Intrahepatic and extrahepatic clinical manifestations and treatment progress for hepatitis type E / 中华肝脏病杂志

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

Consensus on diagnosis and treatment of invasive fungal infection in patients with severe liver disease / 中华肝脏病杂志

The prognosis of severe liver disease combined with invasive fungal infection (IFI) is poor, and the clinical manifestations are often atypical. Moreover, most of the antifungal drugs are metabolized in the liver, with severe toxicities and side effects, making clinical diagnosis and treatment difficult. The Professional Committee for Hepatology, the Chinese Research Hospital Association and the Hepatology Branch of China Medical Association organized relevant experts to formulate an expert consensus based on the characteristics of patients with severe liver disease combined with IFI, in order to provide reference for medical personnel in making decisions on the diagnosis and treatment.

Alleviation of diabetes-induced hepatotoxicity by date palm hydroalcoholic extract in rat model; a biochemical, immunohistochemical and stereological study / Alivio de la hepatotoxicidad inducida por diabetes mediante el extracto hidroalcohólico de palmera datilera en modelo de rata: un estudio bioquímico, inmunohistoquímico y estereológico

SUMMARY: The present study was aimed to investigate the hepatoprotective effects of date palm hydroalcoholic extract (DP)in diabetic rats using biochemical and histopathological approaches. Diabetes was induced by administration of 60 mg/kg of streptozotocin intraperitoneally. In this analysis 32 adult rats were randomly divided into four groups; group 1: non-diabetic control whic received 0.1 mL normal saline, group 2:served as non-diabetic control which treated with 270 mg/kg of DP, group 3: served as untreated diabetic, and group 4: diabetic rats treated with 270 mg/kg of DP. Diabetic rats treated with the DP extracts exhibited lower hepatic oxidative stress and lower hepatic enzymes level. Extract treatment decreased the level of malondealdehyde (MDA) as a marker of lipid peroxidation. Stereological estimations revealed a significant increase in the liver volume in diabetic rats which was reduced in DP-treated rats. Immunofluorescence staining showed high synthesis of acrolein as a byproduct of lipid proxidation. While, optical density measurement revealed significant decrease in acrolein after DP administration. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and necrotic nuclei, whereas, DP treatment attenuated the adverse effects of diabetes on the liver represented by relatively healthy hepatocytes and sinusoids. The obtained results indicated that date pam extract was beneficial in the prevention of diabetes-induced hepatotoxicity due to its natural antioxidant constituents. Further preclinical and clinical studies are needed for considering this plant in management of prediabetes and diabetes hepatic complications.

RESUMEN: El presente estudio tuvo como objetivo investigar los efectos hepatoprotectores del extracto hidroalcohólico (DP) de la palmera datilera en ratas diabéticas utilizando enfoques bioquímicos e histopatológicos. La diabetes fue inducida mediante la administración de 60 mg / kg de estreptozotocina por vía intraperitoneal. Se dividieron al azar 32 ratas adultas en cuatro grupos; grupo 1: control no diabético que recibió 0,1 mL de solución salina normal, grupo 2: control no diabético tratado con 270 mg / kg de DP, grupo 3: fue separado como diabético no tratado, y grupo 4: ratas diabéticas tratadas con 270 mg / kg de DP mg / kg de DP. Las ratas diabéticas tratadas con los extractos de DP mostraron menor estrés oxidativo hepático y menor nivel de enzimas hepáticas. El tratamiento con extracto disminuyó el nivel de malondealdehído (MDA) como marcador de la proxidación de lípidos. Las estimaciones estereológicas revelaron un aumento significativo en el volumen del hígado en ratas diabéticas que se redujo en las ratas tratadas con DP. La tinción por inmunofluorescencia mostró una alta síntesis de acroleína como subproducto de la proxidación de lípidos. Mientras que, la medición de la densidad óptica reveló una disminución significativa de la acroleína después de la administración de DP. El examen histopatológico mostró cambios significativos en el tejido hepático diabético no tratado manifestados por vena porta dilatada, infiltración leucocítica, degeneración grasa y núcleos necróticos, mientras que el tratamiento con DP atenuó los efectos adversos de la diabetes en el hígado representados por hepatocitos y sinusoides relativamente sanos. Los resultados obtenidos indicaron que el extracto de palmera datilera fue beneficioso en la prevención de la hepatotoxicidad inducida por diabetes debido a sus constituyentes antioxidantes naturales. Se necesitan más estudios clínicos para considerar esta planta en el manejo de la prediabetes y las complicaciones hepáticas de la diabetes.

Morfoanatomia foliar de phoradendron obtusissimum(miq ) eichler (viscaceae), "ka'a votyre'y", utilizado con fines medicinales en una comunidad de Colonia Independencia, Paraguay / Leaf morphoanatomy of Phoradendron obtusissimum(Miq) Eichler (V iscaceae), "ka'avotyre'y", used for medicinal purposes in a community of Colonia Independencia, Paraguay

Resumen: El "ka'avotyre'y", Phoradendron obtusissimum (V iscaceae), es una especie empleada con fines medicinales en Paraguay para tratar enfermedades hepáticas. El presente trabajo se desarrolló dentro del marco del proyecto "Conservación, fortalecimiento y uso sostenible de la flora de Itá Azul y San Gervasio, Colonia Independencia, Reserva de Recursos Manejados Ybytyruzu, Paraguay" y tuvo por objetivo describir la morfoanatomía de P . obtusissimum. Los caracteres diferenciales son: estomas paracíticos en ambas epidermis, índice estomático en epidermis adaxial (5,71)-6,62-(8,33) y en epidermis abaxial (6,45)-1 1,20-(14,29); presencia de drusas en todo el mesófilo. Se presentan así elementos de diagnóstico útiles a la hora de identificar a la especie estudiada. Palabras clave: Phoradendron obtusissimum, morfoanatomía, planta medicinal.

Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

Reunião com expertos em hepatotoxicidade da Sociedade Brasileira de Hepatologia: analgésicos, antitérmicos, insumos vegetais, fitoterápicos, homeopáticos e AINEs / Meeting with Society's Hepatotoxic Experts Brazilian Institute of Hepatology: Analgesics, Antipyretics, Vegetable, Phytotherapic, Homeopathic and AINS

No dia 05 de agosto de 2010, no Hotel Blue Tree, no bairro do Morumbi em São Paulo, a Sociedade Brasileira de Hepatologia realizou uma reunião de expertos para discutir alguns assuntos importantes referentes à toxicidade hepática. Esta reunião foi de responsabilidade exclusiva da Sociedade Brasileira de Hepatologia (SBH), sem interferência de agências ou da indústria farmacêutica. Dentre os assuntos discutidos, três deles mereceram destaque pelo volume de solicitações de esclarecimentos encaminhadas diretamente à Sociedade Brasileira de Hepatologia. O site da SBH recebe com frequência tais solicitações de outras sociedades ou diretamente de colegas, assim como do público não-médico, por questões pertinentes a estes assuntos: 1. papel do acetaminofen/paracetamol nas alterações hepáticas da dengue; 2. eficácia e segurança da medicina alternativa (homeopatia, medicina natural, fitoterápicos); 3. alterações hepáticas induzidas por analgésicos, antitérmicos e anti-inflamatórios não-esteroides com foco no seu uso na dengue.Dentro deste contexto, a Sociedade Brasileira de Hepatologia organizou uma sessão durante todo o dia 05 de agosto para discutir unicamente estes temas.

Non-viral chronic active liver disease in Yemeni patients and the possible implication of Qat chewing

Twenty eight Yemeni patients with nonviral chronic active liver disease were retrospectively studied for underlying causes and possible predisposing risk factors. They were 17 males and 11 females with age range between 17 and 42 years [median 29.5 years]. The diagnosis was based on their clinical, biochemical and imaging criteria, and was consistent with severe chronic liver disease that was persistent for more than six months. Seroimmunological markers for autoimmune liver disease were found in 8 patients [4 males and 4 females]. Slit-lamp examination for Kaiser-Fleicher ring, which is characteristic for Wilson's disease, was negative in all patients and serum iron and serum ferritin were normal in two patients over 40 years. Habitual qat chewing was found in 27 patients, of which 20 were daily qat chewers. Meanwhile, good response to immune suppressive treatment was documented in 22 patients. These results indicate that most Yemeni patients with nonviral chronic active liver disease are young, heavy qat chewers and have good response to immune suppressive treatment. These findings may suggest an underlying immunologic pathogenic mechanism for the chronic active liver disease in these patients. Further studies are needed to investigate the nonviral causes of chronic liver disease and the possible implication of qat chewing habit in liver diseases as well as in other diseases in Yemeni population

Hepatoprotective activity of six polyherbal formulations in CCl4-induced liver toxicity in mice.

To evaluate pretreatment of six polyherbal liquid formulations (PLFs) commercially available in India, on CCl4-induced liver injury, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, po) followed by single sc injection of 50% (v/v) CCl4 in arachis oil at a dose of 1 ml/kg. The serum biochemical parameters such as alanine transaminases, aspartate transaminases and alkaline phosphatase were estimated. Phenobarbitone-induced sleeping time and liver histopathology were also carried out. CCl4-treated animals showed significant increase in the levels of liver enzymes, phenobarbitone-induced sleeping time and revealed fatty changes and centrizonal necrosis on histological examination of liver indicating hepatic damage. When pretreated with PLFs at a dose of 5.2 ml/kg body weight/day, the CCl4-induced changes were significantly reversed. The pretreatment with PLFs can prevent acute liver damage induced by CCl4 only at a higher dose. Therefore, it is suggested that a dose adjustment of these PLFs may be necessary for their optimal effects in human liver diseases.

Positive effects of Green Tea on hepatic dysfunction, lipid peroxidation and antioxidant defence depletion induced by cadmium

Cadmium (Cd) is a highly toxic environmental and industrial cumulative pollutant that affects many organs,especially the liver. The present study was designed to evaluate the antioxidant effect of green tea oncadmium-induced hepatic dysfunction and oxidative stress in rats. Adult male Wistar rats were administeredcadmium by injection of 20 ìmoles /kg bw/ every 3 days for six months. This study revealed significant (p <0.05) liver dysfunction, lipid peroxidation and a decline in antioxidant enzyme activities in the liver of cadmium-treated rats compared to control animals. Compared to control rats, the activities of lactate dehydrogenase (LDH), gammaglutamyl transferase (GGT), acid phosphatase (PAC), phosphatase alkaline (PAL), as well as bilirubin and thiobarbituric acid-reactive substances (TBARs), were significantly (p < 0.05)increased in Cd-treated rats. Moreover, antioxidant enzyme activities, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, were significantly (p < 0.05) decreased in the liver of cadmiumtreatedrats. The oral administration of 5% aqueous green tea extract, along with cadmium treatment for six months, caused a significant (p < 0.05) improvement in cadmium-induced toxicity by significantly decreasing(p < 0.05) the activities of enzymatic markers of liver dysfunction (LDH, GGT, PAC, PAL activities, as well as the bilirubin rate). Indeed, green tea extract significantly increased (p < 0.05) antioxidant enzymatic activities (SOD, Catalase, GPX) in rat liver, compared to those given cadmium alone. Thus, the oral administration of green tea, along with cadmium significantly (p < 0.05) improves cadmium-induced liverdysfunction and stress oxidant in rats’ liver.

Efficacy of Psidium guajava leaf extract against liver diseases in guinea pigs

Serum levels of aspartate aminotransfcrase [AST], alanine aminotransferase [ALT] and alkaline phosphatase [ALP] were analysed in guinea pigs after daily treatment with 1 g/kg Psidium guajava [PG] aqueous leaf extract for five days followed by subcutaneous administration of 50 mg/kg CC[1], in order to assess the preventive effect of the extract on liver damage. In addition, the levels of the enzymes in guinea pigs administered with 50 mg/kg CC1[4] followed by 3 and 6 days treatment with the plant extract were determined in order to assess the efficacy of the extract in the cure of liver damage. Guinea pigs orally treated with 1 g/kg leaf extract of PG followed by subcutaneous administration of 50 mg/kg CC1[4] had serum levels of AST, ALT and ALP above the normal range. However, guinea pigs orally treated with 1 g/kg leaf extract of PG for 3 and 6 days following subcutaneous administration of 50 mg/kg CC1[4] had serum levels of AST. ALT and ALP not significantly different [P < 0.05] from those in control guinea pigs. Thus wherever the leaf extract of PG could not effectively prevent CC1[4] induced liver damage, it was found to effectively cure it

Hepatoprotective activity of capparis spinosa root bark against CC1[4] induced hepatic damage in mice

Many hepatoprotective herbal preparations have been recommended in alternative systems of medicine for the treatment of hepatic disorders. No systematic study has been done on protective efficacy of Capparis spinosa [Capparidaceae] to treat hepaticjdiseases. Protective action of C. spinosa ethanolic root bark extract was evaluated by this study in an animal model of hepatotoxicity induced by carbon tetrachloride. Healthy male mice [30-35 g body weight, 6-8 weeks old] were divided into 7 groups. Group 1 was normal control group; Group 2, the hepatotoxic group was given CCL[4]; Group 3 was administered olive oil [vehicle]; Groups 4-6 received different doses of ethanolic root bark extract [100. 200 and 400 mg/kg] with CCL[4]; Group 7 was administered overdose of extract [800 mg/kg]. The parameters studied were alanine transaminase, aspartate transaminase activities and duration of sleep. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCL[4] treated animals showed significant increase in the levels of serum enzyme activities reflecting the liver injury caused by CCL[4]. Whereas blood samples from the animals treated with ethanolic root bark extracts showed significant decrease in the levels of serum markers indicating the protection of hepatic cells. The results revealed that ethanolic root bark extract of C. spinosa could afford significant dose-dependent protection against CCL[4] induced hepatocellular injury

Effect of Curcuma longa or parziquantel on Schistosoma mansoni infected mice liver--histological and histochemical study.

Effect of drug praziquantel (PZQ) and C. longa extract on S. mansoni infected mice is reported. The level of glycogen, alkaline and acid phosphatases (ALP and ACP respectively), and body weight, liver weight and liver weight/body weight ratio were studied in mice infected with S. mansoni. ALP level was increased after infection. C. longa treated mice showed marked reduction in ALP level more than after PZQ-treatment. C. longa enhanced the concentration of glycogen after being reduced by infection, while PZQ-treatment revealed more reduction. C. longa caused enhancement in body weight while PZQ treatment had no effect. The formation of granuloma around schistosome eggs in the liver produced inflammation. C. longa extract and PZQ were effective in reducing granuloma size in infected mice.

Imaging findings in hepatic Langerhans' cell histiocytosis.

We describe ultrasonographic and computed tomographic features of hepatic lesions in two cases of disseminated Langerhans' cell histiocytosis affecting children. In the first case, hyperechoic band like periportal lesions were observed at ultrasonography, which on computed tomography was found to be hypodense admixed with fatty attenuation (HU@23 to - 57) at places. In addition, the caudate lobe was very prominent. In the second case, the hepatic parenchyma showed predominantly hyperechoic diffusely heterogeneous echogenicity. There were features of cirrhosis of liver with portal hypertension in the form of atrophy of right lobe with hypertrophy of left lobe of liver with lobulated outline, prominent main portal vein and splenoportal axis, splenomegaly and gastroesophageal varices. Both the patients were put on chemotherapy as per schedule (Protocol: DAL HX - 83) and are on follow up.

Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine.

Silymarin, a flavonolignan from 'milk thistle' (Silybum marianum) plant is used almost exclusively for hepatoprotection and amounts to 180 million US dollars business in Germany alone. In this review we discuss about its safety, efficacy and future uses in liver diseases. The use of silymarin may replace the polyherbal formulations and will avoid the major problems of standardization, quality control and contamination with heavy metals or bacterial toxins. Silymarin consists of four flavonolignan isomers namely--silybin, isosilybin, silydianin and silychristin. Among them, silybin being the most active and commonly used. Silymarin is orally absorbed and is excreted mainly through bile as sulphates and conjugates. Silymarin offers good protection in various toxic models of experimental liver diseases in laboratory animals. It acts by antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, membrane stabilizing, immunomodulatory and liver regenerating mechanisms. Silymarin has clinical applications in alcoholic liver diseases, liver cirrhosis, Amanita mushroom poisoning, viral hepatitis, toxic and drug induced liver diseases and in diabetic patients. Though silymarin does not have antiviral properties against hepatitis virus, it promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation and protects against glutathione depletion. Silymarin may prove to be a useful drug for hepatoprotection in hepatobiliary diseases and in hepatotoxicity due to drugs. The non traditional use of silymarin may make a breakthrough as a new approach to protect other organs in addition to liver. As it is having a good safety profile, better patient tolerability and an effective drug at an affordable price, in near future new derivatives or new combinations of this drug may prove to be useful.

Role of ursodeoxycholic acid in lowering ALT in chronic liver disease

The objective was to see the efficacy of ursodeoxycholic acid in improving the ALT levels in patients suffering from chronic liver disease. Thirty patients suffering from chronic liver disease [either B or C] were given oral ursodeoxycholic acid in a dose of 250 mg twice a day for 4 months. Their blood biochemistry and haematology were repeated monthly for 7 months i.e. 4 months of therapy and 3 months post therapy to see the response. The mean ALT levels of 30 patients who completed the study was 101+47 IU/L. During therapy 24 cases [80%] showed lowering of their ALT levels while 6 [20%] either showed no response or worsening of ALT levels. Of 24 cases who showed an improvement in their ALT levels; over 25% drop in ALT levels was seen in 217 cases [70%] and less than 25% drop seen in 7 cases [30%]. The mean ALT values during therapy were 75 IU/L showing an overall 25% reduction from the baseline values. Following cessation of therapy the mean ALT levels showed a rise to 90 IU/L which was almost similar to 101 IU/L value in the pre treatment period. The study showed some role of ursodeoxycholic acid in improving the ALT levels in chronic liver disease

A Prospective Study Comparing the Efficacy of Early Administration of Terlipressin and Somatostatin for the Control of Acute Variceal Bleeding in Patients with Cirrhosis / 대한간학회지

BACKGROUND/AIMS: Terlipressin and somatostatin decrease portal venous pressure and they are used for the treatment of variceal bleeding. However, only a few studies have compared the efficacy of these drugs in combination with other procedures for hemostasis. Therefore, we performed a prospective study to compare the efficacy of terlipressin and somatostatin for controlling acute variceal bleeding when used in combination with other procedures for hemostasis. METHODS: A total of 98 patients, who presented with variceal bleeding from September 2003 to May 2005, were randomly divided into the somatostatin group or terlipressin group. We compared the 5-day failure rate (defined as failure to control bleeding, rebleeding or death within 5 days of admission) and the 6-week mortality. The prognostic factors for 5-day failure and 6-week mortality were also evaluated. RESULTS: There were no differences in baseline characteristics between the two groups. The overall 5-day failure rate and the cumulative 6-week mortality were 16.3% and 15.8%, respectively. The five-day failure rate and the cumulative 6-week mortality were not significantly different between the somatostatin and terlipressin groups. Hepatocellular carcinoma, the baseline serum creatinine level and endoscopic treatment for hemostasis were the significant predictors of 5-day failure; the baseline serum creatinine level was the predictor of 6-week mortality. CONCLUSIONS: Both somatostatin and terlipressin were effective and showed comparable efficacy for the control of the acute variceal bleeding in the setting of a combined therapeutic approach. The baseline serum creatinine level may be a significant predictor for patient failure at 5 days and the 6-week mortality.

Terapia hipolipemiante em situações especiais: hipotireoidismo e hepatopatias / Hypolipidemic therapy in special situations: hypothyroidism and liver disease

O hipotireoidismo é comum entre pessoas idosas, especialmente entre as mulheres. A suspeita diagnóstica deve se basear na presença de sinais e sintomas clássicos e a detecção pode ser feita pela elevação dos níveis do hormônio tireo-estimulante (TSH). Anormalidades lipídicas na presença de hipotireoidismo sub-clínico são de menor impacto. Entretanto, a reposição específica de hormônio tireoideano é tão mais importante quanto a magnitude do distúrbio glandular. Na vigência de doença hepática, alguns agentes hipolipemiantes podem levar a um agravamento do quadro, entretanto, estudos recentes têm mostrado que as estatinas podem ser utilizadas na presença de esteatose hepática. Terapia hipolipemiante combinada pode induzir aumentos de enzimas hepáticas e o monitoramento cuidadoso é recomendado nestes pacientes.