentation had longer survival. The overall inference from critical analysis of all available data is that ICC and ICC-like diseases clinically manifest in a child of any age though common in younger ones, and a clinical diagnosis must be made in any child with so-called ‘cryptogenic cirrhosis’. Exposure to exogenous copper in food, milk and water should not be a prerequisite for this consideration. A liver biopsy whenever feasible should be mandatory for confirmation with the understanding that the morphologic changes in liver can present a few other patterns besides the characteristic one currently taken to be diagnostic. The ascribed current decline in encountering ICC is likely to be due partly to missing a diagnosis and partly to a true reduction in incidence consequent on time related economic and socio-cultural changes.

Enfermedad hepática por infiltración grasa no alcohólica: la nueva pandemia del milenio: [revisión] / Non alcoholic fatty liver disease: the new millennium pandemia: [review]

La enfermedad hepática por infiltración grasa no alcohólica (NAFLD) es la más frecuente en las sociedades desarrolladas, comprometiendo 2-8% de la población general, y en las nuestras está en camino de serlo. Es generalmente asintomática o con síntomas y signos inespecíficos como fatiga, hepatomegalia y dolor, o sensación de peso en el hígado. El diagnóstico se sospecha en presencia de pruebas hepáticas o imágenes diagnósticas anormales. La biopsia hepática es el estándar diagnóstico. Existe una clara relación con la obesidad, la diabetes tipo 2, el síndrome metabólico y la resistencia a la insulina. Aproximadamente, 20-25% de los pacientes progresan a cirrosis y sus complicaciones, incluyendo el carcinoma hepatocelular y la necesidad de un trasplante hepático. La corrección de la resistencia a la insulina con modificaciones dietéticas y el aumento de la actividad física es generalmente beneficiosa. La efectividad de los múltiples medicamentos disponibles está por demostrarse.

Non-alcoholic liver disease (NAFLD) is the most common liver disease in affluent societies, affecting 2-8% of the general population, and it will be soon in our societies. It is generally asymptomatic or with a no specific picture of fatigue, hepatic pain or discomfort and hepatomegaly. It is suspected in cases with aminotransferase or imaging abnormalities. Liver biopsy is considered the gold standard for diagnosis. There is a close pathogenic relationship with obesity, type 2 diabetes, hyperlipidemia, metabolic syndrome and insulin resistance. Approximately 20-25% of the cases progress into cirrhosis with all its complications including hepatocellular carcinoma and the need for liver transplantation. Correction of insulin resistance with dietary measures and physical activity is generally beneficial. The efficacy of the multiple medications available remains to be demonstrated.

Cryptogenic cirrhosis: Metabolic liver disease due to insulin resistance.

Objective: Etiopathogenesis of cryptogenic cirrhosis (CC) is not yet well established. Up to 20% of non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, mostly termed as cryptogenic. Insulin resistance and altered metabolic parameters form a major pathogenic link between NAFLD and CC. CC may thus be actually a metabolic liver disease. Materials and Methods: Thirty-four patients of CC and 32 patients having cirrhosis due to chronic hepatitis B (Hep B) were assessed in a cross-sectional study in a tertiary hospital for insulin resistance, % β-cell activity, obesity indices, plasma glucose, lipid profiles, and many other parameters. Results: CC patients had higher homeostasis model assessment (HOMA)-IR compared to Hep B group (P = 0.000016). A positive correlation between IR values and Child-Pugh score among CC patients was found ("r" = 0.87; P < 0.00001). Out of 34 CC patients, 15 (44.1%) had obesity contrary to 6 (18.8%) in the control group (P = 0.0022). Differences were observed in subcutaneous fat (P = 0.0022), intra-abdominal fat (P = 0.0055), waist circumference (P = 0.014), and percentage body fat (P = 0.047) between the two groups. Significant differences were observed in the levels of triglyceride, total cholesterol, and very low density lipoprotein (VLDL). Conclusion: Most of the CC patients showed significantly higher prevalence of HOMA-IR, obesity indices, and various parameters of "lipotoxicity" and metabolic syndrome, suggesting that CC may be the long-term consequence of a type of "metabolic liver disease." Further studies are required to evaluate the role of therapeutic interventions to enhance insulin sensitivity in such patients.

Metabolic syndrome and hepatocellular carcinoma: An advance in epidemiology study / 第二军医大学学报

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third cause of cancer-related death worldwide; meanwhile, it is also one of the fastest growing malignancies. The causes of HCC are multiple; HBV is the most important cause in China, with about 25%-30% of HBV infection patients finally develop hepatic cirrhosis and liver cancer. At present, large scale epidemiological studies revealed that the metabolic syndrome (MS) was closely related to liver cancer, and it even served as an independent risk factor for the occurrence and progression of liver cancer. Non-alcoholic fatty liver disease is a metabolic syndrome clinically manifested in the liver; recently it has been indicated to be closely related with HCC development and progression. This paper reviews the recent researches on metabolic syndrome and liver cancer, so as to provide literature for preventive and therapeutic studies on non-virus-related liver cancer.

Idiopathic non-cirrhotic intrahepatic portal hypertension: common cause of cryptogenic intrahepatic portal hypertension in a Southern Indian tertiary hospital.

Background and aim Patients with intrahepatic portal hypertension and negative etiological work-up for liver disease are often labeled as having cryptogenic cirrhosis. The aim of this study was to evaluate causes of liver disease in patients with unexplained intrahepatic portal hypertension. Methods We retrospectively analyzed cause of liver disease in all patients with cryptogenic intrahepatic portal hypertension who underwent liver biopsies between June 2005 to June 2007 in our center. Results Five hundred and seventeen patients underwent liver biopsies of whom 227 had portal hypertension. Of these, the cause of liver disease could not be detected prior to liver biopsy in 62 patients. Causes of liver disease identified after liver biopsy in these 62 patients were: idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH) (30 patients, 48 ), cirrhosis (14), fatty liver disease (7) and other causes (11). Initial presentations in idiopathic NCIPH patients were splenomegaly and anemia (18 patients), variceal bleed (9) and ascites (3). Median age (range) of patients at first presentation was 32 (15-57) years, and 19 were male. Majority (90 ) were in Child’s class A. Hepatic vein pressure gradient was <5 mmHg in 2 of 7 NCIPH patients tested. Conclusions We identified 30 patients with idiopathic NCIPH at our center over the 2 year study period. The clinical presentation and investigations of NCIPH closely mimic cryptogenic cirrhosis. Idiopathic NCIPH should be considered as a differential diagnosis of cryptogenic cirrhosis in India.

Metabolic syndrome and hepatocellular carcinoma:an advance in epidemiology study / 第二军医大学学报

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third cause of cancer-related death worldwide;meanwhile,it is also one of the fastest growing malignancies.The causes of HCC are multiple;HBV is the most important cause in China,with about 25%-30% of HBV infection patients finally develop hepatic cirrhosis and liver cancer.At present,large scale epidemiological studies revealed that the metabolic syndrome(MS) was closely related to liver cancer,and it even served as an independent risk factor for the occurrence and progression of liver cancer.Non-alcoholic fatty liver disease is a metabolic syndrome clinically manifested in the liver;recently it has been indicated to be closely related with HCC development and progression.This paper reviews the recent researches on metabolic syndrome and liver cancer,so as to provide literature for preventive and therapeutic studies on non-virus-related liver cancer.