The records of 2,377 patients with Laennec's cirrhosis were reviewed for the period 1947-1957. The chief presenting symptom was ascites in 46 per cent, bleeding in 23 per cent, coma in 18 per cent, jaundice in 9 per cent, and both jaundice and ascites in 4 per cent. Nearly half of the patients died during the period under study—one-third from hepatic failure, one-third from gastrointestinal bleeding, and one-third from other causes, most of which were related to alcoholism.
Massive gastrointestinal bleeding occurred in 21 per cent of the patients at some time in their clinical course, and in the 10 per cent of these in whom ulcer was demonstrated, one-fifth died as a result of the hemorrhage. Of those presumed to be bleeding from esophageal varices, 64 per cent died at the first hemorrhage and 10 per cent at subsequent hemorrhages; 85 per cent of all those who bled from varices were dead at the end of one year, and 91 per cent were dead at the end of three years.
The survival curve of a group of patients who bled once and were good operative risks but had received no operative treatment was compared to the survival curve for entire group who survived the first hemorrhage. The three-year survival in the good risk group was 47 per cent; for the group as a whole it was 30 per cent. The difference in mortality rate was primarily due to an increased number of deaths from hepatic failure in the combined group, whereas 60 per cent of the good risk group died of recurrent gastrointestinal hemorrhage.
As 86 per cent of those who were to die of gastrointestinal bleeding did so at the first hemorrhage, it was concluded that any decided improvement in the salvage rate achievable by operation must come from some means of diagnostic forecast of the likelihood of bleeding, with resort to prophylactic operation in such cases.
In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (VA/ Q) ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO2), in oxygen saturation of hemoglobin (SaO2) as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC) with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%), alcoholic 7 (14.24%), cardiac 2 (4.08%), and cryptogenic 3 (6.12%). Complications were: upper gastrointestinal bleeding 24 (48.97), hepatic encephalopathy 20 (40.81%), gastritis 28 (57.14%), hepatoma 5 (10.2%), renal hepatic syndrome 2 (4.01%), HbsAg (+) 24 (48.97%), and hepatic pleural effusions 7 (14.28%). Average PaO2 and SaO2 were 75.2 mmHg and 94.5 mmHg, respectively, compared to 94.2 mmHg and 97.1 mmHg of the control group, respectively (p value in both PaO2 and SaO2 was p<0.01). Respiratory alkalosis, metabolic alkalosis, metabolic acidosis, respiratory acidosis and metabolic acidosis with respiratory alkalosis were acid-base disturbances observed. In conclusion, portopulmonary shunt, intrapulmonary arteriovenous shunt and VA/Q inequality can induce a decrease in PaO2 and SaO2 as well as various acid-base disturbances. As a result, pulmonary resistance is impaired and patients more likely succumb to infections and adult respiratory distress syndrome.
liver cirrhosis; ascites; acid base disturbances; hepatopulmonary syndrome
Liver cirrhosis is a common disease with many known complications. Cirrhosis represents a clinical spectrum, ranging from asymptomatic liver disease to hepatic decompensation. Manifestations of hepatic decompensation include variceal bleeding, ascites, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular carcinoma. There are reports about infarcted regenerative nodules in cirrhotic livers after gastrointestinal hemorrhage.
We report three Caucasian patients (one female and two male patients; ages: 52, 54 and 60 years) with decompensated liver cirrhosis, who showed newly infarcted regenerative nodules at necropsy. Two of them suffered from gastric variceal bleeding. Histopathology showed extensive infarction in all three cases.
Hemorrhage and inflammatory changes were also observed around the infarcted regenerative nodules.
These patients showed focal liver lesions, to be considered in the differential diagnosis of cirrhotic livers. Infarcted regenerative nodules may be underdiagnosed in patients with decompensation of cirrhosis. In order to differentiate these lesions from malignant tumors, serial imaging seems to be helpful. However, the main differential diagnosis should be an abscess. It is important to know the wide spectrum of image appearances of these lesions. Hypotension can lead to a reduction of portal and arterial liver flow. Since variceal bleeding or septic shock can induce hypotension - as observed in our patients - we conclude that this leads to infarction of such nodules.
AIM: To determine the clinical presentation, underlying etiology and short- and long-term outcomes of acute variceal bleeding (AVB).
METHODS: A retrospective descriptive cohort study of cirrhotic patients with AVB who were admitted to King Abdul Aziz University Hospital between January 2005 and December 2009. We obtained demographic data for all patients. For each patient we also obtained the clinical data at presentation; cause of liver cirrhosis, bleeding presentation (hematemesis and/or melena), presence of ascites, hepatic encephalopathy and renal impairment (RI) or hepatorenal syndrome. We carried out complete blood count, prothrombin time evaluation, and liver function tests. We also report all episodes of re-bleeding after the first episode of AVB, both during the initial admission and after discharge. We recorded the length of stay for each patient and thereby calculated the mean duration of stay for all patients. The length of follow-up after the first AVB and the outcome for each patient at the end of the study period were recorded. Causes of mortality either related to liver disease or non-liver disease cause were determined.
RESULTS: A 125 patients were enrolled in the study. The number of episodes of AVB for each patients varied between 1 and 10. Survival from the first attack of AVB to death was 20.38 mo (SD 30.86), while the length of follow-up for the living patients was 53.58 mo (SD 24.94). Total number of AVB admissions was 241. Chronic hepatitis C, the commonest underlying etiology for liver disease, was present in 46 (36.8%) patients. Only 35 (28%) patients had received a primary prophylactic β-blocker before the first bleeding episode. The mean hemoglobin level at the time of admission was 8.59 g/dL (SD 2.53). Most patients had Child-Pugh Class C 41 (32.8%) or Class B 72 (57.6%) disease. Hematemesis was the predominant symptom and was found in 119 (95.2%) patients, followed by melena in 75 (60.0%) patients. Ascites of variable extent was documented in 93 (74.4%) patients. We identified hepatic encephalopathy in 31 (28.8%) patients and spontaneous bacterial peritonitis in 17 (13.6%). Bleeding gastric varices was the cause of AVB in 2 patients. AVB was associated with shock in 22 patients, 13 of whom (59.1%) had Child-Pugh class C disease. RI was noted in 19 (46.3%) of 41 patients in Child-Pugh class C and 14 (19.4%) of 72 patients in Child-Pugh class B. None of the patients with Child-Pugh class A disease had RI. Emergency endoscopy was effective in controlling the bleeding, although the re-bleeding rate was still high, 12 (9.6%) during the same admission and 55 (44%) after discharge. The re-bleeding rate was higher in patients with ascites, occurring in 40/55 (72.2%). The length of hospital stay was 1-54 d with a mean of 8.7 d. Three patients had emergency surgery due to failure of endoscopic treatment and balloon tamponade. The overall long term mortality was 65%. Survival from the first attack of AVB to death was 20.38 ± 30.86 mo, while the length of follow-up for the living patients was 53.58 ± 24.94 mo. Patients with Child-Pugh score C had a higher risk of liver disease-related mortality (67.6%). RI (developed during admission) was the main factor that was associated with mortality (P = 0.045).
CONCLUSION: The majority of patients with liver disease who present at the emergency unit for AVB are at an advanced stage of the disease. The outcome is poorer for patients who develop RI during hospitalization.
Endoscopy; Liver disease; Mortality; Outcome; Varices; Variceal bleeding
BACKGROUND—The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate.
AIM—To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis.
PATIENTS AND METHODS—Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age, sex, and Child-Pugh's score were enrolled in a prospective non-randomised controlled trial. Treated patients received leucocytic interferon alfa, with an escalating schedule for 12 months. The incidence and risk (Cox regression analysis) of clinical complications (hepatocellular carcinoma, ascites, jaundice, variceal bleeding, and encephalopathy) and death were calculated.
RESULTS—Over median follow up periods of 55 months for treated and 58 for untreated subjects, seven and nine patients, respectively, died, and 20 and 32, respectively, developed at least one clinical complication (ns). Hepatocellular carcinoma developed in six treated and 19 untreated patients (p=0.018). Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications. Clinical complications were significantly associated with low albumin, bilirubin, and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon, oesophageal varices, and high α fetoprotein levels. By stratified analysis, the beneficial effect of interferon was statistically evident only in patients with baseline α fetoprotein levels ⩾20 ng/ml.
CONCLUSIONS—Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma. Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up.
Keywords: hepatocellular carcinoma; cirrhosis; hepatitis C virus; interferon alfa
The major cause of portal hypertension in Western countries is nutritional cirrhosis (parenchymal block) related to alcoholism. A third of those patients die of variceal bleeding when increased pressure within the varices precipitates bleeding. Construction of portal systemic shunts is aimed at reducing the pressure within the varices and thereby decreasing the risk of bleeding. However, it increases the incidence of hepatic encephalopathy and hence should be used only in patients who have bled. The remaining function appears to be the main factor that determines survival and the incidence of encephalopathy in obese individuals. Portacaval shunts almost completely eliminate the risk of bleeding. There is a greater incidence of hepatic encephalopathy with this procedure than with other shunts. The splenorenal shunt and the distal splenorenal shunt appear to work well in selected patients. Technically, it is a more difficult procedure. The interposition mesocaval shunt is technically easier and is also helpful in patients with ascites. Its post-shunt encephalopathy rate, however, is higher than the splenorenal shunt or the distal splenorenal shunt, though less than the portacaval shunts. Experience with the newer arterialized portacaval and coronary caval shunts is limited. A non-shunt procedure, such as the one described by Sugiura, with impressive results and follow-up may become more acceptable as experience grows.
Patients with liver cirrhosis may develop upper gastrointestinal hemorrhage from a variety of lesions, which include those that arise by virtue of portal hypertension, namely gastroesophageal varices and portal hypertensive gastropathy and other lesions seen in the general population. Do patients with liver cirrhosis, hemorrhage from varices and other lesions equally, or are they more likely to bleed from varices? The aim of this study is to determine predominant causes of bleeding in patients with liver cirrhosis and upper gastrointestinal bleeding. PATIENTS AND METHODS: A retrospective review of 40 patients with liver cirrhosis based on the clinical and biochemical parameters of the Child-Pugh score, and upper gastrointestinal bleeding was carried out at an inner city hospital. Endoscopy diagnoses were documented. RESULTS: Of 40 patients, 38 patients had cirrhosis associated with alcohol consumption. Twelve of the above 38 patients who consumed alcohol also had hepatitis C virus (HCV) infection. Eleven patients had only varices on endoscopic examination, 17 had varices plus coexisting lesions. From these 17 patients, nine were found to have bled from varices, and eight were found to have bled from coexisting lesions. Twelve patients who had no varices bled from other lesions. Of 40 patients, 28 had varices, and 20 actually bled from varices. In this study there was no correlation between severity of liver cirrhosis as determined by the Child-Pugh score and the absence or presence of varices. CONCLUSION: Patients with liver cirrhosis and upper gastrointestinal bleeding hemorrhage from a variety of lesions. In this study of 40 patients, (70%) had gastroesophageal varices diagnosed at upper endoscopy, while 50% actually bled from varices.
Hyponatremia is a frequent complication of the advanced liver disease, being, as the hepatorenal syndrome, a consequence of the important circulatory dysfunction of cirrhosis. Hyponatremia is determined by the impaired capacity of the kidney to excrete free water, which leads to water retention disproportionate to sodium retention, thus causing low plasma osmolarity. Hyponatremia in cirrhosis is associated with a high morbidity and mortality, its presence suggesting a very advanced liver disease. Current evidence suggests that hyponatremia affects the brain function and predisposes to hepatic encephalopathy. In addition, hyponatremia is a risk factor for liver transplantation, being associated with a high frequency of complication and affecting short and long-term post-transplant survival.
hyponatremia; hypo-osmolarity; circulatory dysfunction; hepatorenal syndrome
Cirrhosis of the liver is a rising epidemic in the United States, affecting 2 out of every 1,000 adults. It is responsible for the deaths of more than 27,000 people each year. The primary diseases that underlie cirrhosis include viral hepatitis, alcoholic liver disease, and nonalcoholic fatty liver disease. Monitoring the extent of fibrosis and aggressively treating the underlying disease is essential for maintaining quality of life and preventing the complications of cirrhosis. As patients progress toward end-stage liver disease, the most common complications include portal hypertension, the development of esophageal varices, and hepatic encephalopathy. Esophageal varices can lead to hemorrhaging, a dangerous complication that is fatal in 30–50% of patients during the first occurrence. Hepatic encephalopathy is another serious complication of end-stage liver disease, as it significantly reduces patient quality of life and places heavy economic and caregiving burdens upon the patient's family. In this clinical roundtable monograph, the latest advances in the monitoring of liver disease and the management of portal hypertension and hepatic encephalopathy are discussed.
Primary biliary cirrhosis (PBC) is sometimes diagnosed based upon a positive antimitochondrial antibody in the appropriate clinical setting without a liver biopsy. While a liver biopsy can assess the extent of liver fibrosis and provide prognostic information, serum fibrosis markers avoid biopsy complications, sampling error, and provide results as a continuous variable, which may be more precise than categorical histological stages. The current study was undertaken to evaluate serum fibrosis markers as predictors of clinical progression in a large cohort of PBC patients.
Serial liver biopsies and serum samples were collected every 2 years in 161 PBC subjects for a median of 7.3 years. Clinical progression was defined as development of one or more of the following events: varices, variceal bleed, ascites, encephalopathy, liver transplant, or liver-related death. Serum HA, TIMP-1, and PIIINP were measured and entered into the previously validated Enhanced Liver Fibrosis (ELF) algorithm. The ability of ELF, histological fibrosis, bilirubin, MELD, and Mayo Risk Score to differentiate between individuals who would experience a clinical event from those who would not was evaluated at different time points.
Event-free survival was significantly lower in those with high baseline ELF. Each 1 point increase in ELF was associated with a 3 fold increase in future complications. The prognostic performance of all tests was similar when performed close to the time of the first event. However, at earlier times in the disease process (4 and 6 years prior to the first event), the prognostic performance of ELF was significantly better than MELD or Mayo R score.
The ELF algorithm is a highly accurate non-invasive measure of PBC disease severity which provides useful long-term prognostic information.
Mayo Risk Score; MELD; Biopsy; Metalloproteinase; Hyaluronic acid
Natural history of HCV related chronic hepatitis is influenced and modified by many factors: virus features, coinfections and host characteristics. In particular, a peculiar genetic background of the host by conditioning the occurrence of intracellular metabolic derangements (i.e., insulin resistance) might contribute to accelerate the rate of progression to cirrhosis and eventually the occurrence of hepatocellular carcinoma (HCC) and death. Likely, direct interplays between virus genotype and host genetic background might be hypothesized at this level. Morbidity and mortality in cirrhosis is primarily associated with complications of liver cirrhosis (ascites, hepatic encephalopathy, jaundice, and gastroesophageal bleeding) and HCC occurrence. Therefore the main goal of therapy is to clear viral infection and decrease liver necro-inflammation that directly relates to development of cirrhosis and HCC. Among patients treated with Interferon-based therapy, those with sustained viral response showed a significant reduction of progression to cirrhosis and development of HCC. However, a residual risk of hepatocellular carcinoma still remains indicating the need for careful follow-up using ultrasonography every six months in cirrhotic patients, even in those showing persistently normal ALT and undetectable HCV RNA levels after antiviral therapy.
Early re-hospitalizations have been well characterized in many disease states, but not among patients with cirrhosis. The aims of this study were to identify the frequency, costs, predictors, and preventable causes of hospital re-admissions among patients with decompensated cirrhosis.
Rates of re-admission were calculated for 402 patients discharged after one of the following complications of cirrhosis: ascites, spontaneous bacterial peritonitis, renal failure, hepatic encephalopathy or variceal hemorrhage. Costs of re-admissions were calculated using the hospital accounting system. Predictors of time to first re-admission were determined using Cox regression, and predictors of hospitalization rate/person-years using negative binomial regression. The independent association between re-admission rate and mortality was determined using Cox regression. Admissions within 30 days of discharge were assessed by two reviewers to determine if preventable.
276 (69%) subjects had at least one non-elective re-admission, with a median time to first re-admission of 67 days. By one week after discharge 14% of subjects had been re-admitted, and 37% were re-admitted within one month. The mean costs for re-admissions within one week and between weeks 1–4 were $28,898 and %20,581, respectively. During a median follow-up of 203 days, the median number of re-admissions was 2 (range 0–40), with an overall rate of 3 hospitalizations/person-years. Patients with more frequent re-admissions had higher risk of subsequent mortality, despite adjustment for confounders including the Model for End-stage Liver Disease score. Predictors of time to first re-admission included MELD score, serum sodium, and number of medications on discharge; predictors of hospitalization rate included these variables as well as the number of cirrhosis complications and being on the transplant list at discharge. Among 165 re-admissions within 30 days, 22% were possibly preventable.
Hospital re-admissions among patients with decompensated cirrhosis are common, costly, moderately predictable, in some cases possibly preventable, and independently associated with mortality. These findings support the development of disease management interventions to prevent re-hospitalization.
Hepatocellular carcinoma (HCC) develops in the context of environmental risk factors like chronic viral hepatitis, diabetes and alcohol exposure, often associated to an increased risk of cirrhosis. Antiviral treatments that are effective to counteract hepatitis B and C may also attenuate the risk of tumor development. However, since hepatitis B-related carcinogenesis is promoted independently of the onset of cirrhosis, such antiviral treatments as nucleo(t)side analogs can promote regression of cirrhosis, prevent clinical decompensation and variceal bleeding but not HCC. This means that in successfully treated patients with cirrhosis, HCC is often the consequence of their extended survival. In hepatitis C patients, a sustained virological response to interferon-based therapies can reduce the rate of HCC development, even in patients with cirrhosis who experience histological regression of their liver disease. Future therapies aimed at this endpoint in at risk populations should take into consideration pretreatment patient stratification for host, viral and environmental risk factors. In this context the recent discovery of single nucleotide polymorphisms involved in the immune system function and tumorigenesis, might permit enrollment of populations of patients enriched with HCC risk factors for targeted chemopreventive therapies. This could finally pave the way to personalized algorithms, as already seen in the diagnosis and treatment schemes for chemoprevention.
Hepatocellular carcinoma; Hepatitis C virus; Peginterferon; Hepatitis B virus; Human immunodeficiency virus; Nucleoside analogues; Sustained virological response; Single nucleotide polymorphisms
Obesity is associated with an aggressive course in chronic viral hepatitis; however its impact in the development of clinical decompensation (CD) in patients with established cirrhosis is uncertain. We evaluated the role of obesity, in relationship to other recognized predictors, in the development of CD in patients with compensated cirrhosis. The study population, a subset of patients included in a randomized trial of beta-blockers in the prevention of varices in whom data on body mass index (BMI) was available, consisted of 161 patients with compensated cirrhosis. Laboratory tests and portal pressure (assessed by the hepatic venous pressure gradient or HVPG) were assessed on inclusion. Patients were followed-up until CD (ascites, hepatic encephalopathy or variceal hemorrhage), or until September 2002.
29% had a normal BMI, 40% were overweight and 30% were obese. In a median follow-up of 59 months, CD occurred in 48/161 (30%) patients with an increasingly higher rate according to BMI group (15% in those with normal BMI; 31% in overweight; 43% in obese patients, p=0.011). The actuarial probability of developing CD was significantly higher in the abnormal BMI groups (p=0.022). In a multivariable model that included parameters previously identified as being predictive of CD (HVPG, albumin, MELD), etiology and treatment group, BMI [HR 1.06 (1.01-1.12), p=0.02] was an independent predictor of decompensation, together with HVPG and albumin.
Obesity has a deleterious effect on the natural history of compensated cirrhosis of all etiologies, independent of portal pressure and liver function. Weight reduction may be a valuable therapeutic measure in this patient population.
Portal pressure; HVPG; ascites; variceal bleeding
Transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective procedure for the treatment of complications of liver cirrhosis, such as refractory ascites, hepatic hydrothorax and refractory variceal bleeding. The aim of this paper is to describe a rare case of liver failure after a TIPS procedure. A 38-year-old diabetic male with Child-Pugh C liver cirrhosis due to chronic hepatitis C infection who had developed refractory ascites was scheduled for a TIPS procedure. Within 24 h following TIPS placement, the patient developed distributive shock, jaundice, persistentgrade 3 hepatic encephalopathy, severe coagulopathy and acute renal failure. He was treated with lactulose enemas, broad-spectrum antibiotics and blood-derived products. Laboratory data revealed a 100-fold increase in aminotransferases and a non-enhanced computed tomography showed an irregular hypodense area in the right posterior segment of the liver. Despite being initially being in a stable condition, the patient developed progressive liver failure and died 2 mo later. Hepatic infarction is an uncommon phenomenon after a TIPS procedure; however, it can greatly complicate the course of a disease in a patient with an already compromised liver function.
Hepatic ischemia; Ischemic hepatitis; Liver infarction; Transjugular intrahepatic portosystemic shunt; Complications
Background—Height of portal
pressure correlates with severity of alcoholic cirrhosis. Portal
pressure indices are not however used routinely as predictors of survival.
Aims—To examine the clinical value
of a single portal pressure measurement in predicting outcome in
cirrhotic patients who have bled.
Methods—A series of 105 cirrhotic
patients who consecutively underwent hepatic venous pressure
measurement were investigated. The main cause of cirrhosis was
alcoholic (64.8%) and prior to admission all patients had bled from varices.
Results—During the follow up period
(median 566 days, range 10-2555), 33 patients died, and 54 developed
variceal haemorrhage. Applying Cox regression analysis, hepatic venous
pressure gradient, bilirubin, prothrombin time, ascites, and previous
long term endoscopic treatment were the only statistically independent
predictors of survival, irrespective of cirrhotic aetiology. The
predictive value of the pressure gradient was much higher if the
measurement was taken within the first or the second week from the
bleeding and there was no association after 15 days. A hepatic venous
pressure gradient of at least 16 mm Hg appeared to identify patients
with a greatly increased risk of dying.
portal pressure is an independent predictor of survival in patients
with both alcoholic and non-alcoholic cirrhosis. In patients with a
previous variceal bleeding episode this predictive value seems to be
better if the measurement is taken within the first two weeks from the
bleeding episode. A greater use of this technique is recommended for
the prognostic assessment and management of patients with chronic liver disease.
chronic liver disease; alcoholic cirrhosis; portal
Background: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients.
Patients and methods: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of α fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy.
Results: In total, 426 patients were followed up for 1664 person years; median 225 (range 12–295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14–236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39–23.89; p<0.001) and 2.84 (95% CI 1.05–7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period.
Conclusion: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.
hepatitis B; genotype; hepatocellular carcinoma; liver cirrhosis; basal core promoter mutations
Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.
Liver cirrhosis; Hepatorenal syndrome; Terlipressin; Gangrene; Osteomyelitis
A 66-year-old female with cryptogenic cirrhosis complicated by ascites, hepatic encephalopathy, variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback technique. Extensive eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein flow. The liver graft was recirculated without any hemodynamic instability. Subsequently, the patient became hypotensive progressing to asystole. She was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right ventricle. The patient was noted to be coagulopathic at the time. She became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus.
Liver transplantation; Cardiac thrombus; Reperfusion injury; Coagulopathy; Transesophageal echocardiogram
Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications, including decompensation, bleeding and liver cancer. Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease. Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis, while cirrhosis requires a specific follow-up including screening for esophageal varices and hepatocellular carcinoma. Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive, costly and prone to sampling errors. Recently, blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis. However, there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available. This is due to an unsatisfactory accuracy for some of them, and to an incomplete validation for others. Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined. Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.
Chronic liver diseases; Hepatic fibrosis; Liver biopsy; Non-invasive methods for liver fibrosis assessment; Combination algorithms; Decisional tree
Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V2-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.
Arginine vasopressin; MELD score; Portal hypertension; Vasopressin receptor antagonists
The clinical picture of liver disease in endemic areas of Schistosomiasis mansoni differs in many ways from that observed in alcoholic and other types of cirrhosis. In hepatosplenic schistosomiasis there is predominance of the clinical manifestations of portal hypertension, e.g., bleeding esophageal varices, while ascites, jaundice, and hepatic precoma or coma are much less common. Ammonia tolerance is usually normal and helps explain the low mortality rate during bleeding. Of special interest is the observation of a high incidence of persistent hepatitis B surface antigenemia among patients with hepatosplenic schistosomiasis, suggesting increased susceptibility of such patients to the development of virus-induced chronic active hepatitis.
Background and aims: The natural history of initially compensated cirrhosis due to hepatitis B (HBV) or hepatitis C (HCV) virus is only partially defined. We have investigated morbidity and mortality rates and the hierarchy of complications in compensated viral cirrhosis over a long follow up period.
Patients and Methods: A cohort of Italian patients with initially compensated cirrhosis of viral aetiology were followed up at six monthly intervals with laboratory tests to identify major complications (ascites, gastrointestinal bleeding, portal-systemic encephalopathy, hepatocellular carcinoma) and to assess the progression of Child’s stage and mortality rate due to liver related causes.
Results: Between 1986 and 1996, 312 patients (43 HBV positive, 254 HCV positive, and 15 HBV and HCV coinfected) were included. During a median follow up of 93 (range 14–194) months, 102 (32.6%) patients developed at least one complication (HCV positive 31.1%; HBV positive 34.8%; HBV and HCV coinfected 53.3%). Overall, the most frequent complication was hepatocellular carcinoma which occurred in 65 (20.8%) cases, followed by ascites (61 cases, 19.5%), gastrointestinal bleeding (14 cases, 4.5%), and portal-systemic encephalopathy (six cases, 1.9%). Progression of Child’s stage was observed in 62 patients (19.8%). Death from liver disease occurred in 58 (18.6%) cases and in 70.7% this was due to hepatocellular carcinoma. Hepatocellular carcinoma was the first complication to develop in 59 cases and represented the most frequent first complication in both HCV and HBV/ HCV related cirrhosis.
Conclusions: These results indicate significant morbidity and mortality during the first decade after diagnosis of compensated cirrhosis due to HBV and/or HCV, and identify hepatocellular carcinoma as the most frequent and life threatening complication, particularly in HCV positive cases.
hepatocellular carcinoma; cirrhosis; viral cirrhosis; hepatitis C virus; hepatitis B virus
Background & Aims
Predictors of clinical outcomes and histological progression among patients with chronic hepatitis C and advanced fibrosis are poorly defined. We developed statistical models to predict clinical and histological outcomes in such patients.
Baseline demographic, clinical, and histological data from Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial participants were subjected to multivariate analyses to determine their ability to predict clinical outcomes (ascites, spontaneous bacterial peritonitis, Child-Turcotte-Pugh score ≥7 on two consecutive visits, variceal bleeding, hepatic encephalopathy, and liver-related death) and histological outcome (≥2-point increase in Ishak fibrosis stage) during the 3.5 years of the trial.
Of 1,050 randomized patients, 135 had one or more clinical outcomes a median of 23 (range 1–45) months after randomization. Factors associated with a clinical outcome in multivariate analyses were higher AST/ALT ratio, lower albumin, lower platelet count, higher total bilirubin, and more advanced Ishak fibrosis score (p<0.0001). The cumulative 3.5-year incidence of a clinical outcome was 2% in the lowest and 65% in the highest risk group. Of 547 patients without cirrhosis at baseline and at least one follow-up biopsy, 152 had a histological outcome. Independent variables associated with a histological outcome were higher body mass index, lower platelet count, and greater hepatic steatosis (p<0.0001).
In patients with chronic hepatitis C and advanced fibrosis, risk of clinical complications and fibrosis progression during 3.5 years can be predicted using baseline laboratory tests and histological data. Our models may be useful in counseling patients and determining the frequency of monitoring.
Chronic hepatitis C; Clinical outcome; Histological outcome
Hepatic encephalopathy (HE) is a frequent and severe complication of cirrhosis. A single determination of ammonia in venous blood correlates poorly with neurological symptoms. Thus, a better biological marker is needed.
To make a diagnosis of HE, we explored the value of ammonia in capillary blood, an equivalent to arterial blood, measured at bedside following an oral glutamine challenge.
We included 57 patients (age 56 yrs; M/F: 37/20) with cirrhosis (alcoholic = 42; MELD score 13.8 [7-29], esophageal varices = 38) and previous episodes of HE (n = 19), but without neurological deficits at time of examination, and 13 healthy controls (age 54 yrs). After psychometric tests and capillary (ear lobe) blood ammonia measurements, 20 gr of glutamine was administered orally. Tests were repeated at 60 minutes (+ blood ammonia at 30'). Minimal HE was diagnosed if values were > 1.5 SD in at least 2 psychometric tests. Follow-up lasted 12 months.
The test was well tolerated (nausea = 1; dizziness = 1). Patients showed higher values of capillary blood ammonia over time as compared to controls (0'-30'-60 minutes: 75, 117, 169 versus 52, 59, 78 umol/L, p < 0.05). At baseline, 25 patients (44%) had minimal HE, while 38 patients (67%) met the criteria for HE at 60 minutes (chi2: p < 0.01). For the diagnosis of minimal HE, using the ROC curve analysis, baseline capillary blood ammonia showed an AUC of 0.541 (CI: 0.38-0.7, p = 0.6), while at 60 minutes the AUC was 0.727 (CI: 0.58-0.87, p < 0.006). During follow-up, 18 patients (31%) developed clinical episodes of HE. At multivariate analysis, the MELD score (1.12 [1.018-1.236]), previous episodes of HE (3.2[1.069-9.58]), but not capillary blood ammonia, were independent predictors of event.
In patients with cirrhosis and normal neurological examination, bedside determination of ammonia in capillary blood following oral glutamine load is well tolerated and achieves a better diagnostic performance for minimal HE than basal capillary ammonia levels. However, capillary blood ammonia is a poor predictor of development of clinically overt HE.