Role of radiologic modalities in the management of non-alcoholic steatohepatitis

During the last decade, the role of radiologic modalities in management of patients who have fatty liver disease has expanded. Ultrasonography has been used as a noninvasive alternative to biopsy for monitoring patients who have hepatic steatosis, but MRI is more appealing than ultrasonography to denote minor changes in hepatic fat content. Distinguishing patients who have non-alcoholic steatohepatitis from steatosis alone has become of clinical importance; however, the differences are not apparent with any radiologic modalities. Several modalities have been developed to noninvasively and accurately quantify hepatic fat content and diagnose steatohepatitis. In the future, radiologic modalities might be used to monitor the natural history of the disease or evaluate therapeutic interventions in patients who have non-alcoholic fatty liver disease.     

Artificial liver

If an effective hepatic assist system existed, it could serve as a bridge to transplantation. Most of the patients waiting for liver transplantation have chronic liver insufficiency but are not in hepatic coma. Various hepatic assist systems have been used to salvage patients with acute liver insufficiency. Most attempts have been disappointing. The methods used have included plasma exchange, plasma adsorption, double filtration, cryofiltration, thermofiltration, the combination of plasma exchange and amino acid hemodialysis, and others. For patients with chronic liver disease with moderate liver function impairment and limited to one or only a few areas of metabolic abnormality, a hepatic assist might allow the life of the patient to be maintained temporarily. The application of hepatic assist methods for chronic liver disease patients treated at the Cleveland Clinic has been encouraging. One of the patients who suffered from sclerosing cholangitis has maintained a near-normal life for almost five years by 170 plasma treatments. This is in spite of the fact that, at the onset of treatment, the patient was nearly comatose. Unfortunately, this patient did not wish to receive a liver transplantation. Based upon this experience, the concept of a bridge to transplantation approach to hepatic assist devices appears feasible. In addition, it is speculated that hepatic assistance during the early recovery stage of liver transplantation and during mild episodes of rejection may be useful.     

Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view

Since the late nineteenth century, protein restriction has been shown to improve hepatic encephalopathy. However, malnutrition has been described in up to 60 % of cirrhotic patients and is associated with increased mortality. Furthermore, emerging clinical evidence has revealed that a large proportion of cirrhotic patients may tolerate normal protein intake. However, approximately one third of cirrhotic patients with hepatic encephalopathy may need a short course of protein restriction, in addition to maximum medical therapy, to ameliorate the clinical course of their hepatic encephalopathy. For patients with chronic hepatic encephalopathy who are protein-sensitive, modifying their sources of nitrogen by using more vegetable protein, less animal protein, and branched-chain amino acids may improve their encephalopathy without further loss of lean body mass. In conclusion, among cirrhotics with hepatic encephalopathy, modulation of normal protein intake must take into account the patient’s hepatic reserve, severity of hepatic encephalopathy, and current nutritional status.     

Spontaneous Rupture of Hemangioma of the Liver: Treatment with Transcatheter Hepatic Arterial Embolization

A case of spontaneous rupture of a cavernous hemangioma of the liver with a successful hepatic resection after transcatheter hepatic arterial embolization is reported. Twenty-eight cases of spontaneous rupture of hepatic hemangioma have been reported in the medical literature. Each of the cases (19 adults and nine children) were reviewed, including the present one reported here. Surgical treatments were carried out on 20 patients, of whom only five survived. Ruptured hemangiomas ranged in size from 3.0 to 25.0 cm, and many were located on the inferior surface of the liver. Surgical resection should be considered for a large hepatic hemangioma located on the inferior surface of the liver if the tumor has a high probability of rupture. Once the hemangioma has ruptured, emergent hepatic resection is recommended for low-risk patients, whereas high-risk patients should receive transcatheter hepatic arterial embolization prior to elective hepatic resection.     

肝性脑病患者的营养支持治疗

肝性脑病是肝衰竭最常见的并发症之一,在住院患者中发病率高,而大多数肝性脑病患者存在不同程度的营养不良。近年来,越来越多的临床试验证实了营养支持治疗对肝性脑病的治疗是有益的,因此营养治疗正逐渐被得到重视。介绍了肝性脑病发生营养不良的机制,并对肝性脑病患者的营养评估和营养治疗方式进行了概述。     

Hepatic schistosomiasis

Opinion statement Praziquantel is the treatment of choice for schistosomiasis because of its efficacy, ease of administration, limited side effects, and low cost. Praziquantel has been so effective that alternative therapies are increasingly difficult to obtain, and the development of novel medications has been limited. The possibility of praziquantel resistance is a grave concern. Low cure rates for praziquantel have been reported in several countries, but despite widespread use, no significant loss of efficacy has occurred to date. The primary goal of antischistosomal therapy is parasite eradication, which reduces the likelihood of chronic complications, including advanced hepatic fibrosis. Mild to moderate hepatic fibrosis results from the immune response to schistosome eggs deposited in the portal venules and reverses with successful treatment. Most individuals clear schistosomiasis with a single course of therapy. Repeat doses cure the majority of patients in whom eradication does not occur after the initial dose. A secondary goal of therapy for patients with persistent or recurrent infection is egg burden reduction, which also reduces the risk of hepatic fibrosis and lowers community spread. Community eradication programs in highly endemic regions use periodic retreatment to limit chronic schistosomiasis’ morbidity. Advanced liver fibrosis and portal hypertension due to chronic schistosomiasis are irreversible. Variceal bleeding is the primary cause of death in hepatic schistosomiasis. The bleeding risk is best reduced through use of β-blocker prophylaxis or endoscopic banding or sclerotherapy. Surgical management of varices, including splenectomy with esophagogastric devascularization or selective shunts such as the distal splenorenal, is effective in patients with recalcitrant bleeding. Because hepatic synthetic function is normal in patients with schistosomiasis, procedures that reduce portal pressures may lower hepatic perfusion and cause hepatic impairment. The risk of encephalopathy after shunt surgery is higher in patients with schistosomiasis than in those with cirrhosis. For these reasons, nonselective shunt surgery such as the proximal splenorenal or the transjugular intrahepatic portosystemic shunt should not be performed in patients with advanced hepatic schistosomiasis.     

Histochemical Study of Hyaluronate in Alcoholic Liver Disease

Recently, it has been reported that serum hyaluronate (hyaluronic acid; HA) concentrations increase in various liver diseases, especially in alcoholic liver disease (ALD), and serum HA concentration has been used as a marker for hepatic fibrosis. However, it is unknown whether hepatic HA contents in ALD increase by alcohol or not. In this study, we histochemically stained HA in liver biopsy specimens obtained from ALD patients while actively drinking and after abstinence to clarify the effects of alcohol on hepatic HA contents. Liver biopsy specimens were obtained from 13 patients with ALD and 10 patients with non-ALD. In ALD patients, liver biopsy was performed twice within 3 days, and 4 to 8 weeks after abstinence when serum levels of AST and ALT normalized. HA in biopsy specimens was stained histochemically with biotinylated HA binding protein. Staining intensity of HA in liver tissue was also determined by computer-assisted imaging analyzer. HA staining was clearly observed in sinusoidal wall and fibrous regions around the portal tract and central vein in liver diseases. HA staining intensities in patients actively drinking with ALD increased markedly, compared with those in patients with non-ALD, and these intensities decreased with abstinence. These results clearly suggest that hepatic HA contents in ALD may be increased by alcohol in addition to hepatic fibrosis, and, therefore, increased HA deposition in the liver may be reversible by abstinence of alcohol.     

Nitric oxide synthase activity in the splanchnic vasculature of patients with cirrhosis: relationship with hemodynamic disturbances.

BACKGROUND/AIMS: It has been demonstrated that an overproduction of nitric oxide plays an important role in the pathogenesis of the hyperdynamic circulation exhibited by cirrhotic patients. Nevertheless, evidence is supported by studies performed in experimental models or by indirect measurements in humans. The purpose of this study has been to evaluate nitric oxide production in splanchnic vasculature of patients with cirrhosis and to investigate its possible relationship with systemic and splanchnic hemodynamics. METHODS: Nitric oxide synthase (NOS) activity was measured in hepatic artery and portal vein tissues of nine cirrhotic patients. Samples were obtained during liver transplantation. Control samples were obtained simultaneously from the corresponding tissues of the liver donors. Hemodynamic parameters were determined with Doppler ultrasonography. RESULTS: NOS activity was significantly higher in hepatic artery of cirrhotic patients than in controls (8.17 +/- 1.30 vs 4.57 +/- 0.61 pmoles/g of tissue/min, P < 0.05). Patients with ascites showed a higher hepatic artery NOS activity than patients without ascites. Highly significant correlation was observed between cardiac output and hepatic artery NOS activity as well as between portal blood flow and hepatic artery NOS activity. CONCLUSIONS: The present study demonstrates an enhanced production of nitric oxide in the splanchnic vasculature of patients with cirrhosis.     

Hepatic artery hypertrophy and sinusoidal hypertension in advanced schistosomiasis.

In 5 patients with portal hypertension caused by schistosomiasis, the sinusoidal pressure (wedged hepatic pressure) varied from 20.7 to 35.4 mm Hg. While the catheter was in an occluded position within the hepatic vein and the patients were undergoing splenectomy, the main trunk of the hepatic artery was clamped. The sinusoidal pressures then fell to levels that varied from 3.7 to 7.4 mm Hg but returned to previous levels when the clamping was released. Wedged hepatic venous pressure levels, which were significantly greater than portal venous pressure values, decreased minimally after splenectomy. Portal venous pressure levels, however, fell to 63% of presplenectomy levels. In a control case with an enlarged spleen (cavernous hemangioma, but with a normal liver, the wedged hepatic pressure was 7.4 mm Hg and showed no alteration after clamping of hepatic artery. These data point out the importance of hepatic artery hypertrophy, that has already been demonstrated in other studies, in causing elevation of the wedged hepatic pressure in advanced hepatic schistosomiasis.     

Ablative therapies for liver metastases of gastroenteropancreatic endocrine tumors

Hepatic metastases are frequent in patients with gastroenteropancreatic (GEP) endocrine tumors. The presence of hepatic metastases affects overall prognosis and quality of life especially in the presence of debilitating functional syndromes. Surgery, although the method of choice for hepatic metastases, is usually impossible due to disease extent. Results of systemic chemotherapy are also disappointing especially in patients with metastases from midgut GEP tumors. These latter patients usually have carcinoid syndrome which can be controlled by somatostatin analogues. Other therapeutic options in the treatment of highly vascular liver metastases from GEP tumors are locoregional strategies by inducing vascular occlusion resulting in ischemia and necrosis of tumoral tissue. Surgical ligation of the hepatic artery or transient hepatic ischemia has been replaced by transcatheter arterial chemoembolization (TACE). TACE has proven effective in controlling symptoms and gives objective tumor response in about half of patients. Other regional destructive methods, used either alone or in combination with surgery, include radiofrequency ablation and cryotherapy. The latter strategies are poorly evaluated to date and are usually adjuncts to surgery and reserved for limited disease.     

Transjugular liver biopsy. An update

Transjugular liver biopsy was first reported in 1967. Since then, this technique has been broadly performed in many medical centers around the world. The number of its indications has increased, and by modifying the needles, the quality of the liver tissue sample has improved. The advantage of transjugular biopsy is that it can be performed in patients in whom the use of percutaneous biopsy is contraindicated Indications for transjugular liver biopsy are, precisely, most of the contraindications for percutaneous liver biopsy. This fact increases the number of patients that can benefit from this procedure. In most cases, the procedure is successfully performed. Minor complications may occur in 1% to 15% and major complications (perforation of the hepatic capsule, cholangitis, and intra-peritoneal bleeding) are observed in 1-3% of the cases. Mortality related to the procedure varies form 0.2 to 0.3%. It has been reported that diagnosis yielded by transjugular liver biopsy induced changes of treatment in 50% of patients with an acute hepatic illness, in 62% of the patients with a chronic hepatic illness, and in 87% of the patients with liver transplants. In conclusion, transjugular liver biopsy is a useful procedure in the diagnosis of hepatic diseases. Its success rate is high; it is a very safe procedure because complications and mortality are rare; and it is well tolerated by patients.     

Gastroduodenal artery used for arterial reconstruction during the Whipple operation

The right hepatic artery and the common hepatic artery originate from the superior mesenteric artery in approximately 10-15% of the population. Reconstruction of the hepatic artery using the gastroduodenal artery has previously been described to repair hepatic artery injury during the performance of biliary and pancreatic resections. We report the utilization of this technique in patients undergoing pancreaticoduodenectomy for a periampullary neoplasm involving a replaced right hepatic artery.     

Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy

The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had greater than 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders.     

Thoracoscopic diaphragmatic repair for refractory hepatic hydrothorax: application of pleural flap and mesh onlay reinforcement

BACKGROUND: Management of hepatic hydrothorax is difficult, and no radical treatment has been established. Based on accumulating evidence that diaphragmatic defects contribute to hepatic hydrothorax, we developed a diaphragmatic repair method for the management of this complex condition. METHODS: From October 2003 to March 2005, 10 patients (age, 32 - 83 years; 6 men and 4 women) with refractory hepatic hydrothorax (Child-Pugh class B-C) underwent thoracoscopic pleura (n = 7) or mesh (n = 3) onlay reinforcement to repair the diaphragmatic defects on which this study focuses, and all patients have since been under follow-up in a prospective observation study. RESULTS: After a mean of 7.7 months of follow-up examinations, no local recurrence occurred in all patients. Two patients died of hemorrhage from esophageal varices two months postoperatively. All patients had a better postoperative pulmonary function. CONCLUSION: The use of pleura and mesh onlay reinforcement of the diaphragm is an encouraging treatment for refractory hepatic hydrothorax.     

Two-staged treatment with local resection and percutaneous isolated hepatic chemoperfusion for advanced pancreatic cancer with multiple liver metastases: report of a case

There have been disappointingly few effective treatment modalities for multiple liver metastases from pancreatic cancer. Percutaneous isolated hepatic perfusion, which was developed by us for delivering dose-intensive chemotherapy to the liver, has a high efficacy in the majority of patients with multiple primary and secondary liver tumors. We herein report the first experience of a two-stage treatment with extended local resection and subsequent two percutaneous isolated hepatic perfusions for advanced pancreatic ductal adenocarcinoma with liver metastases. The second percutaneous isolated hepatic perfusion with high-dose cisplatin and mitomycin G demonstrated a distinct regression of metastatic liver tumors. Although a long-term patient survival was not obtained due to local recurrence, liver metastases have been well controlled ever since. Given that further studies establish the efficacy of percutaneous isolated hepatic perfusion also in this field, this modality would be used as prophylaxis as well as treatment of liver metastasis in patients with advanced pancreatic ductal adenocarcinoma.     

Satavaptan treatment for ascites in patients with cirrhosis: a meta-analysis of effect on hepatic encephalopathy development

Satavaptan, a vasopressin V₂-receptor antagonist, has been shown to improve hyponatraemia in patients with cirrhosis. Hyponatraemia has been associated with an increased risk of hepatic encephalopathy. The objective is to evaluate the efficacy of satavaptan in reducing the risk of new episodes of hepatic encephalopathy. 1,200 patients with cirrhosis and uncomplicated ascites were included in three randomised double-blind studies comparing satavaptan (5–10 mg/day) vs placebo over a one-year treatment period. Effects on incidence of hepatic encephalopathy episodes in individual study and pooled databases were determined with analyses adjusted for hyponatraemia and previous episodes of encephalopathy. Hyponatraemia was improved by satavaptan. Three hundred and ninety-five hepatic encephalopathy episodes were recorded. The risk of an episode and the mean number of episodes were not reduced by satavaptan in any of the three studies in the overall population or in patients who were hyponatraemic on entry. These findings were confirmed in analysis of the pooled data. Satavaptan did not reduce the frequency of hepatic encephalopathy in patients with cirrhosis and ascites.     

Long-lasting remission of primary hepatic lymphoma and hepatitis C virus infection achieved by the alpha-interferon treatment

Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often pursues an aggressive clinical course. Most cases have been described in hepatitis C virus (HCV)-related chronic liver disease patients. Although anthracycline-based chemotherapy has been reported to be highly effective, the best therapeutic strategy has not been defined yet. The prognosis is dismal especially in patients treated with chemotherapy alone or when an advanced liver disease is present. Herein, we describe a case of primary hepatic large B-cell non-Hodgkin's lymphoma, in a patient with HCV chronic infection. After a minor response with eight cycles of CHOP chemotherapy, a complete and sustained remission was obtained with alpha-interferon at the daily dose of 3 MU. HCV-RNA clearance pace from the blood almost paralleled the response of the lymphoma and both diseases went in remission within 1 year of therapy. The possible place of alpha-Interferon in the treatment of primary hepatic lymphoma is discussed.     

Congenital hepatic fibrosis: the long-term prognosis.

The long-term prognosis in congenital hepatic fibrosis has been assessed in 30 patients, 13 treated at Newcastle and 17 from other British centres. Twenty-four patients had been followed-up for more than five years from diagnosis. Shunt operations, performed in 18 patients, were successful in controlling haemorrhage with a low mortality (1/18), low incidence of recurrent haemorrhage (3/18) and portal-systemic encephalopathy (3/18) but with a higher incidence of postoperative jaundice (7/18). About a third of the survivors had some evidence of hepatic dysfunction but none had chronic portal systemic encephalopathy. Intelligence quotient was close to normal but educational achievement and job status were low. Serum albumin fell after shunt surgery and a few patients developed ascites: anaemia and hypersplenism however, were corrected by surgery. Blood ammonia is raised in survivors with congenital hepatic fibrosis and rises further after a normal meal; further observations are needed on cerebral function after several decades of survival.     

Gut ammonia production and its modulation

Systemic hyperammonemia has been largely found in patients with cirrhosis and hepatic encephalopathy, and ammonia plays a major role in the pathogenesis of hepatic encephalopathy. However, controversial points remain: a) the correlation between plasma ammonia levels and neurophysiological impairment. The lack of correlation between ammonia levels and grade of hepatic encephalopathy in some cases has been considered a weakness of the ammonia hypothesis, but new methods for ammonia measurements and the implication of systemic inflammation in the modulation of ammonia neurotoxicity could explain this gap; b) the source of ammonia production. Hyperammonemia has been considered as derived from urea breakdown by intestinal bacteria and the majority of treatments were targeted against bacteria-derived ammonia from the colon. However, some data suggest an important role for small intestine ammonia production: 1) the hyperammonemia after porto-caval shunted rats has been found similar in germ-free than in non-germ-free animals. 2) In cirrhotic patients the greatest hyperammonemia was found in portal drained viscera and derived mainly from glutamine deamination. 3) The amount of time required to increase of ammonia (less than one hour) after oral glutamine challenge supports a small intestine origin of the hyperammonemia. As the main source of ammonia in cirrhotics derives from portal drained viscera owing to glutamine deamidation, increased glutaminase activity in the intestine seems to be responsible for systemic hyperammonemia. Lastly, some genetic alterations in the glutaminase gene such as the haplotype TACC could modulate intestinal ammonia production and the risk of overt hepatic encephalopathy in cirrhotics.     

Hepatic steatosis and hepatitis C: Still unhappy bedfellows?

Hepatic steatosis is commonly seen in patients with chronic hepatitis C virus (HCV) infection, and the prevalence is much higher prevalence than in the general population or in patients with chronic hepatitis B. Hepatic steatosis in patients with chronic hepatitis C can be due to alcohol consumption and host metabolic factors such as high body mass index (BMI), obesity, hyperlipidemia, metabolic syndrome and diabetes mellitus in which insulin resistance plays an important role. However, in genotype 3 HCV infection, hepatic steatosis can result from direct viral cytopathic effect. Demographic and clinical characteristics associated with hepatic steatosis in patients with chronic hepatitis C including older age, higher BMI, more genotype 3 infection, and higher mean serum levels of triglyceride, alanine aminotransferase and γ-glutamyl transpeptidase. The clinical relevance of hepatic steatosis in patients with chronic hepatitis C includes a close correlation with hepatic fibrosis, and a poor response to combination peginterferon and ribavirin treatment. In addition, hepatic steatosis has been reported to associate with increased frequency of hepatocellular carcinoma in patients with chronic HCV infection. Whether life style modification such as weight reduction or adding an insulin resistance reducing agent such as metformin or thiazolidinediones combined with current standard peginterferon plus ribavirin treatment will benefit to the chronic hepatitis C patients with hepatic steatosis deserves further evaluation.