Showing posts with label gallstones. Show all posts
Showing posts with label gallstones. Show all posts

Thursday, March 15, 2018

HCV infection, older age, and cirrhosis correlate with an increased risk of gallstones

Hepatitis C Virus Infection Increases Risk of Gallstone Disease in Elderly Chinese Patients with Chronic Liver Disease

In conclusion, we found that the risk of gallstone development in Chinese CLD patients was significantly associated with the occurrence of liver cirrhosis, older age, and HCV infection. Furthermore, patients infected with HCV formed more gallstones than did patients infected with HBV.

Scientific Reports volume 8, Article number: 4636 (2018)
Received: 12 January 2018 Accepted: 28 February 2018 Published online: 15 March 2018

We investigated possible links between the etiology of liver disease and gallstone risk in Chinese patients with chronic liver disease (CLD). We compared the outcomes of 267 Chinese CLD patients with gallstones and those of a control group of 1,015 CLD patients without gallstones. Logistic regression analyses adjusting for demographic features and other gallstone risk factors revealed that liver cirrhosis increased the risk of gallstone development twofold [adjusted odds ratio (AOR); 95% confidence interval (95% CI): 2.343 (1.710–3.211)]. HCV infection increased gallstone risk 1–2-fold [AOR; 95% CI: 1.582 (1.066–2.347)] higher than did HBV infection. Multivariate analyses of the risk of developing gallstones in patients with liver cirrhosis after an HCV or HBV infection yielded an estimated AOR (95% CI) of 1.601 (1.063–2.413) in patients with an HCV infection. In elderly patients with CLD (≥60 years of age), gallstone risk also increased significantly after an HCV infection [AOR (95% CI): 2.394 (1.066–5.375)]. HCV infection, older age, and liver cirrhosis significantly correlate with an increased risk of gallstone development in Chinese patients with CLD. HCV infection further increases this risk in both patients with liver cirrhosis and in elderly CLD patients (≥60 years of age).

Continue to full-text article......

Tuesday, October 3, 2017

BMJ Case Reports - Man developed serious liver damage after taking epsom salts to treat gallstones

Man develops severe liver damage after taking epsom salts
October 02, 2017
A 38-year-old man developed serious liver damage after taking epsom salts to treat gallstones, reveal doctors in the journal BMJ Case Reports.

The man had lost his appetite and was jaundiced. He was tested for a range of common liver diseases, all of which were negative. But a biopsy specimen showed that he had signs of liver damage.

It emerged that he had been taking three tablespoons of Epsom salts in lukewarm water for 15 days. He had been advised by a naturopath that this would dissolve his gallstones.

Taking too much Epsom salts can cause diarrhoea, abnormal heart rhythm, and kidney damage.

In this case, the man took a large quantity of salts over two weeks, which prompted rapid worsening of fibrosis (tissue scarring).

And the doctors caution that certain conditions might heighten the risk of liver damage when combined with Epsom salts.

The man was advised to stop taking the salts, to drink plenty of fluids, and was given medication to prevent further liver damage. And after around six weeks, his liver function had returned to normal.

View Article Online 
BMJ Case Reports 

Thursday, June 29, 2017

Liver cirrhosis: a risk factor for gallstone disease in chronic hepatitis C patients in China

Research Article: Observational Study
Full Text Article Available Online
Medicine: June 2017 - Volume 96 - Issue 26 - p e7427
doi: 10.1097/MD.0000000000007427

Liver cirrhosis: a risk factor for gallstone disease in chronic hepatitis C patients in China
Li, Xu PhD; Wang, Zhongfeng PhD; Wang, Le MD; Pan, Meng MD; Gao, Pujun PhD*

Abstract: We investigated the possible link between liver cirrhosis and gallstone risk in chronic hepatitis C (CHC) patients in China.

To analyze the association between liver cirrhosis and gallstone development, we compared outcomes of 133 Chinese CHC patients with gallstones and an age-, sex-, and hepatitis C virus RNA level-matched control group of 431 CHC patients without gallstones.

We found that liver cirrhosis was more prevalent in gallstone patients (40.6%) than in the control group (24.4%). Logistic regression analyses adjusting for demographic features and other gallstone risk factors revealed that liver cirrhosis increased the risk of gallstone development 2-fold (adjusted odds ratio [AOR]: 2.122; 95% confidence interval [CI]: 1.408–3.198). Moreover, multivariate analyses comparing the risk of gallstone development in liver cirrhosis patients with decompensated or compensated liver cirrhosis yielded an estimated AOR (95% CI) of 2.869 (1.277–6.450) in patients with decompensated liver cirrhosis. Gallstone risk also increased significantly with older age (>60 years) (AOR: 2.019; 95% CI: 1.017–4.009).

Liver cirrhosis significantly correlates with increased risk of gallstone development in CHC patients in China. Decompensated liver cirrhosis and older age further heighten this risk in patients diagnosed with hepatitis C-related cirrhosis.
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Recommended Reading

Gallstones and gallbladder disease
More than 25 million Americans have gallstones, and a million are diagnosed each year. However, only 1 to 3% of the population complains of symptoms during the course of a year, and fewer than half of these people have symptoms that return.

Women are much more likely than men to develop gallstones. Gallstones occur in nearly 25% of women in the U.S. by age 60, and as many as 50% by age 75. In most cases, they have no symptoms. In general, women are probably at increased risk because estrogen stimulates the liver to remove more cholesterol from blood and divert it into the bile.
Continue reading...

Review Article
Full Text Review Article Available Online
Volume 2017 (2017), Article ID 9749802, 8 pages

Gallstones in Patients with Chronic Liver Diseases
Xu LiXiaolin GuoHuifan JiGe Yu, and Pujun Gao
With prevalence of 10–20% in adults in developed countries, gallstone disease (GSD) is one of the most prevalent and costly gastrointestinal tract disorders in the world. In addition to gallstone disease, chronic liver disease (CLD) is also an important global public health problem. The reported frequency of gallstone in chronic liver disease tends to be higher. The prevalence of gallstone disease might be related to age, gender, etiology, and severity of liver disease in patients with chronic liver disease. In this review, the aim was to identify the epidemiology, mechanisms, and treatment strategies of gallstone disease in chronic liver disease patients.
Read the article published January 2017 online in BioMed Research International.

Sunday, February 19, 2017

Gallstones in Patients with Chronic Liver Diseases

Gallstones in Patients with Chronic Liver Diseases
Greetings from sunny Michigan, not sure what happened but it sure is warm outside, we might hit 60 today. Glad you stopped by folks, in this edition of weekend reading we take a quick look at gallstone disease, cirrhosis and HCV.

Research has shown that people with chronic liver disease, especially those with cirrhosis have a greater tendency to develop gallstones. Although cirrhosis is a known risk factor for gallstones, little is known about gallbladder disease in individuals with chronic hepatitis C - research is sparse. Today's focus is on gallstone disease in chronic liver diseases including risk associated with gallstones occurrence in people with chronic hepatitis C.

The articles or abstracts provided below were found in online journals or accessed through PubMed.

Review Article
Gallstones in Patients with Chronic Liver Diseases
Xu LiXiaolin GuoHuifan JiGe Yu, and Pujun Gao
With prevalence of 10–20% in adults in developed countries, gallstone disease (GSD) is one of the most prevalent and costly gastrointestinal tract disorders in the world. In addition to gallstone disease, chronic liver disease (CLD) is also an important global public health problem. The reported frequency of gallstone in chronic liver disease tends to be higher. The prevalence of gallstone disease might be related to age, gender, etiology, and severity of liver disease in patients with chronic liver disease. In this review, the aim was to identify the epidemiology, mechanisms, and treatment strategies of gallstone disease in chronic liver disease patients.
Read the article published January 2017 online in BioMed Research International.

Hepatitis C Virus Infection Is Positively Associated with Gallstones in Liver Cirrhosis
Zhang F.-M. · Chen L.-H. · Chen H.-T. · Shan G.-D. · Hu F.-L. · Yang M. · Chen W.-G. · Xu G.-Q.
Aim - To elucidate the prevalence and risk factors of gallstone disease (GD) among patients with liver disease and explore their association with the aetiology and severity of hepatic injury.
CONCLUSION: HCV infection is positively associated with gallstone formation especially in those with cirrhosis patients.
Abstract available, here.

Hepatitis C - A Risk Factor For Gallstone Disease
Syed Inamullah Shah, Sajida Shah*, Abdul Hannan
This cross-sectional study aimed to establish an association between HCV infection and gallstones by excluding subjects with all other risk factors for gallstones.
There is a strong association between HCV infection and gallstones. HCV infection is definitely a risk factor for gallstone disease particularly in young males. By invalidating young subjects and rendering them as potential candidates for surgery, this association has a profound effect on health economy. There is a predilection for HCV positive patients to acquire multiple gallstones. Further studies are needed to evaluate the precise cause for this association.
Download the original 2014 article, here.

Hepatitis C Virus Infection is a Risk Factor for Gallstone Disease: A Prospective Hospital-based Study of Patients with Chronic Viral C Hepatitis
M. Acalovschi; C. Buzas; C. Radu; M. Grigorescu
A Prospective Hospital-based Study of Patients with Chronic hepatitis C.

We decided to investigate whether the gallstone risk in patients with chronic HCV infection was linked only to cirrhosis or also to the HCV infection per se.
Our study shows that even HCV patients with chronic hepatitis but not cirrhosis have an increased prevalence of gallstones. Compared with controls, gallstones are present in HCV patients at a younger age and are associated with central obesity and liver steatosis, but not with gallstone heredity, dyslipidaemia, diabetes mellitus or metabolic syndrome. Although we could not establish a temporal relationship, the association between HCV infection and gall stone disease is real and appears to be causally linked, at least in predisposed individuals (obese and with liver steatosis).
Published in Journal of Viral Hepatitis, full text article available @ Medscape.

Gallstones and Liver Disease: an Overview
Dario Conte, Mirella Fraquelli, Mariangela Giunta, Clara Benedetta Conti
Nowadays, there is much interest in discovering the relationship between GS and liver disease and in the last issue Coelho and colleagues [3] decided to assess the prevalence of cholelithiasis in patients undergoing liver transplantation for end stage liver disease. Their study deals with a really interesting and new issue. In fact, whereas many studies observed a higher prevalence of GS in chronic liver disease, up to now none have assessed GS prevalence in the subset of patients subjected to liver transplantation. In addition, this article evaluates this particular issue in Latin America, a geographical area from which few data are available in current literature. The reference standard to detect GS was represented not only by the ultrasonographic scan of the gallbladder but also on the direct examination of the explanted liver. The results of the study by Coelho and colleagues deserve some considerations that could be summarized by answering three main questions:
a) How did we get here?
b) What  is the reason for the increased frequency of gallstones in cirrhosis?
c) Do gallstones worsen the course of liver cirrhosis?
Download the editorial  here..

Gallstones (cholelithiasis) - causes, symptoms, diagnosis & pathology
What are gallstones? Gallstones are solid stones that are produced in the gallbladder when there’s an imbalance in the composition of bile. The main types of gallstones are cholesterol stones, bilirubin stones, and brown stones.

Enjoy the rest of your weekend!

Sunday, November 2, 2014



Good afternoon folks, its a lovely Sunday here in Michigan, a perfect day for a walk around the neighborhood. Did you all have a great Halloween? Our little people sure did, despite a few snowflakes.

Welcome back to another edition of weekend reading. Today's subject is gallbladder disease and HCV. 

Syed Inamullah Shah, Sajida Shah*, Abdul Hannan Department of Surgery, Fauji Foundation Hospital, *Department of Radiology, Combined Military Hospital, Rawalpindi

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BACKGROUND: There is increasing evidence that chronic liver disease is one of the risk factors for gallstone disease. A few published studies have documented the link between Hepatitis C Virus (HCV) related chronic liver disease and increased incidence of gallstones but these studies did not exclude subjects with other risk factors like cirrhosis. This study aimed to establish an association between HCV infection and gallstones by excluding subjects with all other risk factors for gallstones.
METHODS: This cross sectional study was carried out at four hospitals of Rawalpindi, Pakistan, over a period of 18 months. It included all cases referred for ultrasound scan of abdomen. A total of 2000 cases, were included in the study by consecutive, non-probability sampling. Anti-HCV antibody test was carried out in all subjects by ELISA and sonography was done to determine presence or absence of gallstones.
RESULTS:Patients suffering from HCV had a significantly high percentage of gallstones as compared to seronegative subjects (p = 0.001). In seropositive group, more males had gallstones (p = < 0.001) and prevalence of gallstones was significantly high in younger population with age at or below 40 years (p = < 0.001).
CONCLUSION: Risk of gallstone disease is increased in patients suffering from HCV infection. This association is more pronounced in males.

HCV is globally distributed and it is estimated that up to 170 million people (3% of the world’s population) are infected worldwide.1 In Pakistan, about 4.7% of the population is HCV positive. This ranks as the second highest percentage after Egypt (15.5%).

In recent years more and more males have been diagnosed with symptomatic gallstones and their complications including choledocholithiasis, gallstone pancreatitis and cholangitis. A significant proportion of these patients have been observed to be seropositive for HCV.

Association of gallstones with chronic liver disease is documented in medical literature1,3,4 but no such study has been carried out in Pakistan or the subcontinent despite the fact that HCV is endemic in this region. Risk factors described for gallstones include hyperlipidemia5 , obesity6,7, high serum levels of female sex hormones8 , sickle cell disease, and thalassaemia9 among others. Cirrhosis of liver is a known risk factor for gallstones10,11 but very little is known about gallstone disease in individuals with HCV infection without cirrhosis. 1,4 None of the studies previously conducted have investigated HCV infection as a solitary risk factor for gallstones. 

Some findings of these studies have a significant bearing on the health economy. It has been found that HCV positive subjects develop gallstone disease at a younger age3 and are more likely to have gallstones in bile ducts (0.4%) as compared to normal population (0.1%). 12 It was also found that males with HCV infection were more likely to need surgery for gallstone disease compared to women.5 Keeping in view that HCV infection is endemic in Pakistan, the demographics of the affected population and the burden on the hospitals for gallstone related complications would lead to a significant financial burden. A common observation was made in our institution that there was a clear difference in gall stones occurrence in patients with and without HCV infection. Our hypothesis was that HCV infection is a risk factor for gallstone disease. 

The objective of this study was to compare the frequency of gallstones in patients who have hepatitis C virus infection, with seronegative subjects.

This cross-sectional study was carried out from November, 2011 to April, 2013 at the Fauji Foundation Hospital and the Combined Military Hospital at Rawalpindi. Patients from Military Hospital and AlIhsan Hospital were also included. In order to maintain the same standard in sonography, all the scans were performed by the same radiologist.

The study included all cases referred for ultrasound scan of abdomen. Patients in this study were sampled by consecutive nonprobability sampling technique. Data was collected using a structured pro forma. Anti-HCV antibody was tested by ELISA on all subjects. An equal number of patients with and without HCV infection were chosen and presence of any gallstones was observed in both groups. Ultrasound scan of abdomen was done on all subjects and special note was made of gallstones in the gallbladder or the bile ducts and presence or absence of cirrhosis.

Patients diagnosed as suffering from hepatitis C were included in Group-1 while those without Hepatitis C were included in Group-2. Patients of either gender, between and including the ages of 18 years and 70 years, were included. An equal number of HCV positives and HCV negative patients were included without taking into account their gender. Patients who were excluded from study were those with: deranged LFTs due to any cause other than hepatitis C; deranged lipid profile; BMI in obese range; acute or fulminant hepatitis and/or cirrhosis; pregnancy; sickle cell disease; malignancy; thalassemia; and history of abdominal surgery or birth control measures. Anti-HCV antibody detected positive by ELISA at least three months before the ultrasound examination was considered as suffering from HCV infection.

Gallstones were considered present if they were detected on ultrasound. Data was analyzed by SPSS-18. Chi-square test was used to determine the association of HCV infection with gallstones by comparing the frequency of gallstones in the two groups. p-value of <0.05 was considered significant. Odds Ratios with 95% confidence intervals (CI) were also calculated.

A total of 2000 patients were included in the study, 1000 subjects were HCV negative and while the other 1000 subjects were HCV positive. Of the total 2000 participants in the study, 1066 (53.3%) individuals were males while 934 (46.7%) were females. The age of subjects ranged between 19 and 66 years with a mean of 41.66±10.11 years. As far the age groups are concerned, 63.2% of the HCV positive subjects aged 40 years or below, while 60.4% of HCV negative group were above 40 years of age. Males and females with Hepatitis C antibodies were 575 (57.5%) and 425 (42.5%) respectively.

Overall presence of gallstones in both groups was a total of 514 subjects (25.7%). In HCV negative males, gallstones were found in only 0.9% as compared to 13.9% in females. Frequency of gallstones in both groups and their comparison is shown in Table-1.

Gender distribution of gallstones in both groups is detailed in Table-2 whereas Figure-1 shows age distribution. The odds ratio for exposure of HCV and effect of gall stones with 95% confidence interval was 3.39 (95% CI 3.1 to 4.8). The results are statistically significant with a risk range given in the CI for those exposed compared to non-exposed. Distribution of gall stones in either gender showed that frequency of gallstones is high in HCV positive males (p=.001) but decreases in HCV positive females.


Quantity of stones in gallbladder was labeled as single, multiple or no stones. Cross tabulation of number of stones with study group revealed a significant association between multiple gallstones and HCV infection (p=<.001) as shown in Table-3

Presence of gallstones in the common bile duct was evaluated between the two groups. There were more cases of CBD gallstones in HCV positive group (2.5%) as compared to HCV negative group (0.9%). The difference is statistically significant (p=<0.001).

Cholelithiasis has been traditionally associated with middle aged females. Gall stones are of various types but the commonly found calculi are cholesterol stones. Risk factors described for cholesterol stones, in addition to those described above, include rapid weight loss13,14 female sex hormones8,15,16, multiparity and diabetes mellitus.

Cirrhosis has long been known to be a risk factor for gallstones.10,11,18 Stroffolini et al, reported in 2007 that gallstone prevalence was significantly higher in patients with HCV-related cirrhosis than in those with HBV-related or alcoholic cirrhosis.18 Formation of gallstones in cirrhosis is due to many factors such as reduced secretion of bile acids, reduced gallbladder motility19 and reduced synthesis of cholesterol. Although high estrogen levels have been suggested as a possible mechanism of increased gallstone formation in cirrhotic patients, Li et al did not find any significant differences in plasma levels of sex hormones between cirrhotic with and without gallstones.20

In contrast to the abundance of literature on cirrhosis and its association with gallstones, very little is known about gallbladder disease in individuals with HCV infection in the absence of cirrhosis.

There are only three published studies on this subject so far.1,3,4 Probably the first study to establish the link between HCV infection and gallstone disease was carried out in 2000 at Taiwan. In this study by Chang et al3 , the prevalence of gallstones in HCV positive subjects was found to be significantly higher (11.7%) than the control subjects (6%). Bini et al4 examined the data of more than 13000 subjects who participated in a United States national survey for health and nutrition, in 2005, and discovered that 12.5% of those with HCV infection had gallstone disease, most of whom were males. They also discovered that the relative odds of gallstone disease among persons with HCV infection increased with the severity of liver disease as assessed by serum total bilirubin levels, serum albumin levels, and platelet counts. This was construed as demonstrating a direct link between liver disease and gallstone formation.  A 2009 Romanian study by Acalovschi et al1 , reported 19% incidence of gallstones in HCV positive patients. In our study, we found that a total of 37.4% of HCV positive individuals had gallstones as compared to 14% in HCV negative group.

The significant difference between the two groups (p=.001) clearly establishes an association between HCV infection and gallstone disease, keeping in view the fact that we excluded subjects with all other known risk factors for gallstone disease. As compared to previous studies, the prevalence in this study is higher in both groups. It may be argued that this extraordinarily high prevalence in our results is due to the peculiar sampling technique, but the study of Acalovschi et al used a similar technique with comparable sample size and revealed lower overall prevalence.

Therefore, results of our study may partly reflect an actual rise in the incidence of gallstone disease in Pakistani population.

Bini et al found that HCV infection was a strong risk factor for gallstone disease in men but not in women. 4 The reason for this difference is not cited except for the likelihood that the pathophysiology of and risk factors for gallstone formation differ among men and women. This study corroborates this observation as our results that show that 28.2% of HCV positive males had gallstone disease whereas prevalence in HCV positive females was only 8.5%. This difference becomes more significant because only 0.1% HCV negative males in our study had gallstone disease whereas 19.2% HCV negative females had the disease. This means that HCV infection may actually be protective to women against gallstone disease. In contrast, males revealed a strong association (p=.001) between HCV infection and gallstones.

Our results revealed that younger males are more prone to acquire gallstones if they are HCV positive. This age association is statistically significant in males (p=<.001). These results are in conformity with those of Acalovschi et al and Chang et al. 1,3 Younger age group was also found to have a predilection for acquiring multiple gallstones.

There is also a significant association (p=<.001) between HCV infection and development of multiple, as opposed to single gallstones. HCV infection appears to make the patients more prone to suffer from choledocholithiasis.

Various reasons have been postulated for HCV infection causing gallstones. Sluggish function of the liver in synthesizing bile acids has been cited. 21 Direct infection of the gallbladder by HCV22 and gallbladder hypomotility19 has been demonstrated. This direct effect is more probable because an infection by Hepatitis B virus does not increase the risk of gallstone disease4 despite having a similar effect on liver function. Some studies have even suggested a protective effect of hepatitis B in developing gallstones. 23 This direct effect seems to spare the gallbladders in females.

The findings of this study significantly bear on the health economy. As established, males less than 40 years are more prone to develop gallstones if they are HCV positive. These stones are usually multiple with more likelihood of causing obstructive jaundice. These patients are more likely to need surgery for gall stone disease4 and morbidity may be high because of compromised liver function. In economic terms, the breadwinner of the family is disabled, workplace gets affected and hospitals have to allocate more resources for HCV positive patients undergoing surgery.

The strength of our study is in the fact that this is the first attempt to describe association of gallstones with HCV not only in Pakistan but in the entire South Asian region. Secondly, we have been scrupulous in the selection of subjects by excluding those HCV positive individuals who had any other risk factor of gallstone disease. The limitation of this study is that the study sample is not representative of the general population. Subjects were selected from patients coming for treatment to four large hospitals of Rawalpindi.

There is a strong association between HCV infection and gallstones. HCV infection is definitely a risk factor for gallstone disease particularly in young males. By invalidating young subjects and rendering them as potential candidates for surgery, this association has a profound effect on health economy. There is a predilection for HCV positive patients to acquire multiple gallstones. Further studies are needed to evaluate the precise cause for this association.


Tuesday, December 17, 2013

High-Fat Diet Linked to Fewer Gallstones

High-Fat Diet Linked to Fewer Gallstones

Published: Dec 17, 2013 | Updated: Dec 17, 2013

By Cole Petrochko, Staff Writer
MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Patients undergoing rapid weight loss who either received ursodeoxycholic acid (Ursodiol) or ate a high-fat diet had a reduced risk of gallstones, researchers found.

Action Points
In a meta-analysis of randomized controlled trials of participants undergoing weight loss, ursodeoxycholic acid use was associated with a reduced risk of gallstones.

Diets high in fat content also were associated with fewer gallstones, compared with those with low fat content

Compared with control treatments, risk for gallstones was significantly reduced among patients who received daily supplements of ursodeoxycholic acid (RR 0.33, 95% CI 0.18-0.60), according to Frank Lammert, MD, of Saarland University Hospital in Homburg, Germany, and colleagues.

There was also a significant reduction in gallstone formation in patients who consumed a high-fat diet versus a low-fat diet (RR 0.09, 95% CI 0.01-0.61), they wrote online in the journal Clinical Gastroenterology and Hepatology.

A study printed in the journal Hepatology in July 2013 showed a causal relationship between high body mass index (BMI) and gallstones, particularly among women.

Similar findings were reported in the Journal of Pediatric Gastroenterology and Nutrition in August 2012 among overweight or obese children and teens; those who were moderately obese had more than four-fold risks for gallbladder disease compared with normal-weight pediatric patients.

The authors noted that these risks were also present in patients who underwent rapid weight loss or who underwent weight cycling.

The authors reviewed randomized controlled trials of nonsurgical gallbladder stone preventive interventions in adult patients who underwent rapid weight loss through bariatric surgery or with diet alone, an analysis that included 13 studies and 1,837 obese participants combined.

Outcomes included in the analysis were formation of ultrasonically-verified gallstones, mortality, and adverse events. Secondary outcomes included quality of life, cholecystectomy, bile lithogenicity, and weight loss.

Control interventions included placebo treatment, no intervention, or pharmacological and nonpharmacological interventions.

Low- versus high-fat diets were examined in two studies, which included groups receiving 3 g versus 12.2 g of fat, and 2 g versus 30 g of fat, each in daily quantities. Participants in the remaining 11 studies received 300 to 1,200 mg daily of ursodeoxycholic acid at a median 750 mg per day.

Participants were treated from 6 weeks to 18 months and were followed up with for 6 weeks to 24 months.

In the studies of ursodeoxycholic acid, 5% of those in a treatment arm developed gallstones versus 23% of those in the control arm. No deaths occurred in either arms of the studies. Treatment with ursodeoxycholic acid was associated with a reduced risk of cholecystectomy (RR 0.20, 95% CI 0.07-0.53).

Weight loss was equal among groups in all of the ursodeoxycholic acid trials. Among those who received bariatric surgery as their weight-loss intervention, type of surgery did not affect ursodeoxycholic acid-related outcomes, nor did dosage of ursodeoxycholic acid. Quality of life was not assessed in these studies.

In studies comparing high- versus low-fat diets, no patients in the high-fat groups developed gallstones, compared with 45% of control patients. There was no significant difference in weight lost. Quality of life was not assessed. Bile lithogenicity did not differ significantly between the two studies.

There were no adverse events reported with the high- versus low-fat diet studies.

Few serious events were reported related to ursodeoxycholic acid consumption; gastrointestinal-related complaints were the most common adverse events.

The authors noted that the small number of identified trials and low sample sizes in each trial limited their study. In addition, high risk of attrition bias may have also limited outcomes. The research was limited by an inability to perform a meta-analysis of other interventions that reduce cholesterol precipitation in bile.

Primary source: Clinical Gastroenterology and Hepatology
Source reference: Lammert F, et al "Ursodeoxycholic acid and high-fat diets prevent gallbladder stones during weight loss: a meta-analysis of randomized controlled trials" Clin Gastroenterol Hepatol 2013; DOI: 10.1016/j.cgh.2013.11.031.

Monday, July 15, 2013

Obesity May Cause Gallstones

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse

Higher body mass index (BMI) appears to be a causal risk factor for gallstones, particularly for women, Danish researchers found.

In a large population study, increasing BMI was associated with a significantly increased risk of gallstones (HR 2.84, 95% CI 2.32 to 3.46, P<0.001), Anne Tybjaerg-Hansen, MD, of Copenhagen University Hospital, and colleagues reported online in Hepatology.

With regard to causality, they also found a higher risk of gallstones among patients who had more genetic variants tied to obesity (HR 1.43, 95% CI 0.99 to 2.05, P=0.007).

"The concordance between the observational and genetic risk estimates supports that increased BMI per se is a causal risk factor for symptomatic gallstone disease," they wrote.

Elevated BMI has been associated with an increased risk of gallstones, but it's been unclear if the relationship is causal, since it may be that another factor simultaneously raises BMI and causes gallstones, such as a high-fat diet or physical inactivity.

The researchers hypothesized that if BMI caused symptomatic gallstones, an increased BMI due to certain genetic variants should confer a similar increased risk of gallstones.

To test that hypothesis, Tybjaerg-Hansen and colleagues applied the Mendelian randomization approach, which uses genetic variants that are associated with BMI but not with potential confounding factors, to 77,679 patients from the general population.

During a mean follow-up of 5.3 years, 4,106 patients developed symptomatic gallstone disease.

Patients were also genotyped for three common variants associated with BMI -- FTO, MC4R, and TMEM18.

Overall, the researchers found that increasing BMI was associated with an increased risk of gallstones (aHR 2.84, 95% CI 2.32 to 3.46, P<0.001).

That association was significant for both men and women, although it was stronger for women:
Women: HR 3.36, 95% CI 2.62 to 4.31
Men: HR 1.51, 95% CI 1.09 to 2.11

In genetic analyses, patients carrying six BMI-increasing alleles compared with none or just one had a 5.2% increase in BMI overall, with increases of 4.3% in women and 6.1% in men (P<0.001 for all).

The researchers also found a significant interaction between gallstone disease and increasing obesity alleles, with a higher risk of gallstones among patients with six BMI-increasing alleles compared with none or just one (HR 1.43, 95% CI 0.99 to 2.05, P=0.007).

However, that relationship was significant for women but not for men, they reported.

Mechanisms by which obesity may cause gallstone disease include the fact that obesity may increase hepatic de novo cholesterol synthesis and hepatobiliary cholesterol efflux, a key event in the development of cholesterol gallstones, the researchers wrote.

They also noted that increased abdominal fat mass may cause gallbladder hypomotility and bile stasis, another risk factor for gallstone formation, and factors secreted or metabolized by adipocytes may promote the formation of gallstones.

The study was limited by its reliance on hospital ICD codes to determine gallstone disease, and potentially by ascertainment bias since clinicians may be more suspect of gallbladder disease in obese patients, which could lead to overestimation of the association in the study.

The findings also may not be generalizable outside of the Danish population.

Still, the researchers concluded that BMI is likely a causal risk factor for gallstone disease, particularly in women, and the data "provide additional impetus for lifestyle interventions aimed at weight loss among overweight and obese individuals in the general population."

Monday, October 29, 2012

Misinformation on gallstones drew more views on YouTube than useful, medically accurate videos

Misinformation on gallstones drew more views on YouTube than useful, medically accurate videos

October 29, 2012

LAS VEGAS — YouTube videos advocating ineffective or potentially dangerous natural therapies for gallstone disease attracted more viewers than those providing useful information, according to data presented at the 2012 American College of Gastroenterology Annual Scientific Meeting.

Researchers screened 300 YouTube videos after a search for “gallstones,” of which 228 videos were considered relevant. The sources of each video were identified as a health agency (n=20.3%), an independent source (n=70%) and a medical advertisement (n=9.6%), and data on total views, video duration, upload date and content were collected.

Among the 228 relevant videos, investigators considered 121 useful (containing accurate and beneficial information) and 66 were labeled as misleading, with an additional 41 videos excluded for being shorter than 1 minute or not being spoken in English.

Investigators wrote that the misleading videos frequently discussed natural therapies such as yoga, cryptomonadales or barley or flush therapies, many of which have been disproven as ineffective or potentially harmful. Per-day viewership was significantly higher for misleading videos than for useful videos (18.2 views/day compared with 14 views/day; P=.03). Three videos classified as useful provided information refuting the benefits of the natural therapies, explaining why they were not effective or potentially dangerous.

Researcher Aakash Aggarwal, MBBS, a resident at State University of New York Upstate Medical University, told that many people who posted comments on the misleading videos indicated they were interested in alternative therapies because they did not want to undergo surgery for their conditions.

“Not only were they trying therapies that may be harmful, but they’re not going in for surgery, which can lead to other complications,” Aggarwal said. He suggested that health care agencies should consider developing official videos on medical topics to post to social media sites, in order to effectively disseminating useful and accurate information on medical conditions to the public. “Now that people are using those as sources of information, it’s very important for health care agencies to use these great resources to promote public awareness … and [develop] videos that are factually correct.”

For more information:
Aggarwal A. P677: YouTube as a Source of Information for Gallstone Disease. Presented at: the 2012 American College of Gastroenterology Annual Scientific Meeting; Oct. 19-24, Las Vegas.

Tuesday, October 23, 2012

Is it a Liver Tumor…or Spilled Gallstones?

Is it a Liver Tumor…or Spilled Gallstones?

Posted on October 22, 2012
by Kristine Novak, PhD, Science Editor

A man with an abnormal liver mass who was initially believed to have a hepatic tumor was found to have a subphrenic abscess that contained spilled gallstones, shown in a November Image of the Month article in Clinical Gastroenterology and Hepatology.

As described by Takuma Arai et al., a routine checkup with ultrasonography identified an abnormal liver mass in a 65-year-old man. He had no symptoms of cancer and normal results from blood tests. However, he had undergone laparoscopic cholecystectomy for gallstones 4 years earlier.

Computed tomography and magnetic resonance imaging analyses revealed an abnormal mass in the right lobe of his liver, in contact with the diaphragm. Three months later the size of the mass had increased slightly, so the doctors suspected a malignancy.

However, during partial resection of the liver and right diaphragm, they found a subphrenic abscess that contained spilled gallstones (see below figure).

Gallstones can spill during cholecystectomy and become lost. They are frequently found in the right hypochondrium and pelvis, and form abscesses that resemble hepatic tumors.

Arai et al. conclude that it is important to consider the possibility of gallstone retention during analyses of patients with abnormal masses in a subphrenic lesion who have undergone laparoscopic cholecystectomy.

Read the article online.
Araia T, Ikeno T, Miyamoto H. Spilled gallstones mimicking a liver tumor. Clin Gastroenterol Hepatol 2012;10:A32.

Sunday, October 16, 2011

Sunday Hepatitis News Ticker; ANA-598 Non-Nuke Phase 2b study preliminary data

New On The Blog

Anadys laid the foundation for the current Phase IIb clinical trial with prior clinical and preclinical work. In a Phase IIa combination trial in HCV patients, we reported data that showed that setrobuvir added to pegylated interferon and ribavirin accelerated the rate of viral clearance, with comparable response at setrobuvir doses of 200 mg bid and 400 mg bid. A single patient out of more than 60 exhibited viral breakthrough while receiving setrobuvir plus standard of care, corresponding to a low breakthrough rate of < 2%. Setrobuvir also showed an excellent safety profile in the study through the 12 weeks of dosing, with reported adverse events being typical for patients treated with interferon and ribavirin alone, although conclusions regarding safety cannot be made until results in more patients over longer duration are known.
See Full Data Here
Last updated at 6:22 PM on 16th October 2011
Up to 40 per cent of all cancers including brain tumors, cancer of the skin and prostate and leukaemia may be caused by viral infections, according to scientists. If proved, the information could lead to a preventative vaccine and therapies to cure many forms of the disease. While it was already known that some viruses can lead to cancers, the research study suggests that many more viruses are responsible for the condition.

Scientists had discovered hepatitis B and C viruses can cause liver cancer and human papilloma virus (HPV) which can cause cervical cancer. But the new research study using DNA analysis has shown that viruses could be implicated as the cause in 40 per cent of the 200 forms of cancer. German virologist Harold Zur Hausen, who jointly discovered the link between cervical cancer and HPV, said in the paper the discovery could be ground-breaking.
He said: 'Although we know that currently slightly more than 20 per cent of the global cancer incidence is linked to infectious events, some epidemiological observations suggest that this this percentage may increase'. He also said that virus could be involved in skin, breast, guts and lung cancer. An important result of the study was the discovery that an aggressive form of skin cancer, Merkel cell carcinoma, often follows infection by polyomavirus. The virus, which is common in birds and mammals may also be the cause of other types of skin cancer.

Researchers also found that anti-viral therapies slowed down the growth of brain tumours in animals by up to 70 per cent - suggesting evidence of viral involvement in the disease. The discovery is welcomed by sufferers of childhood brain tumours thought to be caused by medulloblastoma, Kerry Edwards was a gymnast tipped to have a promising career before being struck down with the disease. The operation to remove the tumor affected her balance and she still struggles to walk. She told the Sunday Times: 'Anything that can save people from what I have endured has to be a good thing.' It is unknown why viruses cause infection as in most cases they invade a cell before altering it to produce more viruses - ultimately killing it.

However in cancer-causing viruses, it is thought, yet unproven, that they remain hidden in the cells for years, before subverting their hosts so that they cannot repair mutations. Professor Luiz Gissmann a senior scientist at the German Cancer Research Centre told the newspaper: 'Over the years such mutations can build up to the point where cells turn cancerous.' The discovery could be life-changing with the possibilities of vaccinations against the key viruses, cutting the number of cancer sufferers - however the cost of development and trials will be enormous. In Britain 310,000 people are diagnosed with the disease every year, of which 156,000 will die
Alan Rickinson, professor of cancer studies in Birmingham is overseeing trials of a vaccine against the Epstein-Barr virus, identified as causing a rare blood cancer. He said: 'If we can understand how these viruses work we could prevent people from contracting them and even create therapies that use the patient's own immune system to destroy infected or cancerous cells.'

Zania Stamataki1,2*, Samantha Tilakaratne1, David H. Adams1,2, Jane A. McKeating1
1 Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom, 2 National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom

Abstract Only Full Data Available Here
Hepatitis C virus (HCV) infected patients with vasculitis are often treated with the B-cell-depleting anti-CD20 antibody rituximab. Treatment reduces the cryoglobulins that cause vasculitis, yet it also leads to a transient increase in liver enzymes and HCV genomic RNA in the periphery. The mechanism underlying the increased viral load is unclear and both direct and indirect roles have been proposed for B cells in HCV infection. We previously reported that HCV can associate with B cells and can trans-infect hepatocytes. We established an in vitro assay to study the effect(s) of rituximab on B cell-associated HCV infectivity. Rituximab-mediated lysis of B cells in vitro increases the level of infectious HCV released from B cells. Our results, using a model where virus does not replicate in B cells, recapitulate observations seen in patients and may explain in part the rapid increase in blood HCV RNA observed after rituximab treatment.

Noëlla Arnaud1, Stéphanie Dabo1, Daisuke Akazawa2, Masayoshi Fukasawa3, Fumiko Shinkai-Ouchi3, Jacques Hugon4, Takaji Wakita2, Eliane F. Meurs1*
1 Institut Pasteur, Hepacivirus and Innate Immunity, Paris, France, 2 National Institute of Infectious Diseases, Department of Virology II, Tokyo, Japan, 3 National Institute of Infectious Diseases, Department of Biochemistry and Cell Biology, Tokyo, Japan, 4 Institut du Fer à Moulin, INSERM UMRS 839, Paris, France

Abstract Only Full Text Available Here
Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-κB-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response.

Thousands possibly exposed to infection at Ottawa clinicFull story: CTV
Letters will be sent to nearly 7,000 people after a three-month investigation into the possible exposure of HIV, Hepatitis B and Hepatitis C at a non-hospital Ottawa clinic.

By Genevra PittmanNEW YORK Fri Oct 14, 2011 4:24pm EDT
NEW YORK (Reuters Health) - People who have had a kidney stone seem to have a heightened risk of gallstones -- and vice versa, according to a new study.
Researchers already know that obesity, diabetes and having a generally unhealthy diet put people at risk for both types of stones. But even when those common risks were taken into account, the link remained.

The report "raises our antenna to this shared relationship between these two disorders," said Dr. Brian Matlaga, a urologist at the Johns Hopkins University School of Medicine in Baltimore."From an anecdotal standpoint, certainly it's not an uncommon scenario that a patient would have had both," Matlaga, who wasn't involved in the new research, told Reuters Health. But, he continued, "I'm a little bit at a loss trying to define what that relationship would be."That's because stones in the kidney and gallbladder form differently, he said, and are made of two different things -- kidney stones of calcium and gallstones of cholesterol, most of the time.Data for the current analysis came from three different long-term studies of nurses and doctors who completed a health and lifestyle questionnaire, then reported any new medical conditions every two years afterward. In total, more than 240,000 people were followed for between 14 and 24 years.
Over that time, there were about 5,100 new kidney stones diagnosed and close to 18,500 new cases of gallstones.

Depending on the population -- male or female, older or younger -- people with a history of gallstones were between 26 and 32 percent more likely to get a kidney stone than people who hadn't ever had gallstones.

And the link also went in the opposite direction. A past history of kidney stones meant study participants were between 17 and 51 percent more likely to report a new gallstone.That was after factoring in the impact of age, diabetes, high blood pressure, weight and certain aspects of diet on the risk of both kinds of stones.

Researchers led by Eric Taylor from the Maine Medical Center in Portland said it's possible that a shift in the type of bacteria in the intestines might somehow predispose people to both kidney stones and gallstones. But, Taylor said, "the fairest thing is that we just don't know" why the two would be linked.

In their report in the Journal of Urology the researchers echoed Matlaga's call for more detailed research into any explanations for a common cause -- which might help doctors prevent or treat both kidney stones and gallstones, they added.
"They are really two different kinds of stones, so the relationship is not going to be simple between the two conditions," Taylor told Reuters Health.Matlaga said that for now, there are steps people can take to reduce their risk of both gallstones and kidney stones, even if they've already had one condition."You'd like to try to minimize those common risk factors and work on things like weight loss and cholesterol control," he said.Taylor agreed that the findings "emphasize the importance of healthy diet and healthy weight."
SOURCE: Journal of Urology, online September 23, 2011.

Wash your hands before dinner; rinse your vegetables; keep the milk refrigerated–all important habits to keep yourself healthy. But what about the things you can’t control—and usually don’t even consider? What happens when the regulators you assume are inspecting your food aren’t doing their job?

The Food and Drug Administration (FDA) oversees much of the U.S. food system, but according to recent reports by the Government Accountability Office (GAO) and an investigation by News21, the FDA is failing to keep U.S. food safe.
The U.S. only inspects 2 percent of all imported food, according to News21. Of particular risk to Americans is imported seafood because 80 percent of seafood consumed in the U.S. is imported, according to a GAO study.

The tilapia at Whole Foods may look pristine in those giant beds of ice, and bouncing shrimp in fast food commercials might make your mouth water, but chances are they came from an overseas farm or facility far outside the eyes of the FDA.

Of the 13,459 foreign seafood facilities that export seafood to the U.S., only 128 were inspected by the FDA in 2010, according to a GAO report. And 2010 was the best year mentioned in the report. Only 503 facilities in total have been inspected since 2005.

The U.S. has stricter rules about what chemicals and antibiotics can be used to grow fish in factory farms than many other countries, specifically China and countries in Southeast Asia, which are the main seafood exporters to the U.S. The FDA doesn’t have the manpower to inspect all of the seafood imported to the U.S., and has been criticized by the GAO for not putting more emphasis on testing for these drugs.

Brett C. Hall, the deputy commissioner for the Alabama Department of Agriculture and Industries, told News21, “In Vietnam and other foreign countries, there are extreme limitations regarding a desirable water supply.” He added, “In order to grow fish in contaminated water, they would use antibiotics to keep the fish alive.”

Even if you are a proud buyer of good ol’ American seafood, that doesn’t mean you are out of the seaweed. The FDA is failing to address raw Gulf Coast oysters with a potentially deadly, according to the GAO.

The bacteria, Vibrio vulnificus (V. vulnificus), only causes 32 illnesses a year, but half of those people die from their illness. The V. vulnificus bacteria is “the most common cause of death from seafood consumption in the United States,” according to the GAO report.
The bacteria only come from raw oysters, and can be greatly reduced through a variety of post-harvest procedures. The problem is thatthe FDA and the Interstate Shellfish Sanitation Conference (ISSC), a voluntary organization of 22 state officials who promote shellfish safety policies, are at odds over the best way to keep consumers safe.
The GAO concluded that without FDA and ISSC collaboration, “it is unlikely that the states’ efforts to significantly reduce the number of consumption-related V. vulnificus illnesses will be effective.”

It’s just one example of the disconnect often found between federal and state officials when it comes to enforcing food safety rules.

But if you think the lack of inspections of imported food and the poor coordination between state and federal regulators was enough to worry about, there’s also the fact that our farmers are under growing pressure to increase profit margins, often at the expense of safety.
It’s enough to make you swear off seafood. But the better alternative might be to become a more educated consumer.

Check out the FDA’s tips on buying and preparing seafood and Food and Water Watch’s Smart Seafood Guide.

Ultimately, the News21 investigation found the solutions are far from simple:
Food safety advocates like Food & Water Watch say consumers are better off avoiding imported seafood altogether and sticking to locally raised fish or fish caught in the wild.
But Lorenzo Juarez of the National Oceanic and Atmospheric Administration’s Aquaculture Program said that’s not practical.

“There is no more fish from the wild,” he said, and a better approach would be to encourage more domestic aquaculture, which is subject to U.S. standards.
Corrigan’s Food & Water Watch says that’s not good enough.
“We need to find a way to protect people in the United States from seafood and that means more inspections on what’s coming in from our borders,” he said.
Andre Francisco is a POGO Communications Associate.
Cirrhosis is scarring of the liver.

Widespread nodules in the liver combined with fibrosis characterize cirrhosis anatomically. The fibrosis and nodule formation causes distortion of the normal liver architecture, which interferes with blood flow through the liver. Cirrhosis can also lead to an inability of the liver to perform its biochemical functions. To understand the pathophysiology of cirrhosis, the normal anatomy and physiology of the liver must first be briefly reviewed.

Liver Blood Flow
Oxygenated blood that has returned from the lungs to the left ventricle of the heart is pumped to all of the tissues of the body. This is called the systemic circulation.

After reaching the tissues, blood is returned to the right side of the heart, from where it is pumped to the lungs and then returned to the left side of the heart after taking up oxygen and giving off carbon dioxide. This is called the pulmonary circulation.

Systemic and Pulmonary Circulation

Portal Circulation
Blood from the large and small intestines and spleen flow to and through the liver before returning to the right side of the heart. This is called the portal circulation and the large vein through which blood is brought to the liver is called the portal vein. After passing through the liver, blood flows into the hepatic vein, which leads into the inferior vena cava to the right side of the heart. The liver also receives some blood directly from the heart via the hepatic artery. In the esophagus, stomach, small intestine and rectum, the portal circulation and veins of the systemic circulation are connected. Under normal conditions, there is little to no back flow from the portal circulation into the systemic circulation.

Bilirubin Secretion
The liver is the site of bile formation. Bile contains bile salts, fatty acids, cholesterol, bilirubin and other compounds. The components of bile are synthesized and modified in hepatocytes (the predominant cell type in the liver) and secreted into small bile ducts within the liver itself. These small bile ducts form a branching network of progressively larger ducts that ultimately become the common bile duct that takes bile to the small intestine. Bilirubin is a yellow pigment that derives primarily from old red blood cells. Bilirubin is taken up by hepatocytes from the blood, modified in the hepatocytes to a water-soluble form and secreted into the bile.

1. Bile ducts: 2. Intrahepatic bile ducts, 3. Left and right hepatic ducts, 4. Common hepatic duct, 5. Cystic duct, 6. Common bile duct, 7. Ampulla of Vater, 8. Major duodenal papilla
9. Gallbladder, 10-11. Right and left lobes of liver. 12. Spleen.
13. Esophagus. 14. Stomach.
Small intestine: 15. Duodenum, 16. Jejunum 17. Pancreas: 18: Accessory pancreatic duct, 19: Pancreatic duct. 20-21: Right and left kidneys (silhouette). The anterior border of the liver is lifted upwards (brown arrow). Gallbladder with Longitudinal section, pancreas and duodenum with frontal one. Intrahepatic ducts and stomach in transparency.

Biochemical Functions
The liver performs many biochemical functions-over 200 in all. Blood clotting factors are synthesized in the liver. Albumin, the major protein in the blood, is also synthesized in and secreted from the liver. The modification and/or synthesis of bile components also take place in the liver. Many of the body's metabolic functions occur primarily in the liver including the metabolism of cholesterol and the conversion of proteins and fats into glucose. The liver is also where most drugs and toxins, including alcohol, are metabolized.

What Goes Wrong in the Liver with Cirrhosis?
Cirrhosis results from damage to liver cells from toxins, inflammation, metabolic derangements and other causes. Damaged and dead liver cells are replaced by fibrous tissue, which leads to fibrosis (scarring). Liver cells regenerate in an abnormal pattern primarily forming nodules that are surrounded by fibrous tissue. Grossly abnormal liver architecture eventually ensues that can lead to decreased blood flow to and through the liver.

Decreased blood flow to the liver and blood back up in the portal vein and portal circulation leads to some of the serious complications of cirrhosis. Blood can back up in the spleen causing it to enlarge and sequester blood cells. Most often, the platelet count falls because of splenic sequestration. The low platelet count seen in cirrhosis is due to trapping in the spleen, not due to a primary problem with production in the bone marrow. If the pressure in the portal circulation increases because of cirrhosis and blood back up (note: this can also sometimes occur in severe cases of acute hepatitis and liver damage), blood can flow backwards from the portal circulation to the systemic circulation where they are connected. This can lead to varicose veins in the stomach and esophagus (gastric and esophageal varices) and rectum hemorrhoids or rectal varicies). Gastric and esophageal varices can rupture, bleed massively and even cause death. Hypertension in the portal circulation, along with other hormonal, metabolic and kidney abnormalities in cirrhosis, can also lead to fluid accumulation the abdomen (ascites) and the peripheral tissue (peripheral edema).

Decreased bilirubin secretion from hepatocytes in cirrhosis leads to the back up of bilirubin in the blood. This leads to jaundice, the yellow discoloration of the skin and eyes. As the water-soluble form of bilirubin also backs up in the blood, bilirubin can also spill into the urine giving it a bright yellow to dark brown color.

Abnormal biochemical function of the liver in cirrhosis can lead to several complications. The serum albumin concentration falls, which can lead to aggravation of ascites and edema. The metabolism of drugs can change requiring dose adjustments. In men, breast enlargement (gynecomastia) sometimes occurs because metabolism of estrogen in the liver is decreased. Sexual function in men will also become abnormal. Decreased production of blood clotting factors can lead to bleeding complications. Derangements in the metabolism of triglycerides, cholesterol and sugar can occur. In earlier stages, cirrhosis frequently can cause insulin resistance and diabetes mellitus. In later stages or in severe liver failure, blood glucose may be low because it cannot be synthesized from fats or proteins. Cirrhosis, especially in advanced cases, can cause profound abnormalities in the brain. In cirrhosis, some blood leaving the gut bypasses the liver as blood flow through the liver is decreased. Metabolism of components absorbed in the gut can also be decreased as liver cell function deteriorates. Both of these derangements can lead to hepatic encephalopathy as toxic metabolites, normally removed from the blood by the liver, can reach the brain. In its early stages, subtle mental changes such as poor concentration or the inability to construct simple objects occurs. In severe cases, hepatic encephalopathy can lead to stupor, coma, brain swelling and death.
Cirrhosis of the liver can also cause abnormalities in other organ systems. Cirrhosis can lead to immune system dysfunction causing an increased risk of infection. Ascites fluid in the abdomen often becomes infected with bacteria normally present in the gut (spontaneous bacterial peritonitis). Cirrhosis can also lead to kidney dysfunction and failure. In end-stage cirrhosis, a type of kidney dysfunction called hepatorenal syndrome can occur. Hepatorenal syndrome is almost always fatal unless liver transplantation is performed.

Clinical Symptoms and Diagnosis of Cirrhosis
Cirrhosis is usually an easy diagnosis to make when any or all of the above abnormalities and complications are present. This is especially true when the underlying liver disease can be identified. The underlying liver disease is identified in most patients, however, sometimes it will not be discovered. Such cases are called "cryptogenic" cirrhosis. Sometimes, other conditions such as metastatic cancer, hepatic or portal vein thrombosis, severe acute hepatitis or acute bile duct obstruction can cause some of the abnormalities seen in cirrhosis. A careful history combined with special diagnostic tests will usually identify these conditions. I rare cases, despite having cirrhosis of the liver, patients may still have very few, vague complaints. Some patients, especially early in the course of the disease, will have no overt clinical signs or symptoms. Some may have only subtle physical changes such as red palms, red spots that blanch on their upper body (spider angiomata), enlargement of the parotid glands in the face, gynecomastia, or fibrosis of tendons in the palms. Some patients may only have subtle abnormalities on blood tests, and in some cases, all blood tests may be normal. Radiological tests may give clues as to the presence of cirrhosis, but the diagnosis of cirrhosis must often be made by liver biopsy.

Causes of Cirrhosis
There is a general misunderstanding that alcohol is the sole cause of cirrhosis. Alcohol accounts for approximately 50% of the cases of cirrhosis. Almost any chronic liver disease can lead to cirrhosis. This list gives some of the many causes:
  • Alcoholic liver disease - most common cause in the U. S. A.

  • Chronic viral hepatitis B, C and D

  • Chronic autoimmune hepatitis

  • Inherited metabolic diseases (e. g. hemochromatosis, Wilson disease)

  • Chronic bile duct diseases (e. g. primary biliary cirrhosis)

  • Chronic congestive heart failure

  • Parasitic infections (e. g. schistosomiasis)

  • Nonalcoholic steatohepatitis (liver inflammation that can be caused by fatty liver)

  • Long term exposure to toxins or drugs

Cirrhosis of the liver is irreversible but treatment of the underlying liver disease may slow or stop the progression. Such treatment depends upon the underlying etiology. Termination of alcohol intake will stop the progression in alcoholic cirrhosis and for this reason, it is important to make the diagnosis early in a chronic alcohol abuser. Similarly, discontinuation of a hepatotoxic drug or removal of an environmental toxin will stop progression. Treatments of metabolic diseases, such as treatment of iron overload in hemochromatosis or copper overload in Wilson disease, are also effective therapies.
Chronic viral hepatitis B and C may respond to treatment with interferon or recently approved (Boceprevir and telaprevir, 2 NS3 protease inhibitors for the treatment of hepatitis C), and autoimmune hepatitis may improve with prednisone and azathioprine (Imuran). Drugs such as ursodiol (Actigall) may slow the progression of primary biliary cirrhosis and possibly sclerosing cholangitis.

In patients with cirrhosis of the liver, treatment must also be directed at the complications. Bleeding esophageal varices can be treated with endoscopic sclerotherapy or rubber band ligation (banding). Ascites and edema are often responsive to a low sodium diet and such a diet must be emphasized in patients with these symptoms. More advanced ascites and edema can respond to diuretic therapy. A low protein diet and agents such as lactulose may help hepatic encephalopathy. Infections such as spontaneous bacterial peritonitis must be rapidly treated with appropriate antibiotics. Drugs metabolized in the liver must be given with caution. Coagulation/clotting disorders will sometimes respond to vitamin K.

Liver transplantation is an effective for the treatment of end-stage cirrhosis in the proper setting. Transplantation is usually needed when complications such as encephalopathy, ascites or bleeding varices are uncontrollable or when biochemical function is severely depressed. In patients with primary biliary cirrhosis, a rising bilirubin indicates a poor prognosis and such patients should be considered for transplantation as the serum bilirubin concentration begins to rise. Active drug or alcohol abuses are contraindications to liver transplantation. However, alcoholics who have abstained from drinking for an extended period of time (usually more than six months), and have participated in rehabilitation programs and support groups such as Alcoholics Anonymous, can be considered as candidates and will often have a good prognosis. Liver cancer needs to be evaluated on a case-by-case basis. In many cases, it is a contraindication to transplantation. Liver transplantation is usually not performed in patients more than 70 years old.

How are complications of cirrhosis treated?
The abnormal accumulation of fluid may cause swelling of the ankles (edema) and abdomen (ascites). Therefore, patients should reduce the amount of fluid and salt in their diet or use drugs call diuretics that mobilize and excrete the excess fluid through the kidneys. Usually, you’ll be instructed to limit you daily sodium (salt) intake to 2,000 mg of sodium/day or less.
Occasionally, the ascites may become infected, a condition known as Spontaneous Bacterial Peritonitis, and require treatment with antibiotics. This complication is associated with increased complications, and an increased risk of premature death. Liver transplantation needs to be considered at this time should peritonitis develop.When the liver does not efficiently function to cleanse the body of toxins and drugs, the mental state of patients may change dramatically and lead to coma, called Hepatic Encephalopathy. Treatment is directed at reducing the protein in the diet, avoiding sedatives and pain medications, and using laxatives and/or antibiotics to decrease absorption of toxins from the intestines.

Sometimes, bleeding from the esophagus or stomach caused by abnormal veins (varices) may occur and is a life-threatening emergency requiring hospitalization. Variceal bleeding can usually be controlled with the use of a flexible tube (endoscope) that is inserted through the mouth into the esophagus and stomach and used to inject clotting agents into the veins or to rubber band ligate the varices.

Liver failure refers to end stage of liver disease and cirrhosis when the liver stops working and cannot support life. Liver failure is difficult to treat and survival is limited. Therefore, patients with any complication of cirrhosis are considered to be at risk of developing liver failure.
When complications develop, it may be possible to manage them, though more complications are likely to develop. At this time, liver transplantation should be considered

Sunday, May 8, 2011

DDW: Diet affects gastrointestinal illnesses, such as gallstones and celiac disease

Digestive Disease Week

Dietary research offers new explanations and treatments approaches for gastrointestinal disorders

Health outcomes explored at DDW 2011

CHICAGO, IL (May 8, 2011) — Research being presented at Digestive Disease Week® (DDW) offers further evidence that diet affects gastrointestinal illnesses, such as gallstones and celiac disease, and that some patients who think their digestive problems are caused by lactose intolerance are actually reacting to a psychological disorder. DDW is the largest international gathering of physicians and researchers in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"New research is providing critically important, evidence-based results on the effect of diet on gastrointestinal disorders, and this is changing the way we detect and treat a number of digestive diseases," said Mark DeLegge, MD, AGAF, professor of medicine at Medical University of South Carolina. "It is important that patients understand what they eat has an effect on the way their digestive system works and that diet plays an important part in maintaining good health."

Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy (Abstract #322)
High consumption of carbohydrates, starches and fructose increases the risk of developing gallstones during pregnancy, according to a new study from the University of Washington (UW). Pregnant women are frequently diagnosed with gallstones, and gallstone-related diseases are the most common non-obstetric cause of hospitalization in the first year after a woman gives birth. With other studies in men and non-pregnant women tying high carbohydrate intake to gallbladder problems, the UW researchers focused on dietary risk factors for the development of gallstones during pregnancy and the incidence of consequent illnesses and surgeries.

Dr. Ko will present these data on Sunday, May 8, at 8:45 a.m. CT in S401D, McCormick Place.

Do symptoms of lactose intolerance reveal a somatoform disorder? (Abstract #493)
Patients may mistakenly think their digestive problems are caused by lactose intolerance, when actually their problems may be attributed to a somatoform disorder, a psychological disorder characterized by symptoms that mimic physical disease, but for which there is no identifiable physical cause, according to new. These results suggest that symptoms of lactose intolerance could reveal a somatoform disorder and that counterproductive behaviour such as diets excluding milk products should be discouraged as they can contribute to osteoporosis and other calcium deficiencies.
Dr. Basilisco will present these data on Sunday, May 8 at 2:15 p.m. CT in E351, McCormick Place.

Should screen-detected and asymptomatic celiac patients be treated? A prospective and randomized trial (Abstract #620)
A recent study analyzed the benefits of serological screening and maintaining a gluten-free diet in asymptomatic celiac patients. The study results showed that although patients were apparently asymptomatic, they in fact suffered from subclinical gastrointestinal symptoms and lower health-related quality of life when on a regular gluten-containing diet. In contrast, patients on a gluten-free diet saw significant improvements in these parameters and felt that the treatment was valuable and beneficial.
Dr. Kaukinen will present these data on Monday, May 9 at 8:00 a.m. and Tuesday, May 10 at 2:00 p.m. CT in S406B, McCormick Place.

Digestive Disease Week® 2011 (DDW®) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the AGA Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 7 – May 10, 2011 in Chicago, IL. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.