Caffeinated drinks associated with decreased risk of liver scarring

Provided by Baylor School of Medicine

Julia Parsons
713-798-4710 Houston, TX - Apr 14, 2015

Modest daily consumption of caffeinated drinks is associated with less advanced liver scarring in people with hepatitis C, according to a recent study by Baylor College of Medicine researchers that appears online in the journal Clinical Gastroenterology and HepatologyClinical Gastroenterology and Hepatology.

Dr. Hashem El-Serag, chief of gastroenterology and hepatology at Baylor and at the Michael E. DeBakey Veterans Affairs Medical Center and lead author of the study, said the results showed that the risk of liver scarring in hepatitis C patients was decreased when individuals regularly consumed caffeinated coffee, and to a lesser extent tea and soda.

“We found that participants who drank caffeinated coffee daily had the best results,” he said. “This is most likely do to the fact that one coffee drink has more caffeine than tea or sodas.”

He said the researchers saw no benefit to patients who drank decaffeinated coffee, tea and soda.

This cross-sectional study consisted of 910 participants aged 18 to 70 years of age with confirmed hepatitis C who were not receiving antiviral therapy.

“We specifically chose to study hepatitis C patients because they are at an increased risk for hepatic fibrosis (liver scarring), and there is limited data on the effects of coffee or caffeine on the progression of scarring within this patient population,” said El-Serag, also a member of the Dan L. Duncan Cancer Center at Baylor.

Liver scarring can lead to cirrhosis of the liver, liver failure and liver cancer, and may require liver transplantation.

Of the participant study population, 37.6 percent of them had advanced liver scarring while 62.4 percent had milder scarring. Participants with advanced fibrosis were significantly older, more likely to have type 2 diabetes and were more likely to be overweight or obese.

“Most participants reported drinking caffeinated coffee, and about half of those drank one or more cups of coffee per day,” El-Serag said. “Patients with milder liver scarring had a higher average daily intake of caffeinated coffee compared to those with more advanced cases.”

“An estimated 100 milligrams of caffeine from coffee, tea or soda was associated with approximately one-third reduction of advanced scarring, and higher consumption didn’t produce an additional benefit,” he said.

Others who took part in this study include Natalia Khalaf, Donna White, Fasiha Kanwal, David Ramsey, Sahil Mittal, Shahriar Tavakoli-Tabasi and Jill Kuzniarek, all of Baylor.

This research was funded in part by a VA Clinical Research and Development Merit Award (H-22934, PI: El-Serag) and the National Institute of Diabetes Digestive and Kidney Diseases (R03 DK095082, PI:  White).  The efforts of White and El-Serag effort were supported in part by the National Institute of Diabetes Digestive and Kidney Diseases (K24 DK04-107 and K01 DK081736, respectively) and the Houston VA Health Services Research and Development Center of Excellence (HFP90-020).

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Effect of caffeine-containing beverage consumption on serum alanine aminotransferase levels in patients with chronic hepatitis C virus infection: a hospital-based cohort study

PLoS One. 2013 Dec 11;8(12):e83382. doi: 10.1371/journal.pone.0083382.

Sasaki Y¹, Ohfuji S², Fukushima W², Tamori A³, Enomoto M³, Habu D⁴, Iwai S³, Uchida-Kobayashi S³, Fujii H³, Shiomi S⁵, Kawada N³, Hirota Y².

Abstract

INTRODUCTION: To date, there have been no prospective studies examining the effect of coffee consumption on serum alanine aminotransferase (ALT) level among individuals infected with the hepatitis C virus (HCV). We conducted a hospital-based cohort study among patients with chronic HCV infection to assess an association between baseline coffee consumption and subsequent ALT levels for 12 months.

MATERIALS AND METHODS: From 1 August 2005 to 31 July 2006, total 376 HCV-RNA positive patients were recruited. A baseline questionnaire elicited information on the frequency of coffee consumption and other caffeine-containing beverages. ALT level as a study outcome was followed through the patients' medical records during 12 months. The association between baseline beverage consumption and subsequent ALT levels was evaluated separately among patients with baseline ALT levels within normal range (≤45 IU/L) and among those with higher ALT levels (>45 IU/L).

RESULTS: Among 229 patients with baseline ALT levels within normal range, 186 (81%) retained normal ALT levels at 12 months after recruitment. Daily drinkers of filtered coffee were three times more likely to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However, decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147 patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of ≥20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in decaffeinated coffee drinkers, OR could not be calculated because no patients had ALT reduction.

CONCLUSION: Among patients with chronic HCV infection, daily consumption of filtered coffee may have a beneficial effect on the stabilization of ALT levels.

PMID: 24349501 [PubMed - in process]

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Coffee consumption affects cancer risk differently for liver vs. pancreatic cancers

11/01.13

By: TARA HAELLE, IMNG Medical News

^{Lynda Banzi/IMNG Medical Media}

According to two recent studies, consuming coffee of any kind may reduce the risk of the most common liver cancer by as much as 50 percent.

Drinking tea or caffeinated or decaf coffee is unlikely to influence a person’s risk for pancreatic cancer, but consuming coffee of any kind may reduce the risk of the most common liver cancer by as much as 50% (depending on amount consumed), according to two recent studies in Clinical Gastroenterology and Hepatology.

In the pancreatic cancer study, Dr. Nirmala Bhoo-Pathy of University Medical Center Utrecht, the Netherlands, and her colleagues reported, "Our results strengthen the conclusion made by the World Cancer Research Fund and the American Institute of Cancer Research that there is little evidence to support a causal relation between coffee and risk of pancreatic cancer (Clin. Gastroenterol. Hepatol. 2013 [doi:10.1016/j.cgh.2013.05.029]).

Meanwhile, a 16-study meta-analysis of coffee intake and risk for hepatocellular carcinoma, which accounts for more than 90% of worldwide liver cancers, revealed a 40% decreased risk (relative risk, 0.60; 95% confidence interval: 0.50-0.71) for any coffee consumption vs. no consumption. Yet Dr. Francesca Bravi of Università degli Studi di Milano and her colleagues reported that their findings could not establish a causal relationship between coffee drinking and hepatocellular carcinoma (Clin. Gastroenterol. Hepatol. 2013 [doi:10.1016/j.cgh.2013.04.039]).

Even such a causal relationship may have limited clinical significance, however, considering that more than 90% of primary liver cancers worldwide can theoretically be prevented through hepatitis B vaccination, control of hepatitis C transmission, and reduction of alcohol consumption, Dr. Bravi’s team wrote.

In the first study, Dr. Bhoo-Pathy’s investigation involved inspection of 865 first incidences of pancreatic cancers reported in a cohort of 477,312 men and women from 10 European countries tracked prospectively over a mean 11.6 years of follow-up. The participants in the EPIC (European Prospective Investigation Into Nutrition and Cancer) cohort completed a dietary questionnaire at baseline in 1992, then calibrated with a 24-hour dietary recall by the final follow-up in 2000.

The 23 participating centers were in Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom, and median coffee intake across these ranged from 92 mL/day in Italy to 900 mL/day in Denmark. Among the participants with all information on coffee type intake (n = 269,593), half drank only caffeinated coffee (50%), 4% drank only decaf, a third (34%) drank both, and 12% drank no coffee. Two-thirds (66%) of the total cohort drank tea of any kind (caffeinated, green, or herbal).

Neither total intake of coffee (hazard ratio, 1.03; 95% CI: 0.83-1.27 for high vs. low intake) nor consumption of decaffeinated coffee (HR, 1.12; 95% CI: 0.76-1.63) – reported as cups drunk per day, week, or month and then converted to daily milliliters – showed a significant change in pancreatic cancer risk. Tea consumption of any kind similarly had no impact on risk (HR, 1.22; 95% CI: 0.95-1.56). These risks did not change after accounting for a range of confounders nor when analysis was confined to the 608 (70.3%) cancers that were microscopically confirmed.

Confounders included sex, clinic/center, age at diagnosis, height, weight, physical activity, smoking status, diabetes history, education level, and energy intake, including red meat, processed meat, alcohol, soft drink, tea (for coffee analysis), coffee (for tea analysis), and fruit and vegetable intake.

A comparison of moderately low and low caffeinated coffee intake initially revealed a modest increased risk for moderately low consumption (HR, 1.33; 95% CI: 1.02-1.74) that dropped below statistical significance when only microscopically confirmed pancreatic cancer cases were analyzed. Additionally, no dose-response effect was noted among any of the findings for pancreatic cancer risk.

Yet a dose-response effect was seen in Dr. Bravi’s study investigating coffee consumption and hepatocellular carcinoma risk. Her team’s update of a 2007 meta-analysis included an additional four cohort and two case-control studies, for a total of eight cohort and eight case-control studies from 14 English-language articles included in PubMed/MEDLINE between 1966 and September 2012.

When broken down by study type, the 40% overall risk reduction for any coffee consumption found among 3,153 hepatocellular carcinoma cases split into a 44% reduction in the case-control studies (RR, 0.56; 95% CI: 0.42-0.75) and a 36% reduction in the cohort studies (RR, 0.64; 95% CI: 0.52-0.78).

The dose-response relationship was seen in separate comparisons of low and high coffee consumption with no coffee consumption, using three cups a day as the cutoff in nine papers and one cup a day in five papers. Low coffee consumption reduced hepatocellular carcinoma risk by 28% (RR, 0.72; 95% CI: 0.61-0.84) while high consumption reduced it by 56% (RR, 0.44; 95% CI: 0.77-0.84).

Each additional cup of coffee per day resulted in a 20% risk reduction (RR, 0.80; 95% CI: 0.77-0.84). This split into a 23% risk reduction in the case-control studies (RR, 0.77; 95% CI: 0.71-0.83) and a 17% risk reduction in the cohort studies (RR, 0.83; 95% CI: 0.78-0.88). A temporal analysis of risk reduction for any coffee consumption showed an increase from 20% risk reduction in 2000 (RR, 0.8; 95% CI: 0.50-1.29) to 41% in 2007 (RR, 0.59; 95% CI: 0.48-0.72), which has remained stable at about 40% the past several years.

Accounting for the most [significant] risk factors for liver cancer had little effect on the risk ratios. These factors included hepatitis B and C infections, cirrhosis, and other liver diseases, socioeconomic status, alcohol consumption, and smoking.

Dr. Bravi’s team suggested that the risk reduction effect could be a real, causal effect arising from antioxidants and other minerals in coffee that may inhibit liver carcinogenesis or from the inverse association between coffee and cirrhosis or coffee and diabetes, both conditions known risk factors for liver cancer. Or, the effect could result, at least in part, from reduced consumption of coffee among patients with cirrhosis or other liver disease.

"Thus, a reduction of coffee consumption in unhealthy subjects cannot be ruled out, although the inverse relation between coffee and liver cancer also was present in subjects with no history of hepatitis/liver disease," the researchers wrote. Yet, they also noted the potentially limited utility of coffee risk reduction given the greater impact on reducing liver cancer risk from hepatitis B vaccination, prevention of hepatitis C, and reduction of alcoholic drinking.

The pancreatic cancer study was funded by the European Commission and the International Agency for Research on Cancer, with a long list of additional societies, foundations, and educational institutions supporting the individual national cohorts. The hepatocellular carcinoma study was funded by a grant from the Associazione Italiana per la Ricerca sul Cancro. The authors in both studies reported no disclosures.

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Coffee May Offer Real Benefits to the Liver

Provided by Clinical Care options

Mark S. Sulkowski, MD - 8/13/2013 More from this author

Mixed Realities of Alternative Therapies for Hepatitis
Approximately 50% of patients who have failed initial therapy for hepatitis C take some form of alternative or complementary therapy. In my practice, I’m frequently asked by these and other patients: “What can I do to help my liver?” Most have heard of, have taken, or are taking milk thistle, licorice root, ginseng, schisandra, and/or thymus extract—with milk thistle being the most common. Not all alternative therapies are created equal and there are few randomized controlled trials to guide clinicians seeking answers. For instance, the active ingredient in milk thistle, silymarin, has been evaluated and generally found to provide little or no clinical benefit to the liver. In fact, a recent study found that even at higher-than-usual doses, silymarin failed to reduce HCV RNA or ALT levels more than placebo.

There is, however, a growing body of research supporting a beverage I’d wager a majority of you have enjoyed today: coffee.

The Coffee Alternative
Curiously, patients who will spend up to $30 a day or more for milk thistle and its extracts or ingest unproven therapies of varying quality are skeptical about the idea that drinking coffee can actually be good for you. Real and perceived cardiovascular and other effects of coffee have led many patients to view coffee as “unhealthy.” But the reality is that coffee consumption has been linked to a number of potential benefits – lower risk of diabetes, dementia and, yes, liver disease. Coffee contains more than 1000 compounds; one or more of which is responsible for the benefit that has been linked to coffee intake on liver disease in patients with alcoholic and viral hepatitis. Benefits include decreases in markers of liver disease progression and reductions in the risk for fibrosis and hepatocellular carcinoma.

Epidemiologic studies have suggested that there is a cause and effect associated with coffee intake and its benefits on the liver. These findings are supported by the few randomized controlled trials available. In one study comparing patients infected with hepatitis C, those who drank 3 cups of coffee per day or more received the greatest benefit. In order to maximize the effects of the coffee some (but not all) studies suggest that caffeinated coffee may be better for the liver than decaffeinated coffee. However, it seems that caffeine itself does not appear to have a beneficial effect.

There is also an interesting conundrum. Not just any caffeinated beverage will do. For instance, studies evaluating the effect of green tea – popularly considered a “healthier” source of caffeine – have not shown the benefits associated with filtered, caffeinated coffee. This lack of benefit appears to be true for sources of caffeine other than green tea as well.

Lastly, coffee should ideally be prepared by filtration because filtering removes cafestol and kahweol, two substances found in coffee that may increase serum cholesterol.

Continue reading full article here …..

Coffee: Good for us? Or bad for us? Two new studies disagree

Two new reports disagree about the health benefits of coffee and caffeine. (Irfan Khan / Los Angeles Times / December 8, 2012)

By Rene Lynch

August 19, 2013, 3:00 p.m.

Drinking lots of coffee is good for you!! Drinking lots of coffee will kill you!!

These are the competing headlines pinging around the media universe Monday, causing whiplash among those of us who rely on a cup (or more) of the black stuff to fuel our day.

First up, a new study released by Mayo Clinic Proceedings found that, "Drinking large amounts of coffee may be bad" for people under the age of 55.

"A study of more than 40,000 individuals found a statistically significant 21% increased mortality in those drinking more than 28 cups of coffee a week," the report said.

"More than 28 cups of coffee a week" works out to be at least four cups of coffee a day. Admittedly, that's a lot of coffee. But not exactly unheard of, especially during crunch times such as studying for finals, or staring down work deadlines.

Counter that with another study, also making the rounds Monday, suggesting that drinking four cups of coffee a day could reduce the risk of non-alcoholic fatty liver disease, also known as NAFLD.

The study by Duke-NUS Graduate Medical School in Singapore found that increased caffeine intake could reduce the disease that affects an estimated 30% of American adults.

According to the analysis, slated to be published in the September issue of Hepatology: "[T]hese findings suggested that coffee and tea consumption (equivalent to the caffeine intake of four cups a day) may be beneficial in the prevention and protection against the progression of NAFLD in humans."

So, what gives?

Unfortunately, there's no easy answer.

Further confusing the issue is the acknowledgment in the first study that men and women who consumed higher amounts of coffee were more likely to smoke and "had lower levels of cardiorespiratory fitness."

According to the Mayo Clinic document, coffee is a complex mixture of chemicals and while it is a major source of antioxidants and has plenty of beneficial health effects, it also carries with it plenty of potential adverse effects because of caffeine’s ability to, among other things, inhibit insulin activity and increase blood pressure.

As might be suspected, more research is needed, the studies both suggest.

"There continues to be considerable debate about the health effects of caffeine, and coffee specifically," said Dr. Carl J. Lavie of the Department of Cardiovascular Diseases, Ochsner Medical Center, New Orleans, and a co-author of the study.

He told the Los Angeles Times that although more research is needed, it might be a good idea to trim back on the excess coffee intake. "All things in moderation," he said.

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The Effect of Caffeine and Alcohol Consumption on Liver Fibrosis

From Liver International

A Study of 1045 Asian Hepatitis B Patients Using Transient Elastography

Arlinking Ong; Vincent Wai-SunWong; Grace Lai-Hung Wong; Henry Lik-Yuen Chan

Posted: 01/25/2012; Liver International. 2011;31(7):1047-1053. © 2011 Blackwell Publishing

Abstract and Introduction

Abstract

Background: Role of caffeine consumption in chronic hepatitis B virus (HBV)-infected patients and the interaction with alcohol consumption is unclear.
Aim: This study aimed to investigate the relationship between caffeine and alcohol consumption and liver stiffness in chronic HBV-infected patients.
Methods: Chronic HBV-infected patients who underwent transient elastography examination in 2006–2008 were studied. Advanced fibrosis was defined as liver stiffness >9 kPa for patients with normal alanine aminotransferase (ALT) or >12 kPa for those with elevated ALT according to previous validation study. Caffeine and alcohol consumption was recorded using a standardized questionnaire. Excessive alcohol intake was defined as 30 g/day in men and 20 g/day in women.
Results: The liver stiffness of 1045 patients who completed the questionnaire was 8.3 ± 6.2 kPa. Two hundred and sixteen (20.7%) patients had advanced fibrosis. Ninety-five (19.0%) patients who drank ≥1 cup of coffee had advanced fibrosis, compared with 121 (22.2%) patients who drank <1 cup (P=0.21). The amount of caffeine intake had positive correlation with the amount of alcohol intake (r_s=0.167, P<0.001). Although 231 (22.1%) patients reported alcohol consumption, only 11 (1%) had excessive alcohol intake. The prevalence of advanced fibrosis among patients with mild to moderate alcohol intake (26, 18.8%) was comparable to that among non-drinkers (190, 21.0%) (P=0.57).
Conclusion: Caffeine intake does not affect liver stiffness in chronic HBV-infected patients. Patients who drink coffee regularly tend to drink alcohol. Most chronic HBV-infected patients do not have excessive alcohol consumption. The prevalence of advanced fibrosis among mild to moderate alcohol drinkers was low in this population.

Introduction

Chronic hepatitis B virus (HBV) infection is a global health problem affecting over 350 million people. Persistent hepatic inflammation because of chronic HBV infection will result in progressive liver fibrosis, which will eventually result in cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC).^[1]

Alcoholism^[2] is a primary chronic disease with genetic, psychosocial and environmental factors influencing its development and manifestations. Heavy alcohol consumption commonly causes alcoholic liver disease, cirrhosis and even HCC.^[3] However, it is unclear whether consumption of a smaller amount of alcohol is safe in chronic hepatitis B patients.

On the other hand, consumption of coffee or caffeine may reduce liver injury. Greater coffee, and especially caffeine, intake was associated with a lower prevalence of abnormal alanine aminotransferase (ALT) activity in USA^[4] and Japan.^[5] Plasma glutathione was increased by 16% on coffee consumption in an Italian population.^[6] In a prospective study among advanced Hepatitis C-related liver disease, regular coffee consumption was associated with lower rates of disease progression.^[7] In human hepatoma cell lines, coffee and its major components (caffeine, cafestol and kahweol) alter expression and activity of enzymes involved in xenobiotic mechanisms.^[8] Mice pretreated with cafestol and kahweol were protected from carbon tetrachloride toxicity by inhibiting cytochrome CYP 2E1,^[9] an enzyme responsible for carbon tetrachloride bioactivation while caffeine specifically inhibited expression of connective tissue growth factor by interfering with transforming growth factor-β signaling through the SMAD pathway and upregulate peroxisome proliferator activated receptor γ levels. These in vitro and in vivo data suggested that caffeine has antifibrotic effects.^[10]

A recent case control study among chronic hepatitis B carriers showed that coffee consumption reduced the risk of HCC by half with a significant dose-response effect.^[11] It is uncertain if the beneficial effect is mediated through prevention of liver fibrosis and cirrhosis. In the past, large-scaled studies on risk factors of liver fibrosis and cirrhosis were difficult to conduct because the assessment required liver biopsy, which was invasive and not acceptable by all patients. In this study, we aimed to determine the effect of alcohol and caffeine consumption on the prevalence of advanced liver fibrosis among chronic HBV-infected patients using transient elastography.

Methods

Study Population

We prospectively recruited chronic HBV-infected patients regardless of the disease activity for transient elastography. We received referrals from all primary care and hospital clinics in Hong Kong from July 2006 to February 2008.^[12] Chronic HBV infection was diagnosed by positive serology tests for serum HBsAg for at least 6 months. We excluded patients with evidence of other chronic liver disease by screening with antibody against hepatitis C virus, antinuclear antibody, antismooth muscle antibody, antimitochondrial antibody, serum ceruloplasmin, transferrin saturation and ferritin.

From April to May 2008, patients from the original cohort were phone-interviewed with a verbal consent for this study. Questions concerning their alcohol and caffeine consumption (days per week of consumption and amount per day) in the previous year were asked from a standardized questionnaire. Patients who refused to give verbal consent for the phone-interview were not included in this study.

Clinical Evaluation

All patients received comprehensive clinical and laboratory assessment at the time of transient elastography. Serum HBV DNA levels were measured by the TaqMan real-time polymerase chain reaction assay with a range of detection from 100 to 10⁹ copies/ml.^[13] Anthropometric parameters including body weight, body height, hip circumference and waist circumference were measured. Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared. Overweight was defined as BMI≥23 kg/m², and obesity as BMI≥25 kg/m² according to the Asian and Chinese criteria.^[14] We defined moderate and severe obesity as BMI≥28 kg/m² M and ≥30 kg/m² respectively. Excessive alcohol intake was defined as >30 g/day in men and >20 g/day in women.^[15]

Liver Stiffness Measurement by Transient Elastography

Transient elastography (FibroScan®, Echosens, Paris, France) is one of the new noninvasive modality to evaluate liver fibrosis by measuring liver stiffness. It uses an ultrasound-based technique to measure the speed of propagation of the shear wave through the liver. It can assess approximately 1/500 of the liver's total mass thus reducing the sampling error. Transient elastography has been shown to accurately predict histological advanced fibrosis in different liver diseases.^[16–21]

Liver stiffness measurement (LSM) was performed using transient elastography according to the instructions of the manufacturer. Details of the technical background and examination procedure was described previously.^[22] Officially trained operators who had performed at least 50 measurements prior this study were responsible to perform the LSM for the patients who had kept fast for at least 8 h. The LSM was considered reliable only if 10 successful acquisitions were obtained, an interquartile range (IQR)/LSM of ≤30% and the success rate was ≥60%. Liver stiffness was expressed in kPa. We defined advanced fibrosis as liver stiffness >9 kPa for those with normal ALT or >12 kPa for those with elevated ALT (F3 fibrosis on histology).^[23,24]

Hui's Index

Hui's index was a non-invasive model comprising of BMI, platelet count, serum albumin and total bilirubin [predictive probabilities=exp(3.148+0.167 × BMI+0.088 × bilirubin [μM]−0.151 × albumin [g/L]−0.019 × platelet [10⁹/L])/(1+exp(3.148+0.167 × BMI+0.088 × bilirubin [μM]−0.151 × albumin [g/L]−0.019 × platelet [10⁹/L]))] to predict significant fibrosis (F2 fibrosis on histology).^[25] Among 235 chronic hepatitis B patients with liver biopsy, at a cutoff value of 0.15, the sensitivity, specificity, positive and negative predictive values for significant fibrosis were 93, 49, 41 and 95% respectively.

Phone-interview and Questionnaire

A structured questionnaire interview was conducted over the phone to collect data on alcohol and caffeine intake. Participants were specifically asked about the average quantity and frequency of beer, wine, or liquor consumption to estimate the amount of alcohol consumption. The average quantity and frequency of consumption of coffee (regular, instant, ground and decaffeinated), tea (any kind), cola-type soda (regular or decaffeinated) and chocolate (including chocolate milk) was also enquired to estimate the amount of caffeine consumption. Effect of alcohol and caffeine consumption was analyzed with respect to the severity of liver fibrosis as assessed by transient elastography, Hui's Index and other clinical and biochemical parameters

Statistical Analyses

Total caffeine consumption (mg/day) was estimated by summing caffeine from regular coffee (137 mg per cup), regular tea (47 mg per cup), regular and diet cola-type soda (46 mg per bottle or can) and chocolate (7 mg per serving).^[26] As for the coffee cup equivalent, the total caffeine consumption per day was divided by 137 (Table 1). Continuous variables were expressed in mean ± standard deviation or median (IQR) as appropriate. Qualitative and quantitative differences between subgroups were analyzed using χ² or Fisher's exact test for categorical parameters as appropriate, and Student's t-test or Mann–Whitney test for continuous parameters as appropriate. Logistic regression analyses were performed to determine if caffeine and alcohol consumption was associated with liver fibrosis. The multivariate adjusted logistic regression model included covariates that were included in univariate analysis. Spearman's rank correlation was used to correlate caffeine and alcohol intake. All statistical tests were two-sided. Statistical significance was taken as P<0.05. Statistical analysis was performed by Statistical Package for Social Science (SPSS version 17.0, Chicago, IL, USA).

Results

Patient Characteristics

Overall, 22.7% of 1532 patients in this study came from primary care clinics and 77.3% were from hospital clinics. Six patients were excluded because of anti-HCV positivity, 60 patients because of unreliable LSM results and 421 as we failed to contact for phone-interview because of various reasons (e.g. changed telephone numbers or no answer despite multiple attempts). For patients we able to contact via phone, none of them refused to give verbal consent for the phone interview. A total of 1045 chronic hepatitis B patients were thus included in this study. Majority of patients were males (652, 62.4%), of which 175 (26.8%) were overweight and 210 (32.2%) were obese. Two hundred forty seven (37.9%) male patients had elevated ALT with 71% having HBV DNA of more than 4 logs copies/ml. Four hundred and ninety-nine (47.8%) patients consumed one cup of coffee or more per day, while 231 (22.1%) patients drank alcohol. Only 26 (2.5%) patients reported no intake of both coffee and alcohol. The median (IQR) daily consumption of caffeine from food and beverages was 124 (51.6–275.6) mg/day or 1 (0.4–2.0) cup of coffee/day while alcohol consumption of >20 g/day was 1.9% (Table 2). Two hundred and sixteen (20.7%) patients had LSM suggestive of advanced fibrosis.

Caffeine Intake and Liver Fibrosis

Table 3 shows the median total caffeine consumption in mg/day and the coffee cup equivalent according to different patient characteristics where there was no significant difference in caffeine consumption among those with no fibrosis and advanced fibrosis. There was no significant difference in LSM (Table 4). In addition, caffeine intake had no significant correlation with liver stiffness (r_s=0.011, P=0.722) or the Hui's index (r_s=−0.002, P=0.948). Based on LSM and the Hui's index, caffeine intake by univariate and multivariate analysis was not associated with the risk of advanced liver fibrosis (Table 5).

Alcohol Intake and Liver Fibrosis

Majority of patients (77.9%) did not consume alcohol while only 11 out of 231 patients with alcohol consumption had excessive alcohol drinking. The highest alcohol consumption per day was 88 g. Advanced fibrosis was only prevalent in 26 (18.8%) of those with mild to moderate alcohol consumption compared with 190 (21.0%) of those non-alcoholic drinkers (P=0.57).

Those who drink alcohol have significantly higher caffeine consumption than those who do not drink alcohol (Table 3). Caffeine intake had positive correlation with alcohol intake (r_s=0.167, P<0.001).

Discussion

In this large territory-wide observational study with prospective recruitment, we assessed the relationship between caffeine and alcohol consumption and the risk of advanced liver fibrosis in chronic hepatitis B patients with different disease severity. Caffeine intake was not associated with advanced fibrosis. Patients who drank coffee regularly were more likely to consume alcohol. On the other hand, few chronic hepatitis B patients in Hong Kong had excessive alcohol consumption. Mild to moderate alcohol consumption did not increase the risk of advanced fibrosis.

Coffee is a rich source of a number of phenol compounds with antioxidant effects in vitro, with main polyphenols are phenolic acids such as chlorogenic and caffeic acid.^[27] Caffeine and its metabolites, 1-methylxanthine and 1-methyluric acid, have also been shown to have antioxidant properties.^[28] Caffeine has also been reported to inhibit chemical carcinogenesis and ultraviolet B light induced carcinogenesis in mice.^[29,30] Coffee is also found to decrease the progression of liver disease among those with advanced hepatic fibrosis^[7] and even reduce the risk of HCC^[31,32] One study^[33] concluded that approximately 2 coffee cup equivalents/day was associated with less severe hepatic fibrosis, but the beneficial effect was only shown in patients with chronic hepatitis C rather than patients with other liver diseases. A case control study in Italy showed that the protective effect of coffee on HCC was mainly in people who are not chronically infected with HBV.^[31] Overall, previous studies included mostly chronic hepatitis C patients and HBV patients were underrepresented. Based on our results, it appears that liver fibrosis in chronic hepatitis B patients is determined mainly by virological and genetic factors and less affected by caffeine intake.

In previous reports, men who have daily alcohol intake of 30–39 g and women who consumed 20–29 g of alcohol daily would have an increased risk of all cause mortality among the general population.^[34] Seventy-eight percent of our cohort did not drink alcohol at all while only 1% of patient had history of excessive alcohol consumption. Nonetheless, we could not find any deleterious effect of mild to moderate alcohol consumption to liver fibrosis. As alcohol drinkers were mostly coffee drinkers as well, the concomitant caffeine intake might but one of the confounders leading to the absence of increased risk of advanced fibrosis in alcohol drinkers. Nonetheless only a minority (1% of the study population has excessive alcohol intake, we believe that the major reason of the absence of increased risk of advanced fibrosis in alcohol drinkers was the modest instead of excess amount of alcohol use. Because most of our patients had no advanced liver disease as compared with other studies (33, 35–38), our results could not be extrapolated to cirrhotic patients. Less than 20 g of alcohol intake tends not to increase risk of advanced fibrosis in our present study. Controlled prospective studies may be done in the future to verify this.

One of the limitations of our study was the lack of liver biopsy. As liver biopsy is an invasive procedure, studies using histological fibrosis as an endpoint might suffer from the problem of small sample size and selection bias towards patients with active or advanced liver disease.^[39] On the other hand, a non-invasive test such as transient elastography could be applied to a large number of patients with different disease severity. In fact, transient elastography has been shown to be highly accurate in detecting histological advanced fibrosis and cirrhosis in chronic hepatitis B patients,^[16,23] though the accuracy might be limited in settings of grossly elevated transaminase levels,^[16] but not in the presence of steatosis.^[18] Secondly, recall bias might occur during the questionnaire survey and affect the accuracy of the measurement of the caffeine intake measured. We have tried to minimize this bias by using a quantity-frequency questionnaire, which has been previously adapted in a study demonstrating the protective effect of coffee consumption from HCC.^[11] There were 159 (15.2%) participants drinking >2–3 coffee-cup equivalents/day and 103 (9.9%) drinking >3 coffee-cup equivalents/day. Because the above numbers for these groups were low and previous finding showing 2 coffee-cup equivalents/day was associated to less severe liver fibrosis, we combined these groups for analysis. Because this is a cross sectional study, possible unmeasured as well as poorly measured confounding factors that may affect the interpretation of our data such as changes in the drinking habit of the patients, variability of caffeine intake over time, socioeconomic status, educational level were not considered in our analysis.

In conclusion, cross-sectional caffeine intake does not affect liver stiffness in chronic HBV-infected patients. The protective effect of caffeine on HCC demonstrated in previous studies is probably via the pathway other than reducing liver fibrosis. The prevalence of advanced liver fibrosis is low (20%) in chronic hepatitis B patients with daily alcohol consumption below 20 g.

References

1. Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis 2006; 26: 153–61.
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Association Of Caffeine Intake and Histological Features of Chronic Hepatitis C

J Hepatol. 2010 Dec 8. [Epub ahead of print]

Costentin CE, Roudot-Thoraval F, Zafrani ES, Medkour F, Pawlotsky JM, Mallat A, Hézode C.

AP-HP, Service d'Hépatologie et de Gastroentérologie, Groupe Hospitalier Henri Mondor-Albert Chenevier, Créteil, 94000 France.

Abstract

Rational The severity of chronic hepatitis C (CHC) is modulated by host and environmental factors. Several reports suggest that caffeine intake exerts hepatoprotective effects in patients with chronic liver disease. The aim of this study was to evaluate the impact of caffeine consumption on activity grade and fibrosis stage in patients with CHC. Methods 238 treatment-naı¨ve patients with histologically-proven CHC were included. Demographic, epidemiological, environmental, virological and metabolic features were collected, including daily consumptions of alcohol, cannabis, tobacco and caffeine during the six month preceding liver biopsy. Daily caffeine consumption was estimated as the sum of mean intakes of caffeinated coffee, tea and caffeine-containing sodas. Histological activity grade and fibrosis stage were scored according to Metavir. Patients (154 men, 84 women, mean age: 45±11 years) were categorized according to caffeine consumption quartiles: group 1 (<225 mg/day, n=59), group 2 (225-407 mg/day, n=57), group 3 (408-678 mg/day, n=62) and group 4 (>678 mg/day, n=60). Results There was a significant inverse relationship between activity grade and daily caffeine consumption: Activity grade >A2 was present in 78%, 61%, 52% and 48% of patients in group 1, 2, 3 and 4, respectively (p<0.001). By multivariate analysis, daily caffeine consumption greater than 408 mg/day was associated with a lesser risk of activity grade >A2 (OR=0.32 (0.12-0.85)). Caffeine intake showed no relation with the fibrosis stage. Conclusions Caffeine consumption greater than 408 mg/day (3 cups or more) is associated with reduced histological activity in patients with CHC. These findings support potential hepatoprotective properties of caffeine in chronic liver diseases.

Copyright © 2010. Published by Elsevier B.V.

PMID: 21145804 [PubMed - as supplied by publisher]

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